ASN Kidney Week 2014

PHILADELPHIA – An experimental dialysis device safely and dramatically reduced the viral load in a critically ill Ebola patient treated in Frankfurt, Germany.

Dialysis performed using the device resulted in a reduction in viral load from 400,000 copies/mL to 1,000 copies/mL in the 36-year-old patient, said Dr. Helmut Geiger, chief of nephrology at Frankfurt University Hospital, at Kidney Week 2014.

The patient, a pediatrician who had treated Ebola patients in Sierra Leone, was diagnosed in September. He was transferred in October to Frankfurt University Hospital, where he presented with fever, chills, and weakness, and rapidly deteriorated. He developed multiorgan failure – including kidney failure – despite treatment with various experimental therapies.

The patient was placed on dialysis. The experimental device – the Hemopurifier, made by Aethlon Medical of San Diego – was incorporated into the treatment, with special approval from Germany’s Federal Institute for Drugs and Medical Devices, Dr. Geiger said at the meeting, which was sponsored by the American Society of Nephrology.

The Hemopurifier is a first-in-class biofiltration device designed to eliminate viruses and immunosuppressive proteins from the circulatory system of infected individuals, according to Aethlon. The company has been testing the device in patients with hepatitis C and in HIV patients in India. Aethlon plans to initiate U.S. clinical studies under an investigational device exemption approved by the U.S. Food and Drug Administration.

Successful in vitro validation studies have been conducted by researchers at the U.S. Army Medical Research Institute of Infectious Diseases and the Centers for Disease Control and Prevention.

The Hemopurifier is a cylindrical cartridge that attaches to an existing dialysis machine. Inside, a gluelike protein selectively binds to viral particles and fragments, removing them from blood circulation.

The patient treated in Frankfurt by Dr. Geiger and his team underwent a 6.5-hour dialysis procedure using the device, and an analysis performed at a laboratory equipped to handle Ebola virus showed that the device had trapped 242 million copies of the virus, Dr. Geiger said.

The patient is now out of isolation, off dialysis, and in very good condition, he said, noting that the patient would be discharged within days.

Although additional study is needed, it appears that the Hemopurifier device may have contributed to the patient’s recovery, Dr. Geiger said, and no adverse events occurred during the treatment. The device ultimately could play a role in treating multiple types of viral infection, he added.

Use of the Hemopurifier is safe and feasible, the device can be used with intermittent hemodialysis or in the setting of continuous renal replacement therapy, and it represents a promising new supportive tool for severe Ebola infection, he concluded.

Dr. Geiger reported having consultancy agreements with AbbVie, Amgen, and Otsuka, and receiving research funding from Fresenius Medical Care.

imnews@frontlinemedcom.com

PHILADELPHIA – An experimental dialysis device safely and dramatically reduced the viral load in a critically ill Ebola patient treated in Frankfurt, Germany.

Dialysis performed using the device resulted in a reduction in viral load from 400,000 copies/mL to 1,000 copies/mL in the 36-year-old patient, said Dr. Helmut Geiger, chief of nephrology at Frankfurt University Hospital, at Kidney Week 2014.

The patient, a pediatrician who had treated Ebola patients in Sierra Leone, was diagnosed in September. He was transferred in October to Frankfurt University Hospital, where he presented with fever, chills, and weakness, and rapidly deteriorated. He developed multiorgan failure – including kidney failure – despite treatment with various experimental therapies.

The patient was placed on dialysis. The experimental device – the Hemopurifier, made by Aethlon Medical of San Diego – was incorporated into the treatment, with special approval from Germany’s Federal Institute for Drugs and Medical Devices, Dr. Geiger said at the meeting, which was sponsored by the American Society of Nephrology.

The Hemopurifier is a first-in-class biofiltration device designed to eliminate viruses and immunosuppressive proteins from the circulatory system of infected individuals, according to Aethlon. The company has been testing the device in patients with hepatitis C and in HIV patients in India. Aethlon plans to initiate U.S. clinical studies under an investigational device exemption approved by the U.S. Food and Drug Administration.

Successful in vitro validation studies have been conducted by researchers at the U.S. Army Medical Research Institute of Infectious Diseases and the Centers for Disease Control and Prevention.

The Hemopurifier is a cylindrical cartridge that attaches to an existing dialysis machine. Inside, a gluelike protein selectively binds to viral particles and fragments, removing them from blood circulation.

