ACUTE TUBULAR NECROSIS

1. INTRODUCTION
Acute tubular necrosis is a condition that damages part of a person’s kidneys. This can
occur as a result of a lack of oxygen and blood flow to the kidneys. The condition can lead to
acute kidney failure. There are tube-shaped structures in the kidneys called tubules. They
filter out waste products and fluid. These structures are damaged in acute tubular necrosis.
When this happens, acute kidney failure may occur. In acute kidney failure, electrolytes and
fluids increase in the body, possibly past safe levels.
Common causes of ATN include low blood pressure and use of nephrotoxic drugs.[1] The presence of
"muddy brown casts" of epithelial cells found in the urine during urinalysis is pathognomonic for ATN.

2. DEFINITION
1. Acute tubular necrosis (ATN) is a medical condition involving the death of
tubular epithelial cells that form the renal tubules of the kidneys. ATN presents
with acute kidney injury (AKI) and is one of the most common causes of AKI.
2. Acute tubular necrosis is kidney injury caused by damage to the kidney tubule cells
(kidney cells that reabsorb fluid and minerals from urine as it forms).
3. Acute tubular necrosis (ATN) is a kidney disorder involving damage to the tubule cells
of the kidneys, which can lead to acute kidney failure.
4. Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury
and dysfunction. Common causes are hypotension or sepsis that causes renal
hypoperfusion and nephrotoxic drugs.

3. PHASES
ATN follows a well-defined three-part sequence of initiation, maintenance, and recovery.
The initiation phase is characterized by an acute decrease in glomerular filtration rate (GFR)
to very low levels, with a sudden increase in serum creatinine and blood urea nitrogen
(BUN) concentrations.
The maintenance phase is characterized by a sustained severe reduction in GFR that
persists for a variable length of time, most commonly 1-2 weeks. Because the filtration rate
is so low during the maintenance phase, the creatinine and BUN levels continue to rise.
The recovery phase, in which tubular function is restored, is characterized by an increase in
urine volume (if oliguria was present during the maintenance phase) and by a gradual
decrease in BUN and serum creatinine to their preinjury levels.
4. ETIOLOGY
ATN is generally caused by an acute event, either ischemic or toxic.
Causes of ischemic acute tubular necrosis
 Hypovolemic states: Haemorrhage, volume depletion from gastrointestinal (GI) or
renal losses, burns, fluid sequestration
 Low cardiac output states: Heart failure and other diseases of myocardium,
valvulopathy, arrhythmia, pericardial diseases, tamponade
 Systemic vasodilation: Sepsis, anaphylaxis
  Disseminated intravascular coagulation
Causes of nephrotoxic acute tubular necrosis
The kidney is a particularly vulnerable target for toxins, both exogenous and endogenous.
Not only does it have a rich blood supply, receiving 25% of cardiac output, but it also helps
in the excretion of these toxins by glomerular filtration and tubular secretion.
Exogenous nephrotoxins that cause ATN
Aminoglycoside-related toxicity occurs in 10-30% of patients receiving aminoglycosides,
even when blood levels are in apparently therapeutic ranges. Risk factors for ATN in these
patients include the following:
 Preexisting liver or renal disease
 Concomitant use of other nephrotoxins (eg, amphotericin B, radiocontrast media,
cisplatin)
 Shock
 Advanced age
 Female sex
 Higher aminoglycoside level 1 hour after dose (a high trough level has not been shown
to be an independent risk factor)
Amphotericin B nephrotoxicity risk factors include the following:
 Male sex
 High maximum daily dose (nephrotoxicity is more likely to occur if >3 g is
administered)
 Longer duration of therapy
 Hospitalization in the critical care unit at the initiation of therapy
 Concomitant use of cyclosporine
Radiographic contrast media can cause contrast-induced nephropathy (CIN) or
radiocontrast nephropathy (RCN); this commonly occurs in patients with several risk factors,
such as elevated baseline serum creatinine, preexisting renal insufficiency, underlying
diabetic nephropathy, chronic heart failure [CHF], or high or repetitive doses of contrast
media, as well as volume depletion and concomitant use of diuretics, ACE inhibitors, or
ARBs. The 2011 UKRA guidelines recommend that patients at risk of CIN should have a
careful evaluation of volume status and receive volume expansion with 0.9% sodium
chloride or isotonic sodium bicarbonate before the procedure. [7]
Other exogenous nephrotoxins that can cause ATN include the following:
 Cyclosporine and tacrolimus (calcineurin inhibitors)
 Cisplatin
 Ifosfamide
 Foscarnet
 Pentamidine, which is used to treat Pneumocystis jiroveci infection in
immunocompromised individuals (risk factors for nephrotoxicity include volume
depletion and concomitant use of other nephrotoxic antibiotic agents, such as
aminoglycosides, which is common practice in the immunosuppressed)
 Sulfa drugs
 Acyclovir and indinavir
 Mammalian target of rapamycin (mTOR) inhibitors (eg, everolimus, temsirolimus) [8]

