Evaluation of the Efficiency of Allogenic Adipose Tissue Mesenchymal Stem Cells Therapy for Tacrolimus Dose Minimisation in Patients with Acute Kidney Injury after Liver Transplantation


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Abstract

The aim of the study was to evaluate the efficiency and safety of CNI adverse effects minimization in the early postoperative period after liver transplantation by replacement of their immunosuppressive effect with allogenic MSC therapy.MethodsThis is a report of a pilot study designed for the purposes of subsecuent randomized controlled study of the superiority MSC over standard IS in regard of ACR rate and GFR improvement. Inclusion criteria: contraindications for the CNI administration - AKI during the LT, which required the delayed start of tacrolimus. Exclusion criteria and withdrawal from the study were: infectious and other complications, which treatment wasn’t combined with the MSC introduction. MSCs have been obtained from adipose tissue (sub-cutaneous and perirenal depots) of cadaveric donors. MSC introduction was performed on 4 to 14 days after surgery in total dose of 4 million/kg in 4 infusions (2 million cells/kg, 1 million cells/kg, 0.5 million cells/kg and 0.5 million cells/kg) with 3-4 days intervals. The protocol liver biopsies were performed on the 7th (after 1st injection) and 14th day. IS therapy was reduced to a two-circuit (16 mg Medrol + Tac) with Tac concentration (up to 3 ng/ml).ResultsFrequency of ACR at 1st and 2nd protocol biopsy composed 20% and 0%. The severity of ACR was mild (RAI 4). Median GFR at the begining and end of protocol was 25 ± 4 and 53 ± 8 ml/min. Median trough level of tacrolimus was 0,9±0,64 ng/ml with range of 0 to 2,4 ng/ml.There were no severe adverse effects of MSC therapy. After completion of protocol all patients were switched to 3 component IS composed of tacrolimus (5-8 ng/ml), MMF (1g/day) and steroids (medrol 16 mg tapering after 28 POD). Patients with decreased GFR were managed by the minimizing of Tac and substitution of overall IS by prolonged steroids, increased MMF and addition of Everolimus.ConclusionsThe preliminary data shows that MSC therapy can effectively and securely substitute the Tac early after LT in order to allow renal function recover.

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