Abstract
Prostacyclin and thromboxane A2 are important regulators of kidney blood flow. To examine whether changes in their metabolism could be involved in the nephrotoxicity of cyclosporin, we determined urinary excretion of 6-keto PGF1a and dinor-6-keto PGF1a (prostacyclin metabolites) and dinor-TxB2 (thromboxane metabolite) in five newly diagnosed type 1 diabetic patients during and after stopping cyclosporin therapy. In the resting state, cyclosporin had no effect on prostanoid excretion. In response to exercise, urinary excretion of 6-keto PGF1a was reduced by 50% (P<0.02), dinor-6-keto PGF1a by 15% (P<0.05) and dinor-TxB2 by 45% (P<0.02), while albumin excretion increased 4.5-fold (P<0.05) during cyclosporin therapy. Simultaneously, there was a rise in serum creatinine concentration, and renal biopsy specimens obtained from three patients showed periglomerular and interstitial fibrosis and tubular atrophy. After the discontinuation of cyclosporin therapy, serum creatinine concentrations returned to normal, histological changes improved and there was an associated rise in urinary prostanoid excretion. These data suggest that a reduction in renal prostanoid synthesis by cyclosporin may diminish renal blood flow and function, and lead to histological changes in the kidney.
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Koivisto, V.A., Leirisalo-Repo, M., Pelkonen, R. et al. Cyclosporin reduces renal prostanoid excretion in type 1 diabetic patients. Acta Diabetol 29, 1–5 (1992). https://doi.org/10.1007/BF00572820
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DOI: https://doi.org/10.1007/BF00572820