ASN Kidney Week 2015

SAN DIEGO – Among patients with proteinuric diabetic kidney disease, a mean systolic blood pressure greater than 140 mm Hg and a mean diastolic blood pressure greater than 80 mm Hg were associated with worse renal outcomes, a large national analysis showed.

“Proteinuric diabetic kidney disease frequently progresses to end-stage renal disease,” lead study author Dr. David J. Leehey said at a meeting sponsored by the American Society of Nephrology. “Control of blood pressure delays progression, but the optimal blood pressure to improve outcomes remains unclear.”

In a recent report from the Eighth Joint National Committee, panel members recommended a blood pressure of less than 140/90 mm Hg both for patients with diabetes and patients with chronic kidney disease (JAMA. 2014 Feb 5;311[5]:507-20).

“There are few data with regard to target blood pressure in proteinuric diabetic kidney disease, however, leaving physicians uncertain about how aggressively to lower blood pressure in such patients,” said Dr. Leehey, a nephrologist at the Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill.

In an effort to assess the relationship between blood pressure and renal outcomes in proteinuric diabetic kidney disease, the researchers evaluated blood pressure data from all 1,448 patients who were randomized to the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, which evaluated the combination of losartan with lisinopril, compared with losartan alone (N Engl J Med. 2013 Nov 14;369[20]:1892-1903). Randomization occurred between July 2008 and September 2012, but the trial was halted in October of 2012 due to safety reasons (acute kidney injury and hyperkalemic episodes).

For the current analysis, Dr. Leehey and his associates evaluated the associations of mean on-treatment blood pressure with the primary endpoint (defined as a decline in estimated glomerular filtration rate [eGFR], end-stage renal disease [ESRD], or death), the renal endpoint (defined as a decline in eGFR or cystatin C), the rate of eGFR decline, and mortality.

Trough sitting blood pressure measurements were obtained at every visit during the screening, titration, randomization, and treatment phases of VA NEPHRON-D. Mean blood pressure was defined as the average of all on-treatment blood pressures from the randomization visit to the last blood pressure measurement taken.

Dr. Leehey reported that there were 284 primary endpoints: 132 in the combination group and 152 in the monotherapy group. The mean blood pressure was based on a mean of 7.7 readings per participant.

Both mean systolic and mean diastolic blood pressure were strongly associated with the primary endpoint (P less than .001), univariate analysis revealed. The hazard of developing the primary endpoint increased as the mean systolic blood pressure rose from less than 120 mm Hg to greater than 150 mm Hg (P = .018), multivariate analysis showed.

A significant increase in hazard ratio was seen when mean systolic blood pressure was greater than 140 mm Hg (HR, 1.51). The researchers also observed a significant effect of mean diastolic blood pressure on the hazard of developing the primary endpoint (P = .005), with an increase in hazard ratio when mean diastolic blood pressure was greater than 80 mm Hg (HR, 1.54).

“Associations between BP and both renal endpoint and rate of eGFR decline were similar to those with the primary endpoint,” Dr. Leehey said. “There was a U-shaped relationship between rate of eGFR decline and mean diastolic blood pressure, with the lowest rate of eGFR decline seen when diastolic blood pressure was in the 70-79 mm Hg range. No effect of BP with mortality was observed, possibly because of the limited number of mortality events.”

The study was funded by support from the Veterans Administration. Dr. Leehey reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with proteinuric diabetic kidney disease, a mean systolic blood pressure greater than 140 mm Hg and a mean diastolic blood pressure greater than 80 mm Hg were associated with worse renal outcomes, a large national analysis showed.

“Proteinuric diabetic kidney disease frequently progresses to end-stage renal disease,” lead study author Dr. David J. Leehey said at a meeting sponsored by the American Society of Nephrology. “Control of blood pressure delays progression, but the optimal blood pressure to improve outcomes remains unclear.”

In a recent report from the Eighth Joint National Committee, panel members recommended a blood pressure of less than 140/90 mm Hg both for patients with diabetes and patients with chronic kidney disease (JAMA. 2014 Feb 5;311[5]:507-20).

“There are few data with regard to target blood pressure in proteinuric diabetic kidney disease, however, leaving physicians uncertain about how aggressively to lower blood pressure in such patients,” said Dr. Leehey, a nephrologist at the Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill.

In an effort to assess the relationship between blood pressure and renal outcomes in proteinuric diabetic kidney disease, the researchers evaluated blood pressure data from all 1,448 patients who were randomized to the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, which evaluated the combination of losartan with lisinopril, compared with losartan alone (N Engl J Med. 2013 Nov 14;369[20]:1892-1903). Randomization occurred between July 2008 and September 2012, but the trial was halted in October of 2012 due to safety reasons (acute kidney injury and hyperkalemic episodes).

For the current analysis, Dr. Leehey and his associates evaluated the associations of mean on-treatment blood pressure with the primary endpoint (defined as a decline in estimated glomerular filtration rate [eGFR], end-stage renal disease [ESRD], or death), the renal endpoint (defined as a decline in eGFR or cystatin C), the rate of eGFR decline, and mortality.

Trough sitting blood pressure measurements were obtained at every visit during the screening, titration, randomization, and treatment phases of VA NEPHRON-D. Mean blood pressure was defined as the average of all on-treatment blood pressures from the randomization visit to the last blood pressure measurement taken.

Dr. Leehey reported that there were 284 primary endpoints: 132 in the combination group and 152 in the monotherapy group. The mean blood pressure was based on a mean of 7.7 readings per participant.

Both mean systolic and mean diastolic blood pressure were strongly associated with the primary endpoint (P less than .001), univariate analysis revealed. The hazard of developing the primary endpoint increased as the mean systolic blood pressure rose from less than 120 mm Hg to greater than 150 mm Hg (P = .018), multivariate analysis showed.

A significant increase in hazard ratio was seen when mean systolic blood pressure was greater than 140 mm Hg (HR, 1.51). The researchers also observed a significant effect of mean diastolic blood pressure on the hazard of developing the primary endpoint (P = .005), with an increase in hazard ratio when mean diastolic blood pressure was greater than 80 mm Hg (HR, 1.54).

“Associations between BP and both renal endpoint and rate of eGFR decline were similar to those with the primary endpoint,” Dr. Leehey said. “There was a U-shaped relationship between rate of eGFR decline and mean diastolic blood pressure, with the lowest rate of eGFR decline seen when diastolic blood pressure was in the 70-79 mm Hg range. No effect of BP with mortality was observed, possibly because of the limited number of mortality events.”

The study was funded by support from the Veterans Administration. Dr. Leehey reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with proteinuric diabetic kidney disease, a mean systolic blood pressure greater than 140 mm Hg and a mean diastolic blood pressure greater than 80 mm Hg were associated with worse renal outcomes, a large national analysis showed.

“Proteinuric diabetic kidney disease frequently progresses to end-stage renal disease,” lead study author Dr. David J. Leehey said at a meeting sponsored by the American Society of Nephrology. “Control of blood pressure delays progression, but the optimal blood pressure to improve outcomes remains unclear.”

In a recent report from the Eighth Joint National Committee, panel members recommended a blood pressure of less than 140/90 mm Hg both for patients with diabetes and patients with chronic kidney disease (JAMA. 2014 Feb 5;311[5]:507-20).

“There are few data with regard to target blood pressure in proteinuric diabetic kidney disease, however, leaving physicians uncertain about how aggressively to lower blood pressure in such patients,” said Dr. Leehey, a nephrologist at the Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill.

In an effort to assess the relationship between blood pressure and renal outcomes in proteinuric diabetic kidney disease, the researchers evaluated blood pressure data from all 1,448 patients who were randomized to the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, which evaluated the combination of losartan with lisinopril, compared with losartan alone (N Engl J Med. 2013 Nov 14;369[20]:1892-1903). Randomization occurred between July 2008 and September 2012, but the trial was halted in October of 2012 due to safety reasons (acute kidney injury and hyperkalemic episodes).

For the current analysis, Dr. Leehey and his associates evaluated the associations of mean on-treatment blood pressure with the primary endpoint (defined as a decline in estimated glomerular filtration rate [eGFR], end-stage renal disease [ESRD], or death), the renal endpoint (defined as a decline in eGFR or cystatin C), the rate of eGFR decline, and mortality.

Trough sitting blood pressure measurements were obtained at every visit during the screening, titration, randomization, and treatment phases of VA NEPHRON-D. Mean blood pressure was defined as the average of all on-treatment blood pressures from the randomization visit to the last blood pressure measurement taken.

Dr. Leehey reported that there were 284 primary endpoints: 132 in the combination group and 152 in the monotherapy group. The mean blood pressure was based on a mean of 7.7 readings per participant.

Both mean systolic and mean diastolic blood pressure were strongly associated with the primary endpoint (P less than .001), univariate analysis revealed. The hazard of developing the primary endpoint increased as the mean systolic blood pressure rose from less than 120 mm Hg to greater than 150 mm Hg (P = .018), multivariate analysis showed.

