Red Blood Cell Casts on Kidney Biopsy and Progression of IgA Nephropathy

Renal red blood cell casts (RBCC) are common in IgA nephropathy (IgAN), but their role in kidney disease progression of patients with IgAN remains unclear. 1425 patients in Peking University First Hospital IgAN (PKU-IgAN) cohort and 279 patients in TESTING trial were enrolled to test the association between RBCC and kidney outcome. RBCC was defined as positive (+) when at least one cast was identified within the renal tubules by light microscopy. Kidney endpoint was the composite of the first occurrence of a sustained 30% decrease in estimated glomerular filtration rate or end stage kidney disease or death due to kidney disease. Cox regression analysis was used. In PKU-IgAN, 529 patients (37%) had RBCC; in TESTING trial, 78 patients (28%) had RBCC. Patients with RBCC had more crescentic lesions, and less segmental sclerosis compared with patients without RBCC. In PKU-IgAN, after a median follow-up of 54 months, 119 patients (22%) with RBCC and 260 patients (29%) without RBCC reached the composite kidney endpoint (P=0.009). In multivariable analysis, RBCC was independently associated with composite kidney endpoint (HR 0.79; 95%CI 0.63 - 0.99; P=0.038). RBCC and immunosuppressive therapy (IST) had an interaction (P=0.001). RBCC was independently associated with composite kidney endpoint in patients who received IST (HR 0.56; 95%CI 0.40 - 0.77; P<0.001). In TESTING trial, after a median follow-up of 57 months, 26 patients (33%) with RBCC and 96 patients (48%) without RBCC reached the composite kidney endpoint (P=0.041). In univariate analysis, RBCC was associated with composite kidney endpoint (HR 0.64; 95%CI 0.42 - 0.99; P=0.047). Renal RBCC was frequent in IgAN and was associated with a higher incidence of acute active lesions and better renal prognosis, especially in those who received IST, warranting particular attention.