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Avoiding metformin in renal insufficiency
A 47-year-old obese male with type 2 diabetes has been on metformin for the last 2 years with good effect (hemoglobin A1c of 6.8), and with exercise has been able to lose 5-10 pounds. His last two blood tests show creatinine levels of 1.5 and 1.6. What do you recommend?
A) Continue with metformin.
B) Stop metformin, start sulfonylurea.
C) Stop metformin, begin glargine.
D) Stop metformin, begin pioglitazone.
Myth: Metformin should not be used in patients with mild to moderate renal insufficiency because of an increased risk of lactic acidosis.
Metformin is the most commonly used oral agent for the treatment of type 2 diabetes in the United States, but the FDA-approved drug label states that it is contraindicated in patients with an abnormal creatinine clearance or serum creatinine of 1.4 in women and 1.5 in men.<sup/>The concern is for development of lactic acidosis in patients because the renally excreted metformin may build up as a result of decreased renal function.
Metformin was approved for use in the United States in 1995, many years after the drug was introduced in Europe. The first drug in its class, phenformin, was removed from the United States and most European markets in 1977 because of a high incidence of lactic acidosis occurring at therapeutic doses. One in 4,000 patients taking phenformin develops lactic acidosis (J. Emerg. Med. 1998;16:881-6). Phenformin has been shown to cause type B lactic acidosis, without evidence of hypoxia or hypoperfusion, and lactic acidosis because of phenformin carried a 50% mortality rate.
Deep concern for the possibility of a similar problem with metformin played an important role in its delay of availability in the United States. It isn’t clear, however, that diabetes patients on metformin have a higher risk of developing lactic acidosis than diabetes patients who are not on metformin.
A Cochrane review of 347 studies, including 70,490 person-years of metformin use, compared with 55,451 person-years in the nonmetformin group, showed no cases of fatal or nonfatal lactic acidosis in either group (Cochrane Database Syst. Rev. 2010 Apr 14:CD002967). More than half the studies included (53%) allowed for the inclusion of patients with creatinine levels greater than 1.5. There were no differences in lactate levels between metformin-treated patients and patients who did not receive metformin.
In a study using the Saskatchewan Health administrative database, which involved 11,797 patients with 22,296 years of metformin exposure, there were two cases of lactic acidosis (Diabetes Care 1999;22:925-7). This calculates to a rate of 9 cases per 100,000 person years, the same rate as in patients with diabetes who are not taking metformin (9.7 cases per 100,000) (Diabetes Care 1998;21:1659-63).
A recent study looked at the incidence of lactic acidosis in patients taking metformin with and without abnormalities in renal function (Diabetes Care 2014;37:2291-5). There was no statistically significant difference in the rates of lactic acidosis in patients who were on metformin with normal renal function, compared with those with varying degrees of renal insufficiency. The overall rate of lactic acidosis was 10.3 per 100,000 patient years, which is almost identical to the rates in the other studies mentioned, and there were no fatalities.
Several recommendations for using metformin in patients with renal insufficiency have been published (see table) (JAMA 2014;312:2668-75; Diabetes Care 2011;34:1431-7). Metformin has shown cardiovascular mortality benefits, compared with sulfonylureas, in the treatment of diabetes (Diabetes Care 2013;36:1304-11). Avoiding its use in patients with mild to moderate renal insufficiency in favor of other treatments that may not be as beneficial and may well lead to worse outcomes.
There is no evidence that metformin increases the lactic acidosis risk in patients with diabetes, but until there is a change in the FDA labeling, physicians will likely continue to be hesitant to use it in patients with renal insufficiency.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is the Rathmann Family Foundation Chair in Patient-Centered Clinical Education. Contact Dr. Paauw at [email protected].
A 47-year-old obese male with type 2 diabetes has been on metformin for the last 2 years with good effect (hemoglobin A1c of 6.8), and with exercise has been able to lose 5-10 pounds. His last two blood tests show creatinine levels of 1.5 and 1.6. What do you recommend?
A) Continue with metformin.
B) Stop metformin, start sulfonylurea.
C) Stop metformin, begin glargine.
D) Stop metformin, begin pioglitazone.
Myth: Metformin should not be used in patients with mild to moderate renal insufficiency because of an increased risk of lactic acidosis.
Metformin is the most commonly used oral agent for the treatment of type 2 diabetes in the United States, but the FDA-approved drug label states that it is contraindicated in patients with an abnormal creatinine clearance or serum creatinine of 1.4 in women and 1.5 in men.<sup/>The concern is for development of lactic acidosis in patients because the renally excreted metformin may build up as a result of decreased renal function.
Metformin was approved for use in the United States in 1995, many years after the drug was introduced in Europe. The first drug in its class, phenformin, was removed from the United States and most European markets in 1977 because of a high incidence of lactic acidosis occurring at therapeutic doses. One in 4,000 patients taking phenformin develops lactic acidosis (J. Emerg. Med. 1998;16:881-6). Phenformin has been shown to cause type B lactic acidosis, without evidence of hypoxia or hypoperfusion, and lactic acidosis because of phenformin carried a 50% mortality rate.
Deep concern for the possibility of a similar problem with metformin played an important role in its delay of availability in the United States. It isn’t clear, however, that diabetes patients on metformin have a higher risk of developing lactic acidosis than diabetes patients who are not on metformin.
A Cochrane review of 347 studies, including 70,490 person-years of metformin use, compared with 55,451 person-years in the nonmetformin group, showed no cases of fatal or nonfatal lactic acidosis in either group (Cochrane Database Syst. Rev. 2010 Apr 14:CD002967). More than half the studies included (53%) allowed for the inclusion of patients with creatinine levels greater than 1.5. There were no differences in lactate levels between metformin-treated patients and patients who did not receive metformin.
In a study using the Saskatchewan Health administrative database, which involved 11,797 patients with 22,296 years of metformin exposure, there were two cases of lactic acidosis (Diabetes Care 1999;22:925-7). This calculates to a rate of 9 cases per 100,000 person years, the same rate as in patients with diabetes who are not taking metformin (9.7 cases per 100,000) (Diabetes Care 1998;21:1659-63).
A recent study looked at the incidence of lactic acidosis in patients taking metformin with and without abnormalities in renal function (Diabetes Care 2014;37:2291-5). There was no statistically significant difference in the rates of lactic acidosis in patients who were on metformin with normal renal function, compared with those with varying degrees of renal insufficiency. The overall rate of lactic acidosis was 10.3 per 100,000 patient years, which is almost identical to the rates in the other studies mentioned, and there were no fatalities.
Several recommendations for using metformin in patients with renal insufficiency have been published (see table) (JAMA 2014;312:2668-75; Diabetes Care 2011;34:1431-7). Metformin has shown cardiovascular mortality benefits, compared with sulfonylureas, in the treatment of diabetes (Diabetes Care 2013;36:1304-11). Avoiding its use in patients with mild to moderate renal insufficiency in favor of other treatments that may not be as beneficial and may well lead to worse outcomes.
There is no evidence that metformin increases the lactic acidosis risk in patients with diabetes, but until there is a change in the FDA labeling, physicians will likely continue to be hesitant to use it in patients with renal insufficiency.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is the Rathmann Family Foundation Chair in Patient-Centered Clinical Education. Contact Dr. Paauw at [email protected].
A 47-year-old obese male with type 2 diabetes has been on metformin for the last 2 years with good effect (hemoglobin A1c of 6.8), and with exercise has been able to lose 5-10 pounds. His last two blood tests show creatinine levels of 1.5 and 1.6. What do you recommend?
A) Continue with metformin.
B) Stop metformin, start sulfonylurea.
C) Stop metformin, begin glargine.
D) Stop metformin, begin pioglitazone.
Myth: Metformin should not be used in patients with mild to moderate renal insufficiency because of an increased risk of lactic acidosis.
Metformin is the most commonly used oral agent for the treatment of type 2 diabetes in the United States, but the FDA-approved drug label states that it is contraindicated in patients with an abnormal creatinine clearance or serum creatinine of 1.4 in women and 1.5 in men.<sup/>The concern is for development of lactic acidosis in patients because the renally excreted metformin may build up as a result of decreased renal function.
Metformin was approved for use in the United States in 1995, many years after the drug was introduced in Europe. The first drug in its class, phenformin, was removed from the United States and most European markets in 1977 because of a high incidence of lactic acidosis occurring at therapeutic doses. One in 4,000 patients taking phenformin develops lactic acidosis (J. Emerg. Med. 1998;16:881-6). Phenformin has been shown to cause type B lactic acidosis, without evidence of hypoxia or hypoperfusion, and lactic acidosis because of phenformin carried a 50% mortality rate.