A significant increase in hazard ratio was seen when mean systolic blood pressure was greater than 140 mm Hg (HR, 1.51). The researchers also observed a significant effect of mean diastolic blood pressure on the hazard of developing the primary endpoint (P = .005), with an increase in hazard ratio when mean diastolic blood pressure was greater than 80 mm Hg (HR, 1.54).

“Associations between BP and both renal endpoint and rate of eGFR decline were similar to those with the primary endpoint,” Dr. Leehey said. “There was a U-shaped relationship between rate of eGFR decline and mean diastolic blood pressure, with the lowest rate of eGFR decline seen when diastolic blood pressure was in the 70-79 mm Hg range. No effect of BP with mortality was observed, possibly because of the limited number of mortality events.”

The study was funded by support from the Veterans Administration. Dr. Leehey reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients undergoing cardiac bypass surgery, perioperative use of corticosteroids did not alter the risk of acute kidney injury, results from a large randomized trial showed.

“Worldwide, over 20 million cardiac surgeries are done each year, but 4 million are complicated by acute kidney injury, and 200,000 are complicated by severe kidney injury treated with dialysis,” Dr. Amit X. Garg said during a press briefing at the annual meeting of the American Society of Nephrology. “So certainly people would benefit from a therapy to prevent acute kidney injury (AKI) and improve the safety of surgery.”

Dr. Garg, a nephrologist at the London Health Sciences Centre in London, Ontario, Canada, noted that cardiopulmonary bypass initiates a systemic inflammatory response syndrome, “which activates complement, inflammatory cytokines, and other inflammatory mediators, which in turn increases endothelial permeability, organ damage, and increased morbidity and mortality, including acute kidney injury.” Researchers are interested in corticosteroids, “because they suppress this inflammatory response. In other settings, such as acute glomerulonephritis, we successfully use corticosteroids to treat acute inflammation in the kidney,” he said.

In a study known as the Steroids in caRdiac Surgery Trial (SIRS), researchers at 79 centers in 18 countries set out to investigate if methylprednisolone alters the risk of acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass. Between June 2007 and December 2013, 7,286 patients were randomized to intravenous methylprednisolone 250 mg at anesthetic induction and 250 mg at initiation of coronary bypass, or placebo.

AKI was defined as a 0.3 mg/dL increase or greater in postoperative serum creatinine concentration from the preoperative concentration within 14 days following surgery, or a 50% increase from the preoperative value within 14 days following surgery. Secondary outcomes included different stages of AKI and receipt of acute dialysis in the 30 days following surgery. Patients, caregivers, and researchers were blinded to the treatment allocation.

Of the 7,286 patients, 3,647 received methylprednisolone and 3,639 received placebo. The mean age of patients was 60 years, 60% were men, 26% were diabetic, and 25% of patients had combined CABG and valve surgery.

The SIRS Investigators reported that the risk of AKI was similar among patients who received methylprednisolone and those who received placebo (40.9% vs. 39.5%, respectively; relative risk 1.03). Results were similar across multiple categorical definitions of AKI, including AKI or death (41.5% vs 40.2%; RR 1.03); AKI stage of 2 or greater (9.9% vs 9.9%; RR 1.01); AKI stage of 3 or greater (4% vs. 4.5%; RR .89), and being on acute dialysis (2.6% vs. 2.4%; RR 1.08).

“There was no benefit of steroids on the risk of AKI in those with or without preoperative chronic kidney disease,” Dr. Garg said. “The result was also not different in the subpopulation of patients with AKI as defined by Kidney Disease Improving Global Outcomes.” Results from SIRS “would suggest that patients undergoing cardiac surgery with cardiopulmonary bypass should not use prophylactic steroids to prevent AKI. When we consider the side effect profile, the most clinically relevant outcomes, and apply the GRADE framework [the Grading of Recommendations Assessment, Development, and Evaluation] to the available evidence, we would recommend that steroids not be used in this way, with a grade 1B recommendation.”

The study was sponsored by the Population Health Research Institute in Hamilton, Ontario and the Canadian Institutes of Health Research. Dr. Garg reported having no relevant financial disclosures for this study.

[email protected]

SAN DIEGO – Among patients undergoing cardiac bypass surgery, perioperative use of corticosteroids did not alter the risk of acute kidney injury, results from a large randomized trial showed.

“Worldwide, over 20 million cardiac surgeries are done each year, but 4 million are complicated by acute kidney injury, and 200,000 are complicated by severe kidney injury treated with dialysis,” Dr. Amit X. Garg said during a press briefing at the annual meeting of the American Society of Nephrology. “So certainly people would benefit from a therapy to prevent acute kidney injury (AKI) and improve the safety of surgery.”

Dr. Garg, a nephrologist at the London Health Sciences Centre in London, Ontario, Canada, noted that cardiopulmonary bypass initiates a systemic inflammatory response syndrome, “which activates complement, inflammatory cytokines, and other inflammatory mediators, which in turn increases endothelial permeability, organ damage, and increased morbidity and mortality, including acute kidney injury.” Researchers are interested in corticosteroids, “because they suppress this inflammatory response. In other settings, such as acute glomerulonephritis, we successfully use corticosteroids to treat acute inflammation in the kidney,” he said.

In a study known as the Steroids in caRdiac Surgery Trial (SIRS), researchers at 79 centers in 18 countries set out to investigate if methylprednisolone alters the risk of acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass. Between June 2007 and December 2013, 7,286 patients were randomized to intravenous methylprednisolone 250 mg at anesthetic induction and 250 mg at initiation of coronary bypass, or placebo.

AKI was defined as a 0.3 mg/dL increase or greater in postoperative serum creatinine concentration from the preoperative concentration within 14 days following surgery, or a 50% increase from the preoperative value within 14 days following surgery. Secondary outcomes included different stages of AKI and receipt of acute dialysis in the 30 days following surgery. Patients, caregivers, and researchers were blinded to the treatment allocation.

Of the 7,286 patients, 3,647 received methylprednisolone and 3,639 received placebo. The mean age of patients was 60 years, 60% were men, 26% were diabetic, and 25% of patients had combined CABG and valve surgery.

The SIRS Investigators reported that the risk of AKI was similar among patients who received methylprednisolone and those who received placebo (40.9% vs. 39.5%, respectively; relative risk 1.03). Results were similar across multiple categorical definitions of AKI, including AKI or death (41.5% vs 40.2%; RR 1.03); AKI stage of 2 or greater (9.9% vs 9.9%; RR 1.01); AKI stage of 3 or greater (4% vs. 4.5%; RR .89), and being on acute dialysis (2.6% vs. 2.4%; RR 1.08).

“There was no benefit of steroids on the risk of AKI in those with or without preoperative chronic kidney disease,” Dr. Garg said. “The result was also not different in the subpopulation of patients with AKI as defined by Kidney Disease Improving Global Outcomes.” Results from SIRS “would suggest that patients undergoing cardiac surgery with cardiopulmonary bypass should not use prophylactic steroids to prevent AKI. When we consider the side effect profile, the most clinically relevant outcomes, and apply the GRADE framework [the Grading of Recommendations Assessment, Development, and Evaluation] to the available evidence, we would recommend that steroids not be used in this way, with a grade 1B recommendation.”

The study was sponsored by the Population Health Research Institute in Hamilton, Ontario and the Canadian Institutes of Health Research. Dr. Garg reported having no relevant financial disclosures for this study.

[email protected]

SAN DIEGO – Among patients undergoing cardiac bypass surgery, perioperative use of corticosteroids did not alter the risk of acute kidney injury, results from a large randomized trial showed.

“Worldwide, over 20 million cardiac surgeries are done each year, but 4 million are complicated by acute kidney injury, and 200,000 are complicated by severe kidney injury treated with dialysis,” Dr. Amit X. Garg said during a press briefing at the annual meeting of the American Society of Nephrology. “So certainly people would benefit from a therapy to prevent acute kidney injury (AKI) and improve the safety of surgery.”

Dr. Garg, a nephrologist at the London Health Sciences Centre in London, Ontario, Canada, noted that cardiopulmonary bypass initiates a systemic inflammatory response syndrome, “which activates complement, inflammatory cytokines, and other inflammatory mediators, which in turn increases endothelial permeability, organ damage, and increased morbidity and mortality, including acute kidney injury.” Researchers are interested in corticosteroids, “because they suppress this inflammatory response. In other settings, such as acute glomerulonephritis, we successfully use corticosteroids to treat acute inflammation in the kidney,” he said.

In a study known as the Steroids in caRdiac Surgery Trial (SIRS), researchers at 79 centers in 18 countries set out to investigate if methylprednisolone alters the risk of acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass. Between June 2007 and December 2013, 7,286 patients were randomized to intravenous methylprednisolone 250 mg at anesthetic induction and 250 mg at initiation of coronary bypass, or placebo.

