What are the causes of acute kidney injury (AKI) in patients with pre-existing kidney disease, diabetes, hypertension, or heart disease?

Causes of Acute Kidney Injury

AKI in patients with pre-existing kidney disease, diabetes, hypertension, or heart disease is most commonly caused by prerenal factors (>60% of cases), followed by intrinsic renal causes (particularly acute tubular necrosis), with medication-related causes being especially critical in this high-risk population. 1

Prerenal Causes (Most Common)

Prerenal AKI results from decreased renal perfusion without initial structural kidney damage and is potentially reversible if flow is restored promptly 1, 2:

Volume-Related

• Hypovolemia from hemorrhage, gastrointestinal losses, burns, or excessive diuresis 1
• Fluid sequestration in third spaces (pancreatitis, peritonitis) 1, 2
• Severe hypoalbuminemia from nephrotic syndrome causing decreased effective circulating volume 1, 2

Cardiac-Related (Critical in Heart Disease Patients)

• Decreased cardiac output from heart failure, cardiogenic shock, or arrhythmias 1
• Acute congestive heart failure particularly when accompanied by hypoperfusion and hypoxemia 3
• Cardiovascular collapse (shock) and acute myocardial infarction 3

Vascular-Related

• Systemic vasodilation from sepsis, anaphylaxis, or cirrhosis 1
• Renal vasoconstriction from medications or hepatorenal syndrome 1
• Severe prolonged hypertension causing intrarenal vasoconstriction and altered renal hemodynamics 4

Medication-Related Causes (Especially Important in This Population)

Antihypertensive Medications

• ACE inhibitors and ARBs impair autoregulation of glomerular filtration and can reduce renal blood flow 5, 1, 3

  • Critical distinction: Creatinine increases up to 30% from baseline with RAS blockers should NOT be confused with AKI and do not require discontinuation in the absence of volume depletion 5
  • However, these medications increase AKI risk when combined with volume depletion or other nephrotoxic agents 5

• Diuretics cause volume depletion and prerenal azotemia 5, 1

Other Nephrotoxic Medications

• NSAIDs reduce renal perfusion through prostaglandin inhibition 5, 1
• Contrast media particularly in patients with pre-existing kidney disease or diabetes 1, 2
• Metformin in patients with eGFR <30 mL/min/1.73 m² (contraindicated) or during acute illness with hypoxia 3

Intrinsic Renal Causes

Acute Tubular Necrosis (Most Common Intrinsic Cause)

• Ischemic ATN from prolonged prerenal states 1, 6
• Severe hypertension-induced ATN from direct damage to renal parenchyma 4
• Rhabdomyolysis with myoglobin-induced tubular injury 1

Glomerular and Vascular

• Glomerulonephritis from autoimmune conditions or infections 1
• Thrombotic microangiopathy including thrombotic vascular processes 1
• Diabetic kidney disease complications particularly when rapidly progressive 5

Infection-Related

• Sepsis causing multi-organ failure and direct tubular injury 1, 3
• Viral-mediated tubular cell injury (e.g., COVID-19) 1

Postrenal Causes (Less Common but Important to Exclude)

• Ureteral obstruction from stones, blood clots, or external compression 1
• Bladder outlet obstruction from prostatic hypertrophy, bladder stones, or neurogenic bladder 1
• Increased intra-abdominal pressure from tense ascites (particularly in cirrhosis patients) 5

High-Risk Patient Characteristics

Your specific patient population has multiple compounding risk factors 5, 1, 2:

• Age >65 years is an independent risk factor 1, 2
• Pre-existing CKD significantly increases susceptibility 5, 1, 2
• Diabetes mellitus increases risk through multiple mechanisms including altered hemodynamics and increased infection susceptibility 5, 1, 2
• Hypertension causes chronic vascular changes and increases risk of hypertensive nephropathy 4
• Heart disease predisposes to cardiorenal syndrome and decreased renal perfusion 1, 3

Critical Clinical Scenarios in This Population

Infections

• Any infection can precipitate AKI in high-risk patients through sepsis, volume depletion, or direct renal effects 5
• Screening and treatment of infection should be immediate when AKI is detected 5

Cirrhosis-Specific (if applicable)

• Hepatorenal syndrome is a distinct entity requiring specific diagnosis and management 5, 1
• Infections, diuretic-induced excessive diuresis, GI bleeding, and therapeutic paracentesis without adequate volume expansion are common precipitants 5

Procedural

• Contrast imaging should be performed cautiously, particularly in decompensated states or known CKD 5
• Iodinated contrast requires stopping metformin in patients with eGFR 30-60 mL/min/1.73 m² 3

Diagnostic Approach

BUN/creatinine ratio helps differentiate causes 1:

• >20:1 suggests prerenal azotemia
• <15:1 suggests intrinsic kidney disease

Urinalysis findings guide diagnosis 5:

• Red blood cells, white blood cells, or cellular casts suggest intrinsic disease
• Rapidly increasing albuminuria suggests alternative causes requiring nephrology referral

Key Management Principles

Immediate Actions

• Discontinue diuretics irrespective of AKI stage 5
• Stop nephrotoxic medications including NSAIDs, vasodilators, and potentially beta-blockers 5
• Screen for and treat infections immediately 5
• Volume expansion when appropriate based on cause and severity 5

Medication Adjustments

• Do NOT discontinue ACE inhibitors/ARBs for creatinine increases <30% without volume depletion 5
• Adjust all medication doses based on current eGFR 5

Monitoring

• Annual monitoring of both albuminuria and eGFR to detect AKI and CKD progression 5
• More frequent assessment in elderly patients or those at higher risk 5
• 3-month follow-up after any AKI episode to assess for resolution or progression to CKD 2