血管紧张素转换酶（ACE）基因型与ACE抑制剂在慢性蛋白尿性肾病中诱导的肾脏保护作用1 。

ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1.

作者信息

Perna A, Ruggenenti P, Testa A, Spoto B, Benini R, Misefari V, Remuzzi G, Zoccali C

机构信息

Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, "Aldo e Cele Daccò" Villa Camozzi-Ranica, Italy.

出版信息

Kidney Int. 2000 Jan;57(1):274-81. doi: 10.1046/j.1523-1755.2000.00818.x.

DOI:10.1046/j.1523-1755.2000.00818.x

PMID:10620209

Abstract

UNLABELLED

ACE genotype and ACE induced renoprotection in chronic proteinuric nephropathies.

BACKGROUND

Whether angiotensin-converting enzyme (ACE) gene polymorphism affects disease progression and response to ACE inhibitor therapy in nondiabetic proteinuric nephropathies is not clearly established.

METHODS

The relationship between insertion/deletion (I/D) genotypes and proteinuria, rate of glomerular filtration rate decline (DeltaGFR)-centrally evaluated by repeated measures of iohexol plasma clearance-and incidence of end-stage renal disease (ESRD) was prospectively evaluated in 212 patients with nondiabetic proteinuric chronic nephropathies enrolled in the Ramipril Efficacy in Nephropathy (REIN) trial, where patients were randomly assigned to ramipril or conventional treatment.

RESULTS

The DeltaGFR +/- SEM (-0.38 +/- 0.09 vs. -0.50 +/- 0.08 vs. -0.36 +/- 0.06 mL/min/1.73 m2 per month) and incidence of ESRD (19 vs. 22 vs. 25%) in the three subgroups with the II, ID, and DD genotypes, respectively, were comparable. Of note, DeltaGFR (-0.28 +/- 0.07 vs. -0.43 +/- 0.09 mL/min/1.73 m2 per month) and incidence of ESRD [14% vs. 36%, P = 0.04, RR (95% CI), 2.62 (1.02 to 6.71)] were lower in ramipril than in conventionally treated patients in the DD genotype, but not in the II and ID genotype. Either at univariate (P = 0.04) or at multivariate (P = 0.01) analysis, ramipril significantly predicted a lower incidence of events in DD, but not in II and ID patients. At three months, ramipril decreased proteinuria more effectively in DD (-38.2%) than in the II (-26.7%) or ID (-19.2%) genotype. In DD (but not in II or ID) ramipril-treated patients, a short-term reduction in proteinuria correlated with DeltaGFR over the entire follow-up period (P = 0.02, r = -0.41).

CONCLUSIONS

In nondiabetic proteinuric nephropathies, the ACE I/D polymorphism does not predict disease progression, but is a strong predictor of ACE inhibition-associated renoprotection in that proteinuria, DeltaGFR, and progression to ESRD are effectively reduced in patients with the DD, but not in those with the II or ID genotype.

摘要

未标注

血管紧张素转换酶（ACE）基因型与慢性蛋白尿性肾病中ACE诱导的肾脏保护作用。

背景

血管紧张素转换酶（ACE）基因多态性是否会影响非糖尿病性蛋白尿性肾病的疾病进展及对ACE抑制剂治疗的反应尚未明确。

方法

前瞻性评估了212例非糖尿病性蛋白尿性慢性肾病患者的插入/缺失（I/D）基因型与蛋白尿、肾小球滤过率下降速率（ΔGFR）（通过反复测量碘海醇血浆清除率进行中心评估）以及终末期肾病（ESRD）发生率之间的关系。这些患者参加了雷米普利肾病疗效（REIN）试验，患者被随机分配接受雷米普利或传统治疗。

结果

II、ID和DD基因型的三个亚组的ΔGFR±标准误（分别为-0.38±0.09 vs. -0.50±0.08 vs. -0.36±0.06 mL/min/1.73 m²每月）和ESRD发生率（分别为19% vs. 22% vs. 25%）具有可比性。值得注意的是，DD基因型患者中，雷米普利组的ΔGFR（-0.28±0.07 vs. -0.43±0.09 mL/min/1.73 m²每月）和ESRD发生率[14% vs. 36%，P = 0.04，相对危险度（95%可信区间），2.62（1.02至6.71）]低于传统治疗组，但II和ID基因型患者中无此差异。单因素分析（P = 0.04）或多因素分析（P = 0.01）时，雷米普利均显著预测DD基因型患者事件发生率较低，但II和ID基因型患者无此情况。三个月时，雷米普利在DD基因型患者中降低蛋白尿的效果（-38.2%）比II基因型（-26.7%）或ID基因型（-19.2%）更显著。在接受雷米普利治疗的DD基因型（而非II或ID基因型）患者中，短期内蛋白尿的降低与整个随访期的ΔGFR相关（P = 0.02，r = -0.41）。