IMPLICATIONS OF PROTEINURIA REMISSION ON ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) TRAJECTORY IN PATIENTS (PTS) WITH IGA NEPHROPATHY (IGAN) IN PROTECT

Introduction:

In PROTECT, sparsentan (SPAR) reduced proteinuria and increased the proportion of pts achieving complete proteinuria remission (CR; urine protein excretion [UPE] <0.3 g/d) (31%) vs irbesartan (IRB) (11%). Lower proteinuria and CR are associated with slower kidney function decline in IgAN. To explore this relationship in PROTECT, we determined eGFR trajectories in pts whose proteinuria fell to low levels.
 

Methods:

PROTECT is a randomized, double-blind trial of efficacy and safety of SPAR vs active-control IRB in adults with IgAN at risk of progression to kidney failure despite maximum RASi. In this analysis, 404 randomized pts were pooled and grouped by achievement of CR or UPE <0.5 g/d at any time over 110 wk. Outcomes were absolute (abs) change from baseline (BL) in eGFR at wk 110 and chronic (wk 6 to 110) and total (d 1 to wk 110) eGFR slopes (adjusted for BL UPE).

Results:

While BL age, sex, and race were similar in pts achieving low UPE vs those who did not, BL UPE was lower and eGFR higher in the low proteinuria pts (Table). The abs decline in eGFR and the loss of eGFR over time were substantially lower in pts with CR or UPE <0.5 g/d vs those who did not achieve these targets.

Conclusions:

In IgAN, achievement of low proteinuria is strongly predictive of better long-term kidney function. eGFR preservation was more evident in pts who achieved low proteinuria vs those who did not; notably, in pts who achieved CR, the mean rate of kidney function decline (eGFR chronic slope) was <1.0 mL/min/1.73 m2/y. As SPAR-treated pts achieved proteinuria remission more frequently vs IRB in PROTECT, this analysis further supports the benefit of SPAR for long-term preservation of kidney function.

This abstract was also submitted for the American Society of Nephrology Kidney Week 2024 congress.

I have potential conflict of interest to disclose.
Employee and shareholder of Travere Therapeutics, Inc.

I did not use generative AI and AI-assisted technologies in the writing process.