What is the best course of treatment for a patient with acute kidney failure, potentially caused by medication use, infection, or trauma, and with possible underlying medical conditions?

Treatment of Acute Kidney Injury

The best course of treatment for acute kidney injury prioritizes immediate identification and correction of the underlying cause, discontinuation of all nephrotoxic medications, optimization of volume status with isotonic crystalloid resuscitation, and close monitoring for complications requiring renal replacement therapy. 1, 2

Immediate Assessment and Stabilization

Identify and Correct the Underlying Cause

When AKI is diagnosed, immediately reassess the patient to determine the etiology and correct reversible causes. 1

• Categorize AKI as prerenal (hypovolemia, hypoperfusion), intrinsic renal (acute tubular necrosis, glomerulonephritis, interstitial nephritis), or postrenal (obstruction) 3, 4
• For medication-induced AKI, perform temporal assessment to identify causally related drugs and discontinue them immediately 2
• For infection-related AKI (particularly UTI with sepsis), obtain urinalysis and urine culture before starting broad-spectrum antibiotics 5
• For trauma-related AKI with rhabdomyolysis, check plasma creatine phosphokinase (CPK), myoglobin, and potassium levels 6
• Obtain renal ultrasonography in most patients, particularly older men, to rule out obstruction 3, 4

Discontinue All Nephrotoxic Medications

Stop all potentially nephrotoxic drugs immediately, as medications account for 20% of community-acquired AKI and 25% of ICU-related AKI. 2

• Discontinue NSAIDs as the highest priority, especially when combined with diuretics and ACE inhibitors/ARBs (this "triple whammy" dramatically increases AKI risk) 5, 2
• Hold ACE inhibitors and ARBs during the acute phase when GFR is unstable or volume status is not optimized 1, 2
• Stop statins if rhabdomyolysis is present or suspected 2, 6
• Avoid macrolide-statin combinations due to rhabdomyolysis risk from CYP3A4 inhibition 2
• Combining three or more nephrotoxins more than doubles AKI risk, with each additional nephrotoxin presenting 53% greater odds of developing AKI 2

Volume Management Strategy

Fluid Resuscitation for Prerenal AKI

Optimize volume status immediately with aggressive intravenous isotonic crystalloid resuscitation for volume depletion. 2, 7

• Use crystalloids (normal saline or balanced solutions) rather than colloids for most patients 7
• Avoid hydroxyethyl starches entirely 7
• For severe rhabdomyolysis with AKI, administer >6L of intravenous fluids to prevent progression and need for renal replacement therapy 6
• For moderate rhabdomyolysis, administer 3-6L per day of intravenous fluids 6
• Initiate volume resuscitation as early as possible, as delayed initiation is associated with higher rates of AKI development 6

Avoid Volume Overload

Monitor fluid balance closely, as volume overload in AKI is associated with adverse outcomes. 1, 7

• Place bladder catheter to monitor hourly urine output in severe cases 2, 6
• Treat volume overload with diuretics when appropriate 4
• Recognize that oliguria has multiple etiologies beyond hypovolemia, and inappropriate attempts to "reverse" established AKI can result in fluid overload 1

Medication Management and Monitoring

Dose Adjustment Protocol

Perform comprehensive medication reconciliation and adjust all drug doses based on current GFR. 2

• Use validated eGFR equations for dose adjustment, though recognize these require steady-state creatinine and are less accurate in acute settings 1
• Consider creatinine-cystatin C equations or measured GFR for narrow therapeutic window drugs 2
• Monitor therapeutic drug levels for medications with narrow therapeutic windows 2
• Recognize that AKI impairs hepatic cytochrome P450 activity, affecting drug metabolism beyond renal clearance 2

Laboratory Monitoring

Establish intensive monitoring during the acute phase with daily assessment of renal function and electrolytes. 2

• Check daily eGFR and serum creatinine 2
• Monitor electrolytes (especially potassium) daily to twice daily 2
• Obtain urinalysis with fractional excretion of sodium to differentiate prerenal from intrinsic causes 3, 4
• For rhabdomyolysis, monitor plasma CPK, myoglobin, and potassium every 30 minutes to 1 hour during the first 24 hours 6

Cause-Specific Management

Infection-Related AKI

Start broad-spectrum antibiotics immediately when infection is strongly suspected, as treating life-threatening infections may actually prevent or ameliorate AKI. 5, 2

• Select first-line antibiotics based on local antibiogram patterns, considering renal function 5
• For UTI with AKI, nitrofurantoin, TMP-SMX, and fosfomycin are first-line agents but require dose adjustment 5
• Avoid TMP-SMX if creatinine clearance is <15 ml/min 5
• Treat UTI with as short a duration as reasonable, generally no longer than seven days 5
• Obtain urine culture before starting antibiotics to guide definitive therapy 5

Rhabdomyolysis-Related AKI

Initiate aggressive fluid resuscitation immediately with >6L of intravenous fluids for severe rhabdomyolysis. 6

• Remove any retained bee stingers immediately if envenomation is the cause 6
• Discontinue all statins and other medications with nephrotoxic potential 6
• Monitor plasma CPK, myoglobin, and potassium frequently 6
• Place bladder catheter for hourly urine output monitoring 6

Persistent AKI Management

When AKI persists beyond 48-72 hours, this serves as a wake-up call to initiate extended evaluation and reconsider treatment options. 1

• Reassess the etiology, recognizing it is often multifactorial 1
• Perform additional tests including urine sediment evaluation, proteinuria assessment, biomarker measurement, and imaging 1
• Consider specialty consultation for rare causes (tumor lysis syndrome, thrombotic thrombocytopenic purpura, cholesterol embolization syndrome) 1
• Persistence of AKI and stuttering recovery patterns are linked to increased morbidity and mortality 1

Indications for Renal Replacement Therapy

Initiate renal replacement therapy (dialysis) for specific life-threatening complications of AKI. 3, 8, 4

• Refractory hyperkalemia unresponsive to medical management 3, 4
• Volume overload refractory to diuretics 3, 4
• Intractable metabolic acidosis 3, 4
• Uremic complications (encephalopathy, pericarditis, pleuritis) 3, 4
• Removal of certain toxins 3, 4
• The optimal timing of RRT initiation in critically ill patients remains an area of active investigation 1, 7

Critical Pitfalls to Avoid

Never combine multiple nephrotoxins, particularly the "triple whammy" of NSAIDs, diuretics, and ACE inhibitors/ARBs. 5, 2

• Do not treat asymptomatic bacteriuria in patients with AKI 5
• Avoid using standard eGFR equations (MDRD, CKD-EPI) in the ICU setting, as they require steady-state creatinine 1
• Do not delay essential antibiotics for life-threatening infections due to concerns about nephrotoxicity 5, 2
• Never fail to document medication restart plans, particularly for ACE inhibitors/ARBs after GFR stabilizes 1, 2
• Avoid surveillance urine testing in asymptomatic patients 5

Long-Term Considerations

Recognize that AKI is not a self-limited process but is strongly linked to increased risk for chronic kidney disease, subsequent AKI episodes, and future mortality. 7

• Plan for nephrology follow-up after hospital discharge 4
• Educate patients to avoid NSAIDs and new medications without consulting their physician 2
• Consider restarting ACE inhibitors/ARBs only after GFR stabilizes and volume status is optimized 1, 2