Incidence, Severity, and Outcomes of AKI Associated with Dual Renin-Angiotensin System Blockade.
The benefit of dual blockade of the renin-angiotensin system is limited by adverse effects. We performed a secondary analysis of the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) Study to describe the effect of increased intensity of renin-angiotensin system blockade on the incidence, risk factors, and outcomes of AKI.



In the VA NEPHRON-D Study, we randomized 1148 veterans receiving outpatient care with type 2 diabetes mellitus, eGFR of between 30 and 89.9 ml/min per 1.73 m2, and urinary albumin excretion of at least 300 μg/mg creatinine (or a urinary total protein of at least 0.5 mg/mg creatinine) to either combination therapy with losartan and lisinopril or monotherapy with losartan. We identified hospitalized AKI events and their outcomes during a median follow-up of 2.2 years through systematic reporting of serious adverse events.



The incidence of AKI was 12.2 (95% confidence interval, 10.5 to 14.0) versus 6.7 (95% confidence interval, 5.6 to 8.2) per 100 patient-years in the combination arm versus monotherapy arms (P<0.001). Individuals with AKI were more likely to develop the primary study end point of death, ESRD, or decline in kidney function (hazard ratio, 1.78; 95% confidence interval, 1.34 to 2.26; P<0.001). Patients with AKI in the combination arm had greater recovery of kidney function (75.9% versus 66.3%; P=0.04), lower 30-day mortality (4.7% versus 15.0%; P<0.01), and lower hazard for development of the primary study end point (hazard ratio, 0.60; 95% confidence interval, 0.37 to 0.98).



Dual renin-angiotensin system blockade was associated with an increased risk of AKI compared with monotherapy, but AKI in the setting of monotherapy was associated with lower rates of recovery of kidney function, higher mortality, and higher risk of progression of kidney disease.
Medical Service, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.|Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Paul M
PM
Palevsky
Cooperative Studies Program Coordinating Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
Jane H
JH
Zhang
Medical Service, Veterans Affairs Maryland Healthcare System, Baltimore, Maryland.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
Stephen L
SL
Seliger
Medical Service, Edward Hines, Jr. Veterans Affairs Hospital, Hines, Illinois; and.|Department of Medicine, Stritch School of Medicine, Loyola University, Maywood, Illinois.
Nicholas
N
Emanuele
Medical Service, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.|Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Linda F
LF
Fried
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology; D001794:Blood Pressure; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology*; D017706:Lisinopril / Q000009:adverse effects*; D019808:Losartan / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors
D017706:Lisinopril; D019808:Losartan
Albumins; Ambulatory Care; Arm; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Incidence; Kidney Failure, Chronic; Lisinopril; Losartan; Nephrons; Renin-Angiotensin System; Veterans; acute kidney injury; angiotensin converting enzyme inhibitor; angiotensin receptor blocker; chronic kidney disease; creatinine; diabetes mellitus; diabetic nephropathy; glomerular filtration rate; proteinuria; renin angiotensin system; risk factors
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