Acute Tubular Necrosis

Hanif MO, Bali A, Ramphul K. Acute Renal Tubular Necrosis. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507815/

ETIOLOGY - Acute tubular necrosis is precipitated by an acute ischemic or toxic event or sepsis.

Ischemic-Induced Acute Tubular Necrosis

Prerenal azotemia and ischemic acute tubular necrosis have the same spectrum of causes. Any factor that leads to prerenal azotemia can lead to ischemic acute tubular necrosis. Some common causes include hypovolemic states such as diarrhea, vomiting, bleeding, dehydration, burns, renal losses via diuretics or osmotic diuresis, and third fluid sequestration. Edematous states such as heart failure and cirrhosis cause reduced kidney perfusion. Sepsis or anaphylaxis leads to systemic vasodilation. Coagulopathy, such as disseminated intravascular coagulation, can also cause acute tubular necrosis.

Nephrotoxic-Induced Acute Tubular Necrosis

The kidney clears and metabolizes many drugs. Some of these drugs behave as exogenous toxins and can cause direct renal tubular injury or crystal-induced acute kidney injury (AKI), leading to acute tubular necrosis. Drugs such as aminoglycoside, amphotericin B, radiocontrast media, sulfa drugs, acyclovir, cisplatin, calcineurin inhibitors (tacrolimus, cyclosporine), mammalian target of rapamycin mTOR inhibitors (everolimus, temsirolimus), foscarnet, ifosfamide, cidofovir, and intravenous immunoglobulin containing sucrose all can cause acute tubular necrosis.

Heme pigment-containing proteins such as hemoglobin and myoglobin can behave as endotoxins in 3 ways:

• Causing direct proximal tubular injury, tubular obstruction, or renal vasoconstriction.
• Crystal-induced nephropathy due to high cell turnover such as uric acid, calcium phosphate crystals in the setting of ongoing malignancy treatment.
• Light chain accumulation in multiple myeloma is directly toxic to the renal proximal and distal tubules.

Sepsis-Induced Acute Tubular Necrosis

Sepsis also plays a role in causing acute tubular necrosis because of systemic hypotension and renal hypoperfusion. Other mechanisms that are incompletely understood include endotoxemia leading to AKI by renal vasoconstriction and the release of inflammatory cytokines causing enhanced secretion of reactive oxygen species and leading to renal injury.

EVALUATION

Urinalysis (UA)

In prerenal disease, the UA microscopy is normal or may contain hyaline casts. On the other hand, the UA of acute tubular necrosis shows muddy brown casts or renal tubular epithelial cells secondary to the sloughing of tubular cells into the lumen due to ischemia or toxic injury.

Fractional excretion of sodium (FENa)

This is a good test to differentiate between acute tubular necrosis and prerenal disease with a value less than 1% favoring prerenal disease and more than 2%, acute tubular necrosis. However, these values are not always accurate as in chronic prerenal states such as congestive heart failure and cirrhosis in which there is an overlap between both (ATN and prerenal AKI) having a value of less than 1%.

Urine sodium concentration

This test determines that the kidney is sodium avid in hypovolemic states (prerenal) where kidneys try to conserve sodium or lose sodium due to tubular injury with values more than 40 to 50 mEq/L indicating acute tubular necrosis and less than 20 mEq/L suggestive of prerenal disease.

Novel Biomarkers

Numerous biomarkers have evolved to detect AKI/acute tubular necrosis early as compared to serum creatinine. These biomarkers include serum cystatin C to be an early and reliable marker of renal injury as compared to serum creatinine which is often witnessed 48 to 72 hours after the initial insult. Other markers include urinary alpha one microglobulin, beta-2 microglobulin, urinary liver-type fatty acid-binding protein (L-FABP) and kidney injury molecule 1 (KIM-1) for the detection of proximal tubular damage, urinary interleukin-18 (IL-18) is known to differentiate ATN from CKD, urinary tract infection (UTI), and prerenal azotemia. Urinary biomarker neutrophil gelatinase-associated lipocalin (NGAL) is upregulated in the renal ischemia after distal tubular injury.