A multi-center randomized controlled trial to evaluate efficacy and safety of early conversion to a low-dose calcineurin inhibitor combined with sirolimus in renal transplant patients

Although the triple immunosuppressive regimen based on calcineurin inhibitors(CNIs)has greatly improved the short-term prognosis of renal transplantation,the longterm prognosis of renal transplantation has not significantly improved.CNIs associated nephrotoxicity is a major risk factor affecting the graft survival.[1]It is feasible to improve the long-term prognosis by reducing the dose of CNIs or removing the CNIs.Studies have demonstrated that the combination of sirolimus(SRL)with low-dose CNIs can both reduce CNI-related nephrotoxicity and improve graft function without increasing the risk of acute rejection(AR),which helps to improve long-term graft survival.[2]However,the validation of mammalian target of rapamycin inhibitor as an immunosuppression regimen and the timing of its application in renal transplantation is still needed.The aim of this study was to investigate the effects of early conversion to low-dose CNIs and SRL on the long-term prognosis of renal transplantation.

Predictive value of hypothermic machine perfusion parameters combined perfusate biomarkers in deceased donor kidney transplantation

Background:Delayed graft function(DGF)is the main cause of renal function failure after kidney transplantation.This study aims at investigating the value of hypothermic machine perfusion(HMP)parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor(DD)kidney transplantation.Methods:HMP parameters,perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1,2019 to August 31,2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.Results:In this study,the DGF incidence was 17.7%(20/113);The multivariate logistic regression results showed that terminal resistance(OR:1.879,95%CI 1.145-3.56)and glutathione S-transferase(GST)(OR=1.62,95%CI 1.23-2.46)were risk factors for DGF;The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time(HR=0.823,95%CI 0.735-0.981).The model combining terminal resistance and GST(AUC=0.888,95%CI:0.842-0.933)significantly improved the DGF predictability compared with the use of terminal resistance(AUC=0.756,95%CI 0.693-0.818)or GST alone(AUC=0.729,95%CI 0.591-0.806).Conclusion:According to the factors analyzed in this study,the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.

A randomized controlled trial to evaluate efficacy and safety of early conversion to a low-dose calcineurin inhibitor combined with sirolimus in renal transplant patients

Background:The calcineurin inhibitor(CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation;however,the long-term prognosis of grafts has not been significantly improved.The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts.Sirolimus(SRL)has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts.Presently,the regimen and timing of SRL application after renal transplantation vary,and clinical data are scarce.Multicenter prospective randomized controlled studies are particularly rare.This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods:Patients who receive four weeks of a standard regimen with CNI+mycophenolic acid(MPA)+glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study.At week 5,after the operation,patients in the experimental group will receive an additional administration of SRL,a reduction in the CNI drug doses,withdrawal of MPA medication,and maintenance of glucocorticoids.In addition,patients in the control group will receive the maintained standard of care.The patients’vital signs,routine blood tests,routine urine tests,blood biochemistry,serum creatinine,BK virus(BKV)/cytomegalovirus(CMV),and trough concentrations of CNI drugs and SRL at the baseline and weeks 12,24,36,48,72,and 104 after conversion will be recorded.Patient survival,graft survival,and estimated glomerular filtration rate will be calculated,and concomitant medications and adverse events will also be recorded.Conclusion:The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.