Nephrotoxicity of cyclosporin A in humans: effects on glomerular filtration and tubular reabsorption rates

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Abstract
The contention that cyclosporin A (CyA) nephrotoxicity may be due to renal afferent arteriolar constriction was inferred from rat studies showing CyA to increase renal vascular resistance, to reduce glomerular filtration rate (GFR) and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle (Vprox), and to increase proximal fractional reabsorption. In order to test whether the mechanism of human CyA nephrotoxicity is similar to its rat analogue, and whether CyA treatment causes prolonged renal malfunction after drug withdrawal, renal function was investigated with clearance techniques including lithium clearance (CLi) as a measure of Vprox. The subjects were patients (n= 11) with previously normal renal function, given CyA in the treatment of ocular manifestation of extrarenal disease, or bone‐marrow transplant recipients. Nine out of these eleven patients were investigated before and during CyA treatment: GFR (PPPLi was reduced (PP > 0·2). In one of these six patients GFR was reduced to a subnormal value of 26 ml min‐1 (1·73m2 body surface)‐1. In conclusion, human and rat CyA nephrotoxicity have the same pattern of renal functional deterioration. Cyclosporin A nephrotoxicity was evident in patients investigated a mean of 9 months after CyA withdrawal.

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