Division of Nephrology, Department of Medicine, Academic Medical Centre, University of Amsterdam, the Netherlands.
Perit Dial Int. 2011 Jan-Feb;31(1):53-9. doi: 10.3747/pdi.2009.00088. Epub 2010 Jun 3.
Many studies have shown the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in patients with chronic kidney disease stages I-IV. Two randomized controlled trials (RCTs) showed a positive effect of AII inhibitors on residual glomerular filtration rate (rGFR) in peritoneal dialysis (PD) patients. However, these studies were small and were performed in a highly selected group of PD patients. Our aim was to confirm the above findings in a larger number of prospectively followed PD patients.
First we analyzed the time course of decline of rGFR in 452 incident PD patients that were not anuric at the start of dialysis and that had structured follow-up data, with measurements at 3, 6, 12, 18, 24, 30, and 36 months after the start of dialysis. Changes in rGFR over time were analyzed with a linear mixed model for repeated measures. In addition, Cox regression models were used to estimate the risk of developing anuria. In a second approach, we aimed to repeat the above analyses in a selected group of patients that theoretically could have been randomized and therefore resembled the population studied in the 2 mentioned RCTs. In this group the follow-up was restricted to 1 year.
201 patients were treated with ACEi/ARBs and 251 did not take these drugs at the start of PD. More patients from the treated group had diabetes and used more antihypertensive medications. The time course of decline of rGFR was not different between the 2 groups over the 3 years of PD treatment (p = 0.52). Less than 25% of patients from each group became anuric and there was no difference in time to development of complete anuria between the treated and untreated groups. In the second approach, 130 patients were included: 37 were treated with ACEi/ARBs and 93 were not. Again, no difference was found between the 2 groups with respect to the rate of decline of rGFR and time of anuria development.
Our findings are not in line with the results of previous RCTs. The biggest limitation of observational studies is the inability to avoid confounding by indication. However, a RCT in such a setting also does not give a reliable answer. Given all the benefits of ACEi/ARBs, the medications should not be withheld from PD patients. However, their renoprotective effects may often be overruled by other factors influencing the time course of rGFR.
许多研究表明血管紧张素转换酶抑制剂（ACEi）和血管紧张素 II 受体阻滞剂（ARBs）在慢性肾脏病 I-IV 期患者中有肾脏保护作用。两项随机对照试验（RCT）表明 AII 抑制剂对腹膜透析（PD）患者的残余肾小球滤过率（rGFR）有积极影响。然而，这些研究规模较小，且在高度选择的 PD 患者群体中进行。我们的目的是在数量更多的前瞻性随访 PD 患者中证实上述发现。
首先，我们分析了 452 例开始透析时非尿少且具有结构化随访数据的新发 PD 患者的 rGFR 下降时间过程，在透析开始后 3、6、12、18、24、30 和 36 个月进行测量。使用重复测量线性混合模型分析 rGFR 随时间的变化。此外，使用 Cox 回归模型估计发生无尿的风险。在第二种方法中，我们旨在在一组理论上可以随机分组的患者中重复上述分析，因此与上述两项 RCT 研究的人群相似。在该组中，随访时间限制为 1 年。
201 例患者开始 PD 时接受 ACEi/ARBs 治疗，251 例患者未接受这些药物。治疗组中有更多的患者患有糖尿病并使用更多的降压药物。在 PD 治疗的 3 年内，两组 rGFR 下降的时间过程没有差异（p=0.52）。两组中均不到 25%的患者出现无尿，且治疗组和未治疗组发生完全无尿的时间无差异。在第二种方法中，纳入了 130 例患者：37 例接受 ACEi/ARBs 治疗，93 例未接受。同样，两组 rGFR 下降率和无尿发生时间也无差异。
我们的发现与之前 RCT 的结果不一致。观察性研究的最大限制是无法避免指示性混杂。然而，在这种情况下进行 RCT 也不能提供可靠的答案。鉴于 ACEi/ARBs 的所有益处，不应将这些药物拒用于 PD 患者。然而，它们的肾脏保护作用可能经常被其他影响 rGFR 时间过程的因素所抵消。
