Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males

Nigel D. C Sturrock, Chim C. Lang, Lesley J. MacFarlane, Mark E. C. Dockrell, Michael Ryan, David J. Webb, Allan D. Struthers

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    23 Citations (Scopus)

    Abstract

    Objective: To elucidate the sequential mechanisms underlying cyclosporin-induced hypertension and nephrotoxicity.
    Design: A study of healthy males over the first 9 days of drug ingestion to permit the detection of serial changes in renal function and blood pressure in a situation free from the confounding variables of concomitant disease or drugs.
    Methods: Double-blind, placebo-controlled, randomized crossover study with cyclosporin (5 mg/kg twice a day) or placebo. Blood pressure and urinary sodium excretion were measured each day, and glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured on days 1, 4, 7 and 9. Cholesterol, lipoprotein (a) and endothelin were measured on days 1 and 9.
    Results: GFR decreased by 9% with cyclosporin and was significantly lower than with placebo on day 4 of therapy. ERPF fell by 24%. The fall in GFR correlated significantly with suppressed plasma renin activity (P< 0.0001). Cyclosporin-induced hypertension occurred in the absence of any change in urinary sodium output or in plasma endothelin. Cyclosporin did not affect lipoprotein (a) levels during 9 days of cyclosporin therapy.
    Conclusions: Cyclosporin-induced hypertension and renal vasoconstriction are well established after 9 days of cyclosporin 5 mg/kg twice a day. We found no evidence to implicate either circulating endothelin or renal sodium retention in the onset of cyclosporin-induced hypertension. Cyclosporin-induced renal vasoconstriction appeared to occur when the protective mechanism of plasma renin activity suppression became exhausted.
    (C) Lippincott-Raven Publishers.
    Original languageEnglish
    Pages (from-to)667-673
    Number of pages7
    JournalJournal of Hypertension
    Volume13
    Issue number6
    Publication statusPublished - Jun 1995

    Keywords

    • Cyclosporin
    • Hypertension
    • Kidney
    • Renin
    • Endothelin
    • Lipoprotein (a)
    • Man

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