AKI was defined as a 0.3 mg/dL increase or greater in postoperative serum creatinine concentration from the preoperative concentration within 14 days following surgery, or a 50% increase from the preoperative value within 14 days following surgery. Secondary outcomes included different stages of AKI and receipt of acute dialysis in the 30 days following surgery. Patients, caregivers, and researchers were blinded to the treatment allocation.

Of the 7,286 patients, 3,647 received methylprednisolone and 3,639 received placebo. The mean age of patients was 60 years, 60% were men, 26% were diabetic, and 25% of patients had combined CABG and valve surgery.

The SIRS Investigators reported that the risk of AKI was similar among patients who received methylprednisolone and those who received placebo (40.9% vs. 39.5%, respectively; relative risk 1.03). Results were similar across multiple categorical definitions of AKI, including AKI or death (41.5% vs 40.2%; RR 1.03); AKI stage of 2 or greater (9.9% vs 9.9%; RR 1.01); AKI stage of 3 or greater (4% vs. 4.5%; RR .89), and being on acute dialysis (2.6% vs. 2.4%; RR 1.08).

“There was no benefit of steroids on the risk of AKI in those with or without preoperative chronic kidney disease,” Dr. Garg said. “The result was also not different in the subpopulation of patients with AKI as defined by Kidney Disease Improving Global Outcomes.” Results from SIRS “would suggest that patients undergoing cardiac surgery with cardiopulmonary bypass should not use prophylactic steroids to prevent AKI. When we consider the side effect profile, the most clinically relevant outcomes, and apply the GRADE framework [the Grading of Recommendations Assessment, Development, and Evaluation] to the available evidence, we would recommend that steroids not be used in this way, with a grade 1B recommendation.”

The study was sponsored by the Population Health Research Institute in Hamilton, Ontario and the Canadian Institutes of Health Research. Dr. Garg reported having no relevant financial disclosures for this study.

[email protected]

SAN DIEGO – Patients undergoing maintenance hemodialysis who wore an artificial kidney for 24 hours achieved electrolyte, solute, and volume homeostasis, results from a small exploratory trial demonstrated.

“Mortality in dialysis patients is unacceptable high and the cost is enormous,” device inventor Dr. Victor Gura said during a press briefing at the annual meeting of the American Society of Nephrology. “They have a significant amount of heart disease, strokes and infections, and yet it’s a demographic issue with more than 500,000 patients in the U.S. with end-stage renal disease.”

In a trial supported through the FDA’s Center for Devices and Radiological Health, the investigators conducted a human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine based on dialysate-regenerating sorbent technology that is being developed by Blood Purification Technologies. The objective was to determine the safety and efficacy of the device in achieving electrolyte, solute, and volume homeostasis over a 24-hour period in seven patients.

Dr. Gura, a nephrologist at Cedars-Sinai Medical Center and the David Geffen School of Medicine at the University of California, Los Angeles, reported that all patients remained hemodynamically stable, and there were no serious adverse events over the study period. Fluid removal was consistent with prescribed ultrafiltration. Mean BUN, creatinine, and phosphorus clearances during the first hour of treatment were 21, 20, and 22 mL/min, respectively. Treatment was stopped in one patient due to clotting after four hours. Treatment was stopped in a second patient due to discoloration of dialysate observed after 10 hours. The trial was halted after the seventh patient was enrolled due to device-related problems, including carbon dioxide bubbles in the dialysis circuit, tubing kinks, and variable blood/dialysate flow.

Six out of seven patients ambulated while receiving treatment, and all were able to eat a normal diet with ad lib ingestion of water, without restriction on salt, phosphate, or potassium-rich foods. In semi-structured interviews, all patients reported that they would switch to the device if it were commercially available.

In an abstract describing the study, the researchers characterized the findings “as proof-of-concept of the wearable artificial kidney as an important novel alternative dialysis technology that has the potential to enhance autonomy and improve health-related quality of life for patients with end-stage renal disease.”

The study was supported by an unrestricted grant from the Wearable Artificial Kidney Foundation and by Blood Purification Technologies Inc. One of the study investigators, Dr. Matthew B. Rivara, is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Gura reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients undergoing maintenance hemodialysis who wore an artificial kidney for 24 hours achieved electrolyte, solute, and volume homeostasis, results from a small exploratory trial demonstrated.

“Mortality in dialysis patients is unacceptable high and the cost is enormous,” device inventor Dr. Victor Gura said during a press briefing at the annual meeting of the American Society of Nephrology. “They have a significant amount of heart disease, strokes and infections, and yet it’s a demographic issue with more than 500,000 patients in the U.S. with end-stage renal disease.”

In a trial supported through the FDA’s Center for Devices and Radiological Health, the investigators conducted a human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine based on dialysate-regenerating sorbent technology that is being developed by Blood Purification Technologies. The objective was to determine the safety and efficacy of the device in achieving electrolyte, solute, and volume homeostasis over a 24-hour period in seven patients.

Dr. Gura, a nephrologist at Cedars-Sinai Medical Center and the David Geffen School of Medicine at the University of California, Los Angeles, reported that all patients remained hemodynamically stable, and there were no serious adverse events over the study period. Fluid removal was consistent with prescribed ultrafiltration. Mean BUN, creatinine, and phosphorus clearances during the first hour of treatment were 21, 20, and 22 mL/min, respectively. Treatment was stopped in one patient due to clotting after four hours. Treatment was stopped in a second patient due to discoloration of dialysate observed after 10 hours. The trial was halted after the seventh patient was enrolled due to device-related problems, including carbon dioxide bubbles in the dialysis circuit, tubing kinks, and variable blood/dialysate flow.

Six out of seven patients ambulated while receiving treatment, and all were able to eat a normal diet with ad lib ingestion of water, without restriction on salt, phosphate, or potassium-rich foods. In semi-structured interviews, all patients reported that they would switch to the device if it were commercially available.

In an abstract describing the study, the researchers characterized the findings “as proof-of-concept of the wearable artificial kidney as an important novel alternative dialysis technology that has the potential to enhance autonomy and improve health-related quality of life for patients with end-stage renal disease.”

The study was supported by an unrestricted grant from the Wearable Artificial Kidney Foundation and by Blood Purification Technologies Inc. One of the study investigators, Dr. Matthew B. Rivara, is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Gura reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients undergoing maintenance hemodialysis who wore an artificial kidney for 24 hours achieved electrolyte, solute, and volume homeostasis, results from a small exploratory trial demonstrated.

“Mortality in dialysis patients is unacceptable high and the cost is enormous,” device inventor Dr. Victor Gura said during a press briefing at the annual meeting of the American Society of Nephrology. “They have a significant amount of heart disease, strokes and infections, and yet it’s a demographic issue with more than 500,000 patients in the U.S. with end-stage renal disease.”

In a trial supported through the FDA’s Center for Devices and Radiological Health, the investigators conducted a human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine based on dialysate-regenerating sorbent technology that is being developed by Blood Purification Technologies. The objective was to determine the safety and efficacy of the device in achieving electrolyte, solute, and volume homeostasis over a 24-hour period in seven patients.

Dr. Gura, a nephrologist at Cedars-Sinai Medical Center and the David Geffen School of Medicine at the University of California, Los Angeles, reported that all patients remained hemodynamically stable, and there were no serious adverse events over the study period. Fluid removal was consistent with prescribed ultrafiltration. Mean BUN, creatinine, and phosphorus clearances during the first hour of treatment were 21, 20, and 22 mL/min, respectively. Treatment was stopped in one patient due to clotting after four hours. Treatment was stopped in a second patient due to discoloration of dialysate observed after 10 hours. The trial was halted after the seventh patient was enrolled due to device-related problems, including carbon dioxide bubbles in the dialysis circuit, tubing kinks, and variable blood/dialysate flow.

Six out of seven patients ambulated while receiving treatment, and all were able to eat a normal diet with ad lib ingestion of water, without restriction on salt, phosphate, or potassium-rich foods. In semi-structured interviews, all patients reported that they would switch to the device if it were commercially available.

In an abstract describing the study, the researchers characterized the findings “as proof-of-concept of the wearable artificial kidney as an important novel alternative dialysis technology that has the potential to enhance autonomy and improve health-related quality of life for patients with end-stage renal disease.”

The study was supported by an unrestricted grant from the Wearable Artificial Kidney Foundation and by Blood Purification Technologies Inc. One of the study investigators, Dr. Matthew B. Rivara, is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Gura reported having no financial disclosures.

[email protected]

SAN DIEGO – Contrast agents administered through the coronary vessels for invasive angiography led to significantly more kidney damage than contrast agents administered intravenously for coronary computed tomography angiography, according to a randomized study.

In the Coronary Artery Disease-Management (CAD-Man) study, contrast-induced kidney injury was two to three times more likely after intracoronary than after intravenous contrast administration, explained study investigators Dr. Eva Schönenberger and Dr. Marc Dewey of Charité Medical University, Berlin.

Contrast agents used to detect and treat blockages in coronary arteries are known to damage the kidneys in 2%-20% of patients. In the United States, about 4 million doses of contrast are administered directly into the coronary vessels during invasive catheterization, and 40 million into superficial veins, said Dr. Dewey, Heisenberg Professor of Radiology at the German Research Foundation and vice chair of the department of radiology at Charité.

That makes contrast administration a significant clinical decision for physicians, he added, not just because of potential for harm, but also the potential for added costs.

CAD-Man included 326 patients with suspected coronary disease. Researchers randomized 161 patients to intracoronary contrast agent (ICA) for invasive coronary angiography and 165 patients to IV contrast agent for coronary computed tomography angiography (CTA). All patients received the same contrast agent.

Blood samples were taken at baseline before the procedure, and at two time points after: between 18 and 24 hours, and between 46 and 50 hours. Baseline creatinine levels were similar in the two groups. The researchers defined contrast-associated nephrotoxicity as an increase in creatinine of at least 0.5 mg/dL, or 25%.

At follow-up, 21 of 158 ICA patients (13%) and 9 of 160 CTA patients (6%) had contrast-associated nephropathy, a significant difference (P less than .05). In patients without coronary disease, 13% of ICA patients and 4% of CTA patients developed contrast-associated nephropathy, also a significant difference (P less than .05).

Catheter administration concentrates more contrast in the heart and above the kidneys than intravenous administration, Dr. Schönenberger explained at the meeting sponsored by the American Society of Nephrology. Thus, the increased kidney damage in invasive-angiography patients may be due to higher dosages of contrast in their kidneys.

Physicians “have to keep in mind that putting contrast agents directly into the coronaries might produce more of an increase of creatinine, and more acute kidney injury, than just giving it through an IV,” explained Dr. Schönenberger, a nephrologist in the department of anesthesiology and operative intensive care medicine at Charité.

Physicians should take this information into consideration when deciding how to administer contrast for patients suspected of having coronary artery disease, Dr. Dewey noted. “In addition to being noninvasive, cardiac CT may thus also have the advantage of reducing kidney risk.”

Cost should be a big concern as well. Dr. Dewey referred to published literature indicating that contrast-induced kidney injury can lead to “longer hospital and intensive care unit stays, [increased] dialysis, cost of adverse events, and higher mortality rates. The in-hospital cost was $10,000 per contrast-induced acute kidney injury, and the 1-year cost of treatment was more than $11,000.”

Because CAD-Man’s last patient was enrolled in mid-September, the data are still being analyzed, Dr. Schönenberger noted. Therefore, some confounders may be discovered that influenced the results.

For example, cardiologists may select their sicker patients for invasive procedures in order to be ready to insert stents, so there may not be as much flexibility in which approach to use.

Also unclear is the amount of contrast used for each patient in each arm of this study. Some physicians may have used more contrast for patients suspected of having disease that was harder to detect, although that part of the analysis remains under review, Dr. Dewey and Dr. Schönenberger said.

It remains unclear whether the nephrotoxicity found in the invasive angiography group was all due to the contrast, Dr. Schönenberger noted, or whether some of it might have been caused by small particles of hardened cholesterol spreading to blood vessels in the kidneys – a process known as atheroembolic renal disease. That, too, is under review.

The contrast agent used in the study, low-osmolar nonionic Xenetix 350, is used in 96 countries but is not approved by the U.S. Food and Drug Administration, Dr. Schönenberger said. However, it is very similar to those agents that are in use in the United States, she added.

The study was funded by the German Research Foundation through the Heisenberg Professorship Program. The researchers reported no financial disclosures.

SAN DIEGO – Contrast agents administered through the coronary vessels for invasive angiography led to significantly more kidney damage than contrast agents administered intravenously for coronary computed tomography angiography, according to a randomized study.

In the Coronary Artery Disease-Management (CAD-Man) study, contrast-induced kidney injury was two to three times more likely after intracoronary than after intravenous contrast administration, explained study investigators Dr. Eva Schönenberger and Dr. Marc Dewey of Charité Medical University, Berlin.

Contrast agents used to detect and treat blockages in coronary arteries are known to damage the kidneys in 2%-20% of patients. In the United States, about 4 million doses of contrast are administered directly into the coronary vessels during invasive catheterization, and 40 million into superficial veins, said Dr. Dewey, Heisenberg Professor of Radiology at the German Research Foundation and vice chair of the department of radiology at Charité.

That makes contrast administration a significant clinical decision for physicians, he added, not just because of potential for harm, but also the potential for added costs.

CAD-Man included 326 patients with suspected coronary disease. Researchers randomized 161 patients to intracoronary contrast agent (ICA) for invasive coronary angiography and 165 patients to IV contrast agent for coronary computed tomography angiography (CTA). All patients received the same contrast agent.

Blood samples were taken at baseline before the procedure, and at two time points after: between 18 and 24 hours, and between 46 and 50 hours. Baseline creatinine levels were similar in the two groups. The researchers defined contrast-associated nephrotoxicity as an increase in creatinine of at least 0.5 mg/dL, or 25%.

At follow-up, 21 of 158 ICA patients (13%) and 9 of 160 CTA patients (6%) had contrast-associated nephropathy, a significant difference (P less than .05). In patients without coronary disease, 13% of ICA patients and 4% of CTA patients developed contrast-associated nephropathy, also a significant difference (P less than .05).

Catheter administration concentrates more contrast in the heart and above the kidneys than intravenous administration, Dr. Schönenberger explained at the meeting sponsored by the American Society of Nephrology. Thus, the increased kidney damage in invasive-angiography patients may be due to higher dosages of contrast in their kidneys.

Physicians “have to keep in mind that putting contrast agents directly into the coronaries might produce more of an increase of creatinine, and more acute kidney injury, than just giving it through an IV,” explained Dr. Schönenberger, a nephrologist in the department of anesthesiology and operative intensive care medicine at Charité.

Physicians should take this information into consideration when deciding how to administer contrast for patients suspected of having coronary artery disease, Dr. Dewey noted. “In addition to being noninvasive, cardiac CT may thus also have the advantage of reducing kidney risk.”

Cost should be a big concern as well. Dr. Dewey referred to published literature indicating that contrast-induced kidney injury can lead to “longer hospital and intensive care unit stays, [increased] dialysis, cost of adverse events, and higher mortality rates. The in-hospital cost was $10,000 per contrast-induced acute kidney injury, and the 1-year cost of treatment was more than $11,000.”

Because CAD-Man’s last patient was enrolled in mid-September, the data are still being analyzed, Dr. Schönenberger noted. Therefore, some confounders may be discovered that influenced the results.

For example, cardiologists may select their sicker patients for invasive procedures in order to be ready to insert stents, so there may not be as much flexibility in which approach to use.

Also unclear is the amount of contrast used for each patient in each arm of this study. Some physicians may have used more contrast for patients suspected of having disease that was harder to detect, although that part of the analysis remains under review, Dr. Dewey and Dr. Schönenberger said.

It remains unclear whether the nephrotoxicity found in the invasive angiography group was all due to the contrast, Dr. Schönenberger noted, or whether some of it might have been caused by small particles of hardened cholesterol spreading to blood vessels in the kidneys – a process known as atheroembolic renal disease. That, too, is under review.

The contrast agent used in the study, low-osmolar nonionic Xenetix 350, is used in 96 countries but is not approved by the U.S. Food and Drug Administration, Dr. Schönenberger said. However, it is very similar to those agents that are in use in the United States, she added.

The study was funded by the German Research Foundation through the Heisenberg Professorship Program. The researchers reported no financial disclosures.

SAN DIEGO – Contrast agents administered through the coronary vessels for invasive angiography led to significantly more kidney damage than contrast agents administered intravenously for coronary computed tomography angiography, according to a randomized study.

In the Coronary Artery Disease-Management (CAD-Man) study, contrast-induced kidney injury was two to three times more likely after intracoronary than after intravenous contrast administration, explained study investigators Dr. Eva Schönenberger and Dr. Marc Dewey of Charité Medical University, Berlin.

Contrast agents used to detect and treat blockages in coronary arteries are known to damage the kidneys in 2%-20% of patients. In the United States, about 4 million doses of contrast are administered directly into the coronary vessels during invasive catheterization, and 40 million into superficial veins, said Dr. Dewey, Heisenberg Professor of Radiology at the German Research Foundation and vice chair of the department of radiology at Charité.

That makes contrast administration a significant clinical decision for physicians, he added, not just because of potential for harm, but also the potential for added costs.

CAD-Man included 326 patients with suspected coronary disease. Researchers randomized 161 patients to intracoronary contrast agent (ICA) for invasive coronary angiography and 165 patients to IV contrast agent for coronary computed tomography angiography (CTA). All patients received the same contrast agent.

