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Published on: November 8, 2015

Reversal of oliguric tacrolimus nephrotoxicity in children

Gwenn E McLaughlin1, Carolyn L Abitbol

  • 1Department of Pediatrics, University of Miami School of Medicine/Holtz Children's Hospital, Miami, FL 33130, USA. gmclaugh@med.miami.edu

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|April 21, 2005
PubMed
Abstract

Insights

Theophylline (THEO) combined with a loop diuretic (LD) increased urine flow in children with tacrolimus toxicity. This treatment enhanced diuresis and showed a trend towards improved kidney function in patients resistant to standard diuretic therapy.

Area of Science:

  • Pediatric Nephrology
  • Pharmacology
  • Transplant Medicine

Background:

  • Tacrolimus (TAC) is a calcineurin inhibitor used in transplantation, but it can cause nephrotoxicity, characterized by reduced urine output and elevated creatinine.
  • Vasoregulatory mechanisms, including calcium, adenosine, and endothelin, are implicated in TAC-induced kidney damage.
  • Theophylline (THEO), an adenosine-receptor antagonist, has shown potential in mitigating nephrotoxicity caused by vasoconstrictive agents.

Purpose of the Study:

  • To confirm findings that theophylline (THEO) combined with a loop diuretic (LD) enhances diuresis in pediatric patients with acute tacrolimus toxicity.
  • To rigorously evaluate the efficacy of THEO in improving renal function during furosemide-resistant oliguric tacrolimus nephrotoxicity.

Main Methods:

  • A randomized, controlled trial involving pediatric patients with confirmed tacrolimus nephrotoxicity, oliguria, and resistance to loop diuretics.
  • Patients were randomized to receive either theophylline (THEO) or normal saline (NS) placebo alongside a loop diuretic.
  • Key parameters measured included urine flow rate, creatinine clearance, fractional chloride excretion, and distal solute delivery.

Main Results:

  • The group receiving loop diuretic plus theophylline (LD + THEO) demonstrated a 110% increase in urine flow compared to baseline.
  • The loop diuretic plus normal saline (LD + NS) group showed no significant change in urine flow.
  • While not statistically significant (P = 0.09), creatinine clearance showed a trend toward improvement in the LD + THEO group. Fractional excretion of chloride and distal solute delivery increased post-THEO treatment.

Conclusions:

  • Theophylline (THEO) effectively induced a solute diuresis in pediatric patients experiencing furosemide-resistant oliguric tacrolimus toxicity.
  • The combination of theophylline and a loop diuretic shows promise in managing tacrolimus-induced nephrotoxicity and improving renal function in this patient population.

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