Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients

• Main Authors: Virna Nowotny Carpio, Carolina Rech, Evlyn Isabel Eickhoff, Karla Laís Pegas, Maria Isabel Albano Edelweiss, Luiz Felipe Santos Gonçalves, Roberto Ceratti Manfro, Francisco Veríssimo Veronese
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Nefrologia 2011-09-01
• Series: Brazilian Journal of Nephrology
• Subjects: Transplante de rim; Complemento Cd4; Sobrevivência de enxerto; Rejeição de enxerto; Rejeição humoral
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0101-28002011000300009&lng=en&tlng=en

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d-, patients with ABMR C4d+ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.