What is the recommended management for oncotoxic acute kidney injury in an adult undergoing cancer therapy who presents with rising serum creatinine or oliguria?

Management of Oncotoxic Acute Kidney Injury

Immediately discontinue or reduce the dose of the offending nephrotoxic agent and provide supportive care focused on fluid management, as the best management strategies for oncotoxic AKI remain largely unknown but drug cessation or dose reduction is the primary intervention. 1, 2

Initial Assessment and Diagnosis

When a cancer patient presents with rising creatinine or oliguria, rapidly identify the specific anticancer agent and pattern of kidney injury:

• Assess kidney function, acid-base balance, and electrolytes immediately upon presentation, using the CKD-EPI equation for GFR estimation as it is the most accurate and least biased estimator 2
• Add spot urine protein-to-creatinine ratio to standard assessments for patients developing AKI 2
• Differentiate genuine renal toxicity from non-injurious creatinine elevation: ALK inhibitors (crizotinib) and CDK4/CDK6 inhibitors (abemaciclib) cause benign increases in serum creatinine through inhibition of tubular creatinine secretion, not true kidney injury 1, 2

Agent-Specific Management Patterns

Cytotoxic Chemotherapy (Cisplatin, Ifosfamide, Gemcitabine, Methotrexate, Pemetrexed)

• Acute tubular injury (ATI) is the most common lesion pattern with these agents 1, 2, 3
• Provide supportive care with aggressive fluid management for ATI 2
• Reduce dose or discontinue the agent based on severity of AKI 2
• Cisplatin causes the highest nephrotoxic burden among cytotoxic agents and commonly requires dose adjustment 4

Targeted Cancer Agents

Anti-angiogenesis drugs (bevacizumab, ramucirumab):

• Monitor for new or worsened hypertension, proteinuria (sometimes nephrotic range), and thrombotic microangiopathy (TMA) 1, 2
• These agents cause the largest number of renal complications among immunotherapeutics 4

B-Raf and ALK inhibitors:

• Watch for AKI from ATI and acute interstitial nephritis (AIN), though less common than with other agents 1, 2

Proteasome inhibitors:

• Monitor specifically for TMA 1

Cancer Immunotherapies

Immune checkpoint inhibitors:

• AKI occurs primarily from acute interstitial nephritis (AIN), though ATI also occurs 1, 2
• Discontinue the offending agent immediately 2
• Consider corticosteroid therapy for AIN after drug discontinuation 2
• Minimal change disease and immune complex glomerular disease can also occur 1

Interferon:

• Monitor for various glomerulonephritis patterns (focal glomerulosclerosis, membranous nephropathy, lupus-like nephritis, minimal change disease) and TMA 1, 2

High-dose interleukin-2:

• Expect cytokine storm syndrome and capillary leak syndrome causing prerenal AKI and ATI 1, 2

Supportive Management Strategies

• Optimize volume status through careful fluid management, as volume depletion is a major risk factor for worsening nephrotoxicity 5
• Discontinue or temporarily hold other nephrotoxic medications: NSAIDs, antibiotics, proton pump inhibitors, bone-targeted therapies, and the "triple whammy" combination of NSAIDs, diuretics, and renin-angiotensin system inhibitors 6, 5
• Consider temporary discontinuation of ACE inhibitors and ARBs during active cancer treatment to reduce AKI risk 2
• Avoid urinary tract obstruction and treat promptly if present 5

Contrast Media Considerations During AKI

• Do not withhold contrast-enhanced CT scans if benefits outweigh risks, even in patients with CKD, as exaggerated fear of contrast nephropathy can lead to withholding beneficial diagnostic studies 1, 2
• For CKD G4-G5, reduce contrast dose and use iso-osmolar contrast media rather than withholding imaging 1, 2
• Periprocedural IV saline and/or oral hydration may be considered depending on GFR level, though evidence is mixed and recent trials (AMACING, PRESERVE) did not support efficacy of sodium bicarbonate and acetylcysteine 1, 2

Critical Pitfalls to Avoid

• Do not continue full-dose chemotherapy in the setting of AKI: Failure to adjust doses of anticancer drugs in patients with kidney injury is deleterious and impacts both renal recovery and oncological outcomes 1, 7
• Do not assume all creatinine elevations represent true kidney injury: Some agents cause benign creatinine increases through tubular secretion inhibition 1, 2
• Do not delay nephrology consultation: Close monitoring of renal function and early involvement of a nephrologist are strongly recommended given the high risk of complications 3
• Recognize that AKI during chemotherapy negatively impacts survival: Patients developing AKI have worse oncological outcomes and reduced ability to receive planned subsequent treatment courses 7

Monitoring During Ongoing Treatment

• Monitor serum creatinine, BUN, and electrolytes regularly throughout cancer therapy 6
• Watch for decreased urine output, rising creatinine, and electrolyte abnormalities as early signs of AKI 6
• Include nephrotoxicity surveillance in patients treated with immunotherapy and report findings in drug registries 1