The patient treated in Frankfurt by Dr. Geiger and his team underwent a 6.5-hour dialysis procedure using the device, and an analysis performed at a laboratory equipped to handle Ebola virus showed that the device had trapped 242 million copies of the virus, Dr. Geiger said.

The patient is now out of isolation, off dialysis, and in very good condition, he said, noting that the patient would be discharged within days.

Although additional study is needed, it appears that the Hemopurifier device may have contributed to the patient’s recovery, Dr. Geiger said, and no adverse events occurred during the treatment. The device ultimately could play a role in treating multiple types of viral infection, he added.

Use of the Hemopurifier is safe and feasible, the device can be used with intermittent hemodialysis or in the setting of continuous renal replacement therapy, and it represents a promising new supportive tool for severe Ebola infection, he concluded.

Dr. Geiger reported having consultancy agreements with AbbVie, Amgen, and Otsuka, and receiving research funding from Fresenius Medical Care.

imnews@frontlinemedcom.com

PHILADELPHIA – An experimental dialysis device safely and dramatically reduced the viral load in a critically ill Ebola patient treated in Frankfurt, Germany.

Dialysis performed using the device resulted in a reduction in viral load from 400,000 copies/mL to 1,000 copies/mL in the 36-year-old patient, said Dr. Helmut Geiger, chief of nephrology at Frankfurt University Hospital, at Kidney Week 2014.

The patient, a pediatrician who had treated Ebola patients in Sierra Leone, was diagnosed in September. He was transferred in October to Frankfurt University Hospital, where he presented with fever, chills, and weakness, and rapidly deteriorated. He developed multiorgan failure – including kidney failure – despite treatment with various experimental therapies.

The patient was placed on dialysis. The experimental device – the Hemopurifier, made by Aethlon Medical of San Diego – was incorporated into the treatment, with special approval from Germany’s Federal Institute for Drugs and Medical Devices, Dr. Geiger said at the meeting, which was sponsored by the American Society of Nephrology.

The Hemopurifier is a first-in-class biofiltration device designed to eliminate viruses and immunosuppressive proteins from the circulatory system of infected individuals, according to Aethlon. The company has been testing the device in patients with hepatitis C and in HIV patients in India. Aethlon plans to initiate U.S. clinical studies under an investigational device exemption approved by the U.S. Food and Drug Administration.

Successful in vitro validation studies have been conducted by researchers at the U.S. Army Medical Research Institute of Infectious Diseases and the Centers for Disease Control and Prevention.

The Hemopurifier is a cylindrical cartridge that attaches to an existing dialysis machine. Inside, a gluelike protein selectively binds to viral particles and fragments, removing them from blood circulation.

The patient treated in Frankfurt by Dr. Geiger and his team underwent a 6.5-hour dialysis procedure using the device, and an analysis performed at a laboratory equipped to handle Ebola virus showed that the device had trapped 242 million copies of the virus, Dr. Geiger said.

The patient is now out of isolation, off dialysis, and in very good condition, he said, noting that the patient would be discharged within days.

Although additional study is needed, it appears that the Hemopurifier device may have contributed to the patient’s recovery, Dr. Geiger said, and no adverse events occurred during the treatment. The device ultimately could play a role in treating multiple types of viral infection, he added.

Use of the Hemopurifier is safe and feasible, the device can be used with intermittent hemodialysis or in the setting of continuous renal replacement therapy, and it represents a promising new supportive tool for severe Ebola infection, he concluded.

Dr. Geiger reported having consultancy agreements with AbbVie, Amgen, and Otsuka, and receiving research funding from Fresenius Medical Care.

imnews@frontlinemedcom.com

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective for maintaining blood pressure control than was ACE inihibitor monotherapy in patients with moderately advanced autosomal dominant polycystic kidney disease and stage 3 chronic kidney disease.

That finding emerged from a study of the randomized placebo-controlled Halt Progression of Polycystic Kidney Disease (HALD-PKD) trial reported at Kidney Week 2014.

The composite primary outcome of time to death, end-stage renal disease, or 50% reduction from baseline in estimated glomerular filtration rate (eGFR) was similar in 242 patients with stages 1-3 autosomal dominant polcystic kidney disease (ADPKD) randomized to receive lisinopril plus placebo, and in 243 such patients randomized to receive lisinopril plus telmisartan (number of events in the groups, respectively, 116 and 115; hazard ratio, 1.08), said Dr. Vicente E. Torres.

