Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Abstract

Among 73 patients treated with ciclosporin (CS) for autoimmune uveitis, a 50% elevation of serum creatinine was observed in 37% within 3 months of starting CS and in 25% after more than 6 months of relatively uncomplicated therapy. Sequential renal function and histologic evaluations were performed in 17 patients to further characterize the nephrotoxic effects of long-term CS therapy. Inulin clearance remained essentially unchanged in 12 patients despite CS dosage reductions in the majority. In 2 such patients, repeat renal biopsy specimens revealed evidence of progressive irreversible kidney injury even though renal function was stable. Inulin clearance decreased substantially in 3 patients; in 1 case a follow-up renal biopsy showed increased severity of chronic histologic change. For 2 patients, the inulin clearance more than doubled after CS dosage reduction; and in 1 of those cases, repeat renal biopsy showed no evidence of progressive renal scarring. Overall, the morphologic attributes of irreversible kidney injury (designated by a chronicity index including glomerular sclerosis, tubular atrophy and interstitial fibrosis) were increased in 3 of 6 follow-up renal biopsy specimens. Histologic alterations of renal arterioles, including hyaline change, were observed in all CS-treated patients. The hyaline change of arterioles was either extensive in the first renal biopsy specimen or became extensive in the second biopsy in the 3 cases manifesting an increased chronicity index on the follow-up renal biopsy. Thus, parenchymal injury can progress in some cases despite CS dosage reduction and stable renal function; renal arteriolar histologic change is a prominent finding in these patients. Patients that exhibit a substantial improvement in renal function after dosage reduction may experience a more favorable course.

Prospective Randomized Study of Azathioprine versus Cyclosporin in Live-Donor Kidney Transplantation

“…There is some controversy about the long-term nephrotoxocity of Cs. Several investigators have reported severe deteriora tion of kidney function both in renal [5] and non-renal [11][12][13] transplant recipients. However, this finding was not supported by others [14][15][16].…”

Usefulness of the Assessment of Urinary Enzymes and Microproteins in Monitoring Ciclosporin Nephrotoxicity

“…Monitoring these parameters has been shown to be much more reliable and sensible to detect in uveitis patients a clinically yet unrecognizable renal involvement due to CS administra tion. Acute and chronic tubular interstitial lesions have been histologically evidenced in these patients [29,30], Patients affected by uveitis are particularly suitable for this study because of the absence of confounding variables which can interfere in urinary parameters, such as allograft rejection bouts, concomitant treatments, preexisting renal disease [30], In these patients, in fact, the immune target of the underlying affection is other than the renal structures.…”

Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.

“…More recently, CsA has been increasingly used to treat diverse autoimmune disorders refractory to corticosteroids or other immunosuppressive agents (6). Randomized placebo-controlled trials have shown CsA to be effective in autoimmune uveitis (6,192), Behcet's syndrome (193), psoriasis (194), inflammatory dermatoses (6,195), inflammatory bowel disease (196)(197)(198)(199), primary biliary cirrhosis (200), rheumatoid arthritis (6,201,202), aplastic anemia (6), myasthenia gravis (6), chronic inflammatory demyelinating polyneuropathies (6), and nephrotic syndrome (6,137).Concomitant corticosteroid therapy may enhance response (6,199). Improvement may occur promptly (often within 1 to 3 wk of initiation of CsA), but relapse has been frequent upon its discontinuation (6,195,203).…”