Urotoxicity

Urotoxicity is the spectrum of toxic effects of substances on the urinary tract, including the kidneys, bladder, ureters, and urethra. It can arise from medications, chemotherapeutic agents, environmental toxins, radiation, metal exposure, and ischemic injury. A common example is hemorrhagic cystitis caused by acrolein, a metabolite of cyclophosphamide and ifosfamide; prevention with mesna is standard. Other chemicals may cause tubular toxicity or crystal nephropathy, such as uric acid or drug crystals after tumor lysis or inadequate hydration.

Clinical features vary with the site of injury. Bladder involvement often presents with dysuria, frequency, urgency, suprapubic pain, and gross or microscopic hematuria; renal involvement can cause flank pain, oliguria, edema, or acute kidney injury. Radiation to the pelvis can produce late bladder and ureteral dysfunction with hematuria and reduced bladder capacity.

Assessment relies on exposure history, urinalysis (blood, protein, crystals, infection), kidney function tests, and imaging. Ultrasound can detect hydronephrosis or masses; CT urography provides detailed anatomy; cystoscopy may be needed for hematuria or to evaluate the bladder mucosa.

Management focuses on removing or mitigating exposure, ensuring adequate hydration and urine output, and treating complications. Mesna administration with ifosfamide or cyclophosphamide reduces hemorrhagic cystitis risk. For hemorrhagic cystitis, bladder irrigation and intravesical therapies may be required; radiation cystitis may respond to hyperbaric oxygen therapy. Prevention includes dose modification, hydration, uroprotection strategies, and monitoring in high-risk patients.

Prognosis varies; reversible injury is common with early recognition, while chronic or severe cases may lead to lasting urinary tract dysfunction.