Red blood cell casts on kidney biopsy and progression of IgA nephropathy.

Background: 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.

Methods: In total, 1425 patients in a Peking University First Hospital IgAN (PKU-IgAN) cohort and 279 patients in the 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.

Results: In PKU-IgAN, 529 patients (37%) had RBCC; in the 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 = .009). In multivariable analysis, RBCC was independently associated with composite kidney endpoint [hazard ratios (HR) 0.79; 95% confidence interval (CI) 0.63-0.99; P = .038]. RBCC and immunosuppressive therapy (IST) had an interaction (P = .001). RBCC was independently associated with composite kidney endpoint in patients who received IST (HR 0.56; 95%CI 0.40-0.77; P < .001). In the 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 = .041). In univariate analysis, RBCC was associated with composite kidney endpoint (HR 0.64; 95%CI 0.42-0.99; P = .047).

Conclusion: 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.