Centro de Nefrología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Programa de Salud Renal del Uruguay, Montevideo, Uruguay.
Nephron. 2019;143(2):100-107. doi: 10.1159/000500925. Epub 2019 Jun 14.
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria and slow renal disease progression more effectively than other therapies in patients with chronic kidney disease (CKD). However, differences regarding efficacy and safety between these therapies remain controversial.
Aim of this study was to analyze the different treatment effect of ACEI, ARB, and non-ACEI/ARB in CKD progression. The primary outcome was survival to end-stage renal disease (ESRD) and/or death and to ESRD censored by all-cause death, secondary outcomes were proteinuria reduction and hyperkalemia.
We analyzed data from 1,120 patients extracted from the National Renal Healthcare Program cohort, which included 17,238 CKD nondialysis subjects who were successively monitored between -September 1, 2004 and August 31, 2016. Inclusion criteria were at least a 1-year follow-up, 3 clinical visits, and no previous treatment with ACEI or ARB. From the baseline visit onward, patients continued with 3 different treatment schemes: no ACEI/ARB, started on ACEI or ARB, but while avoiding both treatments in combination. Chi2, t test, binary logistic regression, and multivariate regression models (Cox proportional Hazard model and competing risk Fine and Gray model were used for statistical analysis.
Mean age and follow-up were 67.9 (± 15) and 3.8 (± 2) years, respectively. Estimated glomerular filtration rate averaged 42.1 ± 23 mL/min/1.73 m2 and 300 (27%) patients were diabetics. Progression to ESRD was significantly worse in the no ACEI/ARB group (hazard ratio [HR] 4.23, 95% CI 1.28-13.92) versus ACEI (reference group; p = 0.01). The analysis by competing-risks' regression showed significantly higher risk of ESRD in the no ACEI/ARB group (HR 3.63, 95% CI 1.34-9.85) versus ACEI (p = 0.01). There were no significant differences between ACEI and ARB groups (HR 1.31, 95% CI 0.37-4.66) regarding the risk of progression to ESRD. Survival was similar in all 3 groups (p = 0.051). Statistically significantly more patients experienced reductions in proteinuria/albuminuria in ACEI and ARB groups (together) versus no ACEI/ARB group (p = 0.016, OR 1.82, 95% CI 1.12-2.94). No difference in hyperkalemia frequency was found between them (p = 0.17).
In patients with CKD, treatment with ACEI or ARB had a superior effect than no ACEI or ARB treatment on slowing kidney disease progression and on proteinuria reduction. Efficacy of ACEI and ARB was comparable.
血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体阻滞剂(ARB)在慢性肾脏病(CKD)患者中比其他治疗方法更有效地减少蛋白尿并减缓肾脏疾病进展。然而,这些治疗方法的疗效和安全性差异仍然存在争议。
本研究旨在分析 ACEI、ARB 和非 ACEI/ARB 在 CKD 进展中的不同治疗效果。主要结局是终末期肾脏疾病(ESRD)和/或死亡的生存,以及所有原因导致的 ESRD 死亡的生存,次要结局是蛋白尿减少和高钾血症。
我们分析了从国家肾脏医疗保健计划队列中提取的 1120 名患者的数据,该队列包括 17238 名 CKD 非透析患者,他们在 2004 年 9 月 1 日至 2016 年 8 月 31 日期间连续监测。纳入标准是至少随访 1 年,进行 3 次临床访视,并且以前没有接受过 ACEI 或 ARB 治疗。从基线访视开始,患者继续接受 3 种不同的治疗方案:不使用 ACEI/ARB、开始使用 ACEI 或 ARB,但避免联合使用这两种药物。使用卡方检验、t 检验、二项逻辑回归和多变量回归模型(Cox 比例风险模型和竞争风险 Fine 和 Gray 模型)进行统计分析。
平均年龄和随访时间分别为 67.9(±15)和 3.8(±2)年。估计肾小球滤过率平均为 42.1±23mL/min/1.73m2,300(27%)名患者患有糖尿病。与 ACEI(参考组;p=0.01)相比,无 ACEI/ARB 组进展为 ESRD 的风险显著更高(风险比 [HR] 4.23,95%CI 1.28-13.92)。通过竞争风险回归分析,无 ACEI/ARB 组发生 ESRD 的风险显著更高(HR 3.63,95%CI 1.34-9.85,p=0.01)。ACEI 组和 ARB 组之间进展为 ESRD 的风险无显著差异(HR 1.31,95%CI 0.37-4.66)。所有 3 组的生存率相似(p=0.051)。ACEI 和 ARB 组(联合)的蛋白尿/白蛋白尿减少的患者比例显著高于无 ACEI/ARB 组(p=0.016,OR 1.82,95%CI 1.12-2.94)。两组间高钾血症的发生率无差异(p=0.17)。
在 CKD 患者中,与无 ACEI/ARB 治疗相比,ACEI 或 ARB 治疗在减缓肾脏疾病进展和减少蛋白尿方面具有更好的效果。ACEI 和 ARB 的疗效相当。