A total of 28 studies were included in the review. Eighteen studies, comprising a total of 1,615 participants performed a functional evaluation of CsA-induced nephrotoxicity. Ten studies, comprising 378 participants, performed a renal morphological evaluation of CsA.
Functional evaluation of CsA-induced nephrotoxicity: 13 studies measured de novo hypertension and found that 83 out of 741 (11.2%) treated patients developed it.
All 18 papers reported a statistically-significant rise in the serum creatinine level for CsA-treated patients when compared with their baseline level. The increase in serum creatinine level in the cyclosporine group was significantly higher than in the control group in 17 of the 18 studies. In the remaining study, the serum creatinine increase was higher in the control group, in which chloroquine was administered, than in the CsA-treated group. The weighted percentage increase in serum creatinine level of all studies was 17% in the CsA-treated group (N=852) and 1.7% in the control group (N=763).
This impairment of renal function was partially reversible after withdrawal of CsA in 7 studies, and completely reversible in 6 studies.
Risk difference of CsA-induced nephrotoxicity: nephrotoxicity was defined as an increase in serum creatinine of at least 50% above baseline, at least once during the study period. In the CsA-treated group, 102 of the 474 patients (21.5%) exhibited such a rise in serum creatinine, compared with 5 of the 393 patients (1.3%) in the control group. The weighted average risk difference in developing nephrotoxicity between CsA treatment and an alternative therapy was 15.4% (95% confidence interval, CI: 11.8, 18.8). However, heterogeneity was present (Q=77.4, P<0.01) and a correction factor of 0.0242 was determined. The risk difference was then recalculated giving a corrected risk difference of 20.9% (95% CI: 11.6, 30.2).
Morphological evaluation of CsA-induced nephrotoxicity: all of the included papers reported the lesions as being mild to moderate. Only one study found no significant differences between the biopsies of CsA-treated rheumatoid arthritis patients and autopsy material of non-CsA-treated rheumatoid arthritis patients.
Three studies with a pre-treatment and post-treatment biopsy described either an increase or a development of renal morphological lesions. Two of these found a de novo interstititial fibrosis and tubular atrophy in 40 and 65%, respectively, of CsA-treated patients after one year of treatment with a CsA dose of 5 mg/kg at most. The other found an increase in interstitial fibrosis in function of time, in 4 out of 10 patients, when comparing baseline kidney biopsies with biopsies at one and three years of CsA-therapy.