Cyclosporine-induced changes in glomerular filtration rate and urea excretion

Academic Article


  • purpose: Cyclosporine is the mainstay of many immunosuppressant protocols, but confers a significant risk of nephrotoxicity. We sought to clarify the effects of cyclosporine in renal function in renal transplant recipients after induction of mild intravascular volume depletion. patients and methods: Two groups of renal transplant patients with normal allograft function at least 6 months after transplantation whose immunosuppressive regimens differed only by the presence or absence of cyclosporine usage were enrolled in a 10-day in-hospital protocol. After a 3-day control period, intravascular volume depletion was produced by dietary restriction of sodium chloride for 4 days and the administration of furosemide. Creatinine and urea clearances, true glomerular filtration rate (GFR) (by radioisotope technique), and the fractional excretion of sodium were measured. The patients were subsequently given a high amount of sodium chloride by intravenous infusion (3.8 mEq/kg body weight/day) for 3 days and the studies were repeated. results: Ten patients treated with azathioprine and prednisone (azathioprine-treated) and nine patients treated with cyclosporine, azathioprine, and prednisone (cyclosporine-treated) were enrolled. The two groups developed a similar degree of intravascular volume depletion; blood pressure did not change and urine flow rates did not differ between the groups throughout the protocol. The cyclosporine-treated patients showed significant decreases in GFR, creatinine clearance, and urea clearance, and increases in blood urea nitrogen (BUN) and percent urea reabsorption after intravascular volume depletion; these findings resolved after challenge with the sodium chloride load. In contrast, the azathioprine-treated patients' BUN, urea clearance, GFR, and creatinine clearance did not significantly change throughout the protocol. The decrease in the fractional excretion of sodium after intravascular volume depletion was significantly greater in the cyclosporine-treated patients. conclusion: Cyclosporine predisposes to acute reversible nephrotoxicity by compromising the renal compensatory mechanisms. Proximal tubular function, as manifested by urea and sodium reabsorption, remains intact. © 1990.
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    Digital Object Identifier (doi)

    Author List

  • Laskow DA; Curtis JJ; Luke RG; Julian BA; Jones P; Deierhoi MH; Barber WH; Diethelm AG
  • Start Page

  • 497
  • End Page

  • 502
  • Volume

  • 88
  • Issue

  • 5