Losartan in patients with type 2 diabetes and proteinuria: observations from the RENAAL Study.
BACKGROUND
Recently, the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Study demonstrated the benefit of losartan in reducing renal outcomes in patients with type 2 diabetes and proteinuria. Additional questions concerning the reduction of proteinuria and its relationship to end-stage renal disease (ESRD) as well as cardio-renal outcomes and the safety and tolerability of losartan remain to be addressed.


METHODS
Three analyses were performed: (a) the impact of losartan on the relationship between the reduction of proteinuria and ESRD; (b) a time-to-event analysis of the cardio-renal composite endpoint of ESRD, myocardial infarction, stroke or all-cause death; and (c) additional analyses of adverse events, particularly in patients with serum creatinine >or=2.0 mg/dL.


RESULTS
After adjusting the values for proteinuria over the entire study, the reduction of proteinuria accounted for approximately half of the treatment effect of losartan on the risk reduction for ESRD. In addition, losartan was associated with a 21% risk reduction for the composite cardio-renal outcome (P=0.003). The addition of losartan to a conventional antihypertensive regimen did not increase the overall incidence of adverse events, regardless of severity of renal impairment.


CONCLUSIONS
Losartan significantly reduced the risk of cardiorenal outcomes and was well tolerated by patients, including those with serum creatinine levels >or=2.0 g/dL. In addition, although this study shows that the reduction of proteinuria does not completely explain the impact of intervention on outcomes such as ESRD, reduction of proteinuria must remain an important consideration when treating patients with type 2 diabetes and nephropathy. However, the reduction of outcomes such as ESRD should remain the goal of therapy when evaluating renal protection in this patient population.
Shahinfar
Shahnaz
S
Merck and Co., Inc., West Point, Pennsylvania 19486, USA. Shahnaz_Shahinfar@merck.com
Dickson
Tania Z
TZ
Ahmed
Tultul
T
Zhang
Zhonxin
Z
Ramjit
Denise
D
Smith
Ronald D
RD
Brenner
Barry M
BM
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D003404:Creatinine; D019808:Losartan