The effects of cyclosporin a on eicosanoid excretion in patients with rheumatoid arthritis

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Abstract
Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephro‐toxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24‐week period, during which treatment with nonsteroidal anti‐inflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (±SD) serum creatinine level (1.04 ± 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P < 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P < 0.03) in the 2,3‐dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.