Kim Dana, Lv Jicheng, Hladunewich Michelle, Jha Vivekanand, Hooi Lai Seong, Monaghan Helen, Shan Sana, Reich Heather N, Barbour Sean, Billot Laurent, Zhang Hong, Perkovic Vlado, Wong Muh Geot
The George Institute for Global Health, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Kidney Int Rep. 2024 Apr 3;9(7):2168-2179. doi: 10.1016/j.ekir.2024.03.032. eCollection 2024 Jul.
The therapeutic effects of steroids in immunoglobulin A nephropathy (IgAN) global (TESTING) study reported that methylprednisolone reduces the risk of major kidney events in individuals with IgAN at high risk of disease progression compared to supportive care alone but is associated with increased serious adverse events (SAEs) primarily with full-dose therapy. The risk benefit balance of the reduced-dose methylprednisolone regimen is examined in this prespecified analysis of the reduced-dose cohort of the TESTING trial.
Between 2017 and 2019, patients with IgAN, proteinuria ≥1 g/d despite 3 months of renin-angiotensin-system blockade and estimated glomerular filtration rate (eGFR) 30 to 120 ml/min per 1.73 m were randomized to reduced-dose methylprednisolone 0.4 mg/kg/d or placebo. The primary outcome was a composite of a 40% eGFR decline, kidney failure, or death due to kidney disease.
A total of 241 participants were randomized and followed-up with for a median of 2.5 years (mean age: 37 years; baseline eGFR: 65 ml/min per 1.73 m; proteinuria: 2.48 g/d). Methylprednisolone was associated with fewer primary outcome events compared to placebo (7/121 vs. 22/120; hazard ratio [HR]: 0.24; 95% confidence interval [CI]: 0.10-0.58, = 0.002), lowered proteinuria, and reduced eGFR rate of decline from baseline. The mean difference between methylprednisolone and placebo in proteinuria and eGFR from baseline was -1.15 g/d and 7.9 ml/min per 1.73 m ( < 0.001) at 12 months, respectively; however, these benefits were lost over time. There were 7 versus 3 SAEs in the methylprednisolone versus placebo group (HR: 1.97; 95% CI: 0.49-7.90), including 5 versus 2 infections.
Reduced-dose methylprednisolone is effective in improving kidney outcomes in high risk IgAN; however, it is associated with a modestly higher number of SAEs compared to placebo.
免疫球蛋白A肾病（IgAN）全球治疗效果（TESTING）研究报告称，与单纯支持治疗相比，甲泼尼龙可降低疾病进展高风险的IgAN患者发生主要肾脏事件的风险，但主要与全剂量治疗相关的严重不良事件（SAEs）会增加。在TESTING试验的低剂量队列的这项预先指定分析中，研究了低剂量甲泼尼龙方案的风险效益平衡。
2017年至2019年期间，尽管进行了3个月的肾素-血管紧张素系统阻断治疗，但蛋白尿≥1 g/d且估计肾小球滤过率（eGFR）为每1.73平方米30至120 ml/min的IgAN患者被随机分为低剂量甲泼尼龙0.4 mg/kg/d或安慰剂组。主要结局是eGFR下降40%、肾衰竭或因肾病死亡的复合结局。
共有241名参与者被随机分组并随访了中位数2.5年（平均年龄：37岁；基线eGFR：每1.73平方米65 ml/min；蛋白尿：2.48 g/d）。与安慰剂相比，甲泼尼龙组的主要结局事件较少（7/121 vs. 22/120；风险比[HR]：0.24；95%置信区间[CI]：0.10 - 0.58，P = 0.002），蛋白尿降低，且eGFR从基线的下降速率降低。在12个月时，甲泼尼龙组与安慰剂组在蛋白尿和eGFR方面相对于基线的平均差异分别为-1.15 g/d和每1.73平方米7.9 ml/min（P < 0.001）；然而，这些益处随着时间推移而消失。甲泼尼龙组与安慰剂组的严重不良事件分别为7起和3起（HR：1.97；95% CI：0.49 - 7.90），包括感染分别为5起和2起。
低剂量甲泼尼龙可有效改善高风险IgAN患者的肾脏结局；然而，与安慰剂相比，其严重不良事件数量略多。
