Etiology

Prerenal causes include any condition that leads to decreased renal perfusion (∼ 60% of cases of AKI).

• Hypovolemia: e.g., due to hemorrhage, vomiting, diarrhea, sweating, burns, diuretics, poor oral intake, dehydration, hypercalcemia

• Hypotension: e.g., due to sepsis, cardiogenic shock (decreased cardiac output), anaphylactic shock

• Decreased circulating volume (↓ effective arterial volume)

  • Cardiorenal syndrome: e.g., in congestive heart failure

  • Hepatorenal syndrome: e.g., in cirrhosis, liver failure

  • Abdominal compartment syndrome

  • Nephrotic syndrome

  • Acute pancreatitis

• Renal artery stenosis

• Drugs that affect glomerular perfusion: e.g., cyclosporine, tacrolimus, NSAIDs , ACE inhibitors (ACE-Is)

Intrinsic causes include any condition that leads to severe direct kidney damage (∼ 35% of cases of AKI). [1][2][3]

• Acute tubular necrosis (causes ∼ 85% of intrinsic AKIs)

  • Ischemia: e.g., due to prolonged hypotension

  • Nephrotoxic drugs: e.g., radiographic contrast agents, aminoglycosides, cisplatin, methotrexate, ethylene glycol, amphotericin B

  • Endogenous toxins: e.g., hemoglobin in intravascular hemolysis, myoglobin in rhabdomyolysis, uric acid in TLS, Bence-Jones protein light chains in multiple myeloma

• Acute interstitial nephritis

  • Medication: e.g., antibiotics , phenytoin, interferon, PPIs, NSAIDs, cyclosporine

  • Infection

    • Bacterial: e.g., Legionella spp., Streptococcus spp.

    • Fungi: Candida, Histoplasma

    • Viral: e.g., hepatitis C virus, cytomegalovirus, HIV

  • Infiltrative diseases: e.g., sarcoidosis, amyloidosis

• Vascular diseases

  • Hemolytic uremic syndrome (HUS)

  • Thrombotic thrombocytopenic purpura (TTP)

  • Hypertensive emergency

  • Vasculitis, scleroderma renal crisis

  • Renal vein thromboses, renal atheroemboli, renal infarction

• Glomerulonephritis:e.g., rapidly progressive glomerulonephritis

Postrenal causes include any condition that results in bilateral obstruction of urinary flow from the renal pelvis to the urethra (∼ 5% of cases of AKI). [1][2][3]

• Acquired obstructions

  • Benign prostatic hyperplasia (BPH)

  • Iatrogenic: e.g., catheter-associated injuries

  • Tumors: e.g., bladder, prostate, cervical, metastases

  • Stones

  • Bleeding with subsequent blood clot formation

• Neurogenic bladder: e.g., due to multiple sclerosis, spinal cord lesions, or peripheral neuropathy

• Congenital malformations: e.g., posterior urethral valves

As long as the contralateral kidney remains intact, patients with unilateral ureteral obstruction typically maintain normal serum creatinine levels.

• Decreased blood supply to kidneys (due to hypovolemia, hypotension, or renal vasoconstriction) → failure of renal vascular autoregulation to maintain renal perfusion → decreased GFR → activation of renin-angiotensin system → increased aldosterone release → increased reabsorption of Na+, H2O → increased urine osmolality → secretion of antidiuretic hormone → increased reabsorption of H2O and urea

• Creatinine is still secreted in the proximal tubules, so the blood BUN:creatinine ratio increases.

• Damage to a vascular or tubular component of the nephron → necrosis or apoptosis of tubular cells → decreased reabsorption capacity of electrolytes (e.g., Na+), water, and/or urea (depending on the location of injury along the tubular system) → increased Na+ and H2O in the urine → decreased urine osmolality

• Bilateral urinary outflow obstruction (e.g., stones, BPH, neoplasia, congenital anomalies) → increased retrograde hydrostatic pressure within renal tubules → decreased GFR and compression of the renal vasculature → acidosis, fluid overload, and increased BUN, Na+, and K+.

• A normal GFR can be maintained as long as one kidney functions normally.

• May be asymptomatic.

• Oliguria or anuria

• Signs of volume depletion (in prerenal AKI caused by volume loss)

  • Orthostatic or frank hypotension and tachycardia

  • Reduced skin turgor

• Signs of fluid overload (from Na+ and H2O retention)

  • Peripheral and pulmonary edema

  • Hypertension

  • Heart failure

  • Shortness of breath

• Signs of uremia

  • Anorexia, nausea

  • Encephalopathy, asterixis

  • Pericarditis

  • Platelet dysfunction

• Signs of renal obstruction (in postrenal AKI)

  • Distended bladder

  • Incomplete voiding

  • Pain over the bladder or flanks

• Fatigue, confusion, and lethargy

• In severe cases: seizures or coma

• Affected individuals have a higher risk of secondary infection throughout all phases (most common reason for fatalities).