Chapter 17 Acute Renal Failure
Definitions
Epidemiology
The incidence of ARF varies according to the definition used and the population studied. The incidence of hospital-acquired ARF is close to 5% although up to 20% of critically ill patients develop an episode of ARF during their illness.
Pathophysiology
The pathophysiology of ARF is easiest to conceptualize when patients are classified according to the site of the abnormality (Box 17-1).
Box 17-1 Causes of Acute Renal Failure
Pre-Renal
Pre-renal ARF develops when decreased renal perfusion leads to a reduction in the glomerular filtration rate (GFR). This can occur in patients with hypovolemia or reduced effective circulating volume (such as heart failure, cirrhosis, or the nephrotic syndrome) and almost always presents with oliguria. The kidneys attempt to compensate for the reduced blood flow and maintain GFR by dilating afferent arterioles (via prostaglandins) and constricting efferent arterioles (via angiotensin II). Renal failure develops when these compensatory mechanisms are inadequate or impaired as sometimes occurs in hypovolemic patients who are simultaneously receiving a nonsteroidal anti-inflammatory drug (which reduces prostaglandin production) and an angiotensin-converting enzyme inhibitor (which reduces formation of angiotensin II). Initially, the integrity of the renal parenchyma is preserved in all cases of prerenal disease. However, persistent, uncorrected renal hypoperfusion will ultimately lead to ischemic injury.
Intrinsic
Intrinsic ARF occurs when there is injury to the renal glomeruli, tubules, interstitium, or vessels. The most common cause of intrinsic ARF is acute tubular necrosis (ATN), which develops when there is ischemic or toxic injury to the kidney, as can occur with sepsis, aminoglycoside antibiotics, some chemotherapies, and intravenous radiocontrast agents. Pre-renal ARF of sufficient severity and duration will cause ischemic ATN. Other causes of intrinsic ARF include glomerulonephritis, allergic interstitial nephritis (AIN), rhabdomyolysis, atheroembolic disease, and multiple myeloma light-chain proteins.
The mechanisms of rhabdomyolysis-induced ARF include (1) renal vasoconstriction, (2) myoglobin precipitation leading to cast formation and tubular obstruction, and (3) ischemic injury (myoglobin degradation causes free radical production and lipid peroxidation).
Atheroembolic disease (cholesterol embolism) involving the renal arteries, arterioles, and glomerular capillaries can cause sudden ARF or a stepwise decline in renal function over several months. Atheroembolic disease occurs spontaneously, or as a result of atheromatous plaque disruption during an intravascular intervention (such as injury to the aorta during coronary angioplasty), or when administration of anticoagulants prevents healing of an eroded plaque.
Intravenous contrast agents cause direct tubular epithelial cell toxicity and renal medullary ischemia. Risk factors for contrast nephropathy include diabetes mellitus, baseline renal disease, volume depletion, and concurrent nephrotoxic drugs (Box 17-2).
Symptoms and Signs
Most patients with ARF are asymptomatic and are diagnosed based on laboratory data. Patients with prerenal ARF may have a history of vomiting, diarrhea, hypotension, hemorrhage, or excessive diuresis. On physical examination, these patients may have tachycardia, hypotension, postural signs, and dry mucus membranes. Patients with intrinsic ARF may have received nephrotoxic medications or intravenous contrast or may have features of systemic disease, such as rhabdomyolysis or vasculitis. Livedo reticularis (purplish rash over the lower extremities and abdominal wall) suggests atheroembolic disease, which can also present with constitutional symptoms and multisystem involvement. Patients with postrenal ARF may have benign prostatic hypertrophy or abdominal symptoms originating from a tumor. On physical examination, these patients may have a distended bladder, enlarged prostate, or a palpable abdominal mass.
Patients with sufficiently severe ARF, regardless of the cause, may have signs of uremia, including lethargy, nausea, confusion, volume overload, and electrolyte abnormalities (such as hyponatremia and hyperkalemia).