 Endogenous nephrotoxins that cause ATN

 In myoglobinuria, rhabdomyolysis is the most common cause of heme pigment–
associated acute kidney injury (AKI) and can result from traumatic or nontraumatic
injuries. Most cases of rhabdomyolysis are nontraumatic, such as those related to
alcohol abuse or drug-induced muscle toxicity (eg, statins alone or in combination
with fibrates).
 In hemoglobinuria, AKI is a rare complication of hemolysis and hemoglobinuria, and
most often is associated with transfusion reactions (in contrast to myoglobin,
hemoglobin has no apparent direct tubular toxicity, and AKI in this setting is
probably related to hypotension and decreased renal perfusion). [8]
 Acute crystal-induced nephropathy occurs when crystals are generated
endogenously due to high cellular turnover (ie, uric acid, calcium phosphate), as
observed in certain malignancies or the treatment of malignancies. However, this
condition is also associated with ingestion of certain toxic substances (eg, ethylene
glycol) or nontoxic substances (eg, vitamin C). Choudhry et al reported a case of AKI
caused by ingestion of excessive quantities of calcium-containing antacids. [9]
 In multiple myeloma, renal impairment results from the accumulation and
precipitation of light chains, which form casts in the distal tubules that cause renal
obstruction. In addition, myeloma light chains have a direct toxic effect on proximal
renal tubules. [10]

5. PATHPHYSIOLOGY
 6. SIGN AND SYMPTOMS

There are several symptoms that a patient might experience. These include:

 Dehydration or excessive thirst

 A small amount of urine output
 Swelling and fluid retention
 Nausea and vomiting
 Trouble waking up/drowsiness
 Feeling sluggish
 Confusion

Symptoms may include any of the following:

 Decreased consciousness, coma, delirium or confusion, drowsiness, and lethargy

 Decreased urine output or no urine output
 General swelling, fluid retention

 Nausea vomiting

7. DIAGNOSTIC EVALUATION

History
The patient’s history is very important in the diagnosis of acute tubular necrosis (ATN), the
history commonly reveals recent surgery, hypotension, sepsis, muscle necrosis, or volume
depletion, as well as exposure to nephrotoxic agents. Several of those may be present
simultaneously, which increases the risk and severity of ATN.
In addition, pre-existing medical conditions or medication use (eg, diabetes mellitus, multiple
myeloma, nonsteroidal anti-inflammatory drugs) may contribute to the worsening of renal
function. Hence, a thorough medical and medication history can also be key to the diagnosis.

Physical Examination
Physical examination findings are often unremarkable and acute kidney injury (AKI) is
incidentally detected on routine laboratory studies (ie, elevated blood urea nitrogen [BUN]
and creatinine levels).

Findings may suggest hypovolemia (eg, low jugular venous pressure, loss of skin turgor,
orthostatic hypotension, dry mucous membranes, tachycardia) as a cause. Abdominal
distension may raise the concern of intra-abdominal hypertension and compartment
syndrome as a potential cause of ATN. Muscle tenderness could potentially be due to
rhabdomyolysis, which can lead to ATN.

Approach Considerations
Blood studies and urinalysis, along with renal ultrasound findings, are particularly helpful in
identifying the cause of acute tubular necrosis (ATN). Findings on some tests will vary
depending on the cause of ATN. Careful monitoring of the fluid balance, ongoing medication
details, and daily physical examinations should all be considered together with laboratory
tests.
Suggested testing includes the following:
 Complete blood cell count (CBC)
 Blood urea nitrogen (BUN) and serum creatinine
 Serum electrolytes
 Urinalysis
 Urine Electrolytes
 Renal ultrasound, if indicated
 Novel biomarkers, if available

The CBC may reveal anemia. Erythropoietin production is decreased in acute kidney injury
(AKI), and dysfunctional platelets (from uremia) also make bleeding more likely.