Blood samples were taken at baseline before the procedure, and at two time points after: between 18 and 24 hours, and between 46 and 50 hours. Baseline creatinine levels were similar in the two groups. The researchers defined contrast-associated nephrotoxicity as an increase in creatinine of at least 0.5 mg/dL, or 25%.

At follow-up, 21 of 158 ICA patients (13%) and 9 of 160 CTA patients (6%) had contrast-associated nephropathy, a significant difference (P less than .05). In patients without coronary disease, 13% of ICA patients and 4% of CTA patients developed contrast-associated nephropathy, also a significant difference (P less than .05).

Catheter administration concentrates more contrast in the heart and above the kidneys than intravenous administration, Dr. Schönenberger explained at the meeting sponsored by the American Society of Nephrology. Thus, the increased kidney damage in invasive-angiography patients may be due to higher dosages of contrast in their kidneys.

Physicians “have to keep in mind that putting contrast agents directly into the coronaries might produce more of an increase of creatinine, and more acute kidney injury, than just giving it through an IV,” explained Dr. Schönenberger, a nephrologist in the department of anesthesiology and operative intensive care medicine at Charité.

Physicians should take this information into consideration when deciding how to administer contrast for patients suspected of having coronary artery disease, Dr. Dewey noted. “In addition to being noninvasive, cardiac CT may thus also have the advantage of reducing kidney risk.”

Cost should be a big concern as well. Dr. Dewey referred to published literature indicating that contrast-induced kidney injury can lead to “longer hospital and intensive care unit stays, [increased] dialysis, cost of adverse events, and higher mortality rates. The in-hospital cost was $10,000 per contrast-induced acute kidney injury, and the 1-year cost of treatment was more than $11,000.”

Because CAD-Man’s last patient was enrolled in mid-September, the data are still being analyzed, Dr. Schönenberger noted. Therefore, some confounders may be discovered that influenced the results.

For example, cardiologists may select their sicker patients for invasive procedures in order to be ready to insert stents, so there may not be as much flexibility in which approach to use.

Also unclear is the amount of contrast used for each patient in each arm of this study. Some physicians may have used more contrast for patients suspected of having disease that was harder to detect, although that part of the analysis remains under review, Dr. Dewey and Dr. Schönenberger said.

It remains unclear whether the nephrotoxicity found in the invasive angiography group was all due to the contrast, Dr. Schönenberger noted, or whether some of it might have been caused by small particles of hardened cholesterol spreading to blood vessels in the kidneys – a process known as atheroembolic renal disease. That, too, is under review.

The contrast agent used in the study, low-osmolar nonionic Xenetix 350, is used in 96 countries but is not approved by the U.S. Food and Drug Administration, Dr. Schönenberger said. However, it is very similar to those agents that are in use in the United States, she added.

The study was funded by the German Research Foundation through the Heisenberg Professorship Program. The researchers reported no financial disclosures.

SAN DIEGO – Empagliflozin used in conjunction with standard of care significantly improved renal outcomes in adults with type 2 diabetes, results from a large randomized trial showed.

“These benefits were consistent among patients with and without chronic kidney disease at baseline,” Dr. Christoph Wanner said at the annual meeting of the American Society of Nephrology.

Previous studies have demonstrated that in patients with type 2 diabetes, empagliflozin, an inhibitor of the sodium glucose cotransporter 2 in the kidney, leads to significant reductions in hemoglobin A_1c, weight loss, and reductions in blood pressure without increases in heart rate. Developed by Boehringer Ingelheim and Eli Lilly, the drug was approved in 2014 for the treatment of type 2 diabetes in adults. At the meeting Dr. Wanner presented new finding results from the EMPA-REG OUTCOME trial, which was published in September 2015. That study found that patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, compared with placebo, had a lower rate of the primary composite cardiovascular outcome and death from any cause when the study drug was added to standard care.

For the current analysis, the researchers evaluated renal outcomes in the study participants, which consisted of new-onset or worsening nephropathy, including new onset of macroalbuminuria (defined as a urine albumin to creatinine ratio (UACR) of greater than 300 mg/g); doubling of serum creatinine accompanied by an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73m² or less; initiation of renal replacement therapy; or death due to renal disease. There was also a composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease.

The EMPA-REG OUTCOME trial included 2,333 patients in the placebo group and 4,687 in the empagliflozin group who were followed for a median observation time of 3.1 years. The mean age of the study participants was 63 years and 71% were male. Compared with patients in the placebo group, those in the empagliflozin group demonstrated a 39% reduction in new-onset or worsening of nephropathy (hazard ratio, 0.61; P less than .0001). The reduction “started very early,” said Dr. Wanner, who is professor of medicine and head of nephrology at University Hospital of Wurzburg, Germany. “After 3 months you see the curves [between the placebo and treatment groups] separating.”

The impact on empagliflozin on the composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease was even more profound. Compared with patients in the placebo group, those in the empagliflozin demonstrated a 46% reduced risk in the composite outcome (HR, 0.54; P = .0002).

Dr. Wanner went on to present cardiovascular outcomes in patients with chronic kidney disease (CKD). Among those with an eGFR of less than 60 mL/min/1.73m² at baseline, the primary outcome of three-point major adverse cardiac events occurred in 176 of 1,212 patients in the empagliflozin group (15%), compared with 99 of 607 patients in the placebo group (16%; HR, 0.88). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, the primary outcome of three-point major adverse cardiac events occurred in 314 of 3,473 patients in the empagliflozin group (9%), compared with 183 of 1,726 (11%) patients in the placebo group (HR, 0.84). At the same time, the outcome of cardiovascular death occurred in 75 of 1,212 patients in the empagliflozin group (6%), compared with 48 of 607 patients in the placebo group (8%; HR, 0.78). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, cardiovascular death occurred in 97 of 3,473 patients in the empagliflozin group (3%), compared with 89 of 1,726 patients in the placebo group (5%; HR, 0.53). However, there was no detectable benefit for the study medication in reducing the myocardial infarction or stroke in patients with CKD.

Among those with an eGFR of less than 60 mL/min/1.73m² at baseline, hospitalization for heart failure occurred in 51 of 1,212 patients in the empagliflozin group (4%), compared with 43 of 607 patients in the placebo group (7%; HR, 0.59). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, hospitalization for heart failure occurred in 75 of 3,473 patients in the empagliflozin group (2%), compared with 52 of 1,726 patients in the placebo group (3%; HR, 0.70). At the same time, all-cause mortality occurred in 115 of 1,212 patients in the empagliflozin group (9%), compared with 72 of 607 patients in the placebo group (12%; HR, 0.80). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, hospitalization for heart failure occurred in 154 of 3,473 patients in the empagliflozin group (4%), compared with 122 of 1,726 patients in the placebo group (7%; HR, 0.62).

The most common adverse events in patients with CKD related to the study drug were urinary tract infections and genital infections, but there were no detectable signals on acute kidney failure, hyperkalemia, or bone fracture.

“Empagliflozin reduces cardiovascular death, all-cause mortality, and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk,” Dr. Wanner concluded. “Safety and tolerability of empagliflozin in patients with CKD at baseline were similar to the overall trial population and consistent with previous clinical trials.”

The study was supported by Boehringer Ingelheim and Eli Lilly. Dr. Wanner disclosed numerous financial ties to industry.

[email protected]

SAN DIEGO – Empagliflozin used in conjunction with standard of care significantly improved renal outcomes in adults with type 2 diabetes, results from a large randomized trial showed.

“These benefits were consistent among patients with and without chronic kidney disease at baseline,” Dr. Christoph Wanner said at the annual meeting of the American Society of Nephrology.

Previous studies have demonstrated that in patients with type 2 diabetes, empagliflozin, an inhibitor of the sodium glucose cotransporter 2 in the kidney, leads to significant reductions in hemoglobin A_1c, weight loss, and reductions in blood pressure without increases in heart rate. Developed by Boehringer Ingelheim and Eli Lilly, the drug was approved in 2014 for the treatment of type 2 diabetes in adults. At the meeting Dr. Wanner presented new finding results from the EMPA-REG OUTCOME trial, which was published in September 2015. That study found that patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, compared with placebo, had a lower rate of the primary composite cardiovascular outcome and death from any cause when the study drug was added to standard care.

For the current analysis, the researchers evaluated renal outcomes in the study participants, which consisted of new-onset or worsening nephropathy, including new onset of macroalbuminuria (defined as a urine albumin to creatinine ratio (UACR) of greater than 300 mg/g); doubling of serum creatinine accompanied by an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73m² or less; initiation of renal replacement therapy; or death due to renal disease. There was also a composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease.

The EMPA-REG OUTCOME trial included 2,333 patients in the placebo group and 4,687 in the empagliflozin group who were followed for a median observation time of 3.1 years. The mean age of the study participants was 63 years and 71% were male. Compared with patients in the placebo group, those in the empagliflozin group demonstrated a 39% reduction in new-onset or worsening of nephropathy (hazard ratio, 0.61; P less than .0001). The reduction “started very early,” said Dr. Wanner, who is professor of medicine and head of nephrology at University Hospital of Wurzburg, Germany. “After 3 months you see the curves [between the placebo and treatment groups] separating.”

