Time-Weighted Average Proteinuria and Renal Function Decline in IgA Nephropathy: A Retrospective Cohort Study

Area of Science:

• Nephrology
• Immunology

Background:

• IgA nephropathy (IgAN) is a leading cause of glomerulonephritis worldwide, often progressing to end-stage renal disease.
• Proteinuria is a critical indicator of renal function decline in IgAN, but optimal long-term assessment methods remain debated.

Purpose of the Study:

• To investigate the association between time-weighted average proteinuria (TWAP) and the decline of kidney function in patients with IgA nephropathy.
• To evaluate TWAP as a novel metric for cumulative proteinuria exposure in IgAN.

Main Methods:

• A retrospective cohort study of 549 biopsy-confirmed IgAN patients from 2011-2023.
• TWAP, calculated from protein-creatinine ratio, was the primary exposure; changes in estimated glomerular filtration rate (eGFR) were the primary outcome.
• Generalized Additive Mixed Models analyzed associations between TWAP and eGFR trajectories, adjusting for clinical and histological factors (Oxford Classification MEST-C score).

Main Results:

• Higher TWAP levels correlated with accelerated eGFR decline in patients with baseline eGFR 15-60 mL/min/1.73m².
• Compared to TWAP < 0.3 g/g, higher TWAP levels (0.3-0.5, 0.5-1, ≥1 g/g) were associated with significantly greater annual eGFR declines.
• In patients with eGFR ≥60 mL/min/1.73m², TWAP ≥1 g/g was the only significant predictor of accelerated eGFR decline.

Conclusions:

• TWAP is a significant predictor of renal function decline in IgAN, particularly in patients with existing renal impairment.
• Maintaining TWAP below 0.3 g/g may substantially slow IgAN disease progression.
• This study underscores the critical role of stringent proteinuria management in IgAN.