Also, no significant differences were seen between the groups with respect to the individual components of the composite outcome; the hazard ratios for death, end-stage renal disease, and 50% reduction in eGFR were 0.93, 0.78, and 1.05, respectively, Dr. Torres of the Mayo Clinic College of Medicine, Rochester, Minn. said at the meeting, which was sponsored by the American Society of Nephrology.

The findings were simultaneously published online Nov. 15 in the New England Journal of Medicine (N Engl J Med 2014 Nov. 15[doi: 10.1056/NEJMoa1402686]).

The rates of change in eGFR urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, also were similar in the two groups, Dr. Torres said.

Participants in the double-blind study were enrolled from February 2006 through June 2009. They were aged 18 to 64 years and had eGFR of 25 to 60 ml per minute per 1.73 m² of body-surface area. Lisinopril doses in both groups were adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg, and patients were followed for a mean of 5 years. Systolic blood pressures and mean arterial pressures remained within the target range throughout the trial in 73% to 86% and in 70% to 83% of participants, respectively. Diastolic pressures were in the target range in 56% to 65% of participants.

Hypertension develops early and contributes to the progression of disease in patients with ADPKD, and the renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in ADPKD patients. Angiotensin-converting enzyme inhibitors like lisinopril are known to slow the progression of renal dysfunction in non-diabetic kidney disease, and thus have become standard first-line agents for the treatment of hypertension in patients with ADPKD, Dr. Torres said.

“Although ACE inhibitors have become the first-line therapy for hypertension in patients with chronic kidney disease, including ADPKD, their renoprotective effect may be limited by compensatory-feedback increases in renin release and the generation of angiotensin,” he and his colleagues wrote, noting that dual RAAS blockade has been proposed as a strategy to circumvent this compensatory feedback.

The current study showed that adding telmisartan did result in slightly lower blood pressures, but did not reduce the incidence of primary or secondary outcomes.

Both combination therapy and lisinopril monotherapy were safe, with a similar rate of adverse events in the two groups, but the addition of an ARB did not confer additional benefit, Dr. Torres said, concluding that ACE inhibitor monotherapy achieved excellent standard blood pressure control in more than 70% of patients with stages 1-3 ADPKD.The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Torres), the National Center for Research Resources’ General Clinical Research Centers, the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective for maintaining blood pressure control than was ACE inihibitor monotherapy in patients with moderately advanced autosomal dominant polycystic kidney disease and stage 3 chronic kidney disease.

That finding emerged from a study of the randomized placebo-controlled Halt Progression of Polycystic Kidney Disease (HALD-PKD) trial reported at Kidney Week 2014.

The composite primary outcome of time to death, end-stage renal disease, or 50% reduction from baseline in estimated glomerular filtration rate (eGFR) was similar in 242 patients with stages 1-3 autosomal dominant polcystic kidney disease (ADPKD) randomized to receive lisinopril plus placebo, and in 243 such patients randomized to receive lisinopril plus telmisartan (number of events in the groups, respectively, 116 and 115; hazard ratio, 1.08), said Dr. Vicente E. Torres.

Also, no significant differences were seen between the groups with respect to the individual components of the composite outcome; the hazard ratios for death, end-stage renal disease, and 50% reduction in eGFR were 0.93, 0.78, and 1.05, respectively, Dr. Torres of the Mayo Clinic College of Medicine, Rochester, Minn. said at the meeting, which was sponsored by the American Society of Nephrology.

The findings were simultaneously published online Nov. 15 in the New England Journal of Medicine (N Engl J Med 2014 Nov. 15[doi: 10.1056/NEJMoa1402686]).

The rates of change in eGFR urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, also were similar in the two groups, Dr. Torres said.

Participants in the double-blind study were enrolled from February 2006 through June 2009. They were aged 18 to 64 years and had eGFR of 25 to 60 ml per minute per 1.73 m² of body-surface area. Lisinopril doses in both groups were adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg, and patients were followed for a mean of 5 years. Systolic blood pressures and mean arterial pressures remained within the target range throughout the trial in 73% to 86% and in 70% to 83% of participants, respectively. Diastolic pressures were in the target range in 56% to 65% of participants.

Hypertension develops early and contributes to the progression of disease in patients with ADPKD, and the renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in ADPKD patients. Angiotensin-converting enzyme inhibitors like lisinopril are known to slow the progression of renal dysfunction in non-diabetic kidney disease, and thus have become standard first-line agents for the treatment of hypertension in patients with ADPKD, Dr. Torres said.

