Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rare but well-documented serious adverse reaction to the administration of the calcineurin inhibitors tacrolimus and cyclosporine in renal transplant recipients is the development of medication-induced thrombotic microangiopathy. The recently introduced immunosuppressive medication sirolimus has a very similar molecular structure to tacrolimus and also binds to the same intracellular proteins. Despite these similarities with tacrolimus, sirolimus has a different side-effect profile and reportedly lacks documented specific renal toxicity. This is a case report of the isolated administration of sirolimus without a concomitant calcineurin inhibitor being associated with the development of renal transplant biopsy-proven thrombotic microangiopathy. The patient is a 47-year-old African-American woman whose primary cause of renal failure was not thrombotic micrangiopathy, and she received a 5-antigen mismatched cadaveric renal transplant. Because of preexisting nephrosclerosis in the renal transplant, this patient was never administered a calcineurin inhibitor but was always maintained on sirolimus. With recent animal data showing that sirolmus can be nephrotoxic in a renal ischemic-reperfusion model (similar to what happens with a renal transplant), the authors speculate on a mechanism for this adverse reaction.
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PMID:Sirolimus-induced thrombotic microangiopathy in a renal transplant recipient. 1283 Apr 73

New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF) development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as alpha-1-microglobulin, N-acetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, beta-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.
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PMID:Proximal tubular dysfunction as an indicator of chronic graft dysfunction. 1928 1