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CKD: Risk Before, Diet After
Q) In my admitting orders for a CKD patient, I wrote for a “renal diet.” However, the nephrology practitioners changed it to a DASH diet. What is the difference? Why would they not want a “renal diet”?
The answer to this question is: It depends—on the patient, his/her comorbidities, and the need for dialysis treatments (and if so, what type he/she is receiving). Renal diet is a general term used to refer to medical nutrition therapy (MNT) given to a patient with CKD. Each of the five stages of CKD has its own specific MNT requirements.
The MNT for CKD patients often involves modification of the following nutrients: protein, sodium, potassium, phosphorus, and sometimes fluid. The complexity of this therapy often confuses health care professionals when a CKD patient is admitted to the hospital. Let’s examine each nutrient modification to understand optimal nutrition for CKD patients.
Protein. As kidneys fail to excrete urea, protein metabolism is compromised. Thus, in CKD stages 1 and 2, the general recommendations for protein intake are 0.8 to 1.4 g/kg/d. As a patient progresses into CKD stages 3 and 4, these recommendations decrease to 0.6 to 0.8 g/kg/d. In addition, the Kidney Disease Outcomes Quality Initiative (KDOQI) and the Academy of Nutrition and Dietetics recommend that at least 50% of that protein intake be of high biological value (eg, foods of animal origin, soy proteins, dairy, legumes, and nuts and nut butters).2
Why the wide range in protein intake? Needs vary depending on the patient’s comorbidities and nutritional status. Patients with greater need (eg, documented malnutrition, infections, or wounds) will require more protein than those without documented catabolic stress. Additionally, protein needs are based on weight, making it crucial to obtain an accurate weight. When managing a very overweight or underweight patient, an appropriate standard body weight must be calculated. This assessment should be done by a registered dietitian (RD).
Also, renal replacement therapies, once introduced, sharply increase protein needs. Hemodialysis (HD) can account for free amino acid losses of 5 to 20 g per treatment. Peritoneal dialysis (PD) can result in albumin losses of 5 to 15 g/d.2 As a result, protein needs in HD and PD patients are about 1.2 g/kg/d of standard body weight. It has been reported that 30% to 50% of patients are not consuming these amounts, placing them at risk for malnutrition and a higher incidence of morbidity and mortality.2
Sodium. In CKD stages 1 to 4, dietary sodium intake should be less than 2,400 mg/d. The Dietary Approaches to Stop Hypertension (DASH) diet and a Mediterranean diet have been associated with reduced risk for decline in glomerular filtration rate (GFR) and better blood pressure control.3 Both of these diets can be employed, especially in the beginning stages of CKD. But as CKD progresses and urine output declines, recommendations for sodium intake for both HD and PD patients decrease to 2,000 mg/d. In an anuric patient, 2,000 mg/d is the maximum.2
Potassium. As kidney function declines, potassium retention occurs. In CKD stages 1 to 4, potassium restriction is not employed unless the serum level rises above normal.2 The addition of an ACE inhibitor or an angiotensin II receptor blocker to the medication regimen necessitates close monitoring of potassium levels. Potassium allowance for HD varies according to the patient’s urine output and can range from 2 to 4 g/d. PD patients generally can tolerate 3 to 4 g/d of potassium without becoming hyperkalemic, as potassium is well cleared with PD.2
Continue for further examinations >>
Phosphorus. Mineral bone abnormalities begin early in the course of CKD and lead to high-turnover bone disease, adynamic bone disease, fractures, and soft-tissue calcification. Careful monitoring of calcium, intact parathyroid hormone, and phosphorus levels is required throughout all stages of CKD, with hyperphosphatemia of particular concern.
In CKD stages 1 and 2, dietary phosphorus should be limited to maintain a normal serum level.2 As CKD progresses and phosphorus retention increases, 800 to 1,000 mg/d or 10 to 12 mg of phosphorus per gram of protein should be prescribed.
Even with the limitation of dietary phosphorus, phosphate-binding medications may be required to control serum phosphorus in later CKD stages and in HD and PD patients.2 Limiting dietary phosphorus can be difficult for patients because of inorganic phosphate salt additives widely found in canned and processed foods; they are also added to dark colas and to meats and poultry to act as preservatives and improve flavor and texture. Phosphorus additives are 100% bioavailable and therefore more readily absorbed than organic phosphorus.4
Fluid. Lastly, CKD patients need to think about their fluid intake. HD patients with a urine output of > 1,000 mL/24-h period will be allowed up to 2,000 mL/d of fluid. (A 12-oz canned drink is 355 mL.) Those with less than 1,000 mL of urine output will be allowed 1,000 to 1,500 mL/d, with anuric patients capped at 1,000 mL/d. PD patients are allowed 1,000 to 3,000 mL/d depending on urine output and overall status.2 Patients should also be reminded that foods such as soup and gelatin are counted in their fluid allowance.
The complexities of the “renal diet” make patient education by an RD critical. However, a recent article suggested that MNT for CKD patients is underutilized, with limited referrals and lack of education for primary care providers and RDs cited as reasons.5 This is mystifying considering that Medicare will pay for RD services for CKD patients.
The National Kidney Disease Education Program, in association with the Academy of Nutrition and Dietetics, has developed free professional and patient education materials to address this need; they are available at http://nkdep.nih.gov/.
Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey
REFERENCES
1. McMahon GM, Preis SR, Hwang S-J, Fox CS. Mid-adulthood risk factor profiles for CKD. J Am Soc Nephrol. 2014 Jun 26; [Epub ahead of print].
2. Byham-Gray L, Stover J, Wiesen K. A Clinical Guide to Nutrition Care in Kidney Disease. 2nd ed. The Academy of Nutrition and Dietetics; 2013.
3. Crews DC. Chronic kidney disease and access to healthful foods. ASN Kidney News. 2014;6(5):11.
4. Moe SM. Phosphate additives in food: you are what you eat—but shouldn’t you know that? ASN Kidney News. 2014;6(5):8.
5. Narva A, Norton J. Medical nutrition therapy for CKD. ASN Kidney News. 2014;6(5):7.
| Clinician Reviews in partnership with |
 |
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Joanne Hindlet, ACNP, CNN-NP, who practices at Houston Nephrology Group, and Luanne DiGuglielmo, MS, RD, CSR, who practices at DaVita Summit Renal Center in Mountainside, New Jersey, and is the Clinical Coordinator for the Dietetic Internship at the College of Saint Elizabeth in Morristown, New Jersey.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Joanne Hindlet, ACNP, CNN-NP, who practices at Houston Nephrology Group, and Luanne DiGuglielmo, MS, RD, CSR, who practices at DaVita Summit Renal Center in Mountainside, New Jersey, and is the Clinical Coordinator for the Dietetic Internship at the College of Saint Elizabeth in Morristown, New Jersey.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Joanne Hindlet, ACNP, CNN-NP, who practices at Houston Nephrology Group, and Luanne DiGuglielmo, MS, RD, CSR, who practices at DaVita Summit Renal Center in Mountainside, New Jersey, and is the Clinical Coordinator for the Dietetic Internship at the College of Saint Elizabeth in Morristown, New Jersey.
