Acute tubular necrosis overview
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Acute tubular necrosis (ATN) defines a pathologic process rather than a clinical syndrome in which varying degrees of renal tubular injury occur. Clinically, ATN manifests as acute kidney injury although the terms have previously been used interchangeably. ATN is the most common cause of overt AKI. Despite the term, ATN does not necessarily imply cellular necrosis with evidence of non-necrotic injury observed more consistently. Furthermore, clinicopathologic correlation is often irrelevant with severe renal insufficiency sometimes seen with modest pathological findings. ATN can be either ischemic or toxin induced. Classically, ischemic ATN follows hypotension or hypovolemia with patchy involvement usually observed. On the other hand, toxic ATN is usually a dose-dependent injury seen with medications, diagnostic agents, and heavy metals with proximal tubule damage involving almost all nephrons.
Eric and beallduring was the first to publish a article on describing ATN in detail during world war II. In 1938, Councilman was the first to discover the association between systemic infections and the development of ATN.
Classically the course of ischemic ATN has been divided into 3 phases: Initiation, maintenance, and recovery. During the initiation phase, immediately following the insult, sublethal cellular injury occurs, with loss of cell polarity and brush border. The maintenance phase is reached after the irreversible renal parenchymal injury has been established. During the last 2 phases, both tubular cell death and cell regeneration occur simultaneously. Apoptosis has been reported in the initial phase of acute tubular necrosis and during the recovery phase. With initial ischemic or cytotoxic injury, a number of tubular cells may undergo apoptosis. The ET-1 gene has also been shown to be upregulated during ischemic injuries. When exposed to ischemic stress, tubular cells are prone to loss polarity and even detachment of viable cells due to the disruption of key structural anchors. Several important proteins are required for tubular cells to maintain their structure and polarity including the actin cytoskeleton, microvilli, and junctional complexes such as tight junctions and adherens junctions. The most common cause of acute kidney injury (AKI) is acute tubular necrosis (ATN) when the pattern of injury lies within the kidney (intrinsic disease). The term tubular necrosis is a misnomer, as true cellular necrosis is usually minimal, and the alteration is not limited to the tubular structures. Acute tubular necrosis is most common in hospitalized patients and is associated with high morbidity and mortality. The pattern of injury that defines acute tubular necrosis includes renal tubular cell damage and death. Intrarenal vasoconstriction or a direct effect of drug toxicity is caused by an ischemic event, nephrotoxic mechanism, or a mixture of both.
Acute tubular necrosis is commonly caused by renal ischemia resulting from conditions such as volume depletion, hypotension, septic shock, cirrhosis, and DIC. It is also caused by exposure to various nephrotoxic medications including aminoglycosides, amphotericin B, ACE inhibitors, NSAIDs, antiviral drugs, cytotoxic therapy,and also exposure to radio contrast substances.
Differentiating Acute tubular necrosis from Other Diseases
Epidemiology and Demographics
Incidence of acute tubular necrosis is approximately 88 per 100,000 individuals worldwide. The mean age at diagnosis of acute tubular necrosis was 59.5 years. Mortality rate is high with acute tubular necrosis among hospitalized and ICU patients. Acute tubular necrosis affects men and women equally.
Common risk factors in the development of acute tubular necrosis include any condition that lead to decreased renal perfusion such as recent abdominal and cardiac surgery, marked hypovolemia, sepsis, hemorrhagic shock, severe pancreatitis, and diabetes mellitus. Nephrotoxic medications ( eg, ACE inhibitors, NSAIDs, aminoglycosides, radio contrast media) can also be a risk for developing acute tubular necrosis.
Screening for acute tubular necrosis is usually not recommended for asymptomatic individuals. Screening is usually recommended for patients who are at high risk for developing acute tubular necrosis. Screening evaluation includes measurement of serum creatinine, urine output, blood urea nitrogen, urinary and serum electrolytes.
