ALIGN: Atrasentan preserves kidney function with long-term treatment in IgA nephropathy

Compared with placebo, atrasentan modestly slowed the decline in estimated glomerular filtration rate (eGFR) after 2.5 years of treatment in patients with immunoglobulin A (IgA) nephropathy, although it was associated with an increased risk of anaemia and fluid retention.

Prof. Hiddo J.L. Heerspink (University of Groningen, the Netherlands) presented updated results from ALIGN (NCT04573478), an ongoing randomised controlled trial comparing once-daily oral atrasentan with placebo in a 1:1 ratio for 132 weeks [1]. Patients were eligible if they had urinary protein ≥1 g/day, an eGFR ≥30 mL/min/1.73 m², and had been receiving the maximally tolerated dose of renin–angiotensin system (RAS) inhibitors for at least 12 weeks. A separate exploratory cohort included patients receiving concomitant sodium-glucose co-transporter 2 (SGLT2) inhibitors. The key secondary endpoint presented was the change in eGFR from baseline to week 136 in the main cohort. Overall, 340 patients were randomised in the main cohort and 64 in the SGLT inhibitor stratum.

At week 136, the mean change in eGFR from baseline was -7.5 mL/min/1.73 m² in the atrasentan group and -9.9 mL/min/1.73 m² in the placebo group, corresponding to a between-group difference of 2.4 mL/min/1.73 m2 (95% CI -0.1 to 4.8; P=0.054). In the SGLT2 inhibitor stratum, the mean change in eGFR was -1.5 with atrasentan compared with -10.6 with placebo. Furthermore, a clinically meaningful difference was observed in the pooled population, which included both cohorts. Adverse events of special interest related to the mechanism of action of atrasentan included anaemia and fluid retention, both of which occurred more frequently with atrasentan than with placebo.

“With 2.5 years of treatment in ALIGN, the totality of the evidence shows that atrasentan leads to a clinically meaningful reduction in proteinuria and slows kidney function decline,” concluded Prof. Heerspink. “The treatment benefit with atrasentan was consistent regardless of concomitant SGLT2 inhibitor use. Overall, these findings support the use of atrasentan for the treatment of adults with IgA nephropathy.”

Heerspink HJL, et al. Efficacy and safety of atrasentan treatment in participants with IgA nephropathy: 2.5-year eGFR results from the ALIGN trial. ERA 2026, 3–6 June. Glasgow, Scotland.