Ninjanerd - Acute Kidney Injury Overview

Acute Kidney Injury (AKI)

• AKI is a sudden decline in kidney function, marked by a sharp drop in urine output and a rapid increase in serum creatinine.
• AKI is categorized into three types: prerenal, intrarenal, and postrenal.
• Prerenal AKI is primarily caused by reduced blood flow to the kidneys, leading to decreased glomerular filtration rate (GFR).
• Intrarenal AKI results from damage to the nephrons, the functional units of the kidneys, impairing filtration and reabsorption.
• Postrenal AKI is caused by urinary tract obstruction, creating a backflow of urine and raising pressure within the nephrons, hindering filtration.

Pre-renal AKI

• Reduced effective arterial blood volume (EABV) is the core mechanism of prerenal AKI.
• Causes of EABV reduction include:
  • Cardiorenal syndrome: Heart failure (systolic or diastolic dysfunction) lowers cardiac output, decreasing EABV and renal perfusion.
  • Hepatorenal syndrome: Decompensated cirrhosis, marked by reduced albumin production, decreases oncotic pressure and causes fluid leakage from blood vessels, further reducing EABV. Portal hypertension-linked systemic vasodilation, especially in splanchnic vessels, compounds this reduction in EABV.
  • Hypovolemia: Various factors (diarrhea, diuresis, dehydration, blood loss) lower preload, stroke volume, and ultimately cardiac output, leading to reduced EABV.
  • Hypotension and shock states: Severe hypotension (septic, cardiogenic, or hypovolemic shock) dramatically reduces mean arterial pressure (MAP), the pressure driving kidney blood flow, thus decreasing EABV.
• Other contributing factors include:
  • Increased renal vasoconstriction: Medications like NSAIDs, tacrolimus, ACE inhibitors, and ARBs can cause this.
    • NSAIDs inhibit prostaglandin production, which typically dilates afferent arterioles, causing vasoconstriction.
    • ACE inhibitors and ARBs dilate efferent arterioles, decreasing glomerular pressure.
  • Renal artery obstruction: Atherosclerosis and fibromuscular dysplasia narrow the renal artery, reducing kidney blood flow. Bilateral renal artery stenosis, particularly with ACE inhibitor use, significantly contributes to severe AKI.

Intrarenal AKI

• Acute tubular necrosis (ATN) is the most common intrarenal AKI type (85-90% of cases). ATN results from damage to tubular cells, leading to sloughing and obstruction of the tubular lumen, harming filtration and reabsorption.

• Ischemic ATN: Prolonged reduced renal perfusion, often from untreated prerenal AKI (hypotension or hypovolemia), limits oxygen to the tubular cells, causing cell death.

• Nephrotoxic ATN: Direct tubular cell injury from various substances:

  • Medications: Aminoglycosides, vancomycin, amphotericin B, and contrast dye.
  • Pigments: Myoglobin (rhabdomyolysis) and hemoglobin (hemolysis).
  • Crystals: Uric acid (tumor lysis syndrome) and immunoglobulin light chains (multiple myeloma).

• Other intrarenal AKI types include:

  • Acute interstitial nephritis (AIN): Triggered by medications (NSAIDs, beta-lactams, PPIs), leading to interstitium inflammation and tubular cell damage. Fever, rash, and elevated eosinophils in urine and blood are key diagnostic signs.
  • Glomerulonephritis (GN): Inflammation of the glomerulus due to various causes (ANCA-associated vasculitis, anti-GBM disease, infectious GN, immune complex diseases, thrombotic microangiopathy). GN often shows hematuria, proteinuria, and AKI. Rapid GN progression with significant glomerular thickening and crescent formation is called rapidly progressive glomerulonephritis (RPGN), common in ANCA vasculitis and anti-GBM disease.
    • Thrombotic microangiopathy (TMA) causes microthrombi formation, leading to glomerular obstruction, frequently presenting with a triad of hemolytic anemia, thrombocytopenia, and AKI.

