#2111 Prediction of ESRD in IgA nephropathy using IgA: C3 ratio at diagnosis. 10 year cohort

Abstract Background and Aims IgA Nephropathy is the commonest glomerular pathology with a wide range of outcomes depending on the severity of the circulating serological pathophysiology and on the resulting inflammatory response in the kidney. Prediction of kidney loss, which results in renal failure in 20-40% of cases -versus very benign disease, has largely used traditional clinical parameters such as proteinuria, hypertension and already established renal decline at the point of diagnosis. There has been variable utility from biopsy severity scoring. Pathogenicity of IgA immune complexes may result from activation of complement via the alternative pathway and assessment of serum IgA and complement C3 has been suggested as a marker of pathogenicity. We examined the utility of IgA to C3 ratio in predicting outcomes in a cohort over 10 years Method We examined all the electronic records of biopsy proven IgA cases from 2010 onwards when serum electrophoresis and serum complement became been widely tested at all new renal presentations. These cases were followed to end stage kidney disease or death. A subset of diagnosed patients also had MEST-C score. Results Of 319 biopsy proven IgA cases between 2010 and 2023, 216 had serum IgA and complement studies at diagnosis, with median PCR 309 and median serum creatinine 177. 56 patients had IgA:C3 4. Outcome of “death or renal replacement therapy” rather than the surrogate “RRT or doubling serum creatinine” was possible due to the length of follow up. Median follow up was 4.5 years, during which 101 (46%) died or reached ESRD. Among those with IgA:C3 4, 35 (61%) median survival 5 years, versus 67(42%) of those 4 (median survival 10 years). Hazard ratio for IgA:C3 4 was 1.9 (1.2-3.2) Cox Proportional Hazard show this to be independent from presenting creatinine, proteinuria, but not independent of age. A cohort of 107 biopsy proven IgA cases between 2010 and 2015 had data on CMEST score. 62 of this cohort also had IgA and complement measured. There was no correlation with CMEST score, or occurrence of crescents present on biopsy There were no differences in the treatments used following diagnosis of IgA Nephropathy. Similar proportions receiving steroid, calcineurin or mycophenolate. Conclusion IgA to C3 ratio is readily available result which powerfully predicts IgA outcome independently from pathology score and traditional clinical severity estimates. It may well become a useful indicator to target novel immune/complement therapies.