Deep concern for the possibility of a similar problem with metformin played an important role in its delay of availability in the United States. It isn’t clear, however, that diabetes patients on metformin have a higher risk of developing lactic acidosis than diabetes patients who are not on metformin.
A Cochrane review of 347 studies, including 70,490 person-years of metformin use, compared with 55,451 person-years in the nonmetformin group, showed no cases of fatal or nonfatal lactic acidosis in either group (Cochrane Database Syst. Rev. 2010 Apr 14:CD002967). More than half the studies included (53%) allowed for the inclusion of patients with creatinine levels greater than 1.5. There were no differences in lactate levels between metformin-treated patients and patients who did not receive metformin.
In a study using the Saskatchewan Health administrative database, which involved 11,797 patients with 22,296 years of metformin exposure, there were two cases of lactic acidosis (Diabetes Care 1999;22:925-7). This calculates to a rate of 9 cases per 100,000 person years, the same rate as in patients with diabetes who are not taking metformin (9.7 cases per 100,000) (Diabetes Care 1998;21:1659-63).
A recent study looked at the incidence of lactic acidosis in patients taking metformin with and without abnormalities in renal function (Diabetes Care 2014;37:2291-5). There was no statistically significant difference in the rates of lactic acidosis in patients who were on metformin with normal renal function, compared with those with varying degrees of renal insufficiency. The overall rate of lactic acidosis was 10.3 per 100,000 patient years, which is almost identical to the rates in the other studies mentioned, and there were no fatalities.
Several recommendations for using metformin in patients with renal insufficiency have been published (see table) (JAMA 2014;312:2668-75; Diabetes Care 2011;34:1431-7). Metformin has shown cardiovascular mortality benefits, compared with sulfonylureas, in the treatment of diabetes (Diabetes Care 2013;36:1304-11). Avoiding its use in patients with mild to moderate renal insufficiency in favor of other treatments that may not be as beneficial and may well lead to worse outcomes.
There is no evidence that metformin increases the lactic acidosis risk in patients with diabetes, but until there is a change in the FDA labeling, physicians will likely continue to be hesitant to use it in patients with renal insufficiency.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is the Rathmann Family Foundation Chair in Patient-Centered Clinical Education. Contact Dr. Paauw at [email protected].
Acute Kidney Injury: Prevalent in Sugarcane Harvesters
Q) I’ve heard a lot of talk about all the kidney problems that the sugarcane workers in Central America have. Does anyone know why this is happening?
The unusually high rates of chronic kidney disease (CKD) among sugarcane workers in Central America have been a subject of great interest since National Public Radio (NPR) aired a special on this topic.3 There has been a rising epidemic of CKD in otherwise healthy male farm workers (ages 20 to 50), particularly those who harvest sugarcane.4,5 It has been hypothesized that recurrent episodes of acute kidney injury (AKI)—related to dehydration, volume depletion, pollutants, and rhabdomyolysis with inflammatory stress—are the underlying cause.5
Sugarcane harvesters typically work nine-hour days, six days per week, in extremely high temperatures and while wearing heavy, hot clothing. Each worker cuts approximately 10 tons of sugarcane daily, since they are paid based on cutting volume. Workers drink between five and 10 L of water during their shifts.
Santos et al designed a study to prospectively examine the effects of burnt sugarcane harvesting on renal function in healthy male farm workers. Twenty-eight men (ages 19 to 39) with no CKD risk factors (diabetes, smoking, obesity, hypertension, illicit drug or alcohol use) were followed for eight months from preharvest to postharvest. Blood samples were collected at the beginning and at the end of the workday and preharvest and postharvest season.5
Preseason lab values were normal in all 28 men. But postseason, all workers had elevated creatinine levels, with five meeting the criteria for AKI (see Table at left).5,6
Santos and colleagues identified potential causes for AKI in this population. These included
• Dehydration and volume depletion (episodes of tachycardia, increased urine density, lower urinary/serum sodium, higher hematocrit)
• Rhabdomyolysis (increased creatine kinase at the end of each workday)
• Systemic inflammation (increased white blood count, neutrophils, lymphocytes, and monocytes during the workday—possibly indicative of an inflammatory burst)
• Other factors (burning of the sugarcane releasing unknown nephrotoxic substances; unreported NSAIDs use)5
Compared to workers who showed early signs of CKD, those who developed frank AKI were more likely to have hyponatremia. Recommendations to reduce the problem include consumption of water/salt hydrating drinks, use of appropriate clothing, work-hour limitations, and changes to payment structures (ie, from a volume system to an hourly or daily system). Furthermore, education on the need to avoid alcohol, illicit drugs, and NSAIDs during the harvest season should help to decrease incidence of AKI among these workers.
Elizabeth C. Evans, RN, MSN, CNP, DNP
Renal Medicine Associates, Albuquerque, New Mexico
REFERENCES
1. Ayuk J, Gittoes N. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014;51(Pt 2):179-188.
2. Firouzi A, Maadani M, Kiani R, et al. Intravenous magnesium sulfate: new method in prevention of contrast-induced nephropathy in primary percutaneous coronary intervention. Int Urol Nephrol. 2015;47(3):521-525.
3. Beaubien J. Mysterious kidney disease slays farm workers in central America. National Public Radio; 2014. www.npr.org/blogs/health/2014/04/30/306907097/mysterious-kidney-disease-slays-farmworkers-in-central-america. Accessed April 1, 2015.
4. Almaguer M, Herrera R, Orantes CM. Chronic kidney disease of unknown etiology in agricultural communities. MEDICC Rev. 2014;16(2):9-15.
5. Santos UP, Zanetta DMT, Burdmann EA. Burnt sugarcane harvesting is associated with acute renal dysfunction. Kidney Int. 2015;87(4):792-799.
6. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138.
| 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 Debra L. Coplon, DNP, DCC, who practices at the City of Memphis Wellness Clinic in Tennessee, and Elizabeth C. Evans, RN, MSN, CNP, DNP, who practices with Renal Medicine Associates in Albuquerque.
| 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 Debra L. Coplon, DNP, DCC, who practices at the City of Memphis Wellness Clinic in Tennessee, and Elizabeth C. Evans, RN, MSN, CNP, DNP, who practices with Renal Medicine Associates in Albuquerque.
| 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 Debra L. Coplon, DNP, DCC, who practices at the City of Memphis Wellness Clinic in Tennessee, and Elizabeth C. Evans, RN, MSN, CNP, DNP, who practices with Renal Medicine Associates in Albuquerque.
Q) I’ve heard a lot of talk about all the kidney problems that the sugarcane workers in Central America have. Does anyone know why this is happening?
The unusually high rates of chronic kidney disease (CKD) among sugarcane workers in Central America have been a subject of great interest since National Public Radio (NPR) aired a special on this topic.3 There has been a rising epidemic of CKD in otherwise healthy male farm workers (ages 20 to 50), particularly those who harvest sugarcane.4,5 It has been hypothesized that recurrent episodes of acute kidney injury (AKI)—related to dehydration, volume depletion, pollutants, and rhabdomyolysis with inflammatory stress—are the underlying cause.5
Sugarcane harvesters typically work nine-hour days, six days per week, in extremely high temperatures and while wearing heavy, hot clothing. Each worker cuts approximately 10 tons of sugarcane daily, since they are paid based on cutting volume. Workers drink between five and 10 L of water during their shifts.
Santos et al designed a study to prospectively examine the effects of burnt sugarcane harvesting on renal function in healthy male farm workers. Twenty-eight men (ages 19 to 39) with no CKD risk factors (diabetes, smoking, obesity, hypertension, illicit drug or alcohol use) were followed for eight months from preharvest to postharvest. Blood samples were collected at the beginning and at the end of the workday and preharvest and postharvest season.5
Preseason lab values were normal in all 28 men. But postseason, all workers had elevated creatinine levels, with five meeting the criteria for AKI (see Table at left).5,6
Santos and colleagues identified potential causes for AKI in this population. These included
• Dehydration and volume depletion (episodes of tachycardia, increased urine density, lower urinary/serum sodium, higher hematocrit)
• Rhabdomyolysis (increased creatine kinase at the end of each workday)
• Systemic inflammation (increased white blood count, neutrophils, lymphocytes, and monocytes during the workday—possibly indicative of an inflammatory burst)
• Other factors (burning of the sugarcane releasing unknown nephrotoxic substances; unreported NSAIDs use)5
Compared to workers who showed early signs of CKD, those who developed frank AKI were more likely to have hyponatremia. Recommendations to reduce the problem include consumption of water/salt hydrating drinks, use of appropriate clothing, work-hour limitations, and changes to payment structures (ie, from a volume system to an hourly or daily system). Furthermore, education on the need to avoid alcohol, illicit drugs, and NSAIDs during the harvest season should help to decrease incidence of AKI among these workers.