“Although ACE inhibitors have become the first-line therapy for hypertension in patients with chronic kidney disease, including ADPKD, their renoprotective effect may be limited by compensatory-feedback increases in renin release and the generation of angiotensin,” he and his colleagues wrote, noting that dual RAAS blockade has been proposed as a strategy to circumvent this compensatory feedback.

The current study showed that adding telmisartan did result in slightly lower blood pressures, but did not reduce the incidence of primary or secondary outcomes.

Both combination therapy and lisinopril monotherapy were safe, with a similar rate of adverse events in the two groups, but the addition of an ARB did not confer additional benefit, Dr. Torres said, concluding that ACE inhibitor monotherapy achieved excellent standard blood pressure control in more than 70% of patients with stages 1-3 ADPKD.The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Torres), the National Center for Research Resources’ General Clinical Research Centers, the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective for maintaining blood pressure control than was ACE inihibitor monotherapy in patients with moderately advanced autosomal dominant polycystic kidney disease and stage 3 chronic kidney disease.

That finding emerged from a study of the randomized placebo-controlled Halt Progression of Polycystic Kidney Disease (HALD-PKD) trial reported at Kidney Week 2014.

The composite primary outcome of time to death, end-stage renal disease, or 50% reduction from baseline in estimated glomerular filtration rate (eGFR) was similar in 242 patients with stages 1-3 autosomal dominant polcystic kidney disease (ADPKD) randomized to receive lisinopril plus placebo, and in 243 such patients randomized to receive lisinopril plus telmisartan (number of events in the groups, respectively, 116 and 115; hazard ratio, 1.08), said Dr. Vicente E. Torres.

Also, no significant differences were seen between the groups with respect to the individual components of the composite outcome; the hazard ratios for death, end-stage renal disease, and 50% reduction in eGFR were 0.93, 0.78, and 1.05, respectively, Dr. Torres of the Mayo Clinic College of Medicine, Rochester, Minn. said at the meeting, which was sponsored by the American Society of Nephrology.

The findings were simultaneously published online Nov. 15 in the New England Journal of Medicine (N Engl J Med 2014 Nov. 15[doi: 10.1056/NEJMoa1402686]).

The rates of change in eGFR urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, also were similar in the two groups, Dr. Torres said.

Participants in the double-blind study were enrolled from February 2006 through June 2009. They were aged 18 to 64 years and had eGFR of 25 to 60 ml per minute per 1.73 m² of body-surface area. Lisinopril doses in both groups were adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg, and patients were followed for a mean of 5 years. Systolic blood pressures and mean arterial pressures remained within the target range throughout the trial in 73% to 86% and in 70% to 83% of participants, respectively. Diastolic pressures were in the target range in 56% to 65% of participants.

Hypertension develops early and contributes to the progression of disease in patients with ADPKD, and the renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in ADPKD patients. Angiotensin-converting enzyme inhibitors like lisinopril are known to slow the progression of renal dysfunction in non-diabetic kidney disease, and thus have become standard first-line agents for the treatment of hypertension in patients with ADPKD, Dr. Torres said.

“Although ACE inhibitors have become the first-line therapy for hypertension in patients with chronic kidney disease, including ADPKD, their renoprotective effect may be limited by compensatory-feedback increases in renin release and the generation of angiotensin,” he and his colleagues wrote, noting that dual RAAS blockade has been proposed as a strategy to circumvent this compensatory feedback.

The current study showed that adding telmisartan did result in slightly lower blood pressures, but did not reduce the incidence of primary or secondary outcomes.

Both combination therapy and lisinopril monotherapy were safe, with a similar rate of adverse events in the two groups, but the addition of an ARB did not confer additional benefit, Dr. Torres said, concluding that ACE inhibitor monotherapy achieved excellent standard blood pressure control in more than 70% of patients with stages 1-3 ADPKD.The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Torres), the National Center for Research Resources’ General Clinical Research Centers, the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.

PHILADELPHIA– Long-term intake of meat and poultry is independently associated with an increased risk of developing hypertension, according to findings from an analysis of pooled data from three large prospective cohort studies.

The data also suggest that long-term intake of seafood does not protect against hypertension, Dr. Lea Borgi of Brigham and Women’s Hospital, Boston reported at Kidney Week 2014.

