#1444 Albuminuria and subsequent risk of kidney events in patients with IgA nephropathy: a nationwide cohort study

Abstract Background and Aims KDIGO recommends proteinuria 1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high-risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain poorly studied. Method We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between first-recorded urinary albumin-to-creatinine ratio (uACR, in categories 0.3, 0.3-0.5, 0.5-1.0, 1.0-1.5, 1.5-2.0 and 2.0 g/g) and the occurrence of major adverse kidney events (MAKE, a composite of kidney replacement therapy KRT and 30% decline in eGFR). We also explored the risk of MAKE associated with the fold-change in uACR within a year. Results We enrolled 1269 patients with primary IgAN (74% men, median 53 years, mean eGFR 33 mL/min/1.73 m², median uACR 0.7 g/g). Compared to patients with uACR 0.3 g/g, those with higher uACR levels were younger, more often men, had a higher prevalence of hypertension, diabetes, acute kidney injury, lower eGFR and serum albumin level, and were less often prescribed RASi. Over median follow-up of 5.5 2.8;9.2 years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced 30% eGFR decline. In multivariable analyses, and compared with uACR 0.3 g/g, any higher uACR category strongly and incrementally associated with the risk of MAKE (Figure), with Hazard Ratios (HR) ranging from 1.56 95% CI 1.14-2.14 in patients with uACR 0.3-0.5 g/g to 4.53 3.36-6.11 in patients with uACR2g/g. Similar graded relationships were observed for KRT (HR ranging from 1.39 to 4.65), and for 30% decline in eGFR (HR ranging from 1.76 to 3.47). In the 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR. Conclusion Our findings show substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0 g/g, a population currently considered at low-risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR.