What are the causes of acute kidney injury (AKI)?

Causes of Acute Kidney Injury (AKI)

The three major pathological mechanisms of acute kidney injury (AKI) include nephrotoxic agents (including drugs like NSAIDs), decreased renal perfusion, and obstructed outflow of urine.

Nephrotoxic Agents Including Drugs

• Nephrotoxic drugs are a well-established cause of intrarenal (intrinsic) acute kidney injury, characterized by glomerular or tubular cell injury triggered by filtered toxins, tubular obstruction, endothelial dysfunction, or allergic reactions 1
• Drugs account for approximately 20% of community-acquired AKI episodes resulting in hospitalization and occur in about 25% of critically ill patients 2
• NSAIDs are particularly concerning as they can cause AKI through altered intraglomerular hemodynamics and are part of the dangerous "triple whammy" combination with diuretics and ACE inhibitors/ARBs 2
• Antibiotics are one of the most common causes of drug-induced nephrotoxicity through various mechanisms including glomerular injury, tubular injury, and acute interstitial nephritis 3
• The consequences of drug-associated AKI are severe, with rates of dialysis dependence and mortality similar to those of AKI from other etiologies (40-50%) 2

Decreased Renal Perfusion

• Kidney dysfunction can result from systemic hypotension or altered intraglomerular hemodynamics, leading to decreased renal perfusion pressure 2
• If decreased renal perfusion is sustained or severe, it can lead to ischemic injury of the kidney 2
• Renal hypoperfusion can be caused by true volume depletion (hemorrhage, gastrointestinal losses) or effective circulatory volume depletion (heart failure, cirrhosis) 2
• In patients with cirrhosis, decreased renal perfusion is a common cause of AKI, with fractional excretion of sodium typically <1% 2
• Early reversal of AKI from decreased renal perfusion leads to improved survival compared to persistent AKI 2

Obstructed Outflow of Urine

• Urinary tract obstruction is a significant cause of AKI that requires prompt diagnosis and intervention 4
• Obstruction can occur at any level of the urinary collecting system, from the renal tubules to the urethral meatus 2
• Common causes include prostatic hypertrophy in older males, nephrolithiasis, tumors, and strictures 2
• Renal ultrasonography is recommended when risk factors for postrenal obstruction are present 4
• Relief of obstruction is essential for recovery of kidney function and prevention of permanent damage 4

Risk Factors and Prevention Strategies

• The risk of AKI increases significantly when patients receive multiple nephrotoxic medications simultaneously 2
• Escalating the burden of nephrotoxic medications from two to three more than doubles the risk of developing AKI 2
• Patients should receive potentially nephrotoxic medications only when necessary and for the shortest duration possible 2
• Regular monitoring of kidney function is essential in patients exposed to nephrotoxic agents 2
• Pharmacist-led quality-improvement programs can reduce nephrotoxic exposures and rates of AKI in hospital settings 4

Management Considerations

• General management principles include determination of volume status, fluid resuscitation when appropriate, discontinuation of nephrotoxic medications, and adjustment of prescribed drugs according to renal function 4
• In all phases of AKI, selection of less nephrotoxic alternatives and/or avoidance of nephrotoxins should be the goal 2
• Potentially nephrotoxic agents should not be withheld in life-threatening conditions despite concern for AKI 2
• Acute kidney injury care bundles are associated with improved in-hospital mortality rates and reduced risk of progression 4
• Nephrology consultation should be considered for stage 3 or higher AKI, unclear etiology, or when renal replacement therapy is needed 4