Q) In my admitting orders for a CKD patient, I wrote for a “renal diet.” However, the nephrology practitioners changed it to a DASH diet. What is the difference? Why would they not want a “renal diet”?
The answer to this question is: It depends—on the patient, his/her comorbidities, and the need for dialysis treatments (and if so, what type he/she is receiving). Renal diet is a general term used to refer to medical nutrition therapy (MNT) given to a patient with CKD. Each of the five stages of CKD has its own specific MNT requirements.
The MNT for CKD patients often involves modification of the following nutrients: protein, sodium, potassium, phosphorus, and sometimes fluid. The complexity of this therapy often confuses health care professionals when a CKD patient is admitted to the hospital. Let’s examine each nutrient modification to understand optimal nutrition for CKD patients.
Protein. As kidneys fail to excrete urea, protein metabolism is compromised. Thus, in CKD stages 1 and 2, the general recommendations for protein intake are 0.8 to 1.4 g/kg/d. As a patient progresses into CKD stages 3 and 4, these recommendations decrease to 0.6 to 0.8 g/kg/d. In addition, the Kidney Disease Outcomes Quality Initiative (KDOQI) and the Academy of Nutrition and Dietetics recommend that at least 50% of that protein intake be of high biological value (eg, foods of animal origin, soy proteins, dairy, legumes, and nuts and nut butters).2
Why the wide range in protein intake? Needs vary depending on the patient’s comorbidities and nutritional status. Patients with greater need (eg, documented malnutrition, infections, or wounds) will require more protein than those without documented catabolic stress. Additionally, protein needs are based on weight, making it crucial to obtain an accurate weight. When managing a very overweight or underweight patient, an appropriate standard body weight must be calculated. This assessment should be done by a registered dietitian (RD).
Also, renal replacement therapies, once introduced, sharply increase protein needs. Hemodialysis (HD) can account for free amino acid losses of 5 to 20 g per treatment. Peritoneal dialysis (PD) can result in albumin losses of 5 to 15 g/d.2 As a result, protein needs in HD and PD patients are about 1.2 g/kg/d of standard body weight. It has been reported that 30% to 50% of patients are not consuming these amounts, placing them at risk for malnutrition and a higher incidence of morbidity and mortality.2
Sodium. In CKD stages 1 to 4, dietary sodium intake should be less than 2,400 mg/d. The Dietary Approaches to Stop Hypertension (DASH) diet and a Mediterranean diet have been associated with reduced risk for decline in glomerular filtration rate (GFR) and better blood pressure control.3 Both of these diets can be employed, especially in the beginning stages of CKD. But as CKD progresses and urine output declines, recommendations for sodium intake for both HD and PD patients decrease to 2,000 mg/d. In an anuric patient, 2,000 mg/d is the maximum.2
Potassium. As kidney function declines, potassium retention occurs. In CKD stages 1 to 4, potassium restriction is not employed unless the serum level rises above normal.2 The addition of an ACE inhibitor or an angiotensin II receptor blocker to the medication regimen necessitates close monitoring of potassium levels. Potassium allowance for HD varies according to the patient’s urine output and can range from 2 to 4 g/d. PD patients generally can tolerate 3 to 4 g/d of potassium without becoming hyperkalemic, as potassium is well cleared with PD.2
Continue for further examinations >>
Phosphorus. Mineral bone abnormalities begin early in the course of CKD and lead to high-turnover bone disease, adynamic bone disease, fractures, and soft-tissue calcification. Careful monitoring of calcium, intact parathyroid hormone, and phosphorus levels is required throughout all stages of CKD, with hyperphosphatemia of particular concern.
In CKD stages 1 and 2, dietary phosphorus should be limited to maintain a normal serum level.2 As CKD progresses and phosphorus retention increases, 800 to 1,000 mg/d or 10 to 12 mg of phosphorus per gram of protein should be prescribed.
Even with the limitation of dietary phosphorus, phosphate-binding medications may be required to control serum phosphorus in later CKD stages and in HD and PD patients.2 Limiting dietary phosphorus can be difficult for patients because of inorganic phosphate salt additives widely found in canned and processed foods; they are also added to dark colas and to meats and poultry to act as preservatives and improve flavor and texture. Phosphorus additives are 100% bioavailable and therefore more readily absorbed than organic phosphorus.4
Fluid. Lastly, CKD patients need to think about their fluid intake. HD patients with a urine output of > 1,000 mL/24-h period will be allowed up to 2,000 mL/d of fluid. (A 12-oz canned drink is 355 mL.) Those with less than 1,000 mL of urine output will be allowed 1,000 to 1,500 mL/d, with anuric patients capped at 1,000 mL/d. PD patients are allowed 1,000 to 3,000 mL/d depending on urine output and overall status.2 Patients should also be reminded that foods such as soup and gelatin are counted in their fluid allowance.
The complexities of the “renal diet” make patient education by an RD critical. However, a recent article suggested that MNT for CKD patients is underutilized, with limited referrals and lack of education for primary care providers and RDs cited as reasons.5 This is mystifying considering that Medicare will pay for RD services for CKD patients.
The National Kidney Disease Education Program, in association with the Academy of Nutrition and Dietetics, has developed free professional and patient education materials to address this need; they are available at http://nkdep.nih.gov/.
Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey
REFERENCES
1. McMahon GM, Preis SR, Hwang S-J, Fox CS. Mid-adulthood risk factor profiles for CKD. J Am Soc Nephrol. 2014 Jun 26; [Epub ahead of print].
2. Byham-Gray L, Stover J, Wiesen K. A Clinical Guide to Nutrition Care in Kidney Disease. 2nd ed. The Academy of Nutrition and Dietetics; 2013.
3. Crews DC. Chronic kidney disease and access to healthful foods. ASN Kidney News. 2014;6(5):11.
4. Moe SM. Phosphate additives in food: you are what you eat—but shouldn’t you know that? ASN Kidney News. 2014;6(5):8.
5. Narva A, Norton J. Medical nutrition therapy for CKD. ASN Kidney News. 2014;6(5):7.
Q) In my admitting orders for a CKD patient, I wrote for a “renal diet.” However, the nephrology practitioners changed it to a DASH diet. What is the difference? Why would they not want a “renal diet”?
The answer to this question is: It depends—on the patient, his/her comorbidities, and the need for dialysis treatments (and if so, what type he/she is receiving). Renal diet is a general term used to refer to medical nutrition therapy (MNT) given to a patient with CKD. Each of the five stages of CKD has its own specific MNT requirements.
The MNT for CKD patients often involves modification of the following nutrients: protein, sodium, potassium, phosphorus, and sometimes fluid. The complexity of this therapy often confuses health care professionals when a CKD patient is admitted to the hospital. Let’s examine each nutrient modification to understand optimal nutrition for CKD patients.