Elizabeth C. Evans, RN, MSN, CNP, DNP
Renal Medicine Associates, Albuquerque, New Mexico
REFERENCES
1. Ayuk J, Gittoes N. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014;51(Pt 2):179-188.
2. Firouzi A, Maadani M, Kiani R, et al. Intravenous magnesium sulfate: new method in prevention of contrast-induced nephropathy in primary percutaneous coronary intervention. Int Urol Nephrol. 2015;47(3):521-525.
3. Beaubien J. Mysterious kidney disease slays farm workers in central America. National Public Radio; 2014. www.npr.org/blogs/health/2014/04/30/306907097/mysterious-kidney-disease-slays-farmworkers-in-central-america. Accessed April 1, 2015.
4. Almaguer M, Herrera R, Orantes CM. Chronic kidney disease of unknown etiology in agricultural communities. MEDICC Rev. 2014;16(2):9-15.
5. Santos UP, Zanetta DMT, Burdmann EA. Burnt sugarcane harvesting is associated with acute renal dysfunction. Kidney Int. 2015;87(4):792-799.
6. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138.
Q) I’ve heard a lot of talk about all the kidney problems that the sugarcane workers in Central America have. Does anyone know why this is happening?
The unusually high rates of chronic kidney disease (CKD) among sugarcane workers in Central America have been a subject of great interest since National Public Radio (NPR) aired a special on this topic.3 There has been a rising epidemic of CKD in otherwise healthy male farm workers (ages 20 to 50), particularly those who harvest sugarcane.4,5 It has been hypothesized that recurrent episodes of acute kidney injury (AKI)—related to dehydration, volume depletion, pollutants, and rhabdomyolysis with inflammatory stress—are the underlying cause.5
Sugarcane harvesters typically work nine-hour days, six days per week, in extremely high temperatures and while wearing heavy, hot clothing. Each worker cuts approximately 10 tons of sugarcane daily, since they are paid based on cutting volume. Workers drink between five and 10 L of water during their shifts.
Santos et al designed a study to prospectively examine the effects of burnt sugarcane harvesting on renal function in healthy male farm workers. Twenty-eight men (ages 19 to 39) with no CKD risk factors (diabetes, smoking, obesity, hypertension, illicit drug or alcohol use) were followed for eight months from preharvest to postharvest. Blood samples were collected at the beginning and at the end of the workday and preharvest and postharvest season.5
Preseason lab values were normal in all 28 men. But postseason, all workers had elevated creatinine levels, with five meeting the criteria for AKI (see Table at left).5,6
Santos and colleagues identified potential causes for AKI in this population. These included
• Dehydration and volume depletion (episodes of tachycardia, increased urine density, lower urinary/serum sodium, higher hematocrit)
• Rhabdomyolysis (increased creatine kinase at the end of each workday)
• Systemic inflammation (increased white blood count, neutrophils, lymphocytes, and monocytes during the workday—possibly indicative of an inflammatory burst)
• Other factors (burning of the sugarcane releasing unknown nephrotoxic substances; unreported NSAIDs use)5
Compared to workers who showed early signs of CKD, those who developed frank AKI were more likely to have hyponatremia. Recommendations to reduce the problem include consumption of water/salt hydrating drinks, use of appropriate clothing, work-hour limitations, and changes to payment structures (ie, from a volume system to an hourly or daily system). Furthermore, education on the need to avoid alcohol, illicit drugs, and NSAIDs during the harvest season should help to decrease incidence of AKI among these workers.
Elizabeth C. Evans, RN, MSN, CNP, DNP
Renal Medicine Associates, Albuquerque, New Mexico
REFERENCES
1. Ayuk J, Gittoes N. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014;51(Pt 2):179-188.
2. Firouzi A, Maadani M, Kiani R, et al. Intravenous magnesium sulfate: new method in prevention of contrast-induced nephropathy in primary percutaneous coronary intervention. Int Urol Nephrol. 2015;47(3):521-525.
3. Beaubien J. Mysterious kidney disease slays farm workers in central America. National Public Radio; 2014. www.npr.org/blogs/health/2014/04/30/306907097/mysterious-kidney-disease-slays-farmworkers-in-central-america. Accessed April 1, 2015.
4. Almaguer M, Herrera R, Orantes CM. Chronic kidney disease of unknown etiology in agricultural communities. MEDICC Rev. 2014;16(2):9-15.
5. Santos UP, Zanetta DMT, Burdmann EA. Burnt sugarcane harvesting is associated with acute renal dysfunction. Kidney Int. 2015;87(4):792-799.
6. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138.
Acute Kidney Injury: Magnesium for Protection
Q) Our radiology department is discussing use of IV magnesium for diabetic patients to “protect them from kidney injury.” Is this a standard of care now?
Magnesium, the fourth most abundant cation in the body, plays an important physiologic role. Balance is maintained by renal regulation of magnesium reabsorption, and deficiency occurs when there is increased renal excretion initiated by osmotic diuresis. Clinical manifestations of deficiency include cardiac arrhythmias, neuromuscular hyperexcitability, and biochemical abnormalities of hypocalcaemia and hypokalemia.
Diabetes is one of the leading causes of magnesium deficiency, with incidence ranging from 25% to 39%.1 Fluctuations in serum magnesium concentrations are directly correlated with fasting blood glucose, A1C levels, albumin excretion, and the duration of diabetes. It has been postulated that magnesium depletion, via its effect on inositol transport, is pathogenic in the progression of diabetic complications.
Contrast-induced acute kidney injury (CI-AKI) is a potentially adverse consequence of percutaneous coronary interventions (PCI), particularly in diabetic patients. It results in significant morbidity and mortality and adds to the costs of diagnostic and interventional cardiology procedures. Intravenous (IV) agents used during radiologic imaging are notorious for causing acute kidney injury in diabetic patients. Preprocedural hydration and discontinuation of all nephrotoxic medications have proven beneficial in protecting these patients from CI-AKI.
A recent prospective, randomized, open-label clinical trial looked at the effect of administering IV magnesium prior to PCI.2 The control group underwent standard preprocedural hydration and discontinuation of nephrotoxic medications. The study group added IV magnesium to the standard protocol.
In this single-center study, 26.6% of patients in the control group and 14.5% in the study group sustained CI-AKI, a statistically significant result (P = .01). Neither group experienced mortality or required dialysis.
Although not considered standard of care at this time, prophylactic use of IV magnesium (pending pre-op labs), along with the recognized benefit of preprocedural hydration and discontinuation of nephrotoxic medications, can be supported in primary PCI patients. Your radiology department is on the cutting edge of protecting these very high-risk patients.
Debra L. Coplon, DNP, DCC
City of Memphis Wellness Clinic, Tennessee
REFERENCES
1. Ayuk J, Gittoes N. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014;51(Pt 2):179-188.
2. Firouzi A, Maadani M, Kiani R, et al. Intravenous magnesium sulfate: new method in prevention of contrast-induced nephropathy in primary percutaneous coronary intervention. Int Urol Nephrol. 2015;47(3):521-525.
| 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 Debra L. Coplon, DNP, DCC, who practices at the City of Memphis Wellness Clinic in Tennessee, and Elizabeth C. Evans, RN, MSN, CNP, DNP, who practices with Renal Medicine Associates in Albuquerque.
| 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 Debra L. Coplon, DNP, DCC, who practices at the City of Memphis Wellness Clinic in Tennessee, and Elizabeth C. Evans, RN, MSN, CNP, DNP, who practices with Renal Medicine Associates in Albuquerque.
| 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 Debra L. Coplon, DNP, DCC, who practices at the City of Memphis Wellness Clinic in Tennessee, and Elizabeth C. Evans, RN, MSN, CNP, DNP, who practices with Renal Medicine Associates in Albuquerque.
Q) Our radiology department is discussing use of IV magnesium for diabetic patients to “protect them from kidney injury.” Is this a standard of care now?
Magnesium, the fourth most abundant cation in the body, plays an important physiologic role. Balance is maintained by renal regulation of magnesium reabsorption, and deficiency occurs when there is increased renal excretion initiated by osmotic diuresis. Clinical manifestations of deficiency include cardiac arrhythmias, neuromuscular hyperexcitability, and biochemical abnormalities of hypocalcaemia and hypokalemia.
Diabetes is one of the leading causes of magnesium deficiency, with incidence ranging from 25% to 39%.1 Fluctuations in serum magnesium concentrations are directly correlated with fasting blood glucose, A1C levels, albumin excretion, and the duration of diabetes. It has been postulated that magnesium depletion, via its effect on inositol transport, is pathogenic in the progression of diabetic complications.
