Renal Transplant / Nephrotoxicity
Calcitonin is a 32 amino acid peptide hormone that is synthesized and secreted by the C-cells of thyroid gland. High levels of serum calcitonin have earlier been noticed in severe infections and inflammations suggesting serum calcitonin as a useful marker for these conditions. Although a number of calcitonin-based studies have been undertaken in renal failure and hemodialysis the role of calcitonin in renal transplant remains unclear. We therefore determined serum calcitonin in 60 renal transplant patients and the same number of age-matched controls . We also measured alkaline phosphatase, calcium, phosphate, albumin, urea, and creatinine in these subjects. Our results showed that the level of serum calcitonin is markedly elevated in renal transplant patients, this elevation being more significant in female patients. Among the other parameters, only urea and creatinine were significantly higher in transplant patients as compared to controls .
Cyclosporin (CsA) is a commonly used immunosuppressant in renal transplantation. Nephrotoxicity is one of the most significant side-effects associated with CsA therapy and its prolonged usage may lead to irreversible renal damage. Thus novel protective agents to counteract CsA nephrotoxicity without altering its immunosuppressive effect are badly needed to ensure the safe use of CsA. We have studied the effects of antioxidant drugs, N-acetylcysteine (NAC) and quinacrine (QNC) on CsA-induced nephrotoxicity in rats . Our results showed that both NAC and QNC significantly protected rats against CsA-induced increase in blood urea nitrogen (BUN) and serum creatinine. These drugs also significantly reversed the effects of CsA on free radical biomarkers suggesting the role of oxidative stress in CsA-induced nephrotoxicity and beneficial effect of antioxidants .
Figure. Real-time chemiluminescence signals showing the effect of CsA on phagocytic
activity of PMNs in pregnant and non-pregnant rats. The curves represent the average of 4 samples in each group.
In another study we observed synergistic effects of pregnancy and CsA on activation of PMNs resulting in massive and sustained generation of ROS that could be deleterious to both host and fetus . Thus, a combination of pregnancy, CsA therapy and infection or allergic condition should be considered risky and these patients should be closely monitored.
Sobki SH, Henry JG, Mujeebuddin S, Khan HA, Fedial HM, Al Khader A. Serum calcitonin in renal transplant patients. Renal Failure 2001; 23: 107-114.
Al Khader A, Al Sulaiman M, Khan HA, Mohamed T. Prevention of cyclosporin nephrotoxicity by antioxidant therapy. Kidney Forum 2000; 2: 31-36.
Khan HA. Cyclosporin A augments respiratory bursts of whole blood phagocytes in pregnant rats. Immunopharmacol Immunotoxicol 2007 (In Press).