The impact on empagliflozin on the composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease was even more profound. Compared with patients in the placebo group, those in the empagliflozin demonstrated a 46% reduced risk in the composite outcome (HR, 0.54; P = .0002).

Dr. Wanner went on to present cardiovascular outcomes in patients with chronic kidney disease (CKD). Among those with an eGFR of less than 60 mL/min/1.73m² at baseline, the primary outcome of three-point major adverse cardiac events occurred in 176 of 1,212 patients in the empagliflozin group (15%), compared with 99 of 607 patients in the placebo group (16%; HR, 0.88). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, the primary outcome of three-point major adverse cardiac events occurred in 314 of 3,473 patients in the empagliflozin group (9%), compared with 183 of 1,726 (11%) patients in the placebo group (HR, 0.84). At the same time, the outcome of cardiovascular death occurred in 75 of 1,212 patients in the empagliflozin group (6%), compared with 48 of 607 patients in the placebo group (8%; HR, 0.78). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, cardiovascular death occurred in 97 of 3,473 patients in the empagliflozin group (3%), compared with 89 of 1,726 patients in the placebo group (5%; HR, 0.53). However, there was no detectable benefit for the study medication in reducing the myocardial infarction or stroke in patients with CKD.

Among those with an eGFR of less than 60 mL/min/1.73m² at baseline, hospitalization for heart failure occurred in 51 of 1,212 patients in the empagliflozin group (4%), compared with 43 of 607 patients in the placebo group (7%; HR, 0.59). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, hospitalization for heart failure occurred in 75 of 3,473 patients in the empagliflozin group (2%), compared with 52 of 1,726 patients in the placebo group (3%; HR, 0.70). At the same time, all-cause mortality occurred in 115 of 1,212 patients in the empagliflozin group (9%), compared with 72 of 607 patients in the placebo group (12%; HR, 0.80). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, hospitalization for heart failure occurred in 154 of 3,473 patients in the empagliflozin group (4%), compared with 122 of 1,726 patients in the placebo group (7%; HR, 0.62).

The most common adverse events in patients with CKD related to the study drug were urinary tract infections and genital infections, but there were no detectable signals on acute kidney failure, hyperkalemia, or bone fracture.

“Empagliflozin reduces cardiovascular death, all-cause mortality, and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk,” Dr. Wanner concluded. “Safety and tolerability of empagliflozin in patients with CKD at baseline were similar to the overall trial population and consistent with previous clinical trials.”

The study was supported by Boehringer Ingelheim and Eli Lilly. Dr. Wanner disclosed numerous financial ties to industry.

[email protected]

SAN DIEGO – Empagliflozin used in conjunction with standard of care significantly improved renal outcomes in adults with type 2 diabetes, results from a large randomized trial showed.

“These benefits were consistent among patients with and without chronic kidney disease at baseline,” Dr. Christoph Wanner said at the annual meeting of the American Society of Nephrology.

Previous studies have demonstrated that in patients with type 2 diabetes, empagliflozin, an inhibitor of the sodium glucose cotransporter 2 in the kidney, leads to significant reductions in hemoglobin A_1c, weight loss, and reductions in blood pressure without increases in heart rate. Developed by Boehringer Ingelheim and Eli Lilly, the drug was approved in 2014 for the treatment of type 2 diabetes in adults. At the meeting Dr. Wanner presented new finding results from the EMPA-REG OUTCOME trial, which was published in September 2015. That study found that patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, compared with placebo, had a lower rate of the primary composite cardiovascular outcome and death from any cause when the study drug was added to standard care.

For the current analysis, the researchers evaluated renal outcomes in the study participants, which consisted of new-onset or worsening nephropathy, including new onset of macroalbuminuria (defined as a urine albumin to creatinine ratio (UACR) of greater than 300 mg/g); doubling of serum creatinine accompanied by an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73m² or less; initiation of renal replacement therapy; or death due to renal disease. There was also a composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease.

The EMPA-REG OUTCOME trial included 2,333 patients in the placebo group and 4,687 in the empagliflozin group who were followed for a median observation time of 3.1 years. The mean age of the study participants was 63 years and 71% were male. Compared with patients in the placebo group, those in the empagliflozin group demonstrated a 39% reduction in new-onset or worsening of nephropathy (hazard ratio, 0.61; P less than .0001). The reduction “started very early,” said Dr. Wanner, who is professor of medicine and head of nephrology at University Hospital of Wurzburg, Germany. “After 3 months you see the curves [between the placebo and treatment groups] separating.”

The impact on empagliflozin on the composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease was even more profound. Compared with patients in the placebo group, those in the empagliflozin demonstrated a 46% reduced risk in the composite outcome (HR, 0.54; P = .0002).

Dr. Wanner went on to present cardiovascular outcomes in patients with chronic kidney disease (CKD). Among those with an eGFR of less than 60 mL/min/1.73m² at baseline, the primary outcome of three-point major adverse cardiac events occurred in 176 of 1,212 patients in the empagliflozin group (15%), compared with 99 of 607 patients in the placebo group (16%; HR, 0.88). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, the primary outcome of three-point major adverse cardiac events occurred in 314 of 3,473 patients in the empagliflozin group (9%), compared with 183 of 1,726 (11%) patients in the placebo group (HR, 0.84). At the same time, the outcome of cardiovascular death occurred in 75 of 1,212 patients in the empagliflozin group (6%), compared with 48 of 607 patients in the placebo group (8%; HR, 0.78). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, cardiovascular death occurred in 97 of 3,473 patients in the empagliflozin group (3%), compared with 89 of 1,726 patients in the placebo group (5%; HR, 0.53). However, there was no detectable benefit for the study medication in reducing the myocardial infarction or stroke in patients with CKD.

Among those with an eGFR of less than 60 mL/min/1.73m² at baseline, hospitalization for heart failure occurred in 51 of 1,212 patients in the empagliflozin group (4%), compared with 43 of 607 patients in the placebo group (7%; HR, 0.59). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, hospitalization for heart failure occurred in 75 of 3,473 patients in the empagliflozin group (2%), compared with 52 of 1,726 patients in the placebo group (3%; HR, 0.70). At the same time, all-cause mortality occurred in 115 of 1,212 patients in the empagliflozin group (9%), compared with 72 of 607 patients in the placebo group (12%; HR, 0.80). Among those with an eGFR of 60 mL/min/1.73m² or greater at baseline, hospitalization for heart failure occurred in 154 of 3,473 patients in the empagliflozin group (4%), compared with 122 of 1,726 patients in the placebo group (7%; HR, 0.62).

The most common adverse events in patients with CKD related to the study drug were urinary tract infections and genital infections, but there were no detectable signals on acute kidney failure, hyperkalemia, or bone fracture.

“Empagliflozin reduces cardiovascular death, all-cause mortality, and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk,” Dr. Wanner concluded. “Safety and tolerability of empagliflozin in patients with CKD at baseline were similar to the overall trial population and consistent with previous clinical trials.”

The study was supported by Boehringer Ingelheim and Eli Lilly. Dr. Wanner disclosed numerous financial ties to industry.

[email protected]

SAN DIEGO – Among patients with advanced chronic kidney disease (CKD) and type 2 diabetes, a shift in gut microbiota in combination with plasma zonulin may be linked with chronic inflammation and endothelial dysfunction, according to results from an observational study.

“Diabetes patients have compromised gut microbiome due to metabolic disorder,” lead study author Ruchi Singh, Ph.D., said in an interview in advance of Kidney Week 2015. “Due to their hyperglycemic condition they have chronic inflammation and endothelial dysfunction as a baseline. They do have increased gut permeability. Therefore, a change in gut microbiome may have a high impact on this patient population.”

For the study, Dr. Singh, a postdoctoral research associate at Texas Tech University Health Sciences Center, Amarillo, and her associates used 16S ribosomal RNA sequencing and quantitative analysis to evaluate the composition of gut microbiota in 40 patients with CKD and diabetic neuropathy, including 20 age- and gender-matched controls. Markers of interest included serum zonulin, tumor necrosis factor–alpha (TNF-alpha), interleuikin-6 (IL-6), fibroblast growth factor 23 (FGF-23; which is considered to be strongly correlated with cardiovascular health), endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS). The mean age of patients was 59 years, and 38% were male.

Compared with controls matched for age, gender, and diet, CKD patients with diabetes had significantly higher circulating levels of all studied markers except IL-6. “The biggest surprise was that zonulin was positively correlated with FGF-23,” Dr. Singh said. “We do not have a good explanation for this at the moment and further investigation needed is to answer this.”

Zonulin was also positively correlated with TNF-alpha, IL-6, and LPS. “We hope to use zonulin as a therapeutic target which might prevent further progression of chronic kidney disease and improve cardiac health,” she said.

