5.1 Acute Kidney Injury & Electrolyte Derangements

Introduction to Acute Kidney Injury

Acute Kidney Injury (AKI) is characterized by a rapid, usually reversible decline in renal function. This decline results in the accumulation of nitrogenous waste products (azotemia), disruptions in extracellular fluid volume, and severe electrolyte and acid-base disturbances. For the AGACNP, recognizing the etiology and intervening early is crucial to preventing progression to irreversible end-stage renal disease.

The hallmark laboratory findings of AKI include an acute rise in serum creatinine, a decrease in glomerular filtration rate (GFR), and oliguria (urine output < 400 mL/day) or anuria (urine output < 50 mL/day). AKI is classified into three main pathophysiological categories: prerenal, intrinsic (intrarenal), and postrenal.

Prerenal AKI

Prerenal AKI is the most common cause of acute renal failure in the acute care setting. It is fundamentally an issue of renal hypoperfusion without intrinsic damage to the renal parenchyma—at least initially. Common causes include true volume depletion (hemorrhage, gastrointestinal losses, severe dehydration), reduced effective arterial blood volume (heart failure, cirrhosis/hepatorenal syndrome), and altered intrarenal hemodynamics (NSAIDs, ACE inhibitors, bilateral renal artery stenosis).

In prerenal states, the kidneys respond appropriately by avidly reabsorbing sodium and water to restore intravascular volume. This leads to characteristic urinary indices: a low fractional excretion of sodium (FeNa < 1%), a low spot urine sodium (< 20 mEq/L), a high urine osmolality (> 500 mOsm/kg), and a BUN-to-creatinine ratio greater than 20:1. The urinary sediment is typically benign or shows transparent hyaline casts.

Management of prerenal AKI focuses on restoring renal perfusion. In volume-depleted patients, this involves aggressive fluid resuscitation with isotonic crystalloids. In patients with heart failure, optimizing cardiac output with inotropes or diuresis (if fluid overloaded but hypoperfusing) may be required. Discontinuing nephrotoxic agents and medications that alter renal hemodynamics is paramount.

Intrinsic (Intrarenal) AKI

Intrinsic AKI results from structural damage to the renal parenchyma. This can involve the tubules, interstitium, glomeruli, or renal vasculature. The most common cause of intrinsic AKI in hospitalized patients is Acute Tubular Necrosis (ATN), which often occurs as a progression of unresolved prerenal ischemia or due to nephrotoxin exposure (e.g., aminoglycosides, contrast media, amphotericin B, myoglobin from rhabdomyolysis).

Unlike prerenal AKI, the damaged tubules in ATN lose their concentrating and sodium-retaining abilities. Consequently, the BUN-to-creatinine ratio is typically 10-15:1, the FeNa is high (FeNa > 2%), urine sodium is elevated (> 40 mEq/L), and urine osmolality is low (< 350 mOsm/kg). The classic urinary sediment finding in ATN is the presence of muddy brown granular casts and epithelial cell casts.

Other intrinsic causes include acute interstitial nephritis (AIN), which is often drug-induced (penicillins, PPIs, NSAIDs) and presents with a classic triad of fever, rash, and eosinophilia (and eosinophiluria). Glomerulonephritis is less common but presents with hematuria, dysmorphic red blood cells, and red blood cell casts.

Postrenal AKI

Postrenal AKI is due to bilateral obstruction of urinary outflow. Causes include benign prostatic hyperplasia (BPH), pelvic malignancies, bilateral nephrolithiasis, or an obstructed indwelling Foley catheter. Initial evaluation should always involve a bladder scan and a renal ultrasound to detect hydronephrosis. Relief of the obstruction (e.g., catheter placement, nephrostomy tubes) typically results in a rapid improvement in renal function, often followed by a post-obstructive diuresis that requires careful monitoring and fluid replacement.

KDIGO Staging of AKI

The Kidney Disease: Improving Global Outcomes (KDIGO) criteria provide a standardized definition and staging system for AKI based on serum creatinine and urine output.

Critical Electrolyte Derangements

Acute kidney injury severely impairs the kidney's ability to maintain electrolyte and acid-base homeostasis, leading to life-threatening emergencies.

Hyperkalemia is arguably the most lethal complication of AKI. The inability to excrete potassium leads to elevated serum levels. Severe hyperkalemia (> 6.5 mEq/L) can cause cardiac arrhythmias. The classic ECG progression starts with peaked T waves, followed by loss of P waves, a prolonged PR interval, widening of the QRS complex, and ultimately a sine wave pattern leading to ventricular fibrillation or asystole. Management of severe hyperkalemia with ECG changes requires immediate membrane stabilization using intravenous calcium gluconate (or calcium chloride if a central line is present). This is followed by agents that shift potassium intracellularly: intravenous insulin with dextrose (to prevent hypoglycemia) and high-dose nebulized albuterol. Finally, potassium must be eliminated from the body using gastrointestinal cation-exchange resins (e.g., sodium zirconium cyclosilicate), loop diuretics (if making urine), or urgent hemodialysis.

Metabolic Acidosis occurs due to the failure of the kidneys to excrete non-volatile acids and regenerate bicarbonate. This is typically a high anion gap metabolic acidosis (due to uremia), although a non-anion gap component may also be present. Severe acidemia (pH < 7.1) can cause myocardial depression and reduce responsiveness to vasopressors. While sodium bicarbonate therapy is controversial, it is generally considered in severe non-anion gap acidosis or as a temporizing measure in severe acidemia pending dialysis.

Hypocalcemia and Hyperphosphatemia frequently coexist in AKI due to reduced phosphate excretion and impaired activation of vitamin D (calcitriol), which decreases intestinal calcium absorption. Symptomatic hypocalcemia (Chvostek's or Trousseau's sign, tetany, seizures) requires IV calcium replacement. Hyperphosphatemia is managed by restricting dietary phosphorus and administering oral phosphate binders (e.g., sevelamer, calcium acetate) with meals.

Indications for Urgent Renal Replacement Therapy (RRT)

The mnemonic AEIOU is classically used to remember the indications for urgent hemodialysis:

• Acidosis: Severe metabolic acidemia (pH < 7.1) refractory to medical therapy.
• Electrolytes: Severe, refractory hyperkalemia with ECG changes.
• Intoxications: Dialyzable toxins (e.g., lithium, toxic alcohols, salicylates).
• Overload: Volume overload (e.g., pulmonary edema) refractory to aggressive diuretic therapy.
• Uremia: Uremic complications such as encephalopathy (altered mental status, asterixis) or uremic pericarditis (pleuritic chest pain, friction rub).

In the acute setting, Continuous Renal Replacement Therapy (CRRT) may be preferred over intermittent hemodialysis for hemodynamically unstable patients, as it removes fluid and solutes more slowly and is better tolerated.