Protein. As kidneys fail to excrete urea, protein metabolism is compromised. Thus, in CKD stages 1 and 2, the general recommendations for protein intake are 0.8 to 1.4 g/kg/d. As a patient progresses into CKD stages 3 and 4, these recommendations decrease to 0.6 to 0.8 g/kg/d. In addition, the Kidney Disease Outcomes Quality Initiative (KDOQI) and the Academy of Nutrition and Dietetics recommend that at least 50% of that protein intake be of high biological value (eg, foods of animal origin, soy proteins, dairy, legumes, and nuts and nut butters).2
Why the wide range in protein intake? Needs vary depending on the patient’s comorbidities and nutritional status. Patients with greater need (eg, documented malnutrition, infections, or wounds) will require more protein than those without documented catabolic stress. Additionally, protein needs are based on weight, making it crucial to obtain an accurate weight. When managing a very overweight or underweight patient, an appropriate standard body weight must be calculated. This assessment should be done by a registered dietitian (RD).
Also, renal replacement therapies, once introduced, sharply increase protein needs. Hemodialysis (HD) can account for free amino acid losses of 5 to 20 g per treatment. Peritoneal dialysis (PD) can result in albumin losses of 5 to 15 g/d.2 As a result, protein needs in HD and PD patients are about 1.2 g/kg/d of standard body weight. It has been reported that 30% to 50% of patients are not consuming these amounts, placing them at risk for malnutrition and a higher incidence of morbidity and mortality.2
Sodium. In CKD stages 1 to 4, dietary sodium intake should be less than 2,400 mg/d. The Dietary Approaches to Stop Hypertension (DASH) diet and a Mediterranean diet have been associated with reduced risk for decline in glomerular filtration rate (GFR) and better blood pressure control.3 Both of these diets can be employed, especially in the beginning stages of CKD. But as CKD progresses and urine output declines, recommendations for sodium intake for both HD and PD patients decrease to 2,000 mg/d. In an anuric patient, 2,000 mg/d is the maximum.2
Potassium. As kidney function declines, potassium retention occurs. In CKD stages 1 to 4, potassium restriction is not employed unless the serum level rises above normal.2 The addition of an ACE inhibitor or an angiotensin II receptor blocker to the medication regimen necessitates close monitoring of potassium levels. Potassium allowance for HD varies according to the patient’s urine output and can range from 2 to 4 g/d. PD patients generally can tolerate 3 to 4 g/d of potassium without becoming hyperkalemic, as potassium is well cleared with PD.2
Continue for further examinations >>
Phosphorus. Mineral bone abnormalities begin early in the course of CKD and lead to high-turnover bone disease, adynamic bone disease, fractures, and soft-tissue calcification. Careful monitoring of calcium, intact parathyroid hormone, and phosphorus levels is required throughout all stages of CKD, with hyperphosphatemia of particular concern.
In CKD stages 1 and 2, dietary phosphorus should be limited to maintain a normal serum level.2 As CKD progresses and phosphorus retention increases, 800 to 1,000 mg/d or 10 to 12 mg of phosphorus per gram of protein should be prescribed.
Even with the limitation of dietary phosphorus, phosphate-binding medications may be required to control serum phosphorus in later CKD stages and in HD and PD patients.2 Limiting dietary phosphorus can be difficult for patients because of inorganic phosphate salt additives widely found in canned and processed foods; they are also added to dark colas and to meats and poultry to act as preservatives and improve flavor and texture. Phosphorus additives are 100% bioavailable and therefore more readily absorbed than organic phosphorus.4
Fluid. Lastly, CKD patients need to think about their fluid intake. HD patients with a urine output of > 1,000 mL/24-h period will be allowed up to 2,000 mL/d of fluid. (A 12-oz canned drink is 355 mL.) Those with less than 1,000 mL of urine output will be allowed 1,000 to 1,500 mL/d, with anuric patients capped at 1,000 mL/d. PD patients are allowed 1,000 to 3,000 mL/d depending on urine output and overall status.2 Patients should also be reminded that foods such as soup and gelatin are counted in their fluid allowance.
The complexities of the “renal diet” make patient education by an RD critical. However, a recent article suggested that MNT for CKD patients is underutilized, with limited referrals and lack of education for primary care providers and RDs cited as reasons.5 This is mystifying considering that Medicare will pay for RD services for CKD patients.
The National Kidney Disease Education Program, in association with the Academy of Nutrition and Dietetics, has developed free professional and patient education materials to address this need; they are available at http://nkdep.nih.gov/.
Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey
REFERENCES
1. McMahon GM, Preis SR, Hwang S-J, Fox CS. Mid-adulthood risk factor profiles for CKD. J Am Soc Nephrol. 2014 Jun 26; [Epub ahead of print].
2. Byham-Gray L, Stover J, Wiesen K. A Clinical Guide to Nutrition Care in Kidney Disease. 2nd ed. The Academy of Nutrition and Dietetics; 2013.
3. Crews DC. Chronic kidney disease and access to healthful foods. ASN Kidney News. 2014;6(5):11.
4. Moe SM. Phosphate additives in food: you are what you eat—but shouldn’t you know that? ASN Kidney News. 2014;6(5):8.
5. Narva A, Norton J. Medical nutrition therapy for CKD. ASN Kidney News. 2014;6(5):7.
Successful AVF creation a national challenge
CORONADO, CALIF.– Clinicians have a ways to go before they reach the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative Guidelines for vascular access, a recent analysis of national data suggest.
Part of the challenge is because the incidence of renal disease continues to grow over time, Dr. Mark R. Nehler said at the annual meeting of the Western Vascular Society. “The elderly population is growing, and the need for access is growing,” said Dr. Nehler, chief of the section of vascular surgery and endovascular therapy and podiatry at the University of Colorado Anschutz Medical Campus, Aurora. “There’s also large geographic variation in how patients are being treated, and a large percentage of patients do not see a nephrologist before they’re put on dialysis.”
The 2010 targets set by the Kidney Disease Outcomes Quality Initiative Guidelines recommend that clinicians create an arteriovenous fistula (AVF) in 50% of new-onset and 67% of existing hemodialysis patients, respectively, and to use catheters in fewer than 10% of hemodialysis patients. “Over time, the recommendations have become catheter-last rather than fistula-first,” Dr. Nehler said.
According to 2014 incidence data Dr. Nehler presented from Fistula First, a coalition that focuses on increasing the use of AV fistulas and decreasing the use of tunneled dialysis catheters, clinicians are using AVFs in new-onset hemodialysis patients only 20% of the time, 75% are still using catheters, and 5% are using grafts. “If you look at the incidence data for access, we’re not meeting the guidelines,” Dr. Nehler commented. “A fair amount of them have fistulas maturing, but we’re nowhere close to the 50% of patients starting dialysis using a fistula.”
