MORPHOLOGICAL AND FUNCTIONAL RENAL EFFECTS OF LONG-TERM LOW-DOSE CYCLOSPORINE-A TREATMENT IN PATIENTS WITH RHEUMATOID-ARTHRITIS

To explore the possible nephrotoxic effects of low-dose cyclosporin A (CyA) treatment, we analyzed the data from 10 patients, aged 35-66 years (mean 51.8 years), who had a clinical diagnosis of rheumatoid arthritis and no known kidney disease. The study protocol included consecutive kidney biopsies and a pretreatment biopsy in all cases. A second biopsy was taken after 5-20 months (mean 17.8 months) of treatment and, in seven patients, a third biopsy was performed after 30-46 months (mean 38.6 months). Evaluation of the kidney biopsies included a semiquantitative estimation of different histological parameters as well as assessment of a chronicity index (CI). Transmission electronmicroscopic examination was performed on all biopsies. There was a significant reduction of glomerular function at the time of both the second (n = 10; p < 0.01) and third (n = 7; p < 0.05) biopsies. Five patients showed an increase in CI on the second biopsy and five on the third biopsy in comparison to pretreatment values. Only one patient showed a progressive increase in CI on three consecutive biopsies. The mean CI increased on both the second (n = 10) and third (n = 7) biopsies compared with baseline, but there was no increase on the third biopsy from the second. The morphological findings were, as a rule, slight or moderate, and focal interstitial fibrosis, tubular atrophy and arteriolar hyalinosis were the most consistent findings. Although even low-dose CyA treatment may be nephrotoxic and may induce morphological alterations in the kidney, such changes do not occur in all patients and may not necessarily be progressive. These findings are reflections of differences in individual patient susceptibility to CyA. However, the possibility of a progressive renal fibrosis with low-dose CyA for even longer treatment durations cannot be ruled out, and further studies are necessary for clarification. Even with low-dose CyA treatment, the patient follow-up should include kidney biopsy.