Experimental evaluation of novel technologies for acute renal failure preventing and treatment

Kirpatovskiy V.I., Kazachenko A.V., Plotnikov E.Yu., Zorov D.B., Marey M.V., Golovanov S.A., Kudryavcev Yu.V., Nadtochiy O.N., Syromyatnikova E.V.

In rat model perspective of two novel trends of preventing and treatment of acute post-ischemic renal failure (ARF) was investigated, in particular application of two drugs referred to novel class of antioxidants, which are selectively accumulated in mitochondria of renal tubular epithelium, which conditionally denoted as SkQ1 and SkQR, as well as administration of cultured human bone marrow-derived mesenchymal stem cells (BM-MSC) and cultured fetal renal cells (CRC). Pretreatment by SkQ1 and SkQR decreased ARF-related animal death from 82% to 10% and 0% respectively as well as more rapid creatinine recovery and normalization of sodium reabsorption in renal tubuli towards day 7. Eff ectivness of SkQR was slightly more than SkQ1 due to higher protective eff ect in regard to integrity of renal tubular apparatus, expressed in preventing of sodium reabsorption disturbance and decrease of polyuria. Intrarenal and intravenous administration of BM-MSC in case of renal blood fl ow recovering aft er 90 min ischemia decreased rat mortality from 100% to 20% and 17% respectively, with functional normalization in 3-4 weeks. In case of intrarenal administration of CRC rat mortality was 83%, in case of intravenous administration it decreased to 50% and renal function normalization of survived rats was observed within 2 weeks. Tracing the history of injected BM-MSC labeled by fl uorescent dye Calcein AM found out occurrence of viable cells in 7 days aft er injection into the kidney.

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