The Clinical Implication of Inhibiting Platelet Activation on Chronic Renal Allograft Dysfunction: A Prospective Cohort Study

Abstract

Introduction Clinically chronic renal allograft dysfunction (CRAD) manifests as a progressive elevation of serum creatinine (Cr) with an associated deterioration in proteinuria and decrease in glomerular filtration rate (GFR) following the first year after transplantation. Currently, how to delay or reverse CRAD and improve the long-term survival of transplanted kidneys is an intensively researched topic in the transplantation field. Objective The objective of this study was to examine the therapeutic efficacy and safety profile of inhibiting platelet activation on living related donor renal transplant recipients with CRAD. Methods We performed a prospective cohort study to examine the effects of inhibiting platelet activation on the expression of platelet activation markers, namely platelet surface glycoprotein IIIa (CD61), lysosomal enzyme glycoprotein (CD63), and fibrinogen receptor monoclonal antibody (PAC-1); we also studied platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor β 1 (TGF-β 1) in the peripheral blood of renal graft recipients with CRAD. In addition, we correlated this metrics with the function of transplanted kidneys, peripheral blood platelet counts and trough concentrations of immunosuppressants. Results Inhibiting platelet activation decreased the expression of platelet activation markers in peripheral blood: CD61 ( P < .001), CD63 ( P = .031), PAC-1 ( P = .002), PDGF-BB ( P = .013), and TGF-β 1 ( P = .030). Cr and urea nitrogen remained stable compared with the control group, which showed progressive increases. The GFR of transplanted kidneys was improved ( P = .033); however, there was no difference before versus after treatment in the platelet count ( P = .991) or the trough concentration of immunosuppressants (cyclosporine, P = .071; tacrolimus, P = .984). Conclusion Inhibition of platelet activation, which was effective and safe, seemed to treat CRAD probably through improving the microcirculation of transplanted kidneys, down-regulating the expression of TGF-β, and thereby delaying fibrosis.