Xu Ricong, Cao Tao, Liao Ying, Chen Yuna, Yu Yi, Guo Jianying, Zhong Anni, Chen Xiaojie, Xu Yi, Wan Qijun
Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, People's Republic of China.
Int J Nephrol Renovasc Dis. 2025 Mar 29;18:103-110. doi: 10.2147/IJNRD.S517145. eCollection 2025.
IgA nephropathy (IgAN) is the leading primary glomerulonephritis globally, with many patients advancing to end-stage renal disease. Proteinuria is a key predictor of renal function decline in IgAN, yet the best method for long-term assessment is unclear. This study explores the relationship between time-weighted average proteinuria (TWAP), a novel metric of cumulative proteinuria exposure, and renal function decline in IgAN patients.
This single-center retrospective cohort study encompassed 549 patients with biopsy-confirmed primary IgAN from Shenzhen Second People's Hospital from 2011 to 2023. TWAP served as the primary exposure variable, calculated using the protein-creatinine ratio values, while changes in estimated glomerular filtration rate (eGFR) constituted the primary outcome. Covariates included age, sex, blood pressure, and mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and crescents (C) (known as the Oxford Classification MEST-C score system). The associations between TWAP and eGFR trajectories were analyzed using Generalized Additive Mixed Models.
In patients with baseline eGFR 15-60 mL/min/1.73m², higher TWAP levels correlated with accelerated eGFR decline. Compared to TWAP < 0.3 g/g, TWAP 0.3-0.5 g/g, 0.5-1 g/g, and ≥1 g/g were associated with additional annual eGFR declines of 2.04 (95% CI: -3.72 to -0.35), 3.38 (95% CI: -5.12 to -1.65), and 4.04 (95% CI: -6.61 to -1.47) mL/min/1.73m²/year, respectively. For eGFR ≥60 mL/min/1.73m², only TWAP ≥1 g/g significantly accelerated eGFR decline 5.70 (95% CI: -6.84 to -4.55) mL/min/1.73m²/year.
TWAP significantly predicts renal function decline in IgAN, especially in patients with pre-existing renal dysfunction. Maintaining TWAP below 0.3 g/g may significantly slow disease progression, emphasizing the importance of stringent proteinuria control in IgAN management.
IgA肾病（IgAN）是全球主要的原发性肾小球肾炎，许多患者会发展至终末期肾病。蛋白尿是IgAN患者肾功能下降的关键预测指标，但长期评估的最佳方法尚不清楚。本研究探讨了时间加权平均蛋白尿（TWAP）这一累积蛋白尿暴露的新指标与IgAN患者肾功能下降之间的关系。
这项单中心回顾性队列研究纳入了2011年至2023年期间深圳市第二人民医院549例经活检确诊的原发性IgAN患者。TWAP作为主要暴露变量，使用蛋白肌酐比值计算，而估计肾小球滤过率（eGFR）的变化作为主要结局。协变量包括年龄、性别、血压以及系膜细胞增生（M）、内皮细胞增生（E）、节段性肾小球硬化（S）、肾小管萎缩/间质纤维化（T）和新月体（C）（即牛津分类MEST - C评分系统）。使用广义相加混合模型分析TWAP与eGFR轨迹之间的关联。
在基线eGFR为15 - 60 mL/min/1.73m²的患者中，较高的TWAP水平与eGFR加速下降相关。与TWAP < 0.3 g/g相比，TWAP为0.3 - 0.5 g/g、0.5 - 1 g/g和≥1 g/g时，每年eGFR额外下降分别为2.04（95% CI： - 3.72至 - 0.35）、3.38（95% CI： - 5.12至 - 1.65）和4.04（95% CI： - 6.61至 - 1.47）mL/min/1.73m²/年。对于eGFR≥60 mL/min/1.73m²，仅TWAP≥1 g/g显著加速eGFR下降，为5.70（95% CI： - 6.84至 - 4.55）mL/min/1.73m²/年。
TWAP显著预测IgAN患者的肾功能下降，尤其是在已有肾功能不全的患者中。将TWAP维持在0.3 g/g以下可能显著减缓疾病进展，强调了在IgAN管理中严格控制蛋白尿的重要性。
