The Effects of EMMPRIN/CD147 on Late Function and Histopathological Lesions of the Renal Graft

SIMPLE SUMMARY: This study provided innovatory data regarding the role of EMMPRIN in long-term renal graft function and renal biopsy specimens in the form of interstitial fibrosis/tubular atrophy. The main cause of renal fibrosis is identified to be the activation and accumulation of fibroblasts and myofibroblasts in the interstitium, surrounded by increased amounts of extracellular matrix, and EMMPRIN has been proposed as a contributor factor. The study has evidenced that EMMPRIN displays adverse effects on renal graft survival in terms of the frequent occurrence of DGF, poorer short-term and long-term renal graft function, more profound fibrotic lesions in biopsy specimens, and the degree of proteinuria. This represents an opportunity for more accurate prediction of the post-transplant period and early, non-invasive detection of kidney graft dysfunction. Future studies need to further investigate the clinical significance of the presented results. ABSTRACT: Chronic kidney disease (CKD) is associated with renal fibrosis, and develops with the participation of fibroblasts and myofibroblasts from epithelial-to-mesenchymal transition (EMT). In cancer research, the key role of the glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in EMT has been proven. In this study, we evaluate how serum CD147/EMMPRIN affects long-term renal graft function and renal biopsy specimen lesions. In total, 49 renal graft recipients who had a renal biopsy within the last 18 months were retrospectively reviewed. At their most recent appointments, their serum concentrations of CD147/EMMPRIN and renal function were assessed. The occurrence of delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 1-year post-kidney transplantation (Tx) and the subsequent years of the follow-up period, and renal biopsy specimen lesions, mainly those related to renal fibrosis and tubular atrophy, were also evaluated. Results: CD147/EMMPRIN serum concentration correlated negatively with eGFR at the most recent appointment (ME 69 months) and with eGFR at 1 and 2 years after Tx (p < 0.05, R = −0.69, R = −0.39, and R = −0.40, respectively). CD147/EMMPRIN serum levels correlated positively with urine protein concentrations (p < 0.05, R = 0.73). A positive correlation was further found with the severity of renal biopsy specimen lesions such as interstitial fibrosis (CI), tubular atrophy (CT), double contours of the GBM (CG), mesangial matrix expansion (MM), and arteriolar hyalinosis (AH) (p < 0.05, R = 0.39, R = 0.29, R = 0.41, R = 0.32 and R = 0.40, respectively). Patients with a history of DGF had higher CD147/EMMPRIN serum concentrations (<0.05). Conclusions: CD147/EMMPRIN is linked to poorer long-term renal graft function. Additionally, a high serum concentration of CD147/EMMPRIN affects interstitial fibrosis tubular atrophy (IF/TA) lesions and proteinuria.