What are the causes of acute renal failure in patients, particularly in the elderly or those with pre-existing kidney disease?

Causes of Acute Renal Failure

Acute renal failure results from three major etiologic categories: prerenal causes (>60% of cases), intrinsic renal causes, and postrenal causes, with prerenal azotemia from hypovolemia and decreased renal perfusion being the most common and reversible etiology. 1, 2

Prerenal Causes (Most Common)

Prerenal acute renal failure accounts for more than 60% of all AKI cases and results from decreased renal perfusion without structural kidney damage 1, 2. The key mechanisms include:

Hypovolemia and Fluid Loss

• Absolute volume depletion from hemorrhage, gastrointestinal losses (vomiting, diarrhea), renal losses (diuretics, osmotic diuresis), or skin losses (burns) 2, 3
• Third-space fluid sequestration in conditions like pancreatitis, peritonitis, or severe hypoalbuminemia (nephrotic syndrome) 2

Decreased Cardiac Output

• Heart failure and cardiogenic shock reduce effective renal perfusion 1, 2
• Cirrhosis with hepatorenal syndrome causes systemic vasodilation and decreased effective circulating volume 4, 2

Vascular Occlusion

• Renal artery thrombosis or embolism can cause acute prerenal failure 1, 2

Clinical pearl: A BUN/creatinine ratio >20:1 strongly suggests prerenal causes, while <15:1 suggests intrinsic disease 1. Prerenal AKI is potentially reversible if perfusion is restored promptly, but if uncorrected, mortality remains 40-50% 1.

Intrinsic Renal Causes

Nephrotoxic Medications (Most Common Intrinsic Cause)

The following medications cause direct tubular toxicity 1:

• Aminoglycosides (gentamicin, tobramycin, amikacin) - particularly nephrotoxic with prolonged use or inadequate hydration 1, 5
• NSAIDs - reduce renal perfusion through prostaglandin inhibition 1
• Vancomycin and amphotericin B - direct tubular toxicity 1
• Proton pump inhibitors (omeprazole) - carry a 4.35-fold adjusted risk for AKI 1
• Chemotherapeutic agents including cisplatin, methotrexate, and tenofovir 1

Contrast-Induced Nephropathy

Contrast media causes injury through decreased glomerular filtration, renal hypoperfusion, and direct tubular toxicity 1, 2. Most episodes of contrast-induced AKI are non-oliguric, making urine output criteria less applicable for diagnosis 1.

Acute Tubular Necrosis (ATN)

ATN results from prolonged ischemia (from untreated prerenal causes) or direct nephrotoxic injury 6, 3. This represents the transition from reversible prerenal failure to structural kidney damage 3.

Other Intrinsic Causes

• Glomerulonephritis and vasculitis require rapid diagnosis to prevent permanent damage 3
• Interstitial nephritis from medications or infections 3

Postrenal Causes (Obstructive)

Postrenal causes result from urinary tract obstruction and account for a smaller percentage of cases 1, 7:

• Prostatic hypertrophy - most common in elderly men 1
• Nephrolithiasis (kidney stones) 1
• Tumors causing ureteral or bladder outlet obstruction 1, 7
• Strictures of the ureters or urethra 1

Critical action: Renal ultrasound should be performed to identify hydronephrosis and the level of obstruction 7. Urgent urologic intervention with nephrostomy tube placement or ureteral stent insertion is required emergently 7.

High-Risk Populations

The risk of developing acute renal failure increases dramatically with the following factors 1, 8:

• Age >65 years - reduced baseline renal function 1, 8
• Pre-existing chronic kidney disease - 18-fold higher risk in acyanotic patients, 35-fold in cyanotic patients 4, 1
• Diabetes mellitus - diabetics with baseline renal insufficiency represent the highest risk subgroup 1, 8
• Liver disease - altered hemodynamics and hepatorenal syndrome risk 4, 1
• Critical illness and sepsis - clear association with AKI development 8
• Cardiac surgery requiring cardiopulmonary bypass - clinically relevant renal injury develops in ≈30% of cardiac surgery patients 4

Special Considerations in Elderly and CKD Patients

Elderly patients may have reduced renal function not evident in routine screening tests like BUN or serum creatinine 5. Creatinine clearance determination is more useful in this population 5.

For patients with pre-existing CKD, AKI superimposed on CKD represents the highest risk scenario, with a greater than 3-fold increase in creatinine meeting Stage 3 AKI criteria 7. This combination carries the highest risk of progression to end-stage kidney disease and death 7.

Prevention Strategies

Avoiding nephrotoxins when possible is the most effective prevention measure 8:

• Discontinue NSAIDs, ACE inhibitors, ARBs, and diuretics when AKI risk is high 2
• Ensure adequate hydration before contrast administration or nephrotoxic medication use 1, 5
• Use low-osmolar or iso-osmolar contrast media in high-risk patients 2
• Monitor renal function closely during aminoglycoside therapy and maintain adequate hydration 5

Common pitfall: Concurrent use of multiple nephrotoxic agents (e.g., aminoglycosides with diuretics) dramatically increases AKI risk and should be avoided 5, 9, 8.