The BUN and serum creatinine concentrations are increased in AKI. This increase in creatinine
can be monitored at regular intervals and used for staging AKI, as described below.

In addition, hyponatremia, hyperkalemia, hypermagnesemia, hypocalcemia, and

hyperphosphatemia may be present. Metabolic acidosis is also found. There can be
improvement or worsening of acid-base status and electrolytes on inititiation of dialysis, and
further calculations and dose adjustments will be required. [14]
Findings in patients with nephrotoxicity from specific medications include the following:
 Aminoglycoside nephrotoxicity – Patients usually present with nonoliguric renal failure,
with onset of nephrotoxicity (manifested by an elevation in serum creatinine) occurring
after 7-10 days of therapy. Characteristically, an elevated fractional excretion of sodium
(FENa) is accompanied by wasting of potassium, calcium, and magnesium.
 Nephrotoxicity from cyclosporine and tacrolimus – Patients may present with
hypertension, and may also have hyperkalemia and tubular injury–induced urinary
wasting of phosphate and magnesium.
 Ifosfamide nephrotoxicity usually presents as a Fanconi syndrome (proximal tubule
dysfunction), with significant hypokalemia.
 Foscarnet nephrotoxicity is commonly associated with hypocalcemia
  Pentamidine nephrotoxicity is frequently associated with hypomagnesemia and
hyperkalemia
 Acyclovir may lead to the formation of intratubular crystals, which appear as
birefringent, needle-shaped crystals when viewed on microscopy.
Staging of AKI
The degree of acute kidney injury (AKI) is determined using the RIFLE (Risk of renal
dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage renal
disease) criteria. [15]
The primary goal of the Acute Dialysis Quality Initiative (ADQI), created in 2002, was to
develop consensus- and evidence-based guidelines that could be used to treat and prevent
AKI. A uniform, accepted definition of AKI was developed, and, as a result, the RIFLE criteria
were proposed. The RIFLE criteria comprise a classification system for AKI. [15]
Since their creation in 2002, the RIFLE criteria have been validated by different groups around
the world. The AKIN report proposed modifications to the RIFLE criteria to take into account
evidence that smaller changes in serum creatinine than those first proposed in RIFLE are
indicative of adverse outcomes. The AKIN staging system therefore requires only one measure
(serum creatinine or urine output) to be satisfied to meet stage criteria. [16]
For more information on RIFLE and AKIN, see Classification Systems for Acute Kidney Injury.
Urinalysis
Examination of the centrifuged sediment of urine is particularly helpful because it may reveal
pigmented, muddy brown, granular casts, suggesting that established ATN is present (see the
image below). However, remember that these casts may be absent in 20-30% of patients with
ATN.
In addition to the routine urinalysis, urine electrolytes may also help differentiate ATN from
prerenal azotemia. The urinary sediment, electrolyte, and osmolality findings that can help to
separate ATN from prerenal azotemia are listed in the following table.
Table. Laboratory Findings Used to Differentiate Prerenal Azotemia From ATN(Open Table in
a new window)

ATN and/or Intrinsic Renal

Finding Prerenal Azotemia
Disease

Urine osmolarity
>500 < 350
(mOsm/kg)

Urine sodium
< 20 >40
(mmol/d)

Fractional excretion of
sodium (FENa) <1 >2
(%)

Fractional excretion of urea

< 35 >50
(%)
 Bland and/or May show muddy brown
Urine sediment
nonspecific granular casts

Fractional excretion of a substance is calculated by the formula (U/P)z/(U/P)Cr × 100, where

