Established and newly proposed mechanisms of chronic cyclosporine nephropathy.
Cyclosporine (CsA) has improved patient and graft survival rates following solid-organ transplantation and has shown significant clinical benefits in the management of autoimmune diseases. However, the clinical use of CsA is often limited by acute or chronic nephropathy, which remains a major problem. Acute nephropathy depends on the dosage of CsA and appears to be caused by a reduction in renal blood flow related to afferent arteriolar vasoconstriction. However, the mechanisms underlying chronic CsA nephropathy are not completely understood. Activation of the intrarenal renin-angiotensin system (RAS), increased release of endothelin-1, dysregulation of nitric oxide (NO) and NO synthase, up-regulation of transforming growth factor-beta1 (TGF-beta1), inappropriate apoptosis, stimulation of inflammatory mediators, enhanced innate immunity, endoplasmic reticulum stress, and autophagy have all been implicated in the pathogenesis of chronic CsA nephropathy. Reducing the CsA dosage or using other renoprotective drugs (angiotensin II receptor antagonist, mycophenolate mofetil, and statins, etc.) may ameliorate chronic CsA-induced renal injury. This review discusses old and new concepts in CsA nephropathy and preventive strategies for this clinical dilemma.
Yoon
Hye Eun
HE
Division of Nephrology, Transplantation research center, Seoul St. Mary's Hospital, The Catholic University of Korea, Seocho-gu, Seoul, Korea.
Yang
Chul Woo
CW
D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine