Renal transplantation chronic cyclosporine nephrotox

Coffman TM, Carr DR, Yarger WE, Klotman PE. Evidence that renal prostaglandin and thromboxane production is stimulated in chronic cyclosporine nephrotoxicity.Transplantation 1987 43 282-285. 

Filler G,Gellermann J,Zimmering M, Mai I. Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity.TranspI Int 2000 13 201-206. 

Hyperkalemic distal (type IV) RTA resulting from generalized distal tubule defects is less common than hyporeninemic hypoaldosteronism, but is more common than classic distal (type I) RTA. Patients with this defect have impaired tubular potassium secretion in addition to impaired urinary acidification (urine pH >5.5 despite acidemia or acid loading). Urinary obstruction is the most frequent cause of this disorder, which may also be associated with sickle-cell nephropathy, systemic lupus erythematosus, HIV nephropathy, analgesic abuse nephropathy, amyloidosis, renal transplant rejection, and chronic cyclosporine nephrotoxicity. 

The immunosuppressive drug cyclosporine A (CSA) has revolutionized transplant medicine. However, CSA induced-nephrotoxicity still represents a major therapeutic challenge. Chronic CSA nephropathy is characterized by a decrease in glomerular filtration rate (GFR), tubular atrophy, interstitial fibrosis and progressive renal dysfunction. It is difficult to delineate the mechanisms of CSA toxicity from clinical data since the majority of clinical experiences with CSA have been in renal transplant recipients. Animal models of CSA nephropathy have brought some insights, how-... 

The ABCBl genotype of the donor, but not of the recipient, may be a major risk factor for cyclosporine-related chronic nephrotoxicity in recipients of renal transplants. The ABCBl 3435TT genotype, which is associated with lower Pgp... 

Sirolimus is used for tissue transplantation where its major advantage over calci-neurin inhibitors is that it is not nephrotoxic. Chronic renal failure in transplant patients who have taken calcineurin inhibitors for the long term can be prevented by the administration of sirolimus. Steroid-free immunosuppression can be achieved by administering sirolimus alone or in combination with mycophenolate mofetil and cyclosporine or tacrolimus. Since impaired wound healing is one of its potential side effects, some transplant centers use sirolimus only after several weeks of surgery. 

Cyclosporine and tacrolimus have dramatically enhanced the success of solid organ transplantation. Nephrotoxicity, however, remains a major dose-limiting adverse effect of both drugs. " Early acute hemodynamically-mediated renal insufficiency and delayed chronic interstitial nephritis have been observed (see section on chronic interstitial nephritis later in this chapter). ... 

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