Postrenal AKI

• Postrenal AKI is characterized by urinary tract obstruction, causing urine backflow and rising pressure within the kidneys. Obstruction can be proximal or distal.
• Proximal obstruction: Renal pelvis or ureters. Common cause is nephrolithiasis (kidney stones), often requiring bilateral obstruction to cause AKI (except in solitary kidney). Other causes include tumors, masses like ovarian or rectal cancer.
  • Ultrasound: Hydronephrosis (dilated renal pelvis) and unilateral ureteral dilation suggest proximal obstruction.
• Distal obstruction: Bladder or bladder outlet.
  • Neurogenic bladder (lack of bladder muscle contraction): Spinal cord disease, stroke, Parkinson's disease impair bladder contraction.
  • Medications (anticholinergics): Inhibit bladder muscle contraction, causing urine retention.
  • Benign prostatic hyperplasia (BPH): Enlarged prostate hinders urine flow. Prostate cancer may also contribute to obstruction.
  • Ultrasound: Distended bladder, hydronephrosis point to distal obstruction. Post-void residual > 200 mL confirms distal obstruction.

Diagnosis of AKI

• Initial steps: Assess serum creatinine levels (rise of 0.3 mg/dL or more in 48 hours or 1.5 times baseline over 7 days). Evaluate urine output (oliguria < 400 mL/24 hours).
• Identifying the cause:
  • Postrenal AKI: Renal/bladder ultrasound to assess for hydronephrosis, ureteral dilation, and bladder enlargement. History of flank pain, hematuria, nausea, vomiting, or urinary tract infection. Post-void residual > 200 mL. Foley catheterization can alleviate distal obstruction.
  • Intrarenal and Prerenal AKI:
    • Urine sodium (UNa) < 1% and low FeNa suggest prerenal AKI (kidneys reabsorbing sodium).
    • Urine osmolality (> 500 mOsm/kg), Urine urea nitrogen/creatinine ratio (> 20:1) indicate prerenal AKI (kidney conserving water and urea).
    • Urine microscopy: Muddy brown casts (ATN). White cell casts/high eosinophils (AIN). Red cell casts or high proteinuria (GN). FePP stress test can differentiate.
• History and physical examination:
  • Pre-renal AKI: Volume status. Medications: ACE inhibitors, ARBs, NSAIDs.
  • Intrarenal AKI: History of nephrotoxicity, rhabdomyolysis, tumor lysis syndrome, etc. Fever, rash, eosinophilia (AIN).

Complications of AKI

• Metabolic acidosis: Hydrogen ion retention, reduced bicarbonate reabsorption, elevated anion gap (especially in severe uremia). Compensation: Kussmaul respirations. Consequences: Worsened hyperkalemia, decreased myocardial contractility, vasodilation, and lowered blood pressure.
• Hyperkalemia: Decreased potassium excretion due to reduced GFR. ECG changes: Peaked T waves, prolonged PR interval, absent P waves, widened QRS ( > 120 msec), and sine wave pattern (risk of ventricular fibrillation/cardiac arrest).
• Hypervolemia: Water and sodium retention. Clinical manifestations: Pulmonary/pleural effusions, edema, hypertension. Consequences: Impaired oxygenation, shortness of breath, increased heart failure risk. Hypervolemic hyponatremia results from excess water retention.
• Uremia: Retention of waste products, primarily urea. CNS effects: Confusion, lethargy, asterixis, nausea, vomiting. Pericarditis. Platelet dysfunction (epistaxis, bleeding).

Treatment of AKI

• Addressing complications: Metabolic acidosis (sodium bicarbonate), hyperkalemia (loop diuretics, potassium binders, calcium, insulin, albuterol), hypervolemia (loop diuretics), uremia (hemodialysis)
• Underlying causes:
  • Hypovolemia: IV fluids.
  • Cardiorenal syndrome: Inotropes, diuretics, vasodilators.
  • Hepatorenal syndrome: Albumin, vasopressors, octreotide.
  • Hypotension/shock: IV fluids, vasopressors.
  • Renal artery obstruction: Revascularization (angioplasty, stenting).
  • Medication-related AKI: Discontinue offending agents.
• Dialysis: Indications include complicated AKI. Types: CRRT, intermittent hemodialysis. Access: Central venous catheters.
• Pre-renal AKI treatment: Address underlying causes; hypovolemia with fluids, cardiorenal with inotropes/diuretics/vasodilators, and hypotension/shock with fluids/vasopressors.
• Intrarenal AKI treatment: Supportive care, remove nephrotoxic agents.
• Postrenal AKI treatment: Proximal obstruction (stents, nephrostomy); distal obstruction (Foley catheter).

Understanding the Progression of AKI

• AKI progresses through three phases:
  • Oliguric phase: Reduced urine output, increased creatinine, and complications (hyperkalemia, metabolic acidosis, uremia).
  • Polyuric phase: Increased urine output, potentially leading to dehydration and hypokalemia.
  • Recovery phase: Gradually restored kidney function (months/years).