The researchers also observed “a huge difference in microbiome profile of healthy and CKD patients. We are going to look further in microbiome profile and see which bacterial group could have most impact on gut permeability and inflammation.”

Dr. Singh acknowledged certain limitations of the study, including its observational design and the fact that only patients with advanced CKD and multiple comorbidities were included, “which could impact our findings. In future we would like to design a prospective, targeted interventional study.”

The study was funded in part by a postdoctoral training grant from Sanofi/Genzyme. Study author and a mentor of the project, Dr. Tetyana L. Vasylyeva, disclosed that she is a scientific advisor for Alexion. Dr. Singh reported having no financial disclosures. Kidney Week 2015 is sponsored by the American Society of Nephrology.

SAN DIEGO – Among patients with advanced chronic kidney disease (CKD) and type 2 diabetes, a shift in gut microbiota in combination with plasma zonulin may be linked with chronic inflammation and endothelial dysfunction, according to results from an observational study.

“Diabetes patients have compromised gut microbiome due to metabolic disorder,” lead study author Ruchi Singh, Ph.D., said in an interview in advance of Kidney Week 2015. “Due to their hyperglycemic condition they have chronic inflammation and endothelial dysfunction as a baseline. They do have increased gut permeability. Therefore, a change in gut microbiome may have a high impact on this patient population.”

For the study, Dr. Singh, a postdoctoral research associate at Texas Tech University Health Sciences Center, Amarillo, and her associates used 16S ribosomal RNA sequencing and quantitative analysis to evaluate the composition of gut microbiota in 40 patients with CKD and diabetic neuropathy, including 20 age- and gender-matched controls. Markers of interest included serum zonulin, tumor necrosis factor–alpha (TNF-alpha), interleuikin-6 (IL-6), fibroblast growth factor 23 (FGF-23; which is considered to be strongly correlated with cardiovascular health), endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS). The mean age of patients was 59 years, and 38% were male.

Compared with controls matched for age, gender, and diet, CKD patients with diabetes had significantly higher circulating levels of all studied markers except IL-6. “The biggest surprise was that zonulin was positively correlated with FGF-23,” Dr. Singh said. “We do not have a good explanation for this at the moment and further investigation needed is to answer this.”

Zonulin was also positively correlated with TNF-alpha, IL-6, and LPS. “We hope to use zonulin as a therapeutic target which might prevent further progression of chronic kidney disease and improve cardiac health,” she said.

The researchers also observed “a huge difference in microbiome profile of healthy and CKD patients. We are going to look further in microbiome profile and see which bacterial group could have most impact on gut permeability and inflammation.”

Dr. Singh acknowledged certain limitations of the study, including its observational design and the fact that only patients with advanced CKD and multiple comorbidities were included, “which could impact our findings. In future we would like to design a prospective, targeted interventional study.”

The study was funded in part by a postdoctoral training grant from Sanofi/Genzyme. Study author and a mentor of the project, Dr. Tetyana L. Vasylyeva, disclosed that she is a scientific advisor for Alexion. Dr. Singh reported having no financial disclosures. Kidney Week 2015 is sponsored by the American Society of Nephrology.

SAN DIEGO – Among patients with advanced chronic kidney disease (CKD) and type 2 diabetes, a shift in gut microbiota in combination with plasma zonulin may be linked with chronic inflammation and endothelial dysfunction, according to results from an observational study.

“Diabetes patients have compromised gut microbiome due to metabolic disorder,” lead study author Ruchi Singh, Ph.D., said in an interview in advance of Kidney Week 2015. “Due to their hyperglycemic condition they have chronic inflammation and endothelial dysfunction as a baseline. They do have increased gut permeability. Therefore, a change in gut microbiome may have a high impact on this patient population.”

For the study, Dr. Singh, a postdoctoral research associate at Texas Tech University Health Sciences Center, Amarillo, and her associates used 16S ribosomal RNA sequencing and quantitative analysis to evaluate the composition of gut microbiota in 40 patients with CKD and diabetic neuropathy, including 20 age- and gender-matched controls. Markers of interest included serum zonulin, tumor necrosis factor–alpha (TNF-alpha), interleuikin-6 (IL-6), fibroblast growth factor 23 (FGF-23; which is considered to be strongly correlated with cardiovascular health), endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS). The mean age of patients was 59 years, and 38% were male.

Compared with controls matched for age, gender, and diet, CKD patients with diabetes had significantly higher circulating levels of all studied markers except IL-6. “The biggest surprise was that zonulin was positively correlated with FGF-23,” Dr. Singh said. “We do not have a good explanation for this at the moment and further investigation needed is to answer this.”

Zonulin was also positively correlated with TNF-alpha, IL-6, and LPS. “We hope to use zonulin as a therapeutic target which might prevent further progression of chronic kidney disease and improve cardiac health,” she said.

The researchers also observed “a huge difference in microbiome profile of healthy and CKD patients. We are going to look further in microbiome profile and see which bacterial group could have most impact on gut permeability and inflammation.”

Dr. Singh acknowledged certain limitations of the study, including its observational design and the fact that only patients with advanced CKD and multiple comorbidities were included, “which could impact our findings. In future we would like to design a prospective, targeted interventional study.”

The study was funded in part by a postdoctoral training grant from Sanofi/Genzyme. Study author and a mentor of the project, Dr. Tetyana L. Vasylyeva, disclosed that she is a scientific advisor for Alexion. Dr. Singh reported having no financial disclosures. Kidney Week 2015 is sponsored by the American Society of Nephrology.

SAN DIEGO – Among patients with advanced chronic kidney disease (CKD) and type 2 diabetes, a shift in gut microbiota in combination with plasma zonulin may be linked with chronic inflammation and endothelial dysfunction, according to results from an observational study.

“Diabetes patients have compromised gut microbiome due to metabolic disorder,” lead study author Ruchi Singh, Ph.D., said in an interview in advance of Kidney Week 2015. “Due to their hyperglycemic condition they have chronic inflammation and endothelial dysfunction as a baseline. They do have increased gut permeability. Therefore, a change in gut microbiome may have a high impact on this patient population.”

For the study, Dr. Singh, a postdoctoral research associate at Texas Tech University Health Sciences Center, Amarillo, and her associates used 16S ribosomal RNA sequencing and quantitative analysis to evaluate the composition of gut microbiota in 40 patients with CKD and diabetic neuropathy, including 20 age- and gender-matched controls. Markers of interest included serum zonulin, tumor necrosis factor–alpha (TNF-alpha), interleuikin-6 (IL-6), fibroblast growth factor 23 (FGF-23; which is considered to be strongly correlated with cardiovascular health), endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS). The mean age of patients was 59 years, and 38% were male.

Compared with controls matched for age, gender, and diet, CKD patients with diabetes had significantly higher circulating levels of all studied markers except IL-6. “The biggest surprise was that zonulin was positively correlated with FGF-23,” Dr. Singh said. “We do not have a good explanation for this at the moment and further investigation needed is to answer this.”

Zonulin was also positively correlated with TNF-alpha, IL-6, and LPS. “We hope to use zonulin as a therapeutic target which might prevent further progression of chronic kidney disease and improve cardiac health,” she said.

The researchers also observed “a huge difference in microbiome profile of healthy and CKD patients. We are going to look further in microbiome profile and see which bacterial group could have most impact on gut permeability and inflammation.”

Dr. Singh acknowledged certain limitations of the study, including its observational design and the fact that only patients with advanced CKD and multiple comorbidities were included, “which could impact our findings. In future we would like to design a prospective, targeted interventional study.”

The study was funded in part by a postdoctoral training grant from Sanofi/Genzyme. Study author and a mentor of the project, Dr. Tetyana L. Vasylyeva, disclosed that she is a scientific advisor for Alexion. Dr. Singh reported having no financial disclosures. Kidney Week 2015 is sponsored by the American Society of Nephrology.

[email protected]

SAN DIEGO – Among patients with advanced chronic kidney disease (CKD) and type 2 diabetes, a shift in gut microbiota in combination with plasma zonulin may be linked with chronic inflammation and endothelial dysfunction, according to results from an observational study.

“Diabetes patients have compromised gut microbiome due to metabolic disorder,” lead study author Ruchi Singh, Ph.D., said in an interview in advance of Kidney Week 2015. “Due to their hyperglycemic condition they have chronic inflammation and endothelial dysfunction as a baseline. They do have increased gut permeability. Therefore, a change in gut microbiome may have a high impact on this patient population.”

For the study, Dr. Singh, a postdoctoral research associate at Texas Tech University Health Sciences Center, Amarillo, and her associates used 16S ribosomal RNA sequencing and quantitative analysis to evaluate the composition of gut microbiota in 40 patients with CKD and diabetic neuropathy, including 20 age- and gender-matched controls. Markers of interest included serum zonulin, tumor necrosis factor–alpha (TNF-alpha), interleuikin-6 (IL-6), fibroblast growth factor 23 (FGF-23; which is considered to be strongly correlated with cardiovascular health), endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS). The mean age of patients was 59 years, and 38% were male.