Prevalence data from Fistula First is more on target, with 64% of patients using an AVF, but 19% of patients are using a catheter for prevalent access, “so there’s still some work to be done, but these numbers continue to get better.” States doing a good job implementing the guidelines include Colorado, New Mexico, New Hampshire, Washington, and Utah. “Some of the worst performers are in the South and in the East,” Dr. Nehler said. “When you look at the types of patients that don’t do well with fistulas, you realize that it probably has as much to do with the types of patients [clinicians are] taking care of as it has to do with any particular skill set of the surgeons involved.”
He characterized the rate of fistula maturation as “fairly sobering, where you can see a failure rate of 40%-45%, based on results from randomized trials,” he said. “Failure rate has been associated with advanced age, vein size, forearm AVFs especially in diabetics and in nonwhite patients.”
Dr. Nehler reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Clinicians have a ways to go before they reach the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative Guidelines for vascular access, a recent analysis of national data suggest.
Part of the challenge is because the incidence of renal disease continues to grow over time, Dr. Mark R. Nehler said at the annual meeting of the Western Vascular Society. “The elderly population is growing, and the need for access is growing,” said Dr. Nehler, chief of the section of vascular surgery and endovascular therapy and podiatry at the University of Colorado Anschutz Medical Campus, Aurora. “There’s also large geographic variation in how patients are being treated, and a large percentage of patients do not see a nephrologist before they’re put on dialysis.”
The 2010 targets set by the Kidney Disease Outcomes Quality Initiative Guidelines recommend that clinicians create an arteriovenous fistula (AVF) in 50% of new-onset and 67% of existing hemodialysis patients, respectively, and to use catheters in fewer than 10% of hemodialysis patients. “Over time, the recommendations have become catheter-last rather than fistula-first,” Dr. Nehler said.
According to 2014 incidence data Dr. Nehler presented from Fistula First, a coalition that focuses on increasing the use of AV fistulas and decreasing the use of tunneled dialysis catheters, clinicians are using AVFs in new-onset hemodialysis patients only 20% of the time, 75% are still using catheters, and 5% are using grafts. “If you look at the incidence data for access, we’re not meeting the guidelines,” Dr. Nehler commented. “A fair amount of them have fistulas maturing, but we’re nowhere close to the 50% of patients starting dialysis using a fistula.”
Prevalence data from Fistula First is more on target, with 64% of patients using an AVF, but 19% of patients are using a catheter for prevalent access, “so there’s still some work to be done, but these numbers continue to get better.” States doing a good job implementing the guidelines include Colorado, New Mexico, New Hampshire, Washington, and Utah. “Some of the worst performers are in the South and in the East,” Dr. Nehler said. “When you look at the types of patients that don’t do well with fistulas, you realize that it probably has as much to do with the types of patients [clinicians are] taking care of as it has to do with any particular skill set of the surgeons involved.”
He characterized the rate of fistula maturation as “fairly sobering, where you can see a failure rate of 40%-45%, based on results from randomized trials,” he said. “Failure rate has been associated with advanced age, vein size, forearm AVFs especially in diabetics and in nonwhite patients.”
Dr. Nehler reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Clinicians have a ways to go before they reach the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative Guidelines for vascular access, a recent analysis of national data suggest.
Part of the challenge is because the incidence of renal disease continues to grow over time, Dr. Mark R. Nehler said at the annual meeting of the Western Vascular Society. “The elderly population is growing, and the need for access is growing,” said Dr. Nehler, chief of the section of vascular surgery and endovascular therapy and podiatry at the University of Colorado Anschutz Medical Campus, Aurora. “There’s also large geographic variation in how patients are being treated, and a large percentage of patients do not see a nephrologist before they’re put on dialysis.”
The 2010 targets set by the Kidney Disease Outcomes Quality Initiative Guidelines recommend that clinicians create an arteriovenous fistula (AVF) in 50% of new-onset and 67% of existing hemodialysis patients, respectively, and to use catheters in fewer than 10% of hemodialysis patients. “Over time, the recommendations have become catheter-last rather than fistula-first,” Dr. Nehler said.
According to 2014 incidence data Dr. Nehler presented from Fistula First, a coalition that focuses on increasing the use of AV fistulas and decreasing the use of tunneled dialysis catheters, clinicians are using AVFs in new-onset hemodialysis patients only 20% of the time, 75% are still using catheters, and 5% are using grafts. “If you look at the incidence data for access, we’re not meeting the guidelines,” Dr. Nehler commented. “A fair amount of them have fistulas maturing, but we’re nowhere close to the 50% of patients starting dialysis using a fistula.”
Prevalence data from Fistula First is more on target, with 64% of patients using an AVF, but 19% of patients are using a catheter for prevalent access, “so there’s still some work to be done, but these numbers continue to get better.” States doing a good job implementing the guidelines include Colorado, New Mexico, New Hampshire, Washington, and Utah. “Some of the worst performers are in the South and in the East,” Dr. Nehler said. “When you look at the types of patients that don’t do well with fistulas, you realize that it probably has as much to do with the types of patients [clinicians are] taking care of as it has to do with any particular skill set of the surgeons involved.”
He characterized the rate of fistula maturation as “fairly sobering, where you can see a failure rate of 40%-45%, based on results from randomized trials,” he said. “Failure rate has been associated with advanced age, vein size, forearm AVFs especially in diabetics and in nonwhite patients.”
Dr. Nehler reported having no financial disclosures.
On Twitter @dougbrunk
EXPERT ANALYSIS AT THE WESTERN VASCULAR SOCIETY ANNUAL MEETING
Anti-TGF-beta 1 therapy for diabetic nephropathy disappoints
PHILADELPHIA– Anti-TGF-beta 1 therapy was safe and well-tolerated, but failed to slow disease progression in patients with advanced diabetic nephropathy in a randomized, double-masked, phase 2 dose-ranging study.
In fact, the trial was terminated 4 months early for efficacy futility, Dr. James R. Voelker reported at Kidney Week 2014.
In 416 patients with type 1 or type 2 diabetes and a likelihood of rapid disease progression who were randomized to receive subcutaneous treatment with either placebo or various doses of a beta-1-specific humanized monoclonal neutralizing antibody known as LY2382770 (LY).
Treatment at any dose was not significantly more effective than placebo with respect to the primary outcome measure of mean change in serum creatinine. Mean serum creatinine increased from 2.22 to 2.48 mg/dl in the placebo group, and in the treatment groups it increased from 2.15 to 2.49 mg/dl (2 mg/month group), from 2.13 to 2.49 mg/dl (10 mg/month group), and from 2.15 to 2.50 mg/dl (50 mg/month group), Dr. Voelker of Eli Lilly and Co., Indianapolis, said at the meeting, which was sponsored by the American Society of Nephrology.
Patients in the study were adults aged 25 years or older (mean 62.2 years ) with serum creatinine of 1.3 to 3.3 mg/dl for women, and 1.5 to 3.5 mg/dl for men, or estimated glomerular filtration rate of 20 to 60 ml/min/1.73 m2, and they had a 24-hour urine protein/creatinine ratio of at least 800 mg/g. The groups were similar with respect to demographics and baseline characteristic, and most (75%) were men with type 2 diabetes (90%). All patient were receiving stable renin-angiotensin-system inhibition (RASi) therapy.