©camij/thinkstockphotos.com

Of approximately 122,000 women in the Nurses’ Health Study 1, 116,000 women in the Nurses’ Health Study II, and 52,000 men in the Health Professionals Follow-up Study, those with an intake of at least 1 serving daily of meat and poultry (processed meat, beef, lamb, chicken, or turkey) and those with at least 1 serving daily of meat, poultry and seafood (including canned tuna, dark meat fish, shrimp, and lobster) had a greater risk of hypertension than did those with an intake of less than 1 serving monthly (hazard ratios, 1.30 and 1.22, respectively), Dr. Borgi said.

Seafood alone was associated with an increased risk of hypertension in the Nurses’ Health Study 2 (hazard ratio 1.13) and in the Health Professionals Follow-Up Study (hazard ratio, 1.16).

“Now, given that the association of seafood with hypertension was unexpected, we did do a secondary analysis … and we actually were able to analyze different types of seafood such as canned tuna fish, dark meat fish, other fish, shrimp, lobster, or scallops,” she said.

Those who consumed 4-6 servings a week of canned tuna or dark meat fish had an increased risk of hypertension (hazard ratio, 1.13 and 1.24, respectively), she said.

Study subjects ranged in age from 27 to 75 years, and information about diet, behaviors, and health status was updated regularly in each of the studies. The subjects were followed for a mean of about 20 years.

The current analysis was adjusted for numerous hypertension risk factors, including known risk factors like age and body mass index, and factors shown to be associated with hypertension in the cohorts, including analgesia use and consumption of sugar-sweetened and artificially-sweetened beverages. Adjustment was also made for total consumption of fruits, vegetables, and grains, as decreased consumption of these foods may also be associated with hypertension. Random effects meta-analysis was used to derive pooled estimates of effect.

Prospective data on the relationship between red meat, seafood, and poultry consumption and hypertension are scarce, but red and processed meats are generally considered to have an adverse effect on cardiovascular health, while seafood is generally believed to be protective; the effect of poultry is controversial, as study results have been conflicting, Dr. Borgi said.

“Our finding that more meat intake was associated with increased risk of hypertension is broadly consistent with prior studies. We also found that a greater consumption of poultry was independently associated with increased hypertension risk, and we observed a weak increased risk of hypertension with increasing fish consumption overall,” she said, noting that the mechanisms for the relationship are “controversial and hypothetical,” and include a possible relationship between gut microflora and cardiovascular disease, which is supported by a growing body of evidence.

“One of these links is through the conversion of L-carnitine, which is highly found in red meat and salt water fish, to trimethylamine N-oxide (TMAO). Also, another potential mechanism is the production of Maillard reaction products (MRPs), which are chemical products that are formed when animal flesh is cooked at high temperatures,” she said, explaining that TMAO and MRPs are associated with increased oxidative stress and inflammation, which are important mechanisms in the development of hypertension.

Given the increasing prevalence of hypertension in the United States and around the world, the independent and significant association between higher intakes of meat, poultry, and seafood and greater risk of developing hypertension seen in this study has important public health implications, she said, adding that additional studies are needed to further assess the potential mechanisms underlying the association.

Dr. Borgi reported having no disclosures.

PHILADELPHIA– Long-term intake of meat and poultry is independently associated with an increased risk of developing hypertension, according to findings from an analysis of pooled data from three large prospective cohort studies.

The data also suggest that long-term intake of seafood does not protect against hypertension, Dr. Lea Borgi of Brigham and Women’s Hospital, Boston reported at Kidney Week 2014.

©camij/thinkstockphotos.com

Of approximately 122,000 women in the Nurses’ Health Study 1, 116,000 women in the Nurses’ Health Study II, and 52,000 men in the Health Professionals Follow-up Study, those with an intake of at least 1 serving daily of meat and poultry (processed meat, beef, lamb, chicken, or turkey) and those with at least 1 serving daily of meat, poultry and seafood (including canned tuna, dark meat fish, shrimp, and lobster) had a greater risk of hypertension than did those with an intake of less than 1 serving monthly (hazard ratios, 1.30 and 1.22, respectively), Dr. Borgi said.

Seafood alone was associated with an increased risk of hypertension in the Nurses’ Health Study 2 (hazard ratio 1.13) and in the Health Professionals Follow-Up Study (hazard ratio, 1.16).

“Now, given that the association of seafood with hypertension was unexpected, we did do a secondary analysis … and we actually were able to analyze different types of seafood such as canned tuna fish, dark meat fish, other fish, shrimp, lobster, or scallops,” she said.

Those who consumed 4-6 servings a week of canned tuna or dark meat fish had an increased risk of hypertension (hazard ratio, 1.13 and 1.24, respectively), she said.

