Conversion from Calcineurin Inhibitors to Sirolimus Maintenance Therapy in Renal Allograft Recipients with Risk Factors

Background: The efficacy and safety of conversion treatment with sirolimus in renal transplant recipients using the calcineurin inhibitor (CNI) with one or more risk factors was evaluated. Methods: Ninety-three renal transplant recipients were prospectively enrolled. CNIs(CsA and FK506) as main immunosuppressant were converted to SRL immunosuppressant protocol. Rapid conversion with si-rolimus was performed in all patients. The CNI withdrawal was in 2 weeks. At 4 hours after oral administration of cyclosporin A or tacrolimus, the patients took sirolimus. Initial dose of sirolimus was 6 mg, and repeated maintenance dose is 1.0 - 2.0 mg/d. The first concentration of sirolimus was detected at 5 - 7 days after first oral administration, and the target concentration was 6 - 10 μg/L. Results: The symptoms were markedly improved in patients with CNI induced renal toxicity and CNI induced liver toxicity, and the concentration of sirolimus were maintained at (5.1 ± 1.2) μg/L. Serum creatinine levels decreased from (297.72 ± 150.28) μmol/L to (123.76 ± 44.2) μmol/L, and the liver function were recovery in 24 (92.3%) patients. 9 patients with high glucose returned to normal, and 2 patients were improved. Serum creatinine levels decreased more than 25% of primary level in 17 patients, and the effective rate was 51.5%. 10 patients with tumor were appeared 6 - 43 months after renal transplantation, no recurrence was found in 8 of them and 2 patients were dead. Acute rejections were occurred in 3 patients at 6 months after conversion treatment. The complications were included hyperlipidemia and proteinuria. 3 patients were dead, 6 patients returned to dialysis treatment, and 2 patients were removal of grafts. At 3 years after conversion treatment, the survival rates of patients and grafts were 90.9% and 75.8%, respectively. Conclusion: The conversion treatment with SRL and MMF may be a better option for the renal transplant recipients using the CNI with risk factors appeared.

Long-term kidney transplant outcomes in Chinese patients with primary glomerulonephritis:A multicenter study in China

To the Editor:The primary cause of end-stage kidney disease(ESKD)in China is chronic glomerulonephritis(GN),which accounts for 45%of ESKD patients.[1]There is currently no nationwide large-scale study on the longterm prognosis of kidney transplantation in patients with chronic GN in China.Over the past decade,however,few landmark studies from populations in Europe[2,3]and the United States[4]have provided important reference data for this issue.Therefore,we propose to conduct a nationwide multicenter retrospective study,which was launched by the National Clinical Research Center of Kidney Diseases,Jinling Hospital,Nanjing University School of Medicine,from 2017 to 2020.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients:a randomized,double-blind,placebo-controlled phase 2 trial

Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.