Acute tubular necrosis or injury (ATN) is a more common cause of acute kidney injury (AKI) among hospitalized patients than many hospitalists may realize. At least one study found that as much as half of AKI in seriously ill patients was caused by ATN (11. Liaño F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. madrid acute renal failure study group. Kidney Int. 1996;50:811-8. [PMID: 8872955]). The majority of AKI overall is due to prerenal causes, but prerenal AKI may itself progress to ATN (22. Abdel-Kader K, Palevsky PM. Acute kidney injury in the elderly. Clin Geriatr Med. 2009;25:331-58. [PMID: 19765485]).
The distinction between prerenal AKI and ATN has important clinical and coding implications, so precise diagnostic documentation is crucial. The confirmed or presumed underlying cause of AKI should always be clarified if possible.
Like prerenal AKI, ATN can often be promptly corrected if treated aggressively and early with IV fluid resuscitation and correction of any precipitating factors. However, patients with AKI due to ATN, even if mild, have a much greater risk of rapid progression and adverse outcomes than those without ATN. In addition, ATN is considered to have a higher severity of illness classification than prerenal AKI.
The current clinical concept of ATN has changed substantially from historical descriptions (33. Rosen S, Stillman IE. Acute tubular necrosis is a syndrome of physiologic and pathologic dissociation. J Am Soc Nephrol. 2008;19:871-5. [PMID: 18235086]). According to recent studies and authoritative sources like the National Kidney Foundation and International Society of Nephrology, ATN is a functional abnormality of the renal tubules due to toxic or ischemic injury that, if severe, may sometimes progress to necrosis and sloughing of renal tubular cells. While actual histologic necrosis of renal tubules may occur in the most severe cases, the defining feature of ATN is no longer considered to be necrosis.
The term acute tubular injury (ATI) was proposed to emphasize the functional nature of this disorder but unfortunately did not catch on. Clinicians are therefore left with the misnomer of acute tubular necrosis to describe a condition in which necrosis is generally absent, creating widespread confusion about the true nature of what we call ATN.
In a large majority of cases meeting the current definition of ATN, the classic urine sediment findings of muddy-brown granular casts, epithelial cell casts, and free renal tubular epithelial cells may not be present. In fact, the urine sediment may be entirely normal.
Today, the distinction between prerenal AKI and ATN is based on the clinical circumstances leading to AKI and the speed of the creatinine response to IV fluid resuscitation. Most cases of ATN are nonoliguric in nature, and prerenal AKI is typically oliguric.
ATN is associated with certain typical circumstances (listed in Table 1), in contrast to prerenal AKI, where the only identifiable precipitant may be dehydration or volume depletion. Some nephrotoxic medications that can cause ATN are listed in Table 2.
The “gold standard” for recognizing ATN is the timing of the creatinine response to effective IV fluid resuscitation. Prerenal AKI is expected to resolve within 24 to 48 hours, whereas ATN takes at least 72 hours, but often lasts seven days or more.
Clinicians should also be aware that the underlying mechanism of contrast-induced nephropathy is always ATN and that the creatinine level takes at least 72 hours to return to baseline. Postcontrast AKI that corrects promptly (within 24 to 48 hours) is probably due to a prerenal cause and is not likely to be contrast-induced at all.
Rarely, ATN occurs in its classic form, with the findings of tubular necrosis and characteristic urine sediment, leading to extremely high creatinine levels and oliguria followed by a polyuric phase with a prolonged plateau and subsequent slow resolution, sometimes never returning to baseline or even requiring dialysis.
Urinary fractional excretion of sodium (FENa) and urine sodium concentration can be useful in evaluation of suspected ATN but do not provide a definitive diagnosis. Most patients with ATN, but by no means all, have FENa above 2%. If the cause is prerenal, the FENa is more likely to be under 1%. However, some patients with ATN, especially contrast-induced, may have FENa below 1% to 2%. Urine sodium concentration tends to be above 40 mEq/L with ATN and below 20 mEq/L in prerenal AKI, but overlap sometimes occurs.
A normal urine sediment is expected with prerenal AKI and is common in ATN. Urinalysis is now used in suspected ATN primarily to exclude other intrarenal conditions like glomerulonephritis and acute interstitial nephritis, which are characterized by red blood cells, red cell casts, white blood cells, white cell casts, and/or significant proteinuria. Mild proteinuria may occur in ATN, but it is usually not prominent. Renal ultrasound is often performed to rule out obstruction as a cause of AKI.
Documentation of the confirmed or presumed cause of AKI is essential for correct coding because it can have such a significant impact on quality metrics and reimbursement (Table 3). Documentation of just “AKI,” whether unspecified or attributed to a prerenal or postrenal cause, does contribute to severity of illness classification. However, ATN, cortical or medullary (papillary) necrosis, and some forms of glomerulonephritis carry a much higher level of severity than AKI and its other causes. Many forms of glomerulonephritis are also classified at the same level of severity as AKI.