Abstract：
The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown.
Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up.
After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52-4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52-4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99-73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18-3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63-2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m2 greater in the aliskiren group (12.83 vs 5.08; 95% CI - 0.17 to 15.66; P = 0.055).
Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.
Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up.
After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52-4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52-4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99-73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18-3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63-2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m2 greater in the aliskiren group (12.83 vs 5.08; 95% CI - 0.17 to 15.66; P = 0.055).
Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.
摘要：
背景：在最大耐受剂量的ACEi/ARB基础上接受阿利吉仑治疗的活检证实的IgAN患者的长期临床结果仍然未知。
方法：将接受直接肾素抑制剂和ACEi/ARB治疗至少6个月的IgAN患者与1：1propensityscore匹配的队列（包括MEST-C评分和eGFR匹配的12个月暴露前斜率）进行比较接受ACEi/ARB而未接触阿利吉仑，以计算达到复合终点Ge%降低40的主要风险比开始KRT和全因死亡率。次要结果指标包括平均UPCR的变化，血压,eGFR,随访期间高钾血症和其他不良事件的发生率。
结果：经过2.5年的中位随访，8/36（22.2%）阿利吉仑治疗患者和6/36（16.7%）对照患者达到主要复合结局（HR=1.60；95%CI0.52-4.88；P=0.412）。阿利吉仑治疗增加了≥40%eGFR下降的风险(HR=1.60;95%CI0.52-4.88;P=0.412),和高钾血症（HR=8.60；95％CI0.99-73.64；P=0.050）。在10.8岁时，在阿利吉仑组和对照组中,肾脏综合结局分别为69.4%和58.3%(HR=2.16;95%CI1.18-3.98;P=0.013),分别。治疗和对照组之间的平均UPCR降低没有统计学差异（52.7％vs42.5％；95％CI0.63-2.35；P=0.556）。阿利吉仑组60个月eGFR下降的平均组间差异为7.75±3.95ml/min/1.73m2（12.83vs5.08；95％CI-0.17至15.66；P=0.055）。
结论：在IgAN患者中，尽管阿利吉仑最初具有抗蛋白尿作用,但其与不利的长期肾脏结局相关.
方法：将接受直接肾素抑制剂和ACEi/ARB治疗至少6个月的IgAN患者与1：1propensityscore匹配的队列（包括MEST-C评分和eGFR匹配的12个月暴露前斜率）进行比较接受ACEi/ARB而未接触阿利吉仑，以计算达到复合终点Ge%降低40的主要风险比开始KRT和全因死亡率。次要结果指标包括平均UPCR的变化，血压,eGFR,随访期间高钾血症和其他不良事件的发生率。
结果：经过2.5年的中位随访，8/36（22.2%）阿利吉仑治疗患者和6/36（16.7%）对照患者达到主要复合结局（HR=1.60；95%CI0.52-4.88；P=0.412）。阿利吉仑治疗增加了≥40%eGFR下降的风险(HR=1.60;95%CI0.52-4.88;P=0.412),和高钾血症（HR=8.60；95％CI0.99-73.64；P=0.050）。在10.8岁时，在阿利吉仑组和对照组中,肾脏综合结局分别为69.4%和58.3%(HR=2.16;95%CI1.18-3.98;P=0.013),分别。治疗和对照组之间的平均UPCR降低没有统计学差异（52.7％vs42.5％；95％CI0.63-2.35；P=0.556）。阿利吉仑组60个月eGFR下降的平均组间差异为7.75±3.95ml/min/1.73m2（12.83vs5.08；95％CI-0.17至15.66；P=0.055）。
结论：在IgAN患者中，尽管阿利吉仑最初具有抗蛋白尿作用,但其与不利的长期肾脏结局相关.
