Management of Chemotherapy Nephropathy in Cancer Treatment

Introduction to Chemotherapy-Induced Kidney Injury

• Cytotoxic chemotherapeutic drugs, particularly platinum-containing compounds like cisplatin, are the most common cause of kidney injury, with the primary goal of preserving renal function while maintaining effective cancer treatment, as recommended by the Kidney International guidelines 1, 2
• Acute tubular injury (ATI) is the most common kidney lesion pattern in chemotherapy nephropathy, according to the Kidney International guidelines 1, 3

Preventive Strategies for Nephrotoxicity

• For contrast-enhanced imaging during cancer treatment, the Kidney International guidelines recommend not withholding contrast media CT scans if benefits outweigh risks, even in patients with chronic kidney disease (CKD), and considering reducing contrast dose and using iso-osmolar contrast media for patients with CKD G4-G5 4, 5
• Periprocedural IV saline and/or oral hydration may be considered depending on GFR level, although evidence for this practice is mixed, as noted by the Kidney International guidelines 1, 5

Monitoring and Early Detection of Kidney Injury

• The Kidney International guidelines recommend assessing kidney function, acid-base balance, and electrolytes at diagnosis of cancer and regularly during treatment, with a focus on estimating GFR using the CKD-EPI equation, which is the most accurate and least biased estimator 6, 7
• For patients developing acute kidney injury (AKI), adding spot urine protein-to-creatinine ratio to standard assessments is recommended by the Kidney International guidelines 6

Management of Specific Nephrotoxicities

• The Kidney International guidelines recommend providing supportive care with focus on fluid management for acute tubular injury (ATI), and removing or reducing the dose of the nephrotoxic agent 8
• For acute interstitial nephritis (AIN), discontinuing the offending agent and considering corticosteroid therapy are recommended by the Kidney International guidelines 8

Special Considerations for Different Agent Classes

• The Kidney International guidelines recommend monitoring for new or worsened hypertension, proteinuria, and thrombotic microangiopathy (TMA) with anti-angiogenesis drugs, and watching for AKI (ATI and AIN) with B-Raf and ALK inhibitors 1, 2, 3
• For cancer immunotherapies, monitoring for AKI (primarily due to AIN) and proteinuria with immune checkpoint inhibitors, and watching for various types of glomerulonephritis and TMA with interferon, are recommended by the Kidney International guidelines 2, 3

Anemia Management in Chemotherapy Nephropathy

• The Kidney International guidelines recommend targeting hemoglobin levels of 9.0-11.5 g/dl for CKD patients with malignancy, and using nephrologic doses of erythropoietin-stimulating agents (ESAs) for cancer patients with CKD 2, 3

Pitfalls and Caveats

• The Kidney International guidelines recommend not withholding beneficial diagnostic studies due to exaggerated fear of radiocontrast nephropathy, and recognizing that some agents cause non-injurious increases in serum creatinine that should not be confused with genuine renal toxicity 1, 2, 5
• Considering temporary discontinuation of ACE inhibitors and ARBs during cancer treatment to reduce AKI risk is recommended by the Kidney International guidelines 5, 9

Guideline Recommendations for Management of Oncologic Drug‑Induced Acute Kidney Injury

Immediate Management

• Discontinue the offending nephrotoxic anticancer agent or reduce its dose as the primary intervention for oncotoxic AKI, with supportive fluid management. 10

Differentiating True AKI from Benign Creatinine Rise

• Recognize that ALK inhibitors (e.g., crizotinib) and CDK4/6 inhibitors (e.g., abemaciclib) can cause a benign increase in serum creatinine by inhibiting tubular creatinine secretion, which does not reflect genuine renal injury. 10, 11

Agent‑Specific Monitoring

Cytotoxic Chemotherapy (cisplatin, ifosfamide, gemcitabine, methotrexate, pemetrexed)

• Acute tubular injury (ATI) is the predominant renal lesion pattern associated with these agents. 10

Anti‑angiogenesis Agents (bevacizumab, ramucirumab)

• Monitor patients for new or worsening hypertension, proteinuria (including nephrotic‑range proteinuria), and thrombotic microangiopathy (TMA).
• These agents account for the greatest number of renal complications among immunotherapeutic drugs. 10

B‑Raf and ALK Inhibitors

• Although less common, these agents can provoke AKI via ATI and acute interstitial nephritis (AIN). 10

Proteasome Inhibitors

• Specific surveillance for TMA is recommended. 10

Immune Checkpoint Inhibitors

• AKI most often results from AIN, with ATI also observed.
• Additional renal pathologies such as minimal change disease and immune‑complex glomerular disease may occur. 10, 12

Interferon Therapy

• Watch for a spectrum of glomerulonephritis patterns (focal glomerulosclerosis, membranous nephropathy, lupus‑like nephritis, minimal change disease) and for TMA. 10

High‑Dose Interleukin‑2

• Anticipate cytokine‑storm and capillary‑leak syndromes that can cause prerenal AKI and ATI. 10

Contrast Media Use in Patients with AKI or CKD

• Do not withhold contrast‑enhanced CT imaging when the diagnostic benefit outweighs the risk, even in CKD patients. 11
• In CKD stages G4‑G5, reduce contrast volume and preferentially use iso‑osmolar contrast agents rather than omitting the study. 11
• Periprocedural IV saline or oral hydration may be considered, but recent trials (AMACING, PRESERVE) did not demonstrate benefit of sodium bicarbonate or acetylcysteine for preventing contrast‑induced nephropathy. 13, 11

Chemotherapy Dose Adjustment in the Setting of AKI

• Full‑dose chemotherapy should be avoided in patients who develop AKI; dose reduction or temporary discontinuation is essential to promote renal recovery and preserve oncologic outcomes. 14

Surveillance and Reporting

• Implement routine monitoring of serum creatinine, BUN, and electrolytes throughout cancer therapy, and promptly investigate oliguria, rising creatinine, or electrolyte disturbances as early AKI signals.
• Incorporate systematic nephrotoxicity surveillance for patients receiving immunotherapy and report findings to drug registries. 10, 12