Progression risk, urinary protein excretion, and treatment effects of angiotensin-converting enzyme inhibitors in nondiabetic kidney disease.
It is unclear whether patients with nondiabetic kidney disease benefit from angiotensin-converting enzyme inhibitor (ACEI) therapy when they are at low risk for disease progression or when they have low urinary protein excretion. With the use of a combined database from 11 randomized, clinical trials (n = 1860), a Cox proportional hazards model, based on known predictors of risk and the composite outcome kidney failure or creatinine doubling, was developed and used to stratify patients into equal-sized quartiles of risk. Outcome risk and treatment effect were examined across various risk strata. Use of this risk model for targeting ACEI therapy was also compared with a strategy based on urinary protein excretion alone. Control patients in the highest quartile of predicted risk had an annualized outcome rate of 28.7%, whereas control patients in the lowest quartile of predicted risk had an annualized outcome rate of 0.4%. Despite the extreme variation in risk, there was no variation in the degree of benefit of ACEI therapy (P = 0.93 for the treatment x risk interaction). Significant interaction was detected between baseline urine protein and ACEI therapy (P = 0.003). When patients were stratified according to their baseline urinary protein excretion, among the subgroup of patients with proteinuria > or =500 mg/d, significant treatment effect was seen across all patients with a measurable outcome risk, including those at relatively low risk (1.7% annualized risk for progression). However, there was no benefit of ACEI therapy among patients with proteinuria <500 mg/d, even among higher risk patients (control outcome rate 19.7%). Patients with nondiabetic kidney disease vary considerably in their risk for disease progression, but the treatment effect of ACEI does not vary across risk strata. Patients with proteinuria <500 mg/d do not seem to benefit, even when at relatively high risk for progression.
Kent
David M
DM
Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, 750 Washington Street #63, Boston, MA 02111, USA. dkent1@tufts-nemc.org
Jafar
Tazeen H
TH
Hayward
Rodney A
RA
Tighiouart
Hocine
H
Landa
Marcia
M
de Jong
Paul
P
de Zeeuw
Dick
D
Remuzzi
Giuseppe
G
Kamper
Anne-Lise
AL
Levey
Andrew S
AS
D000368:Aged; D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011507:Proteinuria / Q000188:drug therapy* / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012307:Risk Factors
D000806:Angiotensin-Converting Enzyme Inhibitors