Definition:
- Nephrotoxicity is kidney injury caused by drugs or other cancer treatments, leading to impaired renal function, electrolyte disturbances, or acute/chronic kidney disease.
- Common in oncology due to chemotherapy, targeted therapy, immunotherapy, or supportive medications.
Common Nephrotoxic Agents in Oncology
| Drug/Class | Mechanism of Nephrotoxicity | Pharmacist Pearls |
|---|---|---|
| Cisplatin | Direct tubular epithelial cell damage → acute tubular necrosis | Hydration with saline ± mannitol, monitor Cr, Mg, K; cumulative dose limitation |
| Carboplatin | Less nephrotoxic than cisplatin, can still cause renal impairment | Dose adjustment based on CrCl / Calvert formula |
| Ifosfamide | Acrolein metabolite → tubular damage, Fanconi syndrome | Use MESNA + hydration, monitor electrolytes, Cr |
| Methotrexate (high-dose) | Precipitates in renal tubules → acute kidney injury | Hydration + alkalinization of urine, monitor MTX levels, leucovorin rescue |
| Aminoglycosides (supportive therapy) | Nephrotoxicity during febrile neutropenia | Monitor renal function, trough levels |
| Targeted therapy (VEGF inhibitors, e.g., Bevacizumab) | Proteinuria, hypertension → chronic kidney injury | Monitor urinalysis, BP, adjust dose or hold therapy |
Pathophysiology
- Acute tubular necrosis (ATN) → most common
- Interstitial nephritis → immune-mediated (e.g., checkpoint inhibitors)
- Glomerular injury → proteinuria, thrombotic microangiopathy (e.g., VEGF inhibitors)
Clinical Features
- Acute kidney injury: ↑ serum creatinine, ↓ urine output
- Electrolyte disturbances: hypomagnesemia, hypokalemia, hypophosphatemia
- Chronic kidney disease: long-term exposure to nephrotoxic agents
- Proteinuria / hematuria with glomerular injury
Monitoring & Pharmacist Role
-
Baseline assessment:
- Serum creatinine, BUN, electrolytes, urinalysis
- Calculate CrCl / eGFR for dose adjustments
- During therapy:
- Serial renal function monitoring
- Monitor electrolytes for tubular dysfunction
- Track cumulative doses for nephrotoxic drugs
- Prevention & supportive care:
- Hydration before and after nephrotoxic chemo
- Urine alkalinization for methotrexate
- Use MESNA for ifosfamide/cyclophosphamide
- Avoid concomitant nephrotoxins (NSAIDs, aminoglycosides)
- Dose adjustment:
- Reduce or delay nephrotoxic drugs based on CrCl / eGFR
High-Yield Pharmacist Pearls
- Cisplatin: classic nephrotoxic chemo → always hydrate + monitor Mg, K, Na
- Methotrexate: AKI due to precipitation → hydration + urine alkalinization + leucovorin rescue
- Ifosfamide: chronic tubular dysfunction possible → monitor electrolytes, Cr
- VEGF inhibitors: proteinuria and hypertension → may need dose hold or discontinuation