z is the substance, U and P represent urine and plasma concentrations, and Cr stands for
creatinine.
In patients with contrast-induced nephropathy (CIN), FENa tends to be less than 1%. This is
an exception to the rule that FENa below 1% usually indicates prerenal failure.
Although rhabdomyolysis is a common cause of endogenous nephrotoxic ATN, FENa tends to
be less than 1%, characteristically. This is another exception to the rule, along with CIN. An
important finding on urinalysis is that of a positive dipstick test for blood, with typical absence
of red blood cells (RBCs) on microscopy. Furthermore, hyperkalemia, hyperphosphatemia,
and hyperuricemia are characteristic.
Ultrasonography
Renal ultrasonography, preferably with Doppler methods, is a simple procedure that should
be undertaken in all patients who present with AKI. [17] It is extremely useful to exclude
obstructive uropathy and to measure renal size and cortical thickness. According to the 2011
UKRA guidelines, all patients presenting with AKI should have baseline investigations
performed, including a urinalysis and renal ultrasonography within 24 hours (on suspicion of
renal tract obstruction).
Abdominal Radiography
An abdominal radiograph is of limited benefit in AKI. The exception is in patients with
suspected nephrolithiasis. However, up to 30% of renal calculi may not be visible on plain
films. [17]
Computed Tomography
Noncontrast helical computed tomography (CT) is more sensitive than plain radiography for
detection of renal calculi. CT scans can also be used to evaluate for ureteral obstruction, when
ultrasonography shows hydronephrosis but a cause is not detectable. [17]
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) of the abdomen has a potential role for determining the
cause of ureteral obstruction when ultrasonographic results are unclear. MRI with contrast is
preferred, if not contraindicated. [17]
Histologic Findings
Renal biopsy is rarely necessary in patients with suspected ATN. An urgent indication for renal
biopsy is in the setting of clinical and urinary findings that suggest renal vasculitis rather than
ATN, in which case the diagnosis needs to be established quickly so that appropriate
immunomodulatory therapy can be initiated. A biopsy may also be critically important in renal
transplant recipients, to rule out rejection. [18, 19] Otherwise, biopsy should be performed only
when the exact renal cause of AKI is unclear and the course is protracted.
Renal biopsy is performed under ultrasound or CT scan guidance after ascertaining the safety
of the procedure. Renal biopsy findings are shown below.
In most circumstances, the histology demonstrates the loss of tubular cells or the denuded
tubules. As illustrated in the image below, the tubular cells reveal swelling, formation of blebs
over the cellular surface, and exfoliation of the tubular cells into the lumina. The earliest
finding could be loss of the cellular brush border.
Novel Biomarkers
The most commonly used markers of renal function—serum creatinine level, glomerular
filtration rate (GFR), and urinary output—are limited in their ability to determine the
magnitude of renal injury. This has led to research to find more accurate kidney function
biomarkers (serum and/or urine), [20] in the hope that such biomarkers, once identified, will
permit early diagnoses and will aid in rendering appropriate treatment strategies before
permanent damage has occurred. Research has focused on the following potential
biomarkers:
 Neutrophil gelatinase-associated lipocalin (NGAL)
 Interleukin-18 (IL-18)
 Kidney injury molecule 1 (KIM-1)
 Cystatin C
 Sodium/hydrogen exchanger isoform 3 (NHE3)
In a multicenter, prospective cohort study of 102 patients with cirrhosis and acute kidney
injury (AKI), Belcher and colleagues assessed multiple urinary biomarkers used to determine
the three most common etiologies of AKI: ATN, prerenal azotemia, and hepatorenal syndrome
(HRS). Median values of the following biomarkers were significantly higher in patient with
ATN [21] :
 NGAL
 IL-18
 KIM-1
 Liver-type fatty acid binding protein (L-FABP)
 Albumin
Further research is needed before novel renal biomarkers are incorporated into clinical
practice.
Furosemide Stress Testing
In early acute kidney injury (AKI), urine output after a furosemide stress test (FST) can predict
the development of stage 3 AKI. Response to the FST may be used to help the clinician
determine when or whether to start renal replacement therapy. [22,23]
Candidates for FST should be euvolemic and stable. For the test, furosemide is infused
intravenously, in a dose of 1.0 or 1.5 mg/kg, and urine output is measured for 2 hours
afterward. A 2-hour urinary output of 200 ml or less has been shown to have the best
sensitivity and specificity to predict development of stage 3 AKI. To minimize the risk of
hypovolemia, urine output may be replaced ml for ml each hour with Ringer lactate or normal
saline for 6 hours after the FST, unless volume reduction is considered clinically desirable. [23]
In a study by Koyner et al, FST was significantly better than any urinary biomarker tested in
predicting progression to stage 3 AKI (P< 0.05), and was the only test that significantly
predicted receipt of renal replacement therapy. However, these authors found that a higher
area under the curve (AUC) for prediction of adverse patient outcomes was achieved when
FST was combined with biomarkers using specified cutoffs: urinary neutrophil gelatinase-
associated lipocalin (NGAL) >150 ng/mL or urinary tissue inhibitor of metalloproteinases
(TIMP-2) × insulinlike growth factor–binding protein-7 (IGFBP-7) >0.3. [22]