Contrast-induced acute kidney injury (CI-AKI) is a potentially adverse consequence of percutaneous coronary interventions (PCI), particularly in diabetic patients. It results in significant morbidity and mortality and adds to the costs of diagnostic and interventional cardiology procedures. Intravenous (IV) agents used during radiologic imaging are notorious for causing acute kidney injury in diabetic patients. Preprocedural hydration and discontinuation of all nephrotoxic medications have proven beneficial in protecting these patients from CI-AKI.
A recent prospective, randomized, open-label clinical trial looked at the effect of administering IV magnesium prior to PCI.2 The control group underwent standard preprocedural hydration and discontinuation of nephrotoxic medications. The study group added IV magnesium to the standard protocol.
In this single-center study, 26.6% of patients in the control group and 14.5% in the study group sustained CI-AKI, a statistically significant result (P = .01). Neither group experienced mortality or required dialysis.
Although not considered standard of care at this time, prophylactic use of IV magnesium (pending pre-op labs), along with the recognized benefit of preprocedural hydration and discontinuation of nephrotoxic medications, can be supported in primary PCI patients. Your radiology department is on the cutting edge of protecting these very high-risk patients.
Debra L. Coplon, DNP, DCC
City of Memphis Wellness Clinic, Tennessee
REFERENCES
1. Ayuk J, Gittoes N. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014;51(Pt 2):179-188.
2. Firouzi A, Maadani M, Kiani R, et al. Intravenous magnesium sulfate: new method in prevention of contrast-induced nephropathy in primary percutaneous coronary intervention. Int Urol Nephrol. 2015;47(3):521-525.
Q) Our radiology department is discussing use of IV magnesium for diabetic patients to “protect them from kidney injury.” Is this a standard of care now?
Magnesium, the fourth most abundant cation in the body, plays an important physiologic role. Balance is maintained by renal regulation of magnesium reabsorption, and deficiency occurs when there is increased renal excretion initiated by osmotic diuresis. Clinical manifestations of deficiency include cardiac arrhythmias, neuromuscular hyperexcitability, and biochemical abnormalities of hypocalcaemia and hypokalemia.
Diabetes is one of the leading causes of magnesium deficiency, with incidence ranging from 25% to 39%.1 Fluctuations in serum magnesium concentrations are directly correlated with fasting blood glucose, A1C levels, albumin excretion, and the duration of diabetes. It has been postulated that magnesium depletion, via its effect on inositol transport, is pathogenic in the progression of diabetic complications.
Contrast-induced acute kidney injury (CI-AKI) is a potentially adverse consequence of percutaneous coronary interventions (PCI), particularly in diabetic patients. It results in significant morbidity and mortality and adds to the costs of diagnostic and interventional cardiology procedures. Intravenous (IV) agents used during radiologic imaging are notorious for causing acute kidney injury in diabetic patients. Preprocedural hydration and discontinuation of all nephrotoxic medications have proven beneficial in protecting these patients from CI-AKI.
A recent prospective, randomized, open-label clinical trial looked at the effect of administering IV magnesium prior to PCI.2 The control group underwent standard preprocedural hydration and discontinuation of nephrotoxic medications. The study group added IV magnesium to the standard protocol.
In this single-center study, 26.6% of patients in the control group and 14.5% in the study group sustained CI-AKI, a statistically significant result (P = .01). Neither group experienced mortality or required dialysis.
Although not considered standard of care at this time, prophylactic use of IV magnesium (pending pre-op labs), along with the recognized benefit of preprocedural hydration and discontinuation of nephrotoxic medications, can be supported in primary PCI patients. Your radiology department is on the cutting edge of protecting these very high-risk patients.
Debra L. Coplon, DNP, DCC
City of Memphis Wellness Clinic, Tennessee
REFERENCES
1. Ayuk J, Gittoes N. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014;51(Pt 2):179-188.
2. Firouzi A, Maadani M, Kiani R, et al. Intravenous magnesium sulfate: new method in prevention of contrast-induced nephropathy in primary percutaneous coronary intervention. Int Urol Nephrol. 2015;47(3):521-525.
T cells remain best urinary biomarker for lupus nephritis
T cells are still the most accurate urinary biomarker for lupus nephritis, reported Katharina Kopetschke and her coauthors.
In a study of 123 lupus patients between April 2009 and March 2013, the area under the curve values for CD8+ T cells and CD4+ T cells (1.000 and 0.9969, respectively) showed better distinction of active lupus nephritis (LN) than did CD19+ B cells (0.7823), CD14+ macrophages (0.9066), and proteinuria (0.9201), Ms. Kopetschke and her colleagues reported.
The findings indicate that noninvasive urine monitoring “might become a useful tool to facilitate clinical decisions concerning kidney biopsies and treatment of LN,” the investigators said in the paper.
Read the full article in Arthritis Research & Therapy (doi:10.1186/s13075-015-0600-y).
T cells are still the most accurate urinary biomarker for lupus nephritis, reported Katharina Kopetschke and her coauthors.
In a study of 123 lupus patients between April 2009 and March 2013, the area under the curve values for CD8+ T cells and CD4+ T cells (1.000 and 0.9969, respectively) showed better distinction of active lupus nephritis (LN) than did CD19+ B cells (0.7823), CD14+ macrophages (0.9066), and proteinuria (0.9201), Ms. Kopetschke and her colleagues reported.
The findings indicate that noninvasive urine monitoring “might become a useful tool to facilitate clinical decisions concerning kidney biopsies and treatment of LN,” the investigators said in the paper.
Read the full article in Arthritis Research & Therapy (doi:10.1186/s13075-015-0600-y).
T cells are still the most accurate urinary biomarker for lupus nephritis, reported Katharina Kopetschke and her coauthors.
In a study of 123 lupus patients between April 2009 and March 2013, the area under the curve values for CD8+ T cells and CD4+ T cells (1.000 and 0.9969, respectively) showed better distinction of active lupus nephritis (LN) than did CD19+ B cells (0.7823), CD14+ macrophages (0.9066), and proteinuria (0.9201), Ms. Kopetschke and her colleagues reported.
The findings indicate that noninvasive urine monitoring “might become a useful tool to facilitate clinical decisions concerning kidney biopsies and treatment of LN,” the investigators said in the paper.
Read the full article in Arthritis Research & Therapy (doi:10.1186/s13075-015-0600-y).
Gastric bypass patients on calcium had higher rates of kidney stone growth
SAN DIEGO – Patients taking calcium supplementation after gastric bypass surgery had higher rates of kidney stone growth, compared with those who received no calcium supplementation, results from a single-center retrospective study showed.
In addition, the majority of stones in patients taking calcium supplementation were comprised of calcium oxalate monohydrate, which is less amenable to extracorporeal shockwave therapy. “You need more invasive procedures to break up these kinds of stones,” lead author Christopher Loftus said in an interview at the meeting of the Endocrine Society, where the study was presented during a late-breaking abstract session.
Though it has been demonstrated that bariatric surgery is associated with an increased risk of kidney stone formation (Kidney Int. 2014 [doi:10.1038/ki.2014.352]), Mr. Loftus, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine, and his associates set out to determine whether calcium supplementation increases the risk of nephrolithiasis in 60 stone-forming patients after gastric bypass surgery performed at the Cleveland Clinic. For each patient, two unenhanced CT scans at least 1 month apart and less than 2 years apart were selected at the start of the supplementation date and after the gastric bypass surgery date. The researchers calculated the rate of stone growth by the change in consecutive stone burden (the sum of maximum diameters of stones) divided by the elapsed time between scans.
Of the 60 patients, 31 received postoperative calcium supplementation (an average of 500 mg/day) and 29 did not. Compared with patients who did not take calcium supplementation, those who did were younger (a mean of 53 years vs. 58 years, respectively), more likely to be female (81% vs. 69%), and had a higher body mass index (34.5 kg/m2 vs. 32.7 kg/m2). In addition, a greater proportion of patients taking calcium supplements underwent Roux-en-Y bypass (83% vs. 64%; P = .19), had stones comprised of calcium oxalate (81% vs. 67%; P = .56), and a higher rate of stone growth (more than 10 mm/year vs. less than 5 mm/year; P = .0004). “We weren’t expecting such a pronounced effect,” Mr. Loftus said.
In their abstract, the researchers said that further studies are required to elucidate the exact role of calcium supplementation on stone disease in this patient population.
The study was funded in part by a grant from the American Society of Nephrology. Mr. Loftus reported having no relevant financial conflicts.
On Twitter @dougbrunk
SAN DIEGO – Patients taking calcium supplementation after gastric bypass surgery had higher rates of kidney stone growth, compared with those who received no calcium supplementation, results from a single-center retrospective study showed.
In addition, the majority of stones in patients taking calcium supplementation were comprised of calcium oxalate monohydrate, which is less amenable to extracorporeal shockwave therapy. “You need more invasive procedures to break up these kinds of stones,” lead author Christopher Loftus said in an interview at the meeting of the Endocrine Society, where the study was presented during a late-breaking abstract session.
