Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

BACKGROUND AND OBJECTIVES: Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. METHODS: 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. RESULTS: hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. CONCLUSION: hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.

Is their a role for oral L-carnitine therapy in anemia and cardiac dysfunction management in Egyptian patients on maintenance hemodialysis?

L-Carnitine is a short organic hydrosoluble molecule and is present in biological materials like free carnitine and acylcarnitines, which constitute the carnitine system. Long-term intermittent hemodialysis is associated with a reduction in plasma and tissue L-carnitine levels. Available studies on carnitine supplementation suggest the use of this molecule in dialysis, especially for those patients with cardiac complications, impaired exercise and functional capacities, and increased episodes of hypotension. Moreover, in some patients, the improved stability of erythrocyte membranes with L-carnitine supplementation may decrease erythropoietin requirements, thus, leading to a reduction of dialytic costs. To study if there a possible advantageous effects for L-Carnitine oral supplementation in anemia and cardiac dysfunction management in a cohort of Egyptian patients on maintenance hemodialysis. Fifty- five patients with chronic renal failure on maintenance hemodialysis were classified into 2 groups: L- Carnitine group: 20 patients [12 male and 8 female, Mean age 47.66 +/- 17.73 years, hemodialysis duration 51.36 +/- 18.14 months, subjected to three sessions /week reaching Kt/V of 1.48 +/- 0.37] they received oral L-Carnitine therapy 1.500 mg/day and Control group: 35 patients [24 male and 11 female, mean age 37.9 +/- 14.7 years, hemodialysis duration 53.83 +/- 15.17 months, subjected to three sessions /week reaching Kt/V of 1.33 +/- 0.28]. Both groups were on Erythropoietin therapy and IV iron whenever indicated. Echogardiographic studies were performed before and at the end of the study. Serum hemoglobin were comparable in the L- carnitine group and control group at the start and six months after therapy [8.63 +/- 1.77 and 9.39 +/- 2.02 gm/dl, P= 0.18, 10.49 +/- 1.60 and 10.29 +/- 2.48 gm/dl P= 0.76 respectively]. The weekly maintenance dose of Erythropoietin inspite of being lower in L-Carnitine group [Mean = 4750.12 +/- 2137.04 units] compared to control group [Mean= 5515.15 +/- 2292.94 units] it does not reach a statistical significance [P=0.24]. No significant improvement could be observed in echogardiographic findings in the L- Carnitine group after therapy. The role of L-Carnitine in hemodialysis patients is questionable. Our study revealed no observed significant improvement in echocardiographic findings 6 months after therapy. However, -a statistically non significant- reduction in Erythropoietin dose was achieved in the L- carnitine-treated compared to the control group while maintaining comparable target hemoglobin in both groups. Long-term studies including larger number of patients are required to clarify its role in hemodialysis patients