The intent was to select a population with a likelihood of fairly rapid disease progression during the course of the study to enable detection of a treatment effect, Dr. Voelker explained.
“Diabetic nephropathy is a disease of significant unmet medical need, as it is the leading cause of end-stage renal disease in much of the world. Thus. it is incumbent upon the nephrology community to identify new and more effective treatments than are currently available,” Dr. Voelker said.
TGF-beta over-activity has been implicated as a key pathogenic factor in diabetic neuropathy, and it was previously demonstrated that a TGF-beta 1-specific humanized monoclonal antibody was as effective as an antibody against all three TGF-beta isoforms, he said.
“We also had demonstrated that beta 1-specific inhibition in preclinical animal toxicology testing was far more tolerated than when you inhibit all 3 TGF-beta isoforms, which I should mention are all differentially expressed and regulated, but all signal through the same receptor complex,” he added, noting that based on these and other data, it was hypothesized that modulating excessive beta 1 activity with LY would safely slow renal progression in patients with diabetes on background RASi therapy.
The study was overseen by an independent data safety monitoring committee that reviewed unblinded safety data at periodic intervals. No safety issues emerged, but in the later stages of the study the committee did recommend that an unscheduled utility analysis be performed. Based on the results of that analysis, the decision was made to prematurely terminate the study about 4 months before its scheduled completion.
“Unfortunately there was no evidence in any of the study arms of a slowing of the rate of (serum creatinine increase),” Dr. Voelker said, adding that there also was no evidence of a benefit in numerous subgroup analyses, including analyses based on diabetes type.
Dr. Voelker is an employee of Eli Lilly and Co, which sponsored this study.
PHILADELPHIA– Anti-TGF-beta 1 therapy was safe and well-tolerated, but failed to slow disease progression in patients with advanced diabetic nephropathy in a randomized, double-masked, phase 2 dose-ranging study.
In fact, the trial was terminated 4 months early for efficacy futility, Dr. James R. Voelker reported at Kidney Week 2014.
In 416 patients with type 1 or type 2 diabetes and a likelihood of rapid disease progression who were randomized to receive subcutaneous treatment with either placebo or various doses of a beta-1-specific humanized monoclonal neutralizing antibody known as LY2382770 (LY).
Treatment at any dose was not significantly more effective than placebo with respect to the primary outcome measure of mean change in serum creatinine. Mean serum creatinine increased from 2.22 to 2.48 mg/dl in the placebo group, and in the treatment groups it increased from 2.15 to 2.49 mg/dl (2 mg/month group), from 2.13 to 2.49 mg/dl (10 mg/month group), and from 2.15 to 2.50 mg/dl (50 mg/month group), Dr. Voelker of Eli Lilly and Co., Indianapolis, said at the meeting, which was sponsored by the American Society of Nephrology.
Patients in the study were adults aged 25 years or older (mean 62.2 years ) with serum creatinine of 1.3 to 3.3 mg/dl for women, and 1.5 to 3.5 mg/dl for men, or estimated glomerular filtration rate of 20 to 60 ml/min/1.73 m2, and they had a 24-hour urine protein/creatinine ratio of at least 800 mg/g. The groups were similar with respect to demographics and baseline characteristic, and most (75%) were men with type 2 diabetes (90%). All patient were receiving stable renin-angiotensin-system inhibition (RASi) therapy.
The intent was to select a population with a likelihood of fairly rapid disease progression during the course of the study to enable detection of a treatment effect, Dr. Voelker explained.
“Diabetic nephropathy is a disease of significant unmet medical need, as it is the leading cause of end-stage renal disease in much of the world. Thus. it is incumbent upon the nephrology community to identify new and more effective treatments than are currently available,” Dr. Voelker said.
TGF-beta over-activity has been implicated as a key pathogenic factor in diabetic neuropathy, and it was previously demonstrated that a TGF-beta 1-specific humanized monoclonal antibody was as effective as an antibody against all three TGF-beta isoforms, he said.
“We also had demonstrated that beta 1-specific inhibition in preclinical animal toxicology testing was far more tolerated than when you inhibit all 3 TGF-beta isoforms, which I should mention are all differentially expressed and regulated, but all signal through the same receptor complex,” he added, noting that based on these and other data, it was hypothesized that modulating excessive beta 1 activity with LY would safely slow renal progression in patients with diabetes on background RASi therapy.
The study was overseen by an independent data safety monitoring committee that reviewed unblinded safety data at periodic intervals. No safety issues emerged, but in the later stages of the study the committee did recommend that an unscheduled utility analysis be performed. Based on the results of that analysis, the decision was made to prematurely terminate the study about 4 months before its scheduled completion.
“Unfortunately there was no evidence in any of the study arms of a slowing of the rate of (serum creatinine increase),” Dr. Voelker said, adding that there also was no evidence of a benefit in numerous subgroup analyses, including analyses based on diabetes type.
Dr. Voelker is an employee of Eli Lilly and Co, which sponsored this study.
PHILADELPHIA– Anti-TGF-beta 1 therapy was safe and well-tolerated, but failed to slow disease progression in patients with advanced diabetic nephropathy in a randomized, double-masked, phase 2 dose-ranging study.
In fact, the trial was terminated 4 months early for efficacy futility, Dr. James R. Voelker reported at Kidney Week 2014.
In 416 patients with type 1 or type 2 diabetes and a likelihood of rapid disease progression who were randomized to receive subcutaneous treatment with either placebo or various doses of a beta-1-specific humanized monoclonal neutralizing antibody known as LY2382770 (LY).
Treatment at any dose was not significantly more effective than placebo with respect to the primary outcome measure of mean change in serum creatinine. Mean serum creatinine increased from 2.22 to 2.48 mg/dl in the placebo group, and in the treatment groups it increased from 2.15 to 2.49 mg/dl (2 mg/month group), from 2.13 to 2.49 mg/dl (10 mg/month group), and from 2.15 to 2.50 mg/dl (50 mg/month group), Dr. Voelker of Eli Lilly and Co., Indianapolis, said at the meeting, which was sponsored by the American Society of Nephrology.
Patients in the study were adults aged 25 years or older (mean 62.2 years ) with serum creatinine of 1.3 to 3.3 mg/dl for women, and 1.5 to 3.5 mg/dl for men, or estimated glomerular filtration rate of 20 to 60 ml/min/1.73 m2, and they had a 24-hour urine protein/creatinine ratio of at least 800 mg/g. The groups were similar with respect to demographics and baseline characteristic, and most (75%) were men with type 2 diabetes (90%). All patient were receiving stable renin-angiotensin-system inhibition (RASi) therapy.
The intent was to select a population with a likelihood of fairly rapid disease progression during the course of the study to enable detection of a treatment effect, Dr. Voelker explained.
