Background Although pharmacotherapeutic proteinuria lowering was found to be nephroprotective in adults, the predictive value of early drug-induced proteinuria reduction for long-term renal survival in pediatric CKD is unknown. We analyzed data from the ESCAPE Trial for a potential association between initial antiproteinuric effect of standardized angiotensin-converting enzyme (ACE) inhibition and renal disease progression in children with CKD.

Methods In total, 280 eligible children with CKD stages 2–4 (mean age 11.7 years old, median eGFR 46 ml/min per 1.73 m², 71% congenital renal malformations) received a fixed dose of ramipril (6 mg/m² per day) and were subsequently randomized to conventional or intensified BP control. We assessed initial proteinuria reduction from baseline to first measurement on ramipril (at 2.5±1.3 months). We used multivariable Cox modeling to estimate the association between initial proteinuria reduction and the risk of reaching a renal end point (50% eGFR decline or ESRD), which occurred in 80 patients during 5 years of observation.

Results Ramipril therapy lowered proteinuria by a mean of 43.5% (95% confidence interval, 36.3% to 49.9%). Relative to proteinuria reduction <30%, 30%–60% and >60% reduction resulted in hazard ratios (95% confidence intervals) of 0.70 (0.40 to 1.22) and 0.42 (0.22 to 0.79), respectively. This association was independent of age, sex, CKD diagnosis, baseline eGFR, baseline proteinuria, initial BP, and concomitant BP reduction.

Conclusions The early antiproteinuric effect of ACE inhibition is associated with long-term preservation of renal function in children with CKD. Proteinuria lowering should be considered an important target in the management of pediatric CKD.

背景技术尽管降低药物治疗性蛋白尿对成年人具有肾脏保护作用，但早期药物诱发的蛋白尿降低对小儿CKD长期肾脏存活的预测价值尚不清楚。我们分析了ESCAPE试验的数据，以了解标准的血管紧张素转换酶（ACE）抑制作用的初始抗蛋白尿作用与CKD儿童的肾脏疾病进展之间的潜在联系。

方法总共280名资格儿童与CKD级2-4（平均年龄11.7年老，中位数的eGFR46毫升/每分钟1.73米²，71％先天性肾畸形）接收雷米普利的固定剂量（6毫克/米²每天），随后随机分配至常规或强化BP对照。我们评估了雷米普利从基线到首次测量的初始蛋白尿减少（2.5±1.3个月）。我们使用多变量Cox模型来估计初始蛋白尿减少与达到肾脏终点风险（50％eGFR下降或ESRD）之间的关联，在观察的5年中，发生了80位患者。

结果雷米普利治疗可使蛋白尿平均降低43.5％（95％置信区间为36.3％至49.9％）。相对于蛋白尿减少量，<30％，30％–60％和> 60％减少量分别导致危险比（95％置信区间）分别为0.70（0.40至1.22）和0.42（0.22至0.79）。这种关联与年龄，性别，CKD诊断，基线eGFR，基线蛋白尿，初始BP和伴随的BP降低无关。

结论ACE抑制的早期抗蛋白尿作用与CKD儿童肾功能的长期保存有关。降低蛋白尿应被视为儿科CKD治疗的重要目标。