Ifosfamide-induced subclinical tubular nephrotoxicity despite mesna

Area of Science:

• Nephrology
• Oncology
• Pharmacology

Background:

• Ifosfamide is a widely used chemotherapy agent.
• Mesna is administered to mitigate ifosfamide-induced urothelial toxicity.
• Acute tubular damage is a potential adverse effect of ifosfamide.

Purpose of the Study:

• To monitor and assess acute tubular damage in patients receiving ifosfamide and mesna therapy.
• To evaluate urinary markers of renal tubular injury during ifosfamide treatment.
• To investigate the relationship between tumor involvement of the kidneys and the extent of tubular toxicity.

Main Methods:

• Prospective monitoring of 16 patients undergoing a 5-day course of ifosfamide (1.6 g/m2/day) and mesna (1.2 g/m2/day).
• Measurement of urinary alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein concentrations.
• Assessment of serum creatinine levels post-treatment.

Main Results:

• All patients showed increased urinary concentrations of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein.
• Significant inter-patient variability in the extent of tubular toxicity was observed.
• Patients with kidney involvement exhibited the greatest evidence of toxicity.
• Urinary marker changes suggested acute tubular cell necrosis, despite adequate mesna for hemorrhagic cystitis prevention.
• Urinary marker levels normalized post-treatment, with no significant increase in serum creatinine.

Conclusions:

• Ifosfamide therapy can induce acute tubular damage, evidenced by specific urinary markers.
• The degree of nephrotoxicity varies among patients and may be exacerbated by kidney tumor involvement.
• The observed tubular damage occurs independently of mesna's protective effect against hemorrhagic cystitis.
• Renal function, assessed by serum creatinine, remained stable post-treatment, suggesting reversible tubular injury.