POS-373 THE LEVEL OF URINARY C4d IN PATIENTS WITH IgA NEPHROPATHY IS ASSOCIATED WITH DISEASE PROGRESSION: A COHORT STUDY

Abstract

Positive glomerular C4d staining, representative of lectin pathway activation, has been proven to be associated with unfavorable outcomes in IgA nephropathy (IgAN). Our previous study suggested that urinary C4d correlated positively with an increase in crescents. While the relationship between urinary C4d and disease severity and progression remains unelucidated. In this study, we enrolled 168 patients diagnosed of IgAN with varying proportions of crescents formation at the time of biopsy. An independent cohort of 107 IgAN patients were enrolled for validation. Kidney biopsy specimens were stained using immunohistochemistry. Urinay C4d levels at renal biopsy were measured by enzyme-linked immunosorbent assay. The primary endpoint was end-stage kidney disease (ESKD). Levels of urinary C4d/Urine creatine(C4d/Ucr) demonstrated the same tendency as the stepwise increase in glomerular C4d positivity (p for trend <0.001). Higher urinary C4d/Ucr levels were associated with a lower estimated glomerular filtration rate (eGFR); massive proteinuria; hypertension; and severe Oxford-M, Oxford-E, Oxford-T and Oxford-C scores. After a median follow-up of 19 months (interquartile range, 9–27 months), 53 (31.5%) participants reached end-stage of kidney disease (ESKD). High urinary C4d/creatinine ratio levels were independently and significantly associated with a risk of developing ESKD (hazard ratio [HR], per standard deviation increment of log transformed C4d/creatinine of 7.623; 95% confidence interval [CI]: 4.117–14.113). Urinary C4d/creatinine ratio was a potential useful biomarker that was associated with disease severity and progression in patients with IgAN and crescents.