Up to now, no studies have been performed in normal humans to investigate the role of renal hemodynamic abnormalities in relation to acute-cyclosporin A (CsA) renal dysfunction and to verify whether the specific renal vasodilator, dopamine, can counteract these abnormalities. Eight normal subjects were examined both (A) after oral CsA (12 mg/kg body wt) and (B) after oral CsA + dopamine infusion (2 mg/kg body wt/min), under water diuresis. Both in protocols A and in B, four basal renal clearances were performed before CsA and every twenty minutes for four hours after CsA administration. In protocol A, after CsA, insulin (GFR) and PAH clearance (RPF) fell by up to 27% and to 41%, respectively, so that filtration fraction (FF) increased (P <0.01). A slight (not significant) hypertension occurred while renal resistances were markedly raised (P <0.001). Fractional urine and Na+ excretion as well as C(H2O) decreased, while U(Osm) increased (P <0.01). In protocol B, dopamine was infused from 120 to 180 minutes after CsA (that is, when the maximal adverse effects of CsA on renal hemodynamics had been observed in A). Dopamine infusion could reverse completely the effects of CsA on RPF, GFR, fractional urine output and C(H2O); only U(Osm) remained higher than normal in conjunction with an increased fractional excretion of sodium (P <0.01). No changes were observed in plasma renin activity, aldosterone and in urinary epinephrine and norepinephrine excretion both in protocols A and B. In conclusion, our data indicate that, in normal humans: (i) a single-dose of CsA (12 mg/kg body wt per oz) causes marked renal vasoconstriction, impairment in GFR, increase in FF and proximal tubular overreabsorption with fall of fractional urine and sodium excretion and, consequently, reduction in the renal ability to generate free-water (C(H2O)); (ii) the acute changes of glomerular and tubular function observed after oral CsA are accounted for by primary reversible alterations in renal hemodynamics; (iii) these effects are completely reversed by dopamine infusion at low dosage.
|Number of pages||7|
|Publication status||Published - 1989|
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