Study subjects ranged in age from 27 to 75 years, and information about diet, behaviors, and health status was updated regularly in each of the studies. The subjects were followed for a mean of about 20 years.

The current analysis was adjusted for numerous hypertension risk factors, including known risk factors like age and body mass index, and factors shown to be associated with hypertension in the cohorts, including analgesia use and consumption of sugar-sweetened and artificially-sweetened beverages. Adjustment was also made for total consumption of fruits, vegetables, and grains, as decreased consumption of these foods may also be associated with hypertension. Random effects meta-analysis was used to derive pooled estimates of effect.

Prospective data on the relationship between red meat, seafood, and poultry consumption and hypertension are scarce, but red and processed meats are generally considered to have an adverse effect on cardiovascular health, while seafood is generally believed to be protective; the effect of poultry is controversial, as study results have been conflicting, Dr. Borgi said.

“Our finding that more meat intake was associated with increased risk of hypertension is broadly consistent with prior studies. We also found that a greater consumption of poultry was independently associated with increased hypertension risk, and we observed a weak increased risk of hypertension with increasing fish consumption overall,” she said, noting that the mechanisms for the relationship are “controversial and hypothetical,” and include a possible relationship between gut microflora and cardiovascular disease, which is supported by a growing body of evidence.

“One of these links is through the conversion of L-carnitine, which is highly found in red meat and salt water fish, to trimethylamine N-oxide (TMAO). Also, another potential mechanism is the production of Maillard reaction products (MRPs), which are chemical products that are formed when animal flesh is cooked at high temperatures,” she said, explaining that TMAO and MRPs are associated with increased oxidative stress and inflammation, which are important mechanisms in the development of hypertension.

Given the increasing prevalence of hypertension in the United States and around the world, the independent and significant association between higher intakes of meat, poultry, and seafood and greater risk of developing hypertension seen in this study has important public health implications, she said, adding that additional studies are needed to further assess the potential mechanisms underlying the association.

Dr. Borgi reported having no disclosures.

PHILADELPHIA– Long-term intake of meat and poultry is independently associated with an increased risk of developing hypertension, according to findings from an analysis of pooled data from three large prospective cohort studies.

The data also suggest that long-term intake of seafood does not protect against hypertension, Dr. Lea Borgi of Brigham and Women’s Hospital, Boston reported at Kidney Week 2014.

©camij/thinkstockphotos.com

Of approximately 122,000 women in the Nurses’ Health Study 1, 116,000 women in the Nurses’ Health Study II, and 52,000 men in the Health Professionals Follow-up Study, those with an intake of at least 1 serving daily of meat and poultry (processed meat, beef, lamb, chicken, or turkey) and those with at least 1 serving daily of meat, poultry and seafood (including canned tuna, dark meat fish, shrimp, and lobster) had a greater risk of hypertension than did those with an intake of less than 1 serving monthly (hazard ratios, 1.30 and 1.22, respectively), Dr. Borgi said.

Seafood alone was associated with an increased risk of hypertension in the Nurses’ Health Study 2 (hazard ratio 1.13) and in the Health Professionals Follow-Up Study (hazard ratio, 1.16).

“Now, given that the association of seafood with hypertension was unexpected, we did do a secondary analysis … and we actually were able to analyze different types of seafood such as canned tuna fish, dark meat fish, other fish, shrimp, lobster, or scallops,” she said.

Those who consumed 4-6 servings a week of canned tuna or dark meat fish had an increased risk of hypertension (hazard ratio, 1.13 and 1.24, respectively), she said.

Study subjects ranged in age from 27 to 75 years, and information about diet, behaviors, and health status was updated regularly in each of the studies. The subjects were followed for a mean of about 20 years.

The current analysis was adjusted for numerous hypertension risk factors, including known risk factors like age and body mass index, and factors shown to be associated with hypertension in the cohorts, including analgesia use and consumption of sugar-sweetened and artificially-sweetened beverages. Adjustment was also made for total consumption of fruits, vegetables, and grains, as decreased consumption of these foods may also be associated with hypertension. Random effects meta-analysis was used to derive pooled estimates of effect.

Prospective data on the relationship between red meat, seafood, and poultry consumption and hypertension are scarce, but red and processed meats are generally considered to have an adverse effect on cardiovascular health, while seafood is generally believed to be protective; the effect of poultry is controversial, as study results have been conflicting, Dr. Borgi said.