“Diabetic nephropathy is a disease of significant unmet medical need, as it is the leading cause of end-stage renal disease in much of the world. Thus. it is incumbent upon the nephrology community to identify new and more effective treatments than are currently available,” Dr. Voelker said.
TGF-beta over-activity has been implicated as a key pathogenic factor in diabetic neuropathy, and it was previously demonstrated that a TGF-beta 1-specific humanized monoclonal antibody was as effective as an antibody against all three TGF-beta isoforms, he said.
“We also had demonstrated that beta 1-specific inhibition in preclinical animal toxicology testing was far more tolerated than when you inhibit all 3 TGF-beta isoforms, which I should mention are all differentially expressed and regulated, but all signal through the same receptor complex,” he added, noting that based on these and other data, it was hypothesized that modulating excessive beta 1 activity with LY would safely slow renal progression in patients with diabetes on background RASi therapy.
The study was overseen by an independent data safety monitoring committee that reviewed unblinded safety data at periodic intervals. No safety issues emerged, but in the later stages of the study the committee did recommend that an unscheduled utility analysis be performed. Based on the results of that analysis, the decision was made to prematurely terminate the study about 4 months before its scheduled completion.
“Unfortunately there was no evidence in any of the study arms of a slowing of the rate of (serum creatinine increase),” Dr. Voelker said, adding that there also was no evidence of a benefit in numerous subgroup analyses, including analyses based on diabetes type.
Dr. Voelker is an employee of Eli Lilly and Co, which sponsored this study.
Key clinical point: Anti-TGF-beta 1 therapy failed to slow the progression of diabetic kidney disease.
Major finding: Mean serum creatinine increased from 2.22 to 2.48 mg/dl in the placebo group and in the treatment arms; 2.15 to 2.49 mg/dl (2 mg/month), 2.13 to 2.49 mg/dl (10 mg/month), and 2.15 to 2.50 mg/dl (50 mg/month).
Data source: A randomized, double-masked, phase-2 dose-ranging study involving 416 patients.
Disclosures: Dr. Voelker is an employee of Eli Lilly and Co, which sponsored this study.
Lower BP slows disease process in early PKD
PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.
Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.
Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m2 of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.
With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])
With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.
“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.
The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.
Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.
During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.
“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.
This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.
Aggressive blood pressure control, however, was of benefit.
“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.
The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), the National Center for Research Resources General Clinical Research Centers, the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.
Studies A and B of the HALT-PKD trial add to the growing number of studies showing no benefit with dual RAAS blockade over single blockade in patients with kidney disease, therefore, the observation in both studies that an ACE inhibitor used alone is effective for blood pressure control is encouraging, according to Dr. David H. Ellison and Dr. Julie Ingelfinger.
“These two studies provide important guidance for the care of patients with [autosomal dominant polycystic kidney disease}. They show that blood pressure can be controlled with ACE inhibitors, drugs that have an acceptable safety profile. They suggest that rigorous blood-pressure control, early in the disease process, may slow cyst growth and reduce the left-ventricular-mass index, but this approach is complicated by increased dizziness” they wrote in an editorial (N Engl J Med 2014, Nov. 15[doi:10.1056/NEJMe1412586]).
Also, the studies dissociate kidney-volume growth from a decline in renal function, which emphasizes the importance of hard outcomes in clinical trials involving patients with ADPKD, they said.
“Despite these limitations, the studies indicate that, with careful medical care, including meticulous attention to blood pressure, the prognosis for patients with ADPKD remains good,” they concluded.
Dr. Ellison is with Oregon Health and Science University, Portland. Dr. Ingelfinger is with Massachusetts General Hospital, Boston.
Studies A and B of the HALT-PKD trial add to the growing number of studies showing no benefit with dual RAAS blockade over single blockade in patients with kidney disease, therefore, the observation in both studies that an ACE inhibitor used alone is effective for blood pressure control is encouraging, according to Dr. David H. Ellison and Dr. Julie Ingelfinger.
“These two studies provide important guidance for the care of patients with [autosomal dominant polycystic kidney disease}. They show that blood pressure can be controlled with ACE inhibitors, drugs that have an acceptable safety profile. They suggest that rigorous blood-pressure control, early in the disease process, may slow cyst growth and reduce the left-ventricular-mass index, but this approach is complicated by increased dizziness” they wrote in an editorial (N Engl J Med 2014, Nov. 15[doi:10.1056/NEJMe1412586]).
Also, the studies dissociate kidney-volume growth from a decline in renal function, which emphasizes the importance of hard outcomes in clinical trials involving patients with ADPKD, they said.
“Despite these limitations, the studies indicate that, with careful medical care, including meticulous attention to blood pressure, the prognosis for patients with ADPKD remains good,” they concluded.
Dr. Ellison is with Oregon Health and Science University, Portland. Dr. Ingelfinger is with Massachusetts General Hospital, Boston.
Studies A and B of the HALT-PKD trial add to the growing number of studies showing no benefit with dual RAAS blockade over single blockade in patients with kidney disease, therefore, the observation in both studies that an ACE inhibitor used alone is effective for blood pressure control is encouraging, according to Dr. David H. Ellison and Dr. Julie Ingelfinger.
“These two studies provide important guidance for the care of patients with [autosomal dominant polycystic kidney disease}. They show that blood pressure can be controlled with ACE inhibitors, drugs that have an acceptable safety profile. They suggest that rigorous blood-pressure control, early in the disease process, may slow cyst growth and reduce the left-ventricular-mass index, but this approach is complicated by increased dizziness” they wrote in an editorial (N Engl J Med 2014, Nov. 15[doi:10.1056/NEJMe1412586]).
Also, the studies dissociate kidney-volume growth from a decline in renal function, which emphasizes the importance of hard outcomes in clinical trials involving patients with ADPKD, they said.
“Despite these limitations, the studies indicate that, with careful medical care, including meticulous attention to blood pressure, the prognosis for patients with ADPKD remains good,” they concluded.
Dr. Ellison is with Oregon Health and Science University, Portland. Dr. Ingelfinger is with Massachusetts General Hospital, Boston.
PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.
Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.
Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m2 of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.
With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])
With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.
“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.
The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.
Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.
During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.
“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.
This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.
Aggressive blood pressure control, however, was of benefit.
“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.
The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), the National Center for Research Resources General Clinical Research Centers, the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.
PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.
Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.
Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m2 of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.
With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])
With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.
“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.
The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.
Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.
During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.
“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.
This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.
Aggressive blood pressure control, however, was of benefit.
“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.
The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), the National Center for Research Resources General Clinical Research Centers, the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.
Key clinical point: Aggressive blood pressure control may be of benefit in patients with early PKD.
Major finding: Low vs. standard blood pressure control resulted in a 14.2% slower rate of total kidney volume increase.
Data source: The randomized, placebo-controlled HALT-PKD trial (Study A).
Disclosures: The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), The National Center for Research Resources General Clinical Research Centers, the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.
Little benefit seen with ergocalciferol during hemodialysis
philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.
Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.
Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.
Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.
Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.
Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.
The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.
This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.
philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.
Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.
Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.
Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.
Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.
Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.
The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.
This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.
philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.
Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.
Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.
Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.
Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.
Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.
The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.
This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.
Key clinical point: The clinical benefit of vitamin D supplementation in hemodialysis patients remains questionable.
Major finding: Epoetin alfa dose in the placebo and treatment groups did not differ significantly at 6 months (5,400 vs. 5,800 units/week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively).
Data source: A randomized, double-blind, placebo-controlled study of 276 patients.
Disclosures: This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.
Kidney function declines faster with high sleep apnea risk
PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.
Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m2 per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.
This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.
Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.
Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.
Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.
The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.
Dr. Pisoni reported having no disclosures.
PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.
Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m2 per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.
This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.
Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.
Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.
Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.
The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.
Dr. Pisoni reported having no disclosures.
PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.
Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m2 per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.
This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.
Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.
Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.
Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.
The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.
Dr. Pisoni reported having no disclosures.
Key clinical point: Screening for OSA risk might help identify patients at higher risk for CKD progression.
Major finding: Median loss of eGFR was -3.4 vs. 1.5 ml/min/1.73 m2 per year in patients at high vs. low risk for OSA.
Data source: A retrospective cohort study involving 56 patients.
Disclosures: Dr. Pisoni reported having no disclosures.
Adding terlipressin didn’t help hepatorenal syndrome
BOSTON – Treating patients with hepatorenal syndrome type 1 for up to 14 days using terlipressin plus albumin rather than albumin alone did not improve the chances of confirmed reversal of hepatorenal syndrome in a multicenter, randomized, double-blind, placebo-controlled trial in 196 patients.
Investigators confirmed reversal of hepatorenal syndrome type 1 (HRS-1) in 19 of 97 patients on terlipressin plus albumin (20%) and 13 of 99 patients on albumin plus placebo (13%), a difference between groups that was not statistically significant, Dr. Thomas D. Boyer reported at the annual meeting of the American Association for the Study of Liver Diseases.
He and his associates defined confirmed reversal of HRS-1 as two serum creatinine values no higher than 1.5 mg/dL at least 48 hours apart while on treatment, without renal replacement therapy or liver transplant.
Secondary outcomes included reversal of HRS-1, defined as a decrease in serum creatinine to no higher than 1.5 mg/dL. This goal was reached by 23 patients on terlipressin plus albumin, and 15 patients on albumin alone achieved reversal of HRS-1 (24% vs. 15%, respectively), a difference that also was not statistically significant.
Among other secondary outcomes, though, terlipressin showed some potential advantages in subgroup analyses, said Dr. Boyer, professor of medicine and director of the Liver Research Institute at the University of Arizona, Tucson.
Significantly greater improvements in serum creatinine during treatment with terlipressin correlated with survival. Compared with baseline levels, serum creatinine decreased by 1.2 mg/dL in the terlipressin group and 0.6 mg/dL in the placebo group, a statistically significant difference between groups.
All 19 patients who achieve confirmed reversal of HRS-1 on terlipressin were alive without renal replacement therapy at 90-day follow-up, significantly more than the 6 of 13 patients with confirmed reversal of HRS-1 in the placebo group who remained alive at 90 days (46%).
Overall survival and transplant-free survival rates did not differ significantly between groups.
Serious adverse events occurred in 59 patients in the terlipressin group (61%) and 53 patients in the placebo group (54%), rates that did not differ significantly between groups. No new or unexpected adverse events were seen.
The REVERSE trial (Phase III, Multi-Center Randomized, Placebo-Controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 with Lucassin [Terlipressin]) enrolled adults with cirrhosis, ascites, and HRS-1. The study defined HRS-1 as rapidly deteriorating renal function that didn’t improve within 48 hours of diuretic withdrawal and albumin-fluid challenge. Rapidly deteriorating renal function was defined as a serum creatinine level of at least 2.5 mg/dL and actual or projected doubling of serum creatinine within 2 weeks. Improvement in renal function was defined as less than a 20% decrease in serum creatinine and a serum creatinine level of at least 2.5 mg/dL.
Patients received IV infusions of 6 mg terlipressin or placebo every 6 hours, plus albumin.
Ikaria, which markets terlipressin (Lucassin), funded the study. Dr. Boyer is a consultant for Ikaria and he reported financial associations with AbbVie, Gilead, and Merck. His associates reported financial associations with Ikaria and multiple companies.
On Twitter @sherryboschert
BOSTON – Treating patients with hepatorenal syndrome type 1 for up to 14 days using terlipressin plus albumin rather than albumin alone did not improve the chances of confirmed reversal of hepatorenal syndrome in a multicenter, randomized, double-blind, placebo-controlled trial in 196 patients.
Investigators confirmed reversal of hepatorenal syndrome type 1 (HRS-1) in 19 of 97 patients on terlipressin plus albumin (20%) and 13 of 99 patients on albumin plus placebo (13%), a difference between groups that was not statistically significant, Dr. Thomas D. Boyer reported at the annual meeting of the American Association for the Study of Liver Diseases.
He and his associates defined confirmed reversal of HRS-1 as two serum creatinine values no higher than 1.5 mg/dL at least 48 hours apart while on treatment, without renal replacement therapy or liver transplant.
Secondary outcomes included reversal of HRS-1, defined as a decrease in serum creatinine to no higher than 1.5 mg/dL. This goal was reached by 23 patients on terlipressin plus albumin, and 15 patients on albumin alone achieved reversal of HRS-1 (24% vs. 15%, respectively), a difference that also was not statistically significant.
Among other secondary outcomes, though, terlipressin showed some potential advantages in subgroup analyses, said Dr. Boyer, professor of medicine and director of the Liver Research Institute at the University of Arizona, Tucson.
Significantly greater improvements in serum creatinine during treatment with terlipressin correlated with survival. Compared with baseline levels, serum creatinine decreased by 1.2 mg/dL in the terlipressin group and 0.6 mg/dL in the placebo group, a statistically significant difference between groups.
All 19 patients who achieve confirmed reversal of HRS-1 on terlipressin were alive without renal replacement therapy at 90-day follow-up, significantly more than the 6 of 13 patients with confirmed reversal of HRS-1 in the placebo group who remained alive at 90 days (46%).
Overall survival and transplant-free survival rates did not differ significantly between groups.
Serious adverse events occurred in 59 patients in the terlipressin group (61%) and 53 patients in the placebo group (54%), rates that did not differ significantly between groups. No new or unexpected adverse events were seen.
The REVERSE trial (Phase III, Multi-Center Randomized, Placebo-Controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 with Lucassin [Terlipressin]) enrolled adults with cirrhosis, ascites, and HRS-1. The study defined HRS-1 as rapidly deteriorating renal function that didn’t improve within 48 hours of diuretic withdrawal and albumin-fluid challenge. Rapidly deteriorating renal function was defined as a serum creatinine level of at least 2.5 mg/dL and actual or projected doubling of serum creatinine within 2 weeks. Improvement in renal function was defined as less than a 20% decrease in serum creatinine and a serum creatinine level of at least 2.5 mg/dL.