Compared with controls matched for age, gender, and diet, CKD patients with diabetes had significantly higher circulating levels of all studied markers except IL-6. “The biggest surprise was that zonulin was positively correlated with FGF-23,” Dr. Singh said. “We do not have a good explanation for this at the moment and further investigation needed is to answer this.”

Zonulin was also positively correlated with TNF-alpha, IL-6, and LPS. “We hope to use zonulin as a therapeutic target which might prevent further progression of chronic kidney disease and improve cardiac health,” she said.

The researchers also observed “a huge difference in microbiome profile of healthy and CKD patients. We are going to look further in microbiome profile and see which bacterial group could have most impact on gut permeability and inflammation.”

Dr. Singh acknowledged certain limitations of the study, including its observational design and the fact that only patients with advanced CKD and multiple comorbidities were included, “which could impact our findings. In future we would like to design a prospective, targeted interventional study.”

The study was funded in part by a postdoctoral training grant from Sanofi/Genzyme. Study author and a mentor of the project, Dr. Tetyana L. Vasylyeva, disclosed that she is a scientific advisor for Alexion. Dr. Singh reported having no financial disclosures. Kidney Week 2015 is sponsored by the American Society of Nephrology.

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SAN DIEGO – Among patients with advanced chronic kidney disease (CKD) and type 2 diabetes, a shift in gut microbiota in combination with plasma zonulin may be linked with chronic inflammation and endothelial dysfunction, according to results from an observational study.

“Diabetes patients have compromised gut microbiome due to metabolic disorder,” lead study author Ruchi Singh, Ph.D., said in an interview in advance of Kidney Week 2015. “Due to their hyperglycemic condition they have chronic inflammation and endothelial dysfunction as a baseline. They do have increased gut permeability. Therefore, a change in gut microbiome may have a high impact on this patient population.”

For the study, Dr. Singh, a postdoctoral research associate at Texas Tech University Health Sciences Center, Amarillo, and her associates used 16S ribosomal RNA sequencing and quantitative analysis to evaluate the composition of gut microbiota in 40 patients with CKD and diabetic neuropathy, including 20 age- and gender-matched controls. Markers of interest included serum zonulin, tumor necrosis factor–alpha (TNF-alpha), interleuikin-6 (IL-6), fibroblast growth factor 23 (FGF-23; which is considered to be strongly correlated with cardiovascular health), endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS). The mean age of patients was 59 years, and 38% were male.

Compared with controls matched for age, gender, and diet, CKD patients with diabetes had significantly higher circulating levels of all studied markers except IL-6. “The biggest surprise was that zonulin was positively correlated with FGF-23,” Dr. Singh said. “We do not have a good explanation for this at the moment and further investigation needed is to answer this.”

Zonulin was also positively correlated with TNF-alpha, IL-6, and LPS. “We hope to use zonulin as a therapeutic target which might prevent further progression of chronic kidney disease and improve cardiac health,” she said.

The researchers also observed “a huge difference in microbiome profile of healthy and CKD patients. We are going to look further in microbiome profile and see which bacterial group could have most impact on gut permeability and inflammation.”

Dr. Singh acknowledged certain limitations of the study, including its observational design and the fact that only patients with advanced CKD and multiple comorbidities were included, “which could impact our findings. In future we would like to design a prospective, targeted interventional study.”

The study was funded in part by a postdoctoral training grant from Sanofi/Genzyme. Study author and a mentor of the project, Dr. Tetyana L. Vasylyeva, disclosed that she is a scientific advisor for Alexion. Dr. Singh reported having no financial disclosures. Kidney Week 2015 is sponsored by the American Society of Nephrology.

[email protected]

Elevated plasma soluble urokinase-type plasminogen activator receptor (suPAR) levels are associated with declines in estimated glomerular filtration rate (eGFR) and may predict progression to clinical chronic kidney disease, new research suggests.

Data from the Emory Cardiovascular Biobank – a prospective registry of 3,683 patients undergoing cardiac catheterization – showed individuals in the highest quartile of baseline suPAR had a significantly greater annual decline in eGFR than those in the lowest quartile (-4.2 mL/min per 1.73 m² vs. -0.9mL/min per 1.73 m²).

Similarly, those in the highest suPAR quartile had a threefold greater risk of incident chronic kidney disease than those in the lowest quartile, independent of their race or diabetes status and excluding those with acute kidney injury, according to a paper presented at the meeting sponsored by the American Society of Nephrology and published simultaneously online in the Nov. 5 edition of the New England Journal of Medicine.

The relationship between elevated suPAR and eGFR decline was strongest in patients who had a normal eGFR at baseline (N Engl J Med. 2015 Nov 5 [doi:10.1056/NEJMoa1506362]).

The risk classification for chronic kidney disease using suPAR was greater than existing and well-established risk factors such as C-reactive protein and B-type natriuretic peptide, wrote Dr. Salim S. Hayek, from Emory University, Atlanta, Sanja Sever, Ph.D., of Harvard Medical School, Boston, and their coauthors.

“Our results suggest that suPAR meets critical requirements for a biomarker of chronic kidney disease,” the authors said.

The study was supported by the Abraham J. and Phyllis Katz Foundation, the Robert W. Woodruff Health Sciences Center Fund, Emory Heart and Vascular Center, and the National Institutes of Health. Several authors declared grants and personal fees and committee involvement with private industry, and patents relevant to the work.

Elevated plasma soluble urokinase-type plasminogen activator receptor (suPAR) levels are associated with declines in estimated glomerular filtration rate (eGFR) and may predict progression to clinical chronic kidney disease, new research suggests.

Data from the Emory Cardiovascular Biobank – a prospective registry of 3,683 patients undergoing cardiac catheterization – showed individuals in the highest quartile of baseline suPAR had a significantly greater annual decline in eGFR than those in the lowest quartile (-4.2 mL/min per 1.73 m² vs. -0.9mL/min per 1.73 m²).

Similarly, those in the highest suPAR quartile had a threefold greater risk of incident chronic kidney disease than those in the lowest quartile, independent of their race or diabetes status and excluding those with acute kidney injury, according to a paper presented at the meeting sponsored by the American Society of Nephrology and published simultaneously online in the Nov. 5 edition of the New England Journal of Medicine.

The relationship between elevated suPAR and eGFR decline was strongest in patients who had a normal eGFR at baseline (N Engl J Med. 2015 Nov 5 [doi:10.1056/NEJMoa1506362]).

The risk classification for chronic kidney disease using suPAR was greater than existing and well-established risk factors such as C-reactive protein and B-type natriuretic peptide, wrote Dr. Salim S. Hayek, from Emory University, Atlanta, Sanja Sever, Ph.D., of Harvard Medical School, Boston, and their coauthors.

“Our results suggest that suPAR meets critical requirements for a biomarker of chronic kidney disease,” the authors said.

The study was supported by the Abraham J. and Phyllis Katz Foundation, the Robert W. Woodruff Health Sciences Center Fund, Emory Heart and Vascular Center, and the National Institutes of Health. Several authors declared grants and personal fees and committee involvement with private industry, and patents relevant to the work.

Elevated plasma soluble urokinase-type plasminogen activator receptor (suPAR) levels are associated with declines in estimated glomerular filtration rate (eGFR) and may predict progression to clinical chronic kidney disease, new research suggests.

Data from the Emory Cardiovascular Biobank – a prospective registry of 3,683 patients undergoing cardiac catheterization – showed individuals in the highest quartile of baseline suPAR had a significantly greater annual decline in eGFR than those in the lowest quartile (-4.2 mL/min per 1.73 m² vs. -0.9mL/min per 1.73 m²).

Similarly, those in the highest suPAR quartile had a threefold greater risk of incident chronic kidney disease than those in the lowest quartile, independent of their race or diabetes status and excluding those with acute kidney injury, according to a paper presented at the meeting sponsored by the American Society of Nephrology and published simultaneously online in the Nov. 5 edition of the New England Journal of Medicine.

The relationship between elevated suPAR and eGFR decline was strongest in patients who had a normal eGFR at baseline (N Engl J Med. 2015 Nov 5 [doi:10.1056/NEJMoa1506362]).

The risk classification for chronic kidney disease using suPAR was greater than existing and well-established risk factors such as C-reactive protein and B-type natriuretic peptide, wrote Dr. Salim S. Hayek, from Emory University, Atlanta, Sanja Sever, Ph.D., of Harvard Medical School, Boston, and their coauthors.

“Our results suggest that suPAR meets critical requirements for a biomarker of chronic kidney disease,” the authors said.

The study was supported by the Abraham J. and Phyllis Katz Foundation, the Robert W. Woodruff Health Sciences Center Fund, Emory Heart and Vascular Center, and the National Institutes of Health. Several authors declared grants and personal fees and committee involvement with private industry, and patents relevant to the work.