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Digoxin-specific Fab fragments impair renal function in the rabbit.

M P Timsina1, D S Hewick

  • 1Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, UK.

The Journal of Pharmacy and Pharmacology
|October 1, 1992
PubMed
Summary

Digoxin-specific antibody fragments (Fab) temporarily reduced kidney function in rabbits, decreasing creatinine clearance and urine output. However, kidney function recovered within 5 days, indicating no lasting impairment to tubular function.

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Area of Science:

  • Pharmacology
  • Nephrology
  • Toxicology

Background:

  • Digoxin toxicity is a serious clinical concern.
  • Digoxin-specific antibody fragments (Fab) are the primary antidote for severe digoxin poisoning.
  • The renal effects of digoxin-specific Fab fragments require further investigation.

Purpose of the Study:

  • To investigate the impact of digoxin-specific Fab fragments on renal function in a rabbit model.
  • To assess changes in creatinine clearance, urine output, and electrolyte excretion following Fab administration.

Main Methods:

  • A 2 mg/kg intravenous bolus dose of digoxin-specific Fab fragments was administered to rabbits.
  • Creatinine clearance, urine output, plasma creatinine, urinary creatinine, and fractional excretion of sodium (Na+) were measured.

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  • Measurements were taken at baseline, 24 hours, and 5 days post-administration.

    • Main Results:

    • A 28% reduction in creatinine clearance was observed at 24 hours post-administration.
    • Urine output decreased, while plasma and urinary creatinine concentrations remained unchanged and increased, respectively.
    • Fractional excretion of Na+ was significantly reduced, suggesting increased tubular reabsorption.
    • Renal function, indicated by creatinine clearance, returned to normal levels by day 5.

    Conclusions:

    • Intravenous administration of digoxin-specific Fab fragments causes a transient decrease in glomerular filtration rate in rabbits.
    • The observed increase in tubular Na+ reabsorption suggests that tubular function remains intact despite reduced GFR.
    • These findings indicate that digoxin-specific Fab fragments do not cause direct nephrotoxicity and renal function recovers fully.