Acute Kidney Injury in the Intensive Care Unit

Konstantin Abramov

Thejas N. Swamy

I. GENERAL PRINCIPLES

A. Definition.

1. Acute kidney injury (AKI), previously known as acute renal failure (ARF), is characterized by a sudden decline in kidney function. Most important features are azotemia (accumulation of nitrogenous waste products, e.g., urea and creatinine) and oliguria (decrease in urine output to <500 mL/day). New definitions of AKI, based on either reduction of glomerular filtration rate (GFR) or oliguria, are being developed (e.g., RIFLE criteria).

B. Classification.

1. Categorized according to pathophysiologic mechanism.

a. Prerenal azotemia: impaired renal perfusion.

b. Intrinsic or parenchymal AKI: injury to the renal parenchyma.

c. Postrenal AKI: obstruction of the urinary tract.

C. Epidemiology.

1. AKI in the intensive care unit (ICU) setting affects up to 25% of patients and is associated with a high mortality rate.

2. AKI often develops as a consequence of the course or treatment of other disorders.

3. Ischemia is the most common cause of AKI in the ICU and is often etiologically multifactorial.

II. ETIOLOGY

A. Prerenal azotemia.

See Table 59-1.

B. Intrinsic AKI.

See Table 59-2.

C. Postrenal AKI.

See Table 59-3.

For discussion of selected syndromes, see Table 59-6.

III. PATHOGENESIS

For pathogenesis of selected syndromes, see Table 59-6.

TABLE 59-1 Causes of Prerenal Azotemia

Hypovolemia
	Gastrointestinal losses
	Vomiting or NG tube drainage
	Diarrhea
Renal losses
	Osmotic diuresis (hyperglycemia)
	Diuretics
Skin losses
	Burns
	Excessive insensible losses (fever)
Hemorrhage
Translocation of fluid (“third spacing”)
	Postoperative
	Pancreatitis
Reduced effective circulating volume
	Hypoalbuminemia
	Hepatic cirrhosis
	Cardiomyopathy (cardiorenal syndrome)
	Peripheral blood pooling (vasodilator therapy, anesthetics, anaphylaxis, sepsis, toxic shock syndrome)
	Renal artery stenosis
Autoregulatory failure
	Medications (NSAIDs, ARBs, ACEIs, pressor agents, etc.)
NG, nasogastric; NSAIDs, nonsteroidal anti-inflammatory drugs; ARB, angiotensin receptor blocker, ACEI, angiotensin-converting enzyme inhibitor.

A. Prerenal azotemia.

1. Arises from a reduction in renal blood flow from hypovolemia, reduced effective circulating volume, renal artery stenosis, or autoregulatory failure.

2. Reduced renal perfusion leads to intense conservation of solute and water. It is a functional condition that is rapidly reversible with correction of renal perfusion.

3. With reduced effective circulating volume or autoregulatory failure, renal perfusion is compromised despite a euvolemic or hypervolemic state. This may be due to loss of vascular resistance, low cardiac output, or dysregulation of intrarenal hemodynamics.

B. Intrinsic AKI.

1. Acute injury to renal parenchyma from nephrotoxic or ischemic insult, which is not immediately reversible due to damage to nephrons.

2. Acute tubular necrosis (ATN) is very common as renal medulla is extremely susceptible to injury due to relatively poor oxygenation. Ischemia is most common cause, but ATN may result from nephrotoxins or inflammation of the renal tubular epithelium/interstitium.

3. Intratubular obstruction: Drugs (acyclovir, methotrexate, oral sodium phosphate bowel preparation) or toxins (ethylene glycol, myoglobin) can precipitate in and obstruct the tubules.

TABLE 59-2 Causes of Intrinsic (Parenchymal) Acute Kidney Injury

Tubulointerstitial disease
Acute tubular injury (acute tubular necrosis)
Ischemic
Nephrotoxins:
	Radiocontrast
	Medications: aminoglycosides, cisplatin, amphotericin B, foscarnet
	Pigment: myoglobin (rhabdomyolysis), hemoglobin
Tumor lysis syndrome: direct toxicity from uric acid and phosphates causing diffuse nephronal microobstruction and tubular damage
Acute interstitial nephritis (AIN)
	Drug induced: NSAIDs; antibiotics, most commonly penicillins, cephalosporins, sulfas; allopurinol; thiazides
	Infections: Legionella, Epstein-Barr virus, cytomegalovirus, etc.
	Autoimmune diseases: sarcoidosis, Sjögren syndrome
Glomerular disease
	Nephrotic syndrome: minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy
	Nephritic syndrome: membranoproliferative glomerulonephritis, IgA nephropathy, Wegener granulomatosis, vasculitis
Vascular disease
	Thrombosis
	Thromboembolism
	Atheroembolism
	Vasculitis
	Microangiopathy
		Scleroderma
		Malignant hypertension
		Toxemia of pregnancy
		TTP/HUS
		Medications (cyclosporine, mitomycin)
NSAID, nonsteroidal anti-inflammatory drug; IgA, immunoglobulin A; TTP, thrombotic thrombocytopenic purpura; HUS, hemolytic uremic syndrome.