Patients received IV infusions of 6 mg terlipressin or placebo every 6 hours, plus albumin.
Ikaria, which markets terlipressin (Lucassin), funded the study. Dr. Boyer is a consultant for Ikaria and he reported financial associations with AbbVie, Gilead, and Merck. His associates reported financial associations with Ikaria and multiple companies.
On Twitter @sherryboschert
BOSTON – Treating patients with hepatorenal syndrome type 1 for up to 14 days using terlipressin plus albumin rather than albumin alone did not improve the chances of confirmed reversal of hepatorenal syndrome in a multicenter, randomized, double-blind, placebo-controlled trial in 196 patients.
Investigators confirmed reversal of hepatorenal syndrome type 1 (HRS-1) in 19 of 97 patients on terlipressin plus albumin (20%) and 13 of 99 patients on albumin plus placebo (13%), a difference between groups that was not statistically significant, Dr. Thomas D. Boyer reported at the annual meeting of the American Association for the Study of Liver Diseases.
He and his associates defined confirmed reversal of HRS-1 as two serum creatinine values no higher than 1.5 mg/dL at least 48 hours apart while on treatment, without renal replacement therapy or liver transplant.
Secondary outcomes included reversal of HRS-1, defined as a decrease in serum creatinine to no higher than 1.5 mg/dL. This goal was reached by 23 patients on terlipressin plus albumin, and 15 patients on albumin alone achieved reversal of HRS-1 (24% vs. 15%, respectively), a difference that also was not statistically significant.
Among other secondary outcomes, though, terlipressin showed some potential advantages in subgroup analyses, said Dr. Boyer, professor of medicine and director of the Liver Research Institute at the University of Arizona, Tucson.
Significantly greater improvements in serum creatinine during treatment with terlipressin correlated with survival. Compared with baseline levels, serum creatinine decreased by 1.2 mg/dL in the terlipressin group and 0.6 mg/dL in the placebo group, a statistically significant difference between groups.
All 19 patients who achieve confirmed reversal of HRS-1 on terlipressin were alive without renal replacement therapy at 90-day follow-up, significantly more than the 6 of 13 patients with confirmed reversal of HRS-1 in the placebo group who remained alive at 90 days (46%).
Overall survival and transplant-free survival rates did not differ significantly between groups.
Serious adverse events occurred in 59 patients in the terlipressin group (61%) and 53 patients in the placebo group (54%), rates that did not differ significantly between groups. No new or unexpected adverse events were seen.
The REVERSE trial (Phase III, Multi-Center Randomized, Placebo-Controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 with Lucassin [Terlipressin]) enrolled adults with cirrhosis, ascites, and HRS-1. The study defined HRS-1 as rapidly deteriorating renal function that didn’t improve within 48 hours of diuretic withdrawal and albumin-fluid challenge. Rapidly deteriorating renal function was defined as a serum creatinine level of at least 2.5 mg/dL and actual or projected doubling of serum creatinine within 2 weeks. Improvement in renal function was defined as less than a 20% decrease in serum creatinine and a serum creatinine level of at least 2.5 mg/dL.
Patients received IV infusions of 6 mg terlipressin or placebo every 6 hours, plus albumin.
Ikaria, which markets terlipressin (Lucassin), funded the study. Dr. Boyer is a consultant for Ikaria and he reported financial associations with AbbVie, Gilead, and Merck. His associates reported financial associations with Ikaria and multiple companies.
On Twitter @sherryboschert
AT THE LIVER MEETING 2014
Key clinical point: Adding terlipressin to albumin didn’t help reverse hepatorenal syndrome type 1, but there were hints of improved survival.
Major finding: Confirmed reversal of HRS-1 occurred in 20% on terlipressin and albumin and 13% on placebo and albumin.
Data source: A multicenter, randomized, controlled, double-blind trial in 196 adults with cirrhosis, ascites, and HRS-1.
Disclosures: Ikaria, which markets terlipressin (Lucassin), funded the study. Dr. Boyer is a consultant for Ikaria and he reported financial associations with AbbVie, Gilead, and Merck. His associates reported financial associations with Ikaria and multiple companies.
Early Discoid Lupus Onset Protective Against Nephritis
BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.
“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.
He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.
DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.
There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).
To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.
They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.
The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.
In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).
In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).
The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).
The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.
Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.
“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.
Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.
Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.
The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.
BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.
“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.
He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.
DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.
There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).
To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.
They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.
The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.
In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).
In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).
The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).
The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.
Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.
“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.
Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.
Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.
The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.
BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.
“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.
He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.
DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.
There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).
To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.
They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.
The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.
In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).
In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).
The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).
The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.
Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.
“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.
Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.
Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.
The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.
AT THE ACR ANNUAL MEETING
Early discoid lupus onset protective against nephritis
BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.
“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.
He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.
DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.
There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).
To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.
They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.
The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.
In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).
In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).
The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).
The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.
Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.
“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.
Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.
Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.
The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.
BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.
“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.
He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.
DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.
There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).
To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.
They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.
The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.
In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).
In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).
The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).
The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.
Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.
“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.
Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.
Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.
The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.
BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.
“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.
He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.
DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.
There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).
To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.
They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.
The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.
In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).
In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).
The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).
The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.
Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.
“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.
Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.
Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.
The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.
AT THE ACR ANNUAL MEETING
Key clinical point: Discoid lupus erythematosus diagnosed at or before a systemic lupus diagnosis predicts lower risk of lupus nephritis.
Major finding: The hazard ratio for developing subsequent lupus nephritis in patients with early discoid lupus was 0.36 (P = .0006).
Data source: A longitudinal cohort of 839 Latin American patients with SLE and no evidence of lupus nephritis at the time of diagnosis.
Disclosures: The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.
Consider biopsy for active lupus nephritis in pregnancy
PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.
Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.
An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.
“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.
Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.
“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.
“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.
An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.
As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.
Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.
“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.
Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.
In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm3, he said.
However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.
“It’s a low risk, but a real one,” he said.
The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.
Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.
“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.
If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.
Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.
A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.
He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.
If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.
“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.
Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.
Dr. Fine said he had no relevant financial disclosures.
PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.
Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.
An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.
“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.
Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.
“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.
“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.
An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.
As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.
Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.
“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.
Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.
In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm3, he said.
However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.
“It’s a low risk, but a real one,” he said.
The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.
Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.
“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.
If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.
Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.
A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.
He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.
If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.
“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.
Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.
Dr. Fine said he had no relevant financial disclosures.
PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.
Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.
An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.
“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.
Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.
“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.
“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.
An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.
As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.
Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.
“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.
Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.
In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm3, he said.
However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.
“It’s a low risk, but a real one,” he said.
The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.
Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.
“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.
If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.
Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.
A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.
He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.
If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.
“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.
Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.
Dr. Fine said he had no relevant financial disclosures.
EXPERT ANALYSIS AT KIDNEY WEEK 2014
