Mesangial C4d Deposits in Early IgA Nephropathy

Abstract

Background and objectives: The prognostic value of mesangial C4d deposits in IgA nephropathy has been analyzed in patients with reduced GFR but has not been analyzed in those with normal kidney function. The main objective of the study was to analyze the prognostic value of C4d deposits and association with response to treatment in patients with IgA nephropathy and normal GFR.

Design, setting, participants, & measurements: This retrospective cohort study included 190 patients with idiopathic IgA nephropathy diagnosed by kidney biopsy between 1988 and 2005. The patients had GFR≥80 ml/min per 1.73 m² at the time of diagnosis, and they had a paraffin-embedded kidney biopsy with eight glomeruli available.

Results: In total, 170 (89%) and 20 (11%) patients were >18 and <18 years old, respectively; median (interquartile range) follow-up was 15 (12-22) years. Mesangial C4d deposit prevalence was 20% (38 of 190). At diagnosis, C4d-positive versus -negative patients had higher protein-to-creatinine ratio (median [interquartile range]: 1.94 g/g [0.9-3.1] versus 1.45 g/g [0.9-2.2]; P=0.04). During follow-up, C4d-positive patients showed a higher number of nephritic flares (median [range]: 1.4 [0-5] versus 0.9 [0-2]; P=0.04), had a higher protein-to-creatinine ratio (median [interquartile range]: 1.32 g/g [0.7-1.7] versus 0.89 g/g [0.1-1.3]; P<0.01), were more prone to receive repeated treatment with corticosteroids (45% versus 24%; P<0.01), and showed a larger reduction in eGFR (-1.6 versus -0.8 ml/min per 1.73 m² per year; P=0.04). Furthermore, the presence of mesangial C4d deposits was an independent predictor of long-term kidney survival.

Conclusions: C4d deposits may be one of the earliest poor prognostic variables available for patients with idiopathic IgA nephropathy and normal kidney function at the time of diagnosis. However, Cd4 deposits alone are not associated with the response to angiotensin blockers or corticosteroid treatment.

Keywords: Adrenal Cortex Hormones; Biopsy; C4d deposits; Follow-Up Studies; Glomerular Mesangium; Glomerulonephritis, IGA; Humans; IgA nephropathy; Kidney Glomerulus; Paraffin; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; complement activation; creatinine; glomerular filtration rate; kidney; lectin-pathway; prognosis.

Graphical abstract