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Cyclosporine-induced changes in glomerular filtration rate and urea excretion
D A Laskow1, J J Curtis, R G Luke
1Department of Surgery, University of Alabama Medical Center, Birmingham 35294.
Purpose:
Cyclosporine is the mainstay of many immunosuppressant protocols, but confers a significant risk of nephrotoxicity. We sought to clarify the effects of cyclosporine on 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.
Insights
Cyclosporine impairs renal function in transplant patients during volume depletion, causing reversible nephrotoxicity. This effect is linked to compromised kidney compensatory mechanisms, not proximal tubular damage.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pharmacology
Background:
- Cyclosporine is a critical immunosuppressant but carries a risk of nephrotoxicity.
- Understanding cyclosporine's renal effects is vital for managing transplant recipients.
Purpose of the Study:
- To investigate the impact of cyclosporine on renal function during induced intravascular volume depletion in renal transplant recipients.
- To assess the reversibility of cyclosporine-induced renal changes.
Main Methods:
- Two groups of renal transplant patients (cyclosporine vs. no cyclosporine) underwent a 10-day protocol.
- Mild intravascular volume depletion was induced via sodium restriction and furosemide.
- Renal function (GFR, clearances, sodium excretion) was measured before and after volume depletion and a sodium load.
Main Results:
- Cyclosporine-treated patients showed significant decreases in GFR and clearances, with increased BUN post-depletion.
- These renal function impairments in cyclosporine users resolved after intravenous sodium chloride infusion.
- Azathioprine-treated patients exhibited stable renal function throughout the protocol.
Conclusions:
- Cyclosporine predisposes renal transplant recipients to acute, reversible nephrotoxicity.
- This nephrotoxicity arises from impaired renal compensatory mechanisms during volume depletion.
- Proximal tubular function, indicated by urea and sodium reabsorption, remains unaffected.