Differential Diagnoses
 Acute Glomerulonephritis
 Acute Kidney Injury
 Azotemia
 Chronic Kidney Disease
  Pathophysiologic Mechanisms of Selected Types of Nephrotoxicity
 Tubulointerstitial Nephritis

MANAGEMENT

Treatment
In most people, ATN is reversible. The goal of treatment is to prevent life-threatening
complications of acute kidney failure

Treatment focuses on preventing the buildup of fluids and wastes, while allowing the
kidneys to heal.

Treatment may include any of the following:

 Identifying and treating the underlying cause of the problem

 Restricting fluid intake

 Taking medicines to help control potassium level in the blood

 Medicines taken by mouth or through an IV to help remove fluid from the body

Temporary dialysis can remove excess waste and fluids. This can help improve your
symptoms so that you feel better. It may also make kidney failure easier to control. Dialysis
may not be necessary for all people, but is often lifesaving, especially if potassium is
dangerously high.
Dialysis may be needed in the following cases:

 Decreased mental status

 Fluid overload

 Increased potassium level

 Pericarditis (inflammation of the sac-like covering around the heart)

 Removal of toxins that are dangerous to the kidneys

 Total lack of urine production

 Uncontrolled buildup of nitrogen waste products

Approach Considerations
The first step in the management of acute tubular necrosis (ATN) is identification
of patients at risk for it. Patients undergoing major surgery or presenting with shock
or other conditions associated with development of ATN should be proactively
followed and monitored. Measurement of fluid balances and urine output and daily
measurement of creatinine and electrolytes will permit rapid diagnosis of acute
kidney injury (AKI).
Another vulnerable group of patients are those with significant co-morbidities, who
are likely to develop ATN with relatively minor injury and thus need more frequent
and close follow up. This group includes patients with diabetes mellitus, significant
coronary or peripheral vascular disease, multiple myeloma, or dehydration, as well
as those receiving nephrotoxic medications or undergoing contrast-enhanced
imaging studies. Prevention of ATN in these patients is group includes maintaining
euvolemia, avoiding nephrotoxic medications, and supporting blood pressure with
vasopressors if necessary.
Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest using a
stage-based approach to management of AKI/ATN. [24] The guidelines suggest that
the following measures have no role in the prevention of AKI [24] :
 Diuretics to prevent AKI
 Diuretics to treat AKI, except in the management of volume overload
 Low-dose dopamine to prevent or treat AKI
 Fenoldopam to prevent or treat AKI
 Atrial natriuretic peptide (ANP) to prevent or treat AKI

Correction of Oliguria
In the past, the use of diuretics to convert an oliguric AKI to non-oliguric AKI was
sometimes recommended, to help with fluid management. However, several meta-
analyses have shown no reduction in mortality or the need for renal replacement
therapy with the use of diuretics. [25]
The only indication of diuretics would be fluid overload after appropriate
management of sepsis and cardiac dysfunction. Intravenous furosemide or
bumetanide in a single high dose (ie, 100-200 mg of furosemide) is commonly used,
although little evidence indicates that it changes the course of ATN. The drug
should be infused slowly because high doses can lead to hearing loss. If no response
occurs, the treatment should be discontinued.
There is no role for so-called renal dose dopamine in the management of ATN.
Dialysis
Indications for urgent dialysis in patients with ATN include the following:
 Refractory fluid overload
 Severe hyperkalemia
 Signs of uremia (eg, pericarditis, encephalopathy, altered mental status)
 Severe metabolic acidosis (pH < 7.1)
In patients without one of those indications for dialysis, initiating renal replacement
therapy (RRT) prophylactically offers no benefit over performing RRT as and when
required. Several trials and a recent meta-analysis have shown no improvement in
outcome with early versus late RRT for patients with AKI. [27]
Dialysis modality
Continuous renal replacement therapy (CRRT), sustained low-efficiency dialysis
(SLED), and intermittent hemodialysis can all be used for renal replacement in ATN.
None those therapies offers significant benefit over the others, and KDIGO suggests
using these modalities as complementary approaches, especially in
hemodynamically unstable patients. The choice of therapy should be driven by
local expertise. CRRT may be the preferred option for hemodynamically unstable
patients. [24]
Elimination of Nephrotoxins
Generally, the treatment of choice for nephrotoxic ATN is to stop all nephrotoxic
agents to prevent further damage to the kidney. Of note, calcium channel blockers
may have some use in cyclosporine toxicity, as they may reduce the
vasoconstrictive action of cyclosporine. However, their use is typically avoided
because of possible hypotension.