Though it has been demonstrated that bariatric surgery is associated with an increased risk of kidney stone formation (Kidney Int. 2014 [doi:10.1038/ki.2014.352]), Mr. Loftus, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine, and his associates set out to determine whether calcium supplementation increases the risk of nephrolithiasis in 60 stone-forming patients after gastric bypass surgery performed at the Cleveland Clinic. For each patient, two unenhanced CT scans at least 1 month apart and less than 2 years apart were selected at the start of the supplementation date and after the gastric bypass surgery date. The researchers calculated the rate of stone growth by the change in consecutive stone burden (the sum of maximum diameters of stones) divided by the elapsed time between scans.
Of the 60 patients, 31 received postoperative calcium supplementation (an average of 500 mg/day) and 29 did not. Compared with patients who did not take calcium supplementation, those who did were younger (a mean of 53 years vs. 58 years, respectively), more likely to be female (81% vs. 69%), and had a higher body mass index (34.5 kg/m2 vs. 32.7 kg/m2). In addition, a greater proportion of patients taking calcium supplements underwent Roux-en-Y bypass (83% vs. 64%; P = .19), had stones comprised of calcium oxalate (81% vs. 67%; P = .56), and a higher rate of stone growth (more than 10 mm/year vs. less than 5 mm/year; P = .0004). “We weren’t expecting such a pronounced effect,” Mr. Loftus said.
In their abstract, the researchers said that further studies are required to elucidate the exact role of calcium supplementation on stone disease in this patient population.
The study was funded in part by a grant from the American Society of Nephrology. Mr. Loftus reported having no relevant financial conflicts.
On Twitter @dougbrunk
SAN DIEGO – Patients taking calcium supplementation after gastric bypass surgery had higher rates of kidney stone growth, compared with those who received no calcium supplementation, results from a single-center retrospective study showed.
In addition, the majority of stones in patients taking calcium supplementation were comprised of calcium oxalate monohydrate, which is less amenable to extracorporeal shockwave therapy. “You need more invasive procedures to break up these kinds of stones,” lead author Christopher Loftus said in an interview at the meeting of the Endocrine Society, where the study was presented during a late-breaking abstract session.
Though it has been demonstrated that bariatric surgery is associated with an increased risk of kidney stone formation (Kidney Int. 2014 [doi:10.1038/ki.2014.352]), Mr. Loftus, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine, and his associates set out to determine whether calcium supplementation increases the risk of nephrolithiasis in 60 stone-forming patients after gastric bypass surgery performed at the Cleveland Clinic. For each patient, two unenhanced CT scans at least 1 month apart and less than 2 years apart were selected at the start of the supplementation date and after the gastric bypass surgery date. The researchers calculated the rate of stone growth by the change in consecutive stone burden (the sum of maximum diameters of stones) divided by the elapsed time between scans.
Of the 60 patients, 31 received postoperative calcium supplementation (an average of 500 mg/day) and 29 did not. Compared with patients who did not take calcium supplementation, those who did were younger (a mean of 53 years vs. 58 years, respectively), more likely to be female (81% vs. 69%), and had a higher body mass index (34.5 kg/m2 vs. 32.7 kg/m2). In addition, a greater proportion of patients taking calcium supplements underwent Roux-en-Y bypass (83% vs. 64%; P = .19), had stones comprised of calcium oxalate (81% vs. 67%; P = .56), and a higher rate of stone growth (more than 10 mm/year vs. less than 5 mm/year; P = .0004). “We weren’t expecting such a pronounced effect,” Mr. Loftus said.
In their abstract, the researchers said that further studies are required to elucidate the exact role of calcium supplementation on stone disease in this patient population.
The study was funded in part by a grant from the American Society of Nephrology. Mr. Loftus reported having no relevant financial conflicts.
On Twitter @dougbrunk
AT ENDO 2015
Key clinical point: Calcium supplementation for post-gastric bypass surgery patients may increase the risk of kidney stone growth.
Major finding: Compared with patients who did not take calcium supplementation, those who did had a higher rate of kidney stone growth (more than 10 mm/year vs. less than 5 mm/year; P = .0004).
Data source: An analysis of 60 stone-forming patients who underwent gastric bypass surgery at the Cleveland Clinic.
Disclosures: The study was funded in part by a grant from the American Society of Nephrology. Mr. Loftus reported having no relevant financial conflicts.
Acute renal failure biggest short-term risk in I-EVAR explantation
SCOTTSDALE, ARIZ. – Acute renal failure occurred postoperatively in one-third of patients who underwent endograft explantation after endovascular abdominal aortic aneurysm repair (EVAR), according to the results of a small retrospective study.
The perioperative infected EVAR (I-EVAR) mortality across the study’s 36 patient records (83% male patients, average age 69 years), culled from four surgery centers’ data from 1997 to 2014, was 8%. The overall mortality was 25%, according to Dr. Victor J. Davila of Mayo Clinic Arizona, Phoenix, and his colleagues. Dr. Davila presented the findings at the Southern Association for Vascular Surgery annual meeting.
“These data show that I-EVAR explantation can be performed safely, with acceptable morbidity and mortality,” said Dr. Davila, who noted that while acceptable, the rates were still high, particularly for acute renal failure.
“We did not find any difference between the patients who developed renal failure and the type of graft, whether or not there was suprarenal fixation, and an incidence of postoperative acute renal failure,” Dr. Davila said, “However, because acute renal failure is multifactorial, we need to minimize aortic clamp time, as well as minimize the aortic intimal disruption around the renal arteries.”
Three deaths occurred within 30 days post operation, all from anastomotic dehiscence. Additional short-term morbidities included respiratory failure that required tracheostomy in three patients, and bleeding and sepsis in two patients each. Six patients required re-exploration because of infected hematoma, lymphatic leak, small-bowel perforation, open abdomen at initial operation, and anastomotic bleeding. Six more deaths occurred at a mean follow-up of 402 days. One death was attributable to a ruptured aneurysm, another to a progressive inflammatory illness, and four deaths were of indeterminate cause.
Only three of the explantations reviewed by Dr. Davila and his colleagues were considered emergent. The rest (92%) were either elective or urgent. Infected patients tended to present with leukocytosis (63%), pain (58%), and fever (56%), usually about 65 days prior to explantation. The average time between EVAR and presentation with infection was 589 days.
Although most underwent total graft excision, two patients underwent partial excision, including one with a distal iliac limb infection that showed no sign of infection within the main portion of the endograft. Nearly three-quarters of patients had in situ reconstruction.
While nearly a third of patients had positive preoperative blood cultures indicating infection, 81% of intraoperative cultures taken from the explanted graft, aneurysm wall, or sac contents indicated infection.
The gram-positive Staphylococcus and Streptococcus were the most common organisms found in cultures (33% and 17%, respectively), although anaerobics were found in a third of patients, gram negatives in a quarter of patients, and fungal infections in 14%. A majority (58%) of patients received long-term suppressive antibiotic therapy.
Surgeons should reserve the option to keep a graft in situ only in infected EVAR patients who likely would not survive surgical explantation and reconstruction, Dr. Davila said. “Although I believe [medical management] is an alternative, the best course of action is to remove the endograft.”
On Twitter @whitneymcknight
SCOTTSDALE, ARIZ. – Acute renal failure occurred postoperatively in one-third of patients who underwent endograft explantation after endovascular abdominal aortic aneurysm repair (EVAR), according to the results of a small retrospective study.
The perioperative infected EVAR (I-EVAR) mortality across the study’s 36 patient records (83% male patients, average age 69 years), culled from four surgery centers’ data from 1997 to 2014, was 8%. The overall mortality was 25%, according to Dr. Victor J. Davila of Mayo Clinic Arizona, Phoenix, and his colleagues. Dr. Davila presented the findings at the Southern Association for Vascular Surgery annual meeting.
“These data show that I-EVAR explantation can be performed safely, with acceptable morbidity and mortality,” said Dr. Davila, who noted that while acceptable, the rates were still high, particularly for acute renal failure.
“We did not find any difference between the patients who developed renal failure and the type of graft, whether or not there was suprarenal fixation, and an incidence of postoperative acute renal failure,” Dr. Davila said, “However, because acute renal failure is multifactorial, we need to minimize aortic clamp time, as well as minimize the aortic intimal disruption around the renal arteries.”
Three deaths occurred within 30 days post operation, all from anastomotic dehiscence. Additional short-term morbidities included respiratory failure that required tracheostomy in three patients, and bleeding and sepsis in two patients each. Six patients required re-exploration because of infected hematoma, lymphatic leak, small-bowel perforation, open abdomen at initial operation, and anastomotic bleeding. Six more deaths occurred at a mean follow-up of 402 days. One death was attributable to a ruptured aneurysm, another to a progressive inflammatory illness, and four deaths were of indeterminate cause.
Only three of the explantations reviewed by Dr. Davila and his colleagues were considered emergent. The rest (92%) were either elective or urgent. Infected patients tended to present with leukocytosis (63%), pain (58%), and fever (56%), usually about 65 days prior to explantation. The average time between EVAR and presentation with infection was 589 days.
Although most underwent total graft excision, two patients underwent partial excision, including one with a distal iliac limb infection that showed no sign of infection within the main portion of the endograft. Nearly three-quarters of patients had in situ reconstruction.
While nearly a third of patients had positive preoperative blood cultures indicating infection, 81% of intraoperative cultures taken from the explanted graft, aneurysm wall, or sac contents indicated infection.
The gram-positive Staphylococcus and Streptococcus were the most common organisms found in cultures (33% and 17%, respectively), although anaerobics were found in a third of patients, gram negatives in a quarter of patients, and fungal infections in 14%. A majority (58%) of patients received long-term suppressive antibiotic therapy.
Surgeons should reserve the option to keep a graft in situ only in infected EVAR patients who likely would not survive surgical explantation and reconstruction, Dr. Davila said. “Although I believe [medical management] is an alternative, the best course of action is to remove the endograft.”
On Twitter @whitneymcknight
SCOTTSDALE, ARIZ. – Acute renal failure occurred postoperatively in one-third of patients who underwent endograft explantation after endovascular abdominal aortic aneurysm repair (EVAR), according to the results of a small retrospective study.
The perioperative infected EVAR (I-EVAR) mortality across the study’s 36 patient records (83% male patients, average age 69 years), culled from four surgery centers’ data from 1997 to 2014, was 8%. The overall mortality was 25%, according to Dr. Victor J. Davila of Mayo Clinic Arizona, Phoenix, and his colleagues. Dr. Davila presented the findings at the Southern Association for Vascular Surgery annual meeting.
“These data show that I-EVAR explantation can be performed safely, with acceptable morbidity and mortality,” said Dr. Davila, who noted that while acceptable, the rates were still high, particularly for acute renal failure.
“We did not find any difference between the patients who developed renal failure and the type of graft, whether or not there was suprarenal fixation, and an incidence of postoperative acute renal failure,” Dr. Davila said, “However, because acute renal failure is multifactorial, we need to minimize aortic clamp time, as well as minimize the aortic intimal disruption around the renal arteries.”
Three deaths occurred within 30 days post operation, all from anastomotic dehiscence. Additional short-term morbidities included respiratory failure that required tracheostomy in three patients, and bleeding and sepsis in two patients each. Six patients required re-exploration because of infected hematoma, lymphatic leak, small-bowel perforation, open abdomen at initial operation, and anastomotic bleeding. Six more deaths occurred at a mean follow-up of 402 days. One death was attributable to a ruptured aneurysm, another to a progressive inflammatory illness, and four deaths were of indeterminate cause.
Only three of the explantations reviewed by Dr. Davila and his colleagues were considered emergent. The rest (92%) were either elective or urgent. Infected patients tended to present with leukocytosis (63%), pain (58%), and fever (56%), usually about 65 days prior to explantation. The average time between EVAR and presentation with infection was 589 days.
Although most underwent total graft excision, two patients underwent partial excision, including one with a distal iliac limb infection that showed no sign of infection within the main portion of the endograft. Nearly three-quarters of patients had in situ reconstruction.
While nearly a third of patients had positive preoperative blood cultures indicating infection, 81% of intraoperative cultures taken from the explanted graft, aneurysm wall, or sac contents indicated infection.
The gram-positive Staphylococcus and Streptococcus were the most common organisms found in cultures (33% and 17%, respectively), although anaerobics were found in a third of patients, gram negatives in a quarter of patients, and fungal infections in 14%. A majority (58%) of patients received long-term suppressive antibiotic therapy.
Surgeons should reserve the option to keep a graft in situ only in infected EVAR patients who likely would not survive surgical explantation and reconstruction, Dr. Davila said. “Although I believe [medical management] is an alternative, the best course of action is to remove the endograft.”
On Twitter @whitneymcknight
AT THE SAVS ANNUAL MEETING
Key clinical point: Minimizing cross-clamp time may reduce the rate of acute renal failure 30 days post op in infected EVAR explantation patients.
Major finding: One-third of I-EVAR patients had postoperative acute renal failure; perioperative mortality in I-EVAR was 8%, and overall mortality was 25%.
Data source: Retrospective analysis of 36 patients with infected EVAR explants performed between 1997 and 2014 across four surgical centers.
Disclosures: Dr. Davila reported he had no relevant disclosures.
Blacks, Hispanics less likely than whites to receive pre-ESRD care
Black and Hispanic patients with end-stage renal disease caused by lupus nephritis were 27% less likely to receive pre-ESRD care than were their white counterparts, reported Laura C. Plantinga, Ph.D., and her associates at Emory University, Atlanta.
Using data from the United States Renal Data System, the investigators determined that 71.1% out of a total of 6,594 incident LN-ESRD patients who initiated treatment from 2005 to 2011 received pre-ESRD nephrology care. Lack of insurance or being on Medicaid at the start of ESRD start also was associated with inadequate ESRD care, as those with Medicaid or no insurance were 49% and 64% less likely, respectively, than were those with private insurance to be placed on a kidney transplant wait list.
“Our findings also indicate substantial sociodemographic and regional disparities in the translation of quality-of-care measures related to pre-ESRD care, access to transplant, and placement of permanent vascular access among LN-ESRD patients,” the authors wrote.
Read the entire article, published Feb. 25 in Arthritis & Rheumatology (doi:10.1002/art.38983).
Black and Hispanic patients with end-stage renal disease caused by lupus nephritis were 27% less likely to receive pre-ESRD care than were their white counterparts, reported Laura C. Plantinga, Ph.D., and her associates at Emory University, Atlanta.
Using data from the United States Renal Data System, the investigators determined that 71.1% out of a total of 6,594 incident LN-ESRD patients who initiated treatment from 2005 to 2011 received pre-ESRD nephrology care. Lack of insurance or being on Medicaid at the start of ESRD start also was associated with inadequate ESRD care, as those with Medicaid or no insurance were 49% and 64% less likely, respectively, than were those with private insurance to be placed on a kidney transplant wait list.
“Our findings also indicate substantial sociodemographic and regional disparities in the translation of quality-of-care measures related to pre-ESRD care, access to transplant, and placement of permanent vascular access among LN-ESRD patients,” the authors wrote.
Read the entire article, published Feb. 25 in Arthritis & Rheumatology (doi:10.1002/art.38983).
Black and Hispanic patients with end-stage renal disease caused by lupus nephritis were 27% less likely to receive pre-ESRD care than were their white counterparts, reported Laura C. Plantinga, Ph.D., and her associates at Emory University, Atlanta.
Using data from the United States Renal Data System, the investigators determined that 71.1% out of a total of 6,594 incident LN-ESRD patients who initiated treatment from 2005 to 2011 received pre-ESRD nephrology care. Lack of insurance or being on Medicaid at the start of ESRD start also was associated with inadequate ESRD care, as those with Medicaid or no insurance were 49% and 64% less likely, respectively, than were those with private insurance to be placed on a kidney transplant wait list.
“Our findings also indicate substantial sociodemographic and regional disparities in the translation of quality-of-care measures related to pre-ESRD care, access to transplant, and placement of permanent vascular access among LN-ESRD patients,” the authors wrote.
Read the entire article, published Feb. 25 in Arthritis & Rheumatology (doi:10.1002/art.38983).
Can Vitamin D Supplements Help With Hypertension?
Q) One of my patients came in and said he had read that vitamin D supplementation will help with hypertension. Now he wants to quit his blood pressure meds and use vitamin D instead. Do you have any background on this?
Vitamin D is critical for utilization of calcium, a vital nutrient for multiple metabolic and cellular processes; deficiency is associated with worsening of autoimmune disorders, osteoporosis, and certain cardiovascular conditions, among others.7 An association between vitamin D level and blood pressure has been recognized for some time, but the pathophysiology is not well understood.
A literature review of studies from 1988 to 2013 found contradictory results regarding vitamin D deficiency and concurrent elevated blood pressure (systolic and/or diastolic), as well as the impact on blood pressure with restoration of vitamin D levels. The findings were limited by several factors, including differences in study design, variables evaluated, and type of vitamin D compound used. The results suggested a link between the renin-angiotensin-aldosterone system, fibroblast growth factor 23/klotho axis, and vitamin D level.8
A study of 158 subjects (98 with newly diagnosed essential hypertension, 60 with normal blood pressure) found significantly lower 25(OH)D3 serum levels in hypertensive patients. Furthermore, the 25(OH)D3 level was significantly correlated with both systolic (r = –0.33) and diastolic blood pressure (r = –0.26). Using multiple regression analysis, after adjustment for age, smoking status, and BMI, the impact of 25(OH)D3 level accounted for 10% of the variation in systolic blood pressure.9
In a mendelian randomization study of 108,173 subjects from 35 studies, an inverse association between vitamin D level and systolic blood pressure (P = .0003) was found. A reduced risk for essential hypertension with increased vitamin D level (P = .0003) was also noted. However, no association was found between increasing vitamin D level and a reduction in diastolic blood pressure
(P = .37).10
With the ever-increasing access to health information from sources such as “Doctor Google,” it can be difficult for a non–health care professional to separate hype from evidence-based recommendations. While current evidence suggests optimal vitamin D levels may be beneficial for improving blood pressure control and may be a useful adjunctive therapy, there is no evidence to support discontinuing antihypertensive therapy and replacing it with vitamin D therapy.
Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants, South Charleston, West Virginia
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
| 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 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, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
| 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 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, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
| 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 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, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
Q) One of my patients came in and said he had read that vitamin D supplementation will help with hypertension. Now he wants to quit his blood pressure meds and use vitamin D instead. Do you have any background on this?
Vitamin D is critical for utilization of calcium, a vital nutrient for multiple metabolic and cellular processes; deficiency is associated with worsening of autoimmune disorders, osteoporosis, and certain cardiovascular conditions, among others.7 An association between vitamin D level and blood pressure has been recognized for some time, but the pathophysiology is not well understood.
A literature review of studies from 1988 to 2013 found contradictory results regarding vitamin D deficiency and concurrent elevated blood pressure (systolic and/or diastolic), as well as the impact on blood pressure with restoration of vitamin D levels. The findings were limited by several factors, including differences in study design, variables evaluated, and type of vitamin D compound used. The results suggested a link between the renin-angiotensin-aldosterone system, fibroblast growth factor 23/klotho axis, and vitamin D level.8
A study of 158 subjects (98 with newly diagnosed essential hypertension, 60 with normal blood pressure) found significantly lower 25(OH)D3 serum levels in hypertensive patients. Furthermore, the 25(OH)D3 level was significantly correlated with both systolic (r = –0.33) and diastolic blood pressure (r = –0.26). Using multiple regression analysis, after adjustment for age, smoking status, and BMI, the impact of 25(OH)D3 level accounted for 10% of the variation in systolic blood pressure.9
In a mendelian randomization study of 108,173 subjects from 35 studies, an inverse association between vitamin D level and systolic blood pressure (P = .0003) was found. A reduced risk for essential hypertension with increased vitamin D level (P = .0003) was also noted. However, no association was found between increasing vitamin D level and a reduction in diastolic blood pressure
(P = .37).10
With the ever-increasing access to health information from sources such as “Doctor Google,” it can be difficult for a non–health care professional to separate hype from evidence-based recommendations. While current evidence suggests optimal vitamin D levels may be beneficial for improving blood pressure control and may be a useful adjunctive therapy, there is no evidence to support discontinuing antihypertensive therapy and replacing it with vitamin D therapy.
Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants, South Charleston, West Virginia
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
Q) One of my patients came in and said he had read that vitamin D supplementation will help with hypertension. Now he wants to quit his blood pressure meds and use vitamin D instead. Do you have any background on this?
Vitamin D is critical for utilization of calcium, a vital nutrient for multiple metabolic and cellular processes; deficiency is associated with worsening of autoimmune disorders, osteoporosis, and certain cardiovascular conditions, among others.7 An association between vitamin D level and blood pressure has been recognized for some time, but the pathophysiology is not well understood.
A literature review of studies from 1988 to 2013 found contradictory results regarding vitamin D deficiency and concurrent elevated blood pressure (systolic and/or diastolic), as well as the impact on blood pressure with restoration of vitamin D levels. The findings were limited by several factors, including differences in study design, variables evaluated, and type of vitamin D compound used. The results suggested a link between the renin-angiotensin-aldosterone system, fibroblast growth factor 23/klotho axis, and vitamin D level.8
A study of 158 subjects (98 with newly diagnosed essential hypertension, 60 with normal blood pressure) found significantly lower 25(OH)D3 serum levels in hypertensive patients. Furthermore, the 25(OH)D3 level was significantly correlated with both systolic (r = –0.33) and diastolic blood pressure (r = –0.26). Using multiple regression analysis, after adjustment for age, smoking status, and BMI, the impact of 25(OH)D3 level accounted for 10% of the variation in systolic blood pressure.9
In a mendelian randomization study of 108,173 subjects from 35 studies, an inverse association between vitamin D level and systolic blood pressure (P = .0003) was found. A reduced risk for essential hypertension with increased vitamin D level (P = .0003) was also noted. However, no association was found between increasing vitamin D level and a reduction in diastolic blood pressure
(P = .37).10
With the ever-increasing access to health information from sources such as “Doctor Google,” it can be difficult for a non–health care professional to separate hype from evidence-based recommendations. While current evidence suggests optimal vitamin D levels may be beneficial for improving blood pressure control and may be a useful adjunctive therapy, there is no evidence to support discontinuing antihypertensive therapy and replacing it with vitamin D therapy.
Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants, South Charleston, West Virginia
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
Megestrol Acetate for CKD and Dialysis Patients
Q) Some of my CKD patients are malnourished; in fact, some of those on dialysis do not eat well and have low albumin levels. Previously in this column, it was stated that higher albumin levels (> 4 g/dL) confer survival benefits to dialysis patients. Should I consider prescribing megestrol acetate to improve appetite? If I do prescribe it, what dose is safe for CKD and dialysis patients?
Malnutrition affects one-third of dialysis patients,1 and malnutrition-inflammation complex syndrome (MICS) is common in those with stage 5 CKD. Albumin is used as an indicator of MICS in dialysis patients; however, since other factors (stress, infection, inflammation, comorbidities) affect nutritional status,2 serum albumin alone may not be sufficient to assess it.
In fact, a recent consensus statement on malnutrition from the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition excluded serum albumin as a diagnostic characteristic; the criteria included percentage of energy requirement, percentage of weight loss and time frame, loss of body fat and muscle mass, presence of edema, and reduced grip strength.3 These may be better measures of malnutrition in dialysis patients and could be used as criteria for determining when to prescribe an appetite stimulant, such as megestrol acetate.
In recent years, megestrol acetate (an antineoplastic drug) has been used to improve appetite, weight, albumin levels, and MICS in patients receiving maintenance dialysis.1,4-6 Rammohan et al found significant increases in weight, BMI, body fat, triceps skinfold thickness, protein/energy intake, and serum albumin in 10 dialysis patients who took megestrol acetate (400 mg/d) for 16 weeks.4
Continue for megestrol acetate's effects >>
In a 20-week randomized, double-blind, placebo-controlled trial, Yeh et al found significant increases in weight, body fat, and fat-free mass in elderly hemodialysis patients receiving megestrol acetate (800 mg/d). The treatment group also demonstrated greater improvement in ability to exercise.5
Monfared and colleagues looked specifically at megestrol acetate’s effect on serum albumin levels in dialysis patients.1 Using a much lower dose (40 mg bid for two months), they found a significant increase in serum albumin in the treatment group. Although an increase in appetite was noted, the researchers did not observe any significant change in total weight following treatment.1
In a letter to the editor of the Journal of Renal Nutrition, Golebiewska et al reported their use of megestrol acetate in maintenance hemodialysis and peritoneal dialysis patients.6 Hypoalbuminemic patients were given megestrol acetate (160 mg/d). Significant increases in weight, BMI, subjective global assessment scores (a measure of nutritional status based on clinical indices such as weight, appetite, muscle, and fat mass), and serum albumin levels were seen. Only 12 of the 32 patients completed the study; the others dropped out due to adverse effects, including high intradialytic weight gain (the amount of fluid gained between dialysis sessions), dyspnea, diarrhea, and nausea.6
Currently, there is no consensus in the literature regarding the most effective dosage of megestrol acetate. Furthermore, evidence is lacking as to whether megestrol acetate–induced increases in appetite, oral intake, weight, and serum albumin level bestow any survival benefit or affect outcomes in dialysis patients.4 However, the increased sense of well-being a patient experiences when appetite returns and weight is restored may be worth the effort.
Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
| 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 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, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
| 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 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, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
| 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 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, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
Q) Some of my CKD patients are malnourished; in fact, some of those on dialysis do not eat well and have low albumin levels. Previously in this column, it was stated that higher albumin levels (> 4 g/dL) confer survival benefits to dialysis patients. Should I consider prescribing megestrol acetate to improve appetite? If I do prescribe it, what dose is safe for CKD and dialysis patients?
Malnutrition affects one-third of dialysis patients,1 and malnutrition-inflammation complex syndrome (MICS) is common in those with stage 5 CKD. Albumin is used as an indicator of MICS in dialysis patients; however, since other factors (stress, infection, inflammation, comorbidities) affect nutritional status,2 serum albumin alone may not be sufficient to assess it.
In fact, a recent consensus statement on malnutrition from the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition excluded serum albumin as a diagnostic characteristic; the criteria included percentage of energy requirement, percentage of weight loss and time frame, loss of body fat and muscle mass, presence of edema, and reduced grip strength.3 These may be better measures of malnutrition in dialysis patients and could be used as criteria for determining when to prescribe an appetite stimulant, such as megestrol acetate.
In recent years, megestrol acetate (an antineoplastic drug) has been used to improve appetite, weight, albumin levels, and MICS in patients receiving maintenance dialysis.1,4-6 Rammohan et al found significant increases in weight, BMI, body fat, triceps skinfold thickness, protein/energy intake, and serum albumin in 10 dialysis patients who took megestrol acetate (400 mg/d) for 16 weeks.4
Continue for megestrol acetate's effects >>
In a 20-week randomized, double-blind, placebo-controlled trial, Yeh et al found significant increases in weight, body fat, and fat-free mass in elderly hemodialysis patients receiving megestrol acetate (800 mg/d). The treatment group also demonstrated greater improvement in ability to exercise.5
Monfared and colleagues looked specifically at megestrol acetate’s effect on serum albumin levels in dialysis patients.1 Using a much lower dose (40 mg bid for two months), they found a significant increase in serum albumin in the treatment group. Although an increase in appetite was noted, the researchers did not observe any significant change in total weight following treatment.1
In a letter to the editor of the Journal of Renal Nutrition, Golebiewska et al reported their use of megestrol acetate in maintenance hemodialysis and peritoneal dialysis patients.6 Hypoalbuminemic patients were given megestrol acetate (160 mg/d). Significant increases in weight, BMI, subjective global assessment scores (a measure of nutritional status based on clinical indices such as weight, appetite, muscle, and fat mass), and serum albumin levels were seen. Only 12 of the 32 patients completed the study; the others dropped out due to adverse effects, including high intradialytic weight gain (the amount of fluid gained between dialysis sessions), dyspnea, diarrhea, and nausea.6
Currently, there is no consensus in the literature regarding the most effective dosage of megestrol acetate. Furthermore, evidence is lacking as to whether megestrol acetate–induced increases in appetite, oral intake, weight, and serum albumin level bestow any survival benefit or affect outcomes in dialysis patients.4 However, the increased sense of well-being a patient experiences when appetite returns and weight is restored may be worth the effort.
Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
Q) Some of my CKD patients are malnourished; in fact, some of those on dialysis do not eat well and have low albumin levels. Previously in this column, it was stated that higher albumin levels (> 4 g/dL) confer survival benefits to dialysis patients. Should I consider prescribing megestrol acetate to improve appetite? If I do prescribe it, what dose is safe for CKD and dialysis patients?
Malnutrition affects one-third of dialysis patients,1 and malnutrition-inflammation complex syndrome (MICS) is common in those with stage 5 CKD. Albumin is used as an indicator of MICS in dialysis patients; however, since other factors (stress, infection, inflammation, comorbidities) affect nutritional status,2 serum albumin alone may not be sufficient to assess it.
In fact, a recent consensus statement on malnutrition from the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition excluded serum albumin as a diagnostic characteristic; the criteria included percentage of energy requirement, percentage of weight loss and time frame, loss of body fat and muscle mass, presence of edema, and reduced grip strength.3 These may be better measures of malnutrition in dialysis patients and could be used as criteria for determining when to prescribe an appetite stimulant, such as megestrol acetate.
In recent years, megestrol acetate (an antineoplastic drug) has been used to improve appetite, weight, albumin levels, and MICS in patients receiving maintenance dialysis.1,4-6 Rammohan et al found significant increases in weight, BMI, body fat, triceps skinfold thickness, protein/energy intake, and serum albumin in 10 dialysis patients who took megestrol acetate (400 mg/d) for 16 weeks.4
Continue for megestrol acetate's effects >>
In a 20-week randomized, double-blind, placebo-controlled trial, Yeh et al found significant increases in weight, body fat, and fat-free mass in elderly hemodialysis patients receiving megestrol acetate (800 mg/d). The treatment group also demonstrated greater improvement in ability to exercise.5
Monfared and colleagues looked specifically at megestrol acetate’s effect on serum albumin levels in dialysis patients.1 Using a much lower dose (40 mg bid for two months), they found a significant increase in serum albumin in the treatment group. Although an increase in appetite was noted, the researchers did not observe any significant change in total weight following treatment.1
In a letter to the editor of the Journal of Renal Nutrition, Golebiewska et al reported their use of megestrol acetate in maintenance hemodialysis and peritoneal dialysis patients.6 Hypoalbuminemic patients were given megestrol acetate (160 mg/d). Significant increases in weight, BMI, subjective global assessment scores (a measure of nutritional status based on clinical indices such as weight, appetite, muscle, and fat mass), and serum albumin levels were seen. Only 12 of the 32 patients completed the study; the others dropped out due to adverse effects, including high intradialytic weight gain (the amount of fluid gained between dialysis sessions), dyspnea, diarrhea, and nausea.6
Currently, there is no consensus in the literature regarding the most effective dosage of megestrol acetate. Furthermore, evidence is lacking as to whether megestrol acetate–induced increases in appetite, oral intake, weight, and serum albumin level bestow any survival benefit or affect outcomes in dialysis patients.4 However, the increased sense of well-being a patient experiences when appetite returns and weight is restored may be worth the effort.
Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
Smoking linked to many ‘new’ causes of death
Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.
“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.
The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.
For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.
As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.
For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]). In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.
The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.
The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.
The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.
Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.
In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.
This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.
The findings reported by Carter et al. substantiate that until now, estimates of premature deaths due to smoking have markedly underestimated the burden of tobacco use on U.S. society. Attributing 60,000-120,000 additional deaths each year to smoking would have an important public health impact, since it is comparable to the number of annual deaths attributed to excess alcohol intake.
Many people see the war against smoking as one that we have already won, given that rates have declined so much since the 1960s. But these findings show that although we have had some major victories, the war on smoking is far from over.
Dr. Graham A. Colditz is at Washington University, St. Louis. He reported having no financial disclosures. Dr. Colditz made these remarks in an editorial accompanying Mr. Carter’s report (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMe1414318]).
The findings reported by Carter et al. substantiate that until now, estimates of premature deaths due to smoking have markedly underestimated the burden of tobacco use on U.S. society. Attributing 60,000-120,000 additional deaths each year to smoking would have an important public health impact, since it is comparable to the number of annual deaths attributed to excess alcohol intake.
Many people see the war against smoking as one that we have already won, given that rates have declined so much since the 1960s. But these findings show that although we have had some major victories, the war on smoking is far from over.
Dr. Graham A. Colditz is at Washington University, St. Louis. He reported having no financial disclosures. Dr. Colditz made these remarks in an editorial accompanying Mr. Carter’s report (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMe1414318]).
The findings reported by Carter et al. substantiate that until now, estimates of premature deaths due to smoking have markedly underestimated the burden of tobacco use on U.S. society. Attributing 60,000-120,000 additional deaths each year to smoking would have an important public health impact, since it is comparable to the number of annual deaths attributed to excess alcohol intake.
Many people see the war against smoking as one that we have already won, given that rates have declined so much since the 1960s. But these findings show that although we have had some major victories, the war on smoking is far from over.
Dr. Graham A. Colditz is at Washington University, St. Louis. He reported having no financial disclosures. Dr. Colditz made these remarks in an editorial accompanying Mr. Carter’s report (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMe1414318]).
Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.
“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.
The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.
For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.
As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.
For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]). In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.
The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.
The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.
The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.
Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.
In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.
This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.
Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.
“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.
The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.
For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.
As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.
For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]). In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.
The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.
The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.
The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.
Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.
In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.
This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.
Key clinical point: Smoking is now thought to cause many deaths from infections; renal failure; liver cirrhosis; digestive diseases; and breast, prostate, and other cancers.
Major finding: Several diseases that previously have not been attributable to tobacco use accounted for 17% of smokers’ excess mortality.
Data source: An analysis of pooled data from five large cohort studies involving 954,029 people aged 55 years and older followed for 12 years to examine associations between smoking and 52 possible causes of death.
Disclosures: This study was supported by the American Cancer Society. Mr. Carter reported having no financial disclosures; one of his associates reported receiving grant support from Novo Nordisk.