Natural History, Complications, and Prognosis
Acute tubular necrosis may usually develop through 3 phases, initiation, maintenance and recovery. Common complications of acute tubular necrosis include electrolyte imbalance(eg, hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis), platelet dysfunction and altered consciousness or coma. Prognosis depends on the underlying etiology and severity of kidney damage. When compared to ischemic acute tubular necrosis, nephrotoxic and mixed acute tubular necrosis have the good prognosis.
Diagnostic Study of Choice
There is no single diagnostic study of choice for the diagnosis of acute tubular necrosis, but acute tubular necrosis can be diagnosed based on serum creatinine and BUN levels, urinalysis, urine electrolytes (urine sodium, fractional excretion of sodium concentration), and ultrasonography with doppler imaging.
History and Symptoms
History taking is an important aspect in making a diagnosis of acute tubular necrosis. It provides clues to precipitating factors, causes and associated comorbid conditions leading to decreased renal perfusion and kidney injury. Most common symptoms of acute tubular necrosis include decreased or absent urinary output, postural dizziness, edema, excess thirst, tachycardia, altered mental status and easy fatiguability.
On physical examination, patients with acute tubular necrosis may show the findings of volume depletion. They usually appear ill, dehydrated, and lethargic. Common physical examinationfindings of acute tubular necrosis include orthostatic hypotension and other signs of hypovolemia (dry mucous membranes, sunken eyes, poor skin turgor and delayed capillary refill, and decreased jugular venous pressure).
CBC, urinalysis with sediment microscopy, urine electrolytes, osmolarity, serum electrolytes, blood urea nitrogen and serum creatinine, and urine dipstick are commonly performed in patients to evaluate acute tubular necrosis and other causes of acute renal failure. Urine sediment may show tubular epithelial cells and epithelial cell casts or brown muddy granular casts. Increased urine sodium concentration >40 mEq/L, urine fractional excretion of sodium greater than 2 percent along with elevated serum creatinine concentration at a rate greater than 0.3 mg/dL/day may be found in acute tubular necrosis. However, these tests may have some limitations.
There are no specific x-ray findings associated with acute tubular necrosis. However, an abdominal x-ray may be helpful in diagnosing renal calculi, and areas of obstruction.
Echocardiography and Ultrasound
Ultrasound with doppler imaging can be helpful in the diagnosis of acute tubular necrosis. Findings on an ultrasound include normal or increased kidney size, alterations in cortical echogenicityand increased RI. There are no echocardiography findings associated with acute tubular necrosis. However, an echocardiography may be helpful in the diagnosis of complications of acute tubular necrosis.
CT scan findings of patients with acute tubular necrosis may include alterations in kidney size, striate nephrogram, accumulation of fluid around kidneys. CT scan can also detect hydronephrosis that cannot be detectable on ultrasound.
Other Imaging Findings
There are no other imaging findings associated with acute tubular necrosis.
Other Diagnostic Studies
Renal biopsy and detection of various novel biomarkers in the serum and urine can be helpful in diagnosing acute tubular necrosis.
According to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines, management approach of acute tubular necrosis include examination of all patients thoroughly to identify the cause, precipitating factors, and comorbid conditions leading to a rapid reduction in GFR, which may be reversible and regular monitor patients for serum creatinine, BUN, and urine output to assess the severity of renal damage.
Surgery is not the first-line treatment option for patients with acute tubular necrosis.
Effective measures for the primary prevention of acute tubular necrosis include identification of individuals who are at high risk and prompt treatment for underlying conditions, maintain volume status and adequate renal perfusion by proper hydration or isotonic fluid administration, monitoring fluid intake, urine output and serum creatinine levels regular intervals to ensure normal renal function and avoiding or decreasing dose of nephrotoxins and contrast media.
Secondary preventive measures of acute tubular necrosis are similar to primary prevention.
- Rosen S, Stillman IE (2008). "Acute tubular necrosis is a syndrome of physiologic and pathologic dissociation". J Am Soc Nephrol. 19 (5): 871–5. doi:10.1681/ASN.2007080913. PMID 18235086.
- Fogo A, Cohen AH, Colvin RB et al. Fundamentals of Renal Pathology. Springer 2013. Acute Tubular Necrosis. http://dx.doi.org/10.1007/978-3-642-39080-7_15