Histopathology and biomarkers in prediction of renal function in children after kidney transplantation

Background: Early detection of chronic allograft injury is a major challenge after kidney transplantation (RTx) in adults and children. We correlated the expression of four immunohistochemical biomarkers, P-selectin glycoprotein ligand-1 (PSGL-1), vimentin, a-smooth muscle actin (alpha-SMA) and collagen IV, to the kidney graft histology and function in pediatric RTx patients. Methods: We analyzed the histopathology and immunohistochemical stainings of 165 biopsies from 56 patients. Histopathology was scored according to Banff '05 classification and biomarker expression semiquantitatively. Glomerular filtration rate (GFR) was measured annually by Cr-51-EDTA clearance. Results: In protocol biopsies, the expression of all four biomarkers correlated with the interstitial fibrosis and tubular atrophy (IF/TA) changes, which increased during the first 36 months after RTx. At the time of 18 month biopsy, we observed the deterioration of GFR in patients with high (>= 2) IF/TA score (50 vs. 68 ml/min/1.73 m(2), p = 0.004) or collagen IV expression (45 vs. 65 ml/min/1.73 m(2), p = 0.016). Intense stainings of IF/TA, collagen IV and vimentin are also associated with poor GFR at 36 and 48 months, however, the biomarker scores revealed no additional predictive value for concomitant or late GFR compared to IF/TA score. Patients with high and low biomarker expressions showed no significant differences in annual deterioration of GFR, which declined on average 2.2 ml/min/1.73 m(2)/year over the 7 years follow-up. Conclusions: Overall, the results suggest that traditional histopathology is a sufficient predictor for graft function, and the routine use of these histochemical markers as surrogates for graft function deterioration is questioned. (C) 2014 Elsevier B.V. All rights reserved.