Clinicopathological Correlation with Mesangial C4d Deposition in Primary Immunoglobulin A Nephropathy - A Descriptive study

Abstract

In immunoglobulin A (IgA) nephropathy, activation of lectin pathway leads to severe renal damage and more pronounced histological damage. As C4d is a marker of lectin pathway activation, the presence of mesangial C4d positivity will help in identifying those patients at risk. The study was conducted to study the prevalence of mesangial C4d positivity in patients with primary IgA nephropathy and to compare the clinical and histopathological features with C4d-positive and C4d-negative cases. It is a retrospective study conducted for four years. The inclusion criterion was IgA nephropathy with a minimum of four viable glomeruli. Biopsies with >25% of nonsclerotic glomeruli with mesangial positivity will be considered as positive for C4d. Seventy-six patients of IgA nephropathy were included of which mesangial C4d positivity was noted in 33 patients (43%). The mean age was 35 years. The male:female ratio was 2.3:1. The most common presentation was edema (56%) followed by microscopic hematuria (28%). Fifty-four patients were hypertensive. Among the clinical and laboratory parameters, absence of hematuria (P = 0.04) and presence of proteinuria (P = 0.02) showed a significant association with C4d positivity. The histological parameters in Oxford classification which had significant association with C4d positivity were segmental sclerosis (P = 0.01) and tubular atrophy (P = 0.001). Among 45 patients on follow-up with a maximum duration of 51 months, 10 developed end-stage renal disease of which four had C4d expression (0.05%) in the biopsy. Nearly half of IgA nephropathy patients have mesangial C4d positivity. Elevated creatinine with chronicity changes is more common in C4d-positive patients. Hence, C4d can be used as a marker for poor prognosis.