Campbell Kirk N, Pennese Natali, Zaffalon Andrea, Magalhaes Barbara, Faiella Marina, Caster Dawn J, Radhakrishnan Jai, Tesar Vladimir, Trachtman Howard
Icahn School of Medicine at Mount Sinai, New York, NY.
LatticePoint Consulting, Geneva, Switzerland.
Kidney Med. 2022 Mar 24;4(5):100457. doi: 10.1016/j.xkme.2022.100457. eCollection 2022 May.
Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy (renin-angiotensin-aldosterone system [RAAS] inhibitor) to control proteinuria in primary and genetic focal segmental glomerulosclerosis (FSGS) follows guidelines based on other proteinuria-related kidney diseases. There is no consensus on the efficacy and safety of RAAS inhibitor therapies in primary and genetic FSGS. This systematic review assessed the effects of RAAS inhibitor therapy on kidney outcomes in these patients.
Systematic review of randomized controlled trials, interventional nonrandomized studies, observational studies, and retrospective studies.
SETTING & STUDY POPULATIONS: Patients with primary and genetic FSGS.
PubMed, Cochrane Library, and Embase.
2 investigators independently screened studies and extracted data.
Results were summarized as the ratio of means (ROM) between baseline and follow-up measurements or as the hazard ratio using random-effects models.
30 publications were selected; 5 were controlled trials (4 randomized controlled trials). 8 assessed RAAS inhibitor monotherapy, while the rest studied RAAS inhibitors in combination with other drugs, mainly immunosuppressants. On average, a 32% proteinuria reduction (ROM, 0.68; 95% CI, 0.47-0.98) and no change in creatinine clearance (ROM, 0.95; 95% CI, 0.77-1.16) from baseline to the last reported follow-up was observed in patients treated with RAAS inhibitor monotherapy. When a RAAS inhibitor was combined with other drugs, a 72% proteinuria reduction was observed from baseline to the last reported follow-up (ROM, 0.24; 95% CI, 0.08-0.75). The published data did not allow for the assessment of the effects of RAAS inhibitor monotherapy on estimated glomerular filtration rate and end-stage kidney disease risks.
Large study heterogeneity in design, patient populations, and treatment regimens. No access to individual patient-level data.
This review supports the tendency to observe a proteinuria reduction with RAAS inhibitors in patients with primary FSGS. RAAS inhibitor monotherapy was associated with maintained kidney function, as shown by no change in creatinine clearance. Strong evidence to quantify the effects of RAAS inhibitor monotherapy on end-stage kidney disease and glomerular filtration rate was lacking. Larger, well-designed clinical trials are needed to better understand the effects of RAAS inhibitors on primary FSGS.
血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂疗法（肾素-血管紧张素-醛固酮系统[RAAS]抑制剂）用于控制原发性和遗传性局灶节段性肾小球硬化（FSGS）中的蛋白尿，遵循基于其他蛋白尿相关肾脏疾病的指南。对于RAAS抑制剂疗法在原发性和遗传性FSGS中的疗效和安全性尚无共识。本系统评价评估了RAAS抑制剂疗法对这些患者肾脏结局的影响。
对随机对照试验、非随机干预性研究、观察性研究和回顾性研究进行系统评价。
原发性和遗传性FSGS患者。
PubMed、Cochrane图书馆和Embase。
2名研究人员独立筛选研究并提取数据。
结果总结为基线和随访测量之间的均值比（ROM）或使用随机效应模型的风险比。
共筛选出30篇文献；5篇为对照试验（4篇随机对照试验）。8项评估了RAAS抑制剂单药治疗，其余研究了RAAS抑制剂与其他药物联合使用，主要是免疫抑制剂。平均而言，接受RAAS抑制剂单药治疗的患者从基线到最后一次报告的随访期间，蛋白尿减少32%（ROM，0.68；95%CI，0.47 - 0.98），肌酐清除率无变化（ROM，0.95；95%CI，0.77 - 1.16）。当RAAS抑制剂与其他药物联合使用时，从基线到最后一次报告的随访期间观察到蛋白尿减少72%（ROM，0.24；95%CI，0.08 - 0.75）。已发表的数据无法评估RAAS抑制剂单药治疗对估计肾小球滤过率和终末期肾病风险的影响。
研究在设计、患者人群和治疗方案方面存在较大异质性。无法获取个体患者层面的数据。
本综述支持在原发性FSGS患者中观察到RAAS抑制剂可降低蛋白尿的趋势。RAAS抑制剂单药治疗与肾功能维持相关，如肌酐清除率无变化所示。缺乏量化RAAS抑制剂单药治疗对终末期肾病和肾小球滤过率影响的有力证据。需要开展更大规模、设计良好的临床试验，以更好地了解RAAS抑制剂对原发性FSGS的影响。
