Beraprost Sodium (Prostaglandin I2 analogue) Delays Deterioration of allograft Dysfunction in Kidney Transplant Recipient Treated With Calcineurin Inhibitors.

Abstract

Purpose: Calcineurin inhibitors(CNIs) have considerably improved renal allograft survival. However, long-term use of CNIs can cause nephrotoxicity. The purpose of this study was to evaluate the effect of beraprost sodium(prostaglandin I2 analogue) on renal allograft in patients treated with CNIs. Methods: In this prospective, open-label, comparative, single center study, 40 patients who underwent first kidney-only transplants were included. They were divided randomly into two groups: control and treatment group. The patients in treatment group received beraprost sodium(120μg/day) for a year. The changes of estimated glomerular filtration rate(eGFR), blood pressure, and histologic results were compared between two groups. Results Ninteen patients in treatment group and 14 patients in control group completed the study. All, except one patient in control group treated cyclosporine, were treated with tacrolimus and the trough levels were in the range of 4.8-5.8ng/ml. The decline in eGFR was significantly lower in treatment group than that of control(62.9±14.15 to 61.8 ±14.96, vs. 68.8±15.31 to 62.8±15.17ml/min/1.73m2,P=0.048). The changes of blood pressure did not differ between two groups. From histologic results, the mean scores for arteriolar hyaline were decreased in treatment group and progressed in control group, however, the differences could not reach the statistical differences(0.21±0.535 to 0.11±0.315 vs. 0 to 0.14±0.363,P=0.105). The mean scores for interstitial fibrosis and tubular atrophy(IFTA), glomuerulosclerosis were not significantly different between two groups. However, the proportion of patients with IFTA score higher than one was increased in control and maintained in treatement group. The scores for epithelial-mesenchymal transition markers(vimentin, ß-catenin) were decreased in treatment group and progressed in control group, however, the differences could not reach the statistical differences. Conclusions Beraprost sodium has a beneficial effect on renal allograft function in patients exposed to CNIs. However, the change of structural damage is not obvious with the conditions of low levels of CNIs and short-term use of beraprost sodium. Further follow-up is needed to demonstrate the changes of structural damage.