“Our finding that more meat intake was associated with increased risk of hypertension is broadly consistent with prior studies. We also found that a greater consumption of poultry was independently associated with increased hypertension risk, and we observed a weak increased risk of hypertension with increasing fish consumption overall,” she said, noting that the mechanisms for the relationship are “controversial and hypothetical,” and include a possible relationship between gut microflora and cardiovascular disease, which is supported by a growing body of evidence.

“One of these links is through the conversion of L-carnitine, which is highly found in red meat and salt water fish, to trimethylamine N-oxide (TMAO). Also, another potential mechanism is the production of Maillard reaction products (MRPs), which are chemical products that are formed when animal flesh is cooked at high temperatures,” she said, explaining that TMAO and MRPs are associated with increased oxidative stress and inflammation, which are important mechanisms in the development of hypertension.

Given the increasing prevalence of hypertension in the United States and around the world, the independent and significant association between higher intakes of meat, poultry, and seafood and greater risk of developing hypertension seen in this study has important public health implications, she said, adding that additional studies are needed to further assess the potential mechanisms underlying the association.

Dr. Borgi reported having no disclosures.

PHILADELPHIA – Children and young adults with increased systolic and diastolic indices and decreased nocturnal dipping on ambulatory blood pressure monitoring are at increased risk for cognitive dysfunction, according to findings from a cross-sectional study.

In 152 subjects aged 8-25 years, systolic index and diastolic indices – after controlling for chronic kidney disease (CKD) versus control group, race, and maternal education – were negatively associated with performance in several domains, including attention, inhibitory control, and verbal memory. For the attention domain, there was a 0.02 increase in z score for every 1% increase in diastolic dip. For the verbal memory and inhibitory control domains, there was a decrease of 0.14 and 0.06 in z score, respectively, for every 10% increase in diastolic load, Nina Laney of Children’s Hospital of Philadelphia reported.

Systolic dipping was negatively associated with set shifting, with a decrease of 0.03 in z score (P = .04) for every 1% decrease in systolic dipping.

“Hypertension is a well known risk factor for cognitive dysfunction in adults both with and without kidney disease. There are fewer studies that look at this in children, but those that have identify many of the same areas of dysfunction, including executive function, attention, memory, and verbal and visual skills,” Ms. Laney said at the meeting sponsored by the American Society of Nephrology.

The current findings suggest that hypertension affects cognitive function in younger patients, particularly given the decreased rate of comorbidities in children, compared with adults, and this has important implications for early detection and treatment, she said.

Study subjects were 96 patients with CKD and 56 healthy controls. Those with CKD had a mean age of 15.7 years and mean estimated glomerular filtration rate (eGFR) of 48.6 mL/min/1.73m². The healthy controls had a mean age of 15.1 years and mean eGFR of 103.1 mL/min/1.73m².

Each patient completed the ambulatory blood pressure measurement as well as a neurocognitive battery consisting of measures of language, attention, inhibitory control, problem solving, set shifting, visuospatial memory (verbal and visual), working memory (verbal and visual), and executive function.

Among the proposed mechanisms for the relationship between hypertension and cognitive dysfunction are impaired cerebral blood flow, autoregulation, decreased microvascular reactivity, and brain volume reduction in gray matter, she noted.

She noted, however, that the study is limited by relatively small sample size, the use of some assumptions while grouping tests into domains, and assessments only once for both the blood pressure and neuropositive assessments. Also, the results were not adjusted for multiple comparisons.

“For future analyses, we will use neuropositive results, blood pressure results, and neuroimaging to look at specific regions of interest in the brain and correlate them with performance in our neurocognitive testing,” she said.

This study was funded by the Pennsylvania Department of Health. Ms. Laney reported having no disclosures.

PHILADELPHIA – Children and young adults with increased systolic and diastolic indices and decreased nocturnal dipping on ambulatory blood pressure monitoring are at increased risk for cognitive dysfunction, according to findings from a cross-sectional study.

In 152 subjects aged 8-25 years, systolic index and diastolic indices – after controlling for chronic kidney disease (CKD) versus control group, race, and maternal education – were negatively associated with performance in several domains, including attention, inhibitory control, and verbal memory. For the attention domain, there was a 0.02 increase in z score for every 1% increase in diastolic dip. For the verbal memory and inhibitory control domains, there was a decrease of 0.14 and 0.06 in z score, respectively, for every 10% increase in diastolic load, Nina Laney of Children’s Hospital of Philadelphia reported.

Systolic dipping was negatively associated with set shifting, with a decrease of 0.03 in z score (P = .04) for every 1% decrease in systolic dipping.

“Hypertension is a well known risk factor for cognitive dysfunction in adults both with and without kidney disease. There are fewer studies that look at this in children, but those that have identify many of the same areas of dysfunction, including executive function, attention, memory, and verbal and visual skills,” Ms. Laney said at the meeting sponsored by the American Society of Nephrology.

The current findings suggest that hypertension affects cognitive function in younger patients, particularly given the decreased rate of comorbidities in children, compared with adults, and this has important implications for early detection and treatment, she said.

Study subjects were 96 patients with CKD and 56 healthy controls. Those with CKD had a mean age of 15.7 years and mean estimated glomerular filtration rate (eGFR) of 48.6 mL/min/1.73m². The healthy controls had a mean age of 15.1 years and mean eGFR of 103.1 mL/min/1.73m².

Each patient completed the ambulatory blood pressure measurement as well as a neurocognitive battery consisting of measures of language, attention, inhibitory control, problem solving, set shifting, visuospatial memory (verbal and visual), working memory (verbal and visual), and executive function.

Among the proposed mechanisms for the relationship between hypertension and cognitive dysfunction are impaired cerebral blood flow, autoregulation, decreased microvascular reactivity, and brain volume reduction in gray matter, she noted.

She noted, however, that the study is limited by relatively small sample size, the use of some assumptions while grouping tests into domains, and assessments only once for both the blood pressure and neuropositive assessments. Also, the results were not adjusted for multiple comparisons.

“For future analyses, we will use neuropositive results, blood pressure results, and neuroimaging to look at specific regions of interest in the brain and correlate them with performance in our neurocognitive testing,” she said.

This study was funded by the Pennsylvania Department of Health. Ms. Laney reported having no disclosures.

PHILADELPHIA – Children and young adults with increased systolic and diastolic indices and decreased nocturnal dipping on ambulatory blood pressure monitoring are at increased risk for cognitive dysfunction, according to findings from a cross-sectional study.

In 152 subjects aged 8-25 years, systolic index and diastolic indices – after controlling for chronic kidney disease (CKD) versus control group, race, and maternal education – were negatively associated with performance in several domains, including attention, inhibitory control, and verbal memory. For the attention domain, there was a 0.02 increase in z score for every 1% increase in diastolic dip. For the verbal memory and inhibitory control domains, there was a decrease of 0.14 and 0.06 in z score, respectively, for every 10% increase in diastolic load, Nina Laney of Children’s Hospital of Philadelphia reported.

Systolic dipping was negatively associated with set shifting, with a decrease of 0.03 in z score (P = .04) for every 1% decrease in systolic dipping.

“Hypertension is a well known risk factor for cognitive dysfunction in adults both with and without kidney disease. There are fewer studies that look at this in children, but those that have identify many of the same areas of dysfunction, including executive function, attention, memory, and verbal and visual skills,” Ms. Laney said at the meeting sponsored by the American Society of Nephrology.

The current findings suggest that hypertension affects cognitive function in younger patients, particularly given the decreased rate of comorbidities in children, compared with adults, and this has important implications for early detection and treatment, she said.

Study subjects were 96 patients with CKD and 56 healthy controls. Those with CKD had a mean age of 15.7 years and mean estimated glomerular filtration rate (eGFR) of 48.6 mL/min/1.73m². The healthy controls had a mean age of 15.1 years and mean eGFR of 103.1 mL/min/1.73m².

Each patient completed the ambulatory blood pressure measurement as well as a neurocognitive battery consisting of measures of language, attention, inhibitory control, problem solving, set shifting, visuospatial memory (verbal and visual), working memory (verbal and visual), and executive function.

Among the proposed mechanisms for the relationship between hypertension and cognitive dysfunction are impaired cerebral blood flow, autoregulation, decreased microvascular reactivity, and brain volume reduction in gray matter, she noted.

She noted, however, that the study is limited by relatively small sample size, the use of some assumptions while grouping tests into domains, and assessments only once for both the blood pressure and neuropositive assessments. Also, the results were not adjusted for multiple comparisons.

“For future analyses, we will use neuropositive results, blood pressure results, and neuroimaging to look at specific regions of interest in the brain and correlate them with performance in our neurocognitive testing,” she said.

This study was funded by the Pennsylvania Department of Health. Ms. Laney reported having no disclosures.