Abstract

The depression of renal function caused by cyclosporin does not generally reflect permanent kidney damage but is caused by a reversible vasoconstriction, with no relevant changes in tubular function. Serum creatinine may remain within the normal range during therapy, but any decline in renal function can be detected by a rise in serum creatinine above the baseline value. Measurements of glomerular filtration rate before and during therapy have shown the degree of renal dysfunction in individual patients to correspond to their rise in serum creatinine. The cause of renal vasoconstriction is uncertain but animal experiments have highlighted several possibilities. These include: (1) albumin leakage with circulatory volume contraction; (2) enhanced Ca mobilization in contractile cells; (3) activation of a renin-like enzyme in vessel walls; and (4) renin accumulation in the renin-producing cells of the afferent arteriole. Such mechanisms, although seeming to operate at different doses, may act in unison at high doses, when renal function is most severely depressed.

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