What are the causes and management of acute kidney injury (AKI) in a patient with chronic kidney disease (CKD)?

Causes of AKI in Patients with CKD

In patients with CKD, acute kidney injury is most commonly caused by prerenal factors (volume depletion, hypoperfusion), nephrotoxic medications (NSAIDs, aminoglycosides, contrast agents), sepsis, and obstructive uropathy—with the critical understanding that AKI etiology is typically multifactorial and requires immediate reassessment to identify and correct reversible causes. 1, 2

Primary Etiologic Categories

Prerenal Causes

• Volume depletion and inadequate perfusion pressure are leading causes, particularly in elderly CKD patients with comorbidities 2, 3
• Cardiorenal syndrome represents a moderate-evidence cause requiring functional hemodynamic monitoring 1
• Hypotension and shock states, especially sepsis-related, predominate in hospitalized patients 4

Nephrotoxic Medications (Most Preventable)

• NSAIDs, ACE inhibitors/ARBs during acute illness, aminoglycosides, vancomycin, and radiocontrast agents must be stopped immediately 1, 2, 3
• Drug-drug interactions (e.g., statins with CYP3A4 inhibitors causing rhabdomyolysis) increase AKI risk 1
• Nephrotoxin exposure during the acute kidney disease (AKD) phase (7-90 days post-AKI) can cause re-injury 1

Intrinsic Renal Causes

• Acute tubular necrosis from prolonged ischemia or nephrotoxin exposure 5
• Glomerulonephritis and vasculitis require consideration when etiology remains unclear 1
• Rare causes include tumor lysis syndrome, thrombotic thrombocytopenic purpura, and cholesterol embolization syndrome requiring specialty consultation 1

Postrenal/Obstructive Causes

• Prostatic hypertrophy, nephrolithiasis, pelvic malignancy, and strictures must be evaluated with renal ultrasound 6
• Complete obstruction presents with anuria or severe oliguria 6

Critical Diagnostic Approach

Immediate Evaluation When AKI Diagnosed

• Reassess the etiology systematically—it is multifactorial in most cases and can occur in early, middle, or late hospital phases 1
• Perform urine sediment analysis, assess proteinuria, and consider biomarker evaluation 1
• Obtain renal ultrasound to exclude obstruction, especially in older men 6, 5
• Review all medications for nephrotoxic agents and drug-drug interactions 1, 2

Risk Factors Specific to CKD Patients

• Pre-existing CKD is the most significant risk factor for developing AKI 1, 4
• Elderly age, diabetes mellitus, hypertension, and metabolic syndrome increase vulnerability 7, 5
• Severity, duration, and frequency of prior AKI episodes predict AKD development 7

Management Priorities

Immediate Interventions (Cannot Wait for Staging)

• Stop all nephrotoxic medications immediately—this is the highest priority intervention 2, 3
• Adjust ALL renally eliminated medications based on current eGFR, not baseline CKD level 2
• Ensure adequate volume status and perfusion pressure with isotonic crystalloids (lactated Ringer's preferred), targeting MAP ≥65 mmHg 1, 3
• Avoid hyperglycemia 1

Diagnostic Workup for Persistent AKI

• Consider kidney biopsy for unresolving AKI or when etiology remains unclear after initial workup 1, 2
• Monitor serum creatinine and electrolytes every 12-24 hours during acute phase 3
• Assess for hyperkalemia requiring urgent intervention with ECG monitoring 3
• Track daily fluid balance—positive fluid balance predicts poor outcomes 2

Critical Measurement Limitations

• Do NOT use eGFR equations (MDRD, CKD-EPI) during AKI—they require steady-state creatinine and will be inaccurate 1, 6
• Timed urine creatinine clearance is the best available estimate once steady state is achieved, though it overestimates GFR 1, 6
• Kinetic eGFR and Jelliffe equations show promise but require further validation 1

Acute Kidney Disease Phase (7-90 Days Post-AKI)

Highest-Risk Period Management

• AKD represents the highest-risk period for progression to advanced CKD or kidney failure 2
• Continue nephrotoxin avoidance throughout the entire AKD period—caution applies even during recovery phase 1, 2
• Arrange nephrology consultation during AKD, as this reduces mortality, major adverse cardiovascular events, and sepsis 2

Patient Education and Follow-up

• Document the AKI/AKD episode prominently in the medical record 2
• Educate patients to avoid NSAIDs and any new medications without consulting their nephrologist 1, 2
• Instruct on cautious use of ACE inhibitors, decongestants, antivirals, antibiotics, and herbal products 1, 2
• Arrange nephrology follow-up within 3 months—patients with AKI on CKD face dramatically elevated risks of progression to kidney failure, cardiovascular events, and death 2

Common Pitfalls to Avoid

• Do NOT wait until AKI stage 2 to adjust medication doses 2
• Do NOT continue nephrotoxic medications during recovery phase 2, 6
• Do NOT perform aggressive fluid resuscitation in established AKI with volume overload 2
• Do NOT fail to arrange nephrology follow-up 2
• Avoid subclavian catheters if possible to preserve future vascular access 1

Renal Replacement Therapy Considerations

• Do not delay RRT when clear indications present: refractory hyperkalemia, volume overload, intractable acidosis, uremic complications 2, 5
• Individualize timing based on overall clinical condition rather than specific creatinine thresholds 3
• Consider earlier initiation in hypercatabolic states (rhabdomyolysis, tumor lysis syndrome) 3