Asociación entre la remisión completa de la proteinuria y la función renal en el ensayo de fase 3 PROTECT de sparsentán en la nefropatía por IgA

In the phase 3, randomized, double-blind PROTECT (NCT03762850) trial, sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA), reduced proteinuria and preserved kidney function compared to maximum labeled dose irbesartan in adults with immunoglobulin A nephropathy. In this post hoc analysis of PROTECT, we assessed the association between complete remission of proteinuria (CR) and preservation of kidney function.

This analysis compared kidney function in patients who achieved CR (urine protein excretion <0.3 g/day) by Week 36 (CR36) or at any time up to Week 110 (CR110) vs. those who did not (non-CR), regardless of original treatment allocation. Endpoints assessed by CR status were change in proteinuria, estimated glomerular filtration rate (eGFR), and blood pressure, rate of eGFR decline, a composite kidney endpoint, and safety.

Of 404 patients who were randomized and received study drug, 43 (11%) achieved CR36 and 85 (21%) achieved CR110. CR patients demonstrated greater and more rapid reductions in proteinuria compared with non-CR patients. CR110 patients had a smaller absolute change in eGFR vs. non-CR patients (-4.0 vs. -8.6 mL/min/1.73 m2) and a slower rate of eGFR decline (Day 1-Week 110; -0.7 vs. -4.2 mL/min/1.73 m2/year). Fewer CR110 patients (1%) reached the composite kidney endpoint vs. non-CR patients (14%). CR110 patients were more likely to experience treatment-emergent adverse events (TEAEs) associated with hypotension (hypotension, orthostatic hypotension, or blood pressure systolic decreased) and less likely to experience TEAEs of hypertension than non-CR patients. More non-CR patients vs. CR110 patients discontinued treatment due to adverse events (11% vs. 4%, respectively) or patient decision (8% vs. 2%, respectively).

Participants in PROTECT who achieved CR36 or CR110 showed greater eGFR preservation, fewer kidney failure events, and similar safety profiles compared to non-CR participants. These data reinforce recommendations to maintain proteinuria levels ideally <0.3 g/day and underscore its relationship with kidney function preservation.