Complications
Traditional complications of ATN include the following [28] :
 Volume overload
 Acid-base and electrolyte imbalances, especially hyperkalemia, acidosis,
hyperphosphatemia, and hypocalcemia
 Uremia, leading to problems such as prolonged bleeding, altered mental
status, and pericardial disease
Non-traditional complications of ATN include the following [28] :
 Infections
 Respiratory disorders
 Cardiac disorders
 Chronic kidney disease

Altered fluid and electrolyte balance

Specific fluid imbalances vary with the phase of illness. During oliguria, salt and
water retention often leads to hypertension, edema, and heart failure. The polyuric
phase of ATN may lead to hypovolemia and create a setting for prerenal azotemia
and perpetuation of ATN.
Clearly, the maintenance of fluid and electrolyte balance is critical. ATN may lead
to dangerous electrolyte imbalances, especially hyperkalemia and hyponatremia.
Hyperkalemia can be associated with life-threatening cardiac arrhythmias (eg,
ventricular tachycardia or fibrillation, complete heart block, bradycardia, asystole).
Arrhythmias have been reported in up to 30% of patients. On electrocardiography
(ECG), hyperkalemia manifests as peaked T waves, prolonged PR interval, P wave
flattening, and a widened QRS complex. In addition to these worrisome cardiac
effects, hyperkalemia can also lead to neuromuscular dysfunction and, potentially,
respiratory failure. Hyperkalemia can be treated with glucose and insulin, binding
resins, or, if necessary, dialysis.
Hyponatremia is cause for concern because of its effects on the central nervous
system. In general, correction of hyponatremia should be of sufficient rapidity and
magnitude to reverse the manifestations of hypotonicity, but not be so rapid
orlarge as to potentiate the risk of osmotic demyelination. The most recent
published guidelines on treatment of hyponatremia recommend rates of correction
of serum sodium ranging from 8 to 12 mmol/L per 24 h. [29] Go to Hyponatremia for
complete information on this topic.
Other electrolyte disturbances include hyperphosphatemia, hypocalcemia, and
hypermagnesemia. Hypocalcemia may be secondary to both deposition of calcium
phosphate and reduced levels of 1,25-dihydroxyvitamin D. It is usually
asymptomatic, but hypocalcemia may result in nonspecific ECG changes, muscle
cramps, or seizures.
In rhabdomyolysis, hypocalcemia results from deposition of calcium in the injured
muscle. The deposited calcium is eventually released back into the circulation
during the recovery phase, thereby accounting for transient hypercalcemia. For this
reason, calcium administration is generally not recommended for hypocalcemia
during the acute phase of rhabdomyolysis, unless the patient is symptomatic.
The 2011 UK Renal Association guidelines recommend administering 0.9% sodium chloride
and sodium bicarbonate for intravenous volume expansion in patients at risk of developing
AKI secondary to rhabdomyolysis. [7] Metabolic acidosis may occur. It may be treated with
bicarbonate or dialysis as well.
Uremia
Uremia results from the accumulation of nitrogenous waste. It is a potentially life-threatening
complication associated with AKI. This may manifest as pericardial disease, gastrointestinal
symptoms (ie, nausea, vomiting, cramping), and/or neurologic symptoms (ie, lethargy,
confusion, asterixis, seizures). Platelet dysfunction is common and can lead to life-threatening
hemorrhage. Fortunately, uremia is becoming rarer with the earlier start of renal replacement
therapy and better availability of resources, at least in the developed world.
Infections
Aggressive treatment of infections is prudent. Infections remain the leading cause of
morbidity and mortality and can occur in 30-70% of patients with AKI. Infections are more
likely in these patients because of impairment of the immune system (eg, from uremia,
inappropriate use of antibiotics) and because of increased use of indwelling catheters and
intravