Acute Kidney Injury Causes

Prerenal Causes

• Prerenal AKI accounts for more than 60% of all cases and results from decreased renal perfusion without initial structural kidney damage 1
• Hypovolemia from fluid losses, such as hemorrhage, gastrointestinal losses, burns, or excessive diuresis, can cause prerenal AKI 2, 3
• Fluid sequestration in third spaces, such as pancreatitis or peritonitis, can lead to prerenal AKI 1
• Severe hypoalbuminemia from nephrotic syndrome can cause decreased effective circulating volume, resulting in prerenal AKI 1
• Decreased cardiac output from heart failure, cardiogenic shock, or arrhythmias can cause prerenal AKI 2
• Systemic vasodilation from sepsis, anaphylaxis, or cirrhosis can lead to prerenal AKI 2
• Renal vasoconstriction from medications, such as NSAIDs, ACE inhibitors, or ARBs, or hepatorenal syndrome can cause prerenal AKI 2

Intrarenal Causes

• Rhabdomyolysis with myoglobin-induced tubular injury can cause intrinsic AKI 3, 4
• Glomerulonephritis from autoimmune conditions or infections can lead to intrinsic AKI 3, 4
• Thrombotic microangiopathy, including thrombotic vascular processes, can cause intrinsic AKI 3, 4
• Viral-mediated tubular cell injury with direct kidney infection, such as COVID-19, can cause intrinsic AKI 3, 4
• Multi-organ failure associated with severe COVID-19 can lead to intrinsic AKI 3, 4
• Proximal tubular injury with Fanconi syndrome, manifesting as hypokalaemia, hypophosphataemia, and salt wasting, can occur in COVID-19 patients 3, 4

Postrenal Causes

• Ureteral obstruction from stones, blood clots, or external compression can cause postrenal AKI 2
• Bladder outlet obstruction from prostatic hypertrophy, bladder stones, or neurogenic bladder can lead to postrenal AKI 2
• Urethral obstruction from strictures or external compression can cause postrenal AKI 2

High-Risk Patient Populations

• Age >65 years represents an independent risk factor for AKI 1, 5
• Pre-existing chronic kidney disease significantly increases susceptibility to AKI 1, 5
• Diabetes mellitus increases AKI risk through multiple mechanisms 1, 5
• Liver disease increases risk through altered hemodynamics and hepatorenal syndrome 1

Critical Medication-Related Causes

• ACE inhibitors and ARBs can impair autoregulation of glomerular filtration, leading to AKI 3, 5
• NSAIDs can reduce renal perfusion through prostaglandin inhibition, causing AKI 3, 5
• Diuretics can cause volume depletion and prerenal azotemia, leading to AKI 3, 5
• Contrast media can cause AKI, especially in patients with pre-existing kidney disease or diabetes 1

Diagnostic Approach

• The BUN/creatinine ratio helps differentiate prerenal from intrinsic causes, with >20:1 suggesting prerenal azotemia and <15:1 suggesting intrinsic kidney disease 1, 2

Acute Kidney Injury Causes and Management

Patient Risk Factors and Medication-Related Causes

• The American Diabetes Association recommends that ACE inhibitors and ARBs impair autoregulation of glomerular filtration and can reduce renal blood flow in patients with diabetes, and 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 6
• The American Diabetes Association suggests that diuretics cause volume depletion and prerenal azotemia in patients with diabetes 6
• The American Diabetes Association notes that NSAIDs reduce renal perfusion through prostaglandin inhibition in patients with diabetes 6
• The European Association for the Study of the Liver recommends that increased intra-abdominal pressure from tense ascites, particularly in cirrhosis patients, is a postrenal cause of AKI 7

Diagnostic Approach and Monitoring

• The American Diabetes Association recommends that urinalysis findings, such as red blood cells, white blood cells, or cellular casts, suggest intrinsic disease, and rapidly increasing albuminuria suggests alternative causes requiring nephrology referral 6
• The European Association for the Study of the Liver suggests that annual monitoring of both albuminuria and eGFR to detect AKI and CKD progression is necessary 6

Key Management Principles

• The European Association for the Study of the Liver recommends that discontinue diuretics irrespective of AKI stage, stop nephrotoxic medications including NSAIDs, vasodilators, and potentially beta-blockers, screen for and treat infections immediately, and volume expansion when appropriate based on cause and severity 7
• The American Diabetes Association suggests that do NOT discontinue ACE inhibitors/ARBs for creatinine increases <30% without volume depletion, and adjust all medication doses based on current eGFR 6

Hypertension‑Induced Acute Kidney Injury Mechanisms

Types of AKI Associated with Hypertension

• Hypertension can precipitate prerenal AKI by impairing renal perfusion, intrinsic (intrarenal) AKI through direct parenchymal damage in malignant hypertension, and post‑renal AKI when severe hypertension raises intra‑abdominal pressure and obstructs urine flow. 8, 9

Medication‑Induced Prerenal AKI

• Renal vasoconstriction caused by antihypertensive agents (ACE inhibitors, ARBs, and diuretics) reduces intravascular volume, renal blood flow, and glomerular filtration, leading to prerenal azotemia. 10, 11

Cirrhosis‑Related Prerenal AKI

• Systemic vasodilation in cirrhosis (splanchnic vasodilation from portal hypertension) lowers effective arterial blood volume, activates vasoconstrictor pathways, and impairs renal perfusion, resulting in prerenal AKI. 12