POS-203 LONG-TERM OUTCOMES OF ADD-ON DIRECT RENIN INHIBITION IN IMMUNOGLOBULIN A NEPHROPATHY: A RETROSPECTIVE, PROPENSITY SCORE-MATCHED COHORT STUDY

Abstract

The addition of the direct renin inhibitor (DRI) aliskiren to an angiotensin II receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEi) in IgA nephropathy (IgAN) has been shown to confer additional antiproteinuric effects in two short-term clinical trials. The long-term effect of this combination remains unknown and hence neglected in clinical practice. Thirty six patients with IgAN who had been treated with DRI and ARB for at least 6 months between 2009 to 2010 were identified and retrieved from a linked electronic database. A 1:1 propensity-score matching cohort from the same period that received ARB without aliskiren exposure was used to calculate the hazard ratio of reaching the primary endpoint, defined as a composite of a 40% reduction in estimated glomerular filtration rate (eGFR), initiation of kidney replacement therapy (KRT) and all-cause mortality. Secondary outcome measures included changes in mean urine protein-to-creatinine ratio (UPCR), blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up. After a median follow-up of 10.8 years, 25/36 (69.4%) patients in the aliskiren group and 21/36 (58.3%) patients in the control group reached the primary composite outcome (HR=2.17; 95% CI: 1.18 to 3.98; P=0.013). Aliskiren treatment was associated with an increased risk of >40% eGFR decline (HR=2.17; 95% CI: 1.18 to 3.98; P=0.013), initiation of KRT (HR=1.97; 95% CI: 0.92 to 4.21; P=0.079), and all-cause mortality (HR=2.08; 95% CI: 0.19 to 22.70; P=0.556). The incidence of hyperkalemia was significantly higher in the aliskiren group (HR=5.13; 95%CI: 1.68 to 15.63; P=0.004). After a follow up of 60 months, 16/36 (44.4%) in aliskiren and 9/36 (25.0%) in control group subjects reached the primary composite outcome (HR=2.19; 95%CI: 0.94 to 5.13, P=0.070). The mean UPCR reduction was 10.2% more in the aliskiren group (52.7% vs 42.5%; 95%CI: 0.63 to 2.35;P=0.556). Mean intergroup difference in eGFR decline over 60 months was 7.75±3.95 ml/min/1.73m 2 more in the aliskiren group (12.83 vs 5.08; 95%CI: -0.17 to 15.66; P=0.055). Although add-on aliskiren reduced proteinuria in short-term studies, it was associated with less favourable long-term kidney outcomes among patients with IgAN.