Stamellou Eleni, Nadal Jennifer, Hendry Bruce, Mercer Alex, Seikrit Claudia, Bechtel-Walz Wibke, Schmid Matthias, Moeller Marcus J, Schiffer Mario, Eckardt Kai-Uwe, Kramann Rafael, Floege Jürgen
Division of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany.
Department of Nephrology, School of Medicine, University of Ioannina, Ioannina, Greece.
Clin Kidney J. 2024 Jul 22;17(8):sfae230. doi: 10.1093/ckj/sfae230. eCollection 2024 Aug.
The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established.
From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study ( = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.73 m and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model.
The mean age of IgAN patients at baseline was 51.6 years (± 13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9 ± 8.1 years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4 g/g [interquartile range (IQR) 0.1-0.8] and mean eGFR was 52.5 ± 22.4 ml/min/1.73 m. Over a follow-up of 6.5 years, 64 (15.2%) patients experienced a >40% eGFR decline, 3 (0.7%) reached eGFR <15 ml/min/1.73 m, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to <0.1 g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1-0.6 g/g, 0.6-1.4 g/g, 1.4-2.2 g/g and >2.2 g/g were 2.03 [95% confidence interval (CI) 1.02-4.05], 3.8 (95% CI 1.92-7.5), 5.64 (95% CI 2.58-12.33) and 5.02 (95% CI 2.29-11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11-5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations.
In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes.
在原发性免疫球蛋白A肾病(IgAN)中,与蛋白尿相比,白蛋白尿在预测肾脏预后方面的重要性尚未明确。
2010年至2012年,421例经活检证实的IgAN患者被纳入德国慢性肾脏病(GCKD)队列研究,这是一项前瞻性观察性队列研究(n = 5217)。判定的终点包括复合肾脏终点(CKE),其由估算肾小球滤过率(eGFR)下降>40%、eGFR<15 ml/min/1.73 m²以及开始肾脏替代治疗组成;CKE的各个组成部分;以及合并的主要不良心血管事件(MACE),包括非致命性心肌梗死、非致命性中风和全因死亡率。使用Cox比例风险回归模型分析CKE发生率与基线因素之间的关联,这些基线因素包括人口统计学、实验室检查值和合并症。
IgAN患者基线时的平均年龄为51.6岁(±13.6),67%为男性。患者报告的基线疾病持续时间为5.9±8.1年。基线尿白蛋白:肌酐比值(UACR)中位数为0.4 g/g[四分位间距(IQR)0.1 - 0.8],平均eGFR为52.5±22.4 ml/min/1.73 m²。在6.5年的随访中,64例(15.2%)患者eGFR下降>40%,3例(0.7%)患者eGFR<15 ml/min/1.73 m²,53例(12.6%)患者开始肾脏替代治疗,28%的患者发生CKE。与<0.1 g/g相比,白蛋白尿与CKE的相关性最强。UACR为0.1 - 0.6 g/g、0.6 - 1.4 g/g、1.4 - 2.2 g/g和>2.2 g/g时的风险比(HR)分别为2.03[95%置信区间(CI)1.02 - 4.05]、3.8(95%CI 1.92 - 7.5)、5.64(95%CI 2.58 - 12.33)和5.02(95%CI 2.29 - 11.03)。关于MACE,糖尿病的存在[HR 2.53(95%CI 1.11 - 5.78)]是最密切相关的因素,而UACR和eGFR未显示出显著关联。
在GCKD IgAN亚队列中,超过四分之一的患者在6.5年内发生了CKE事件。我们的研究结果支持将白蛋白尿作为评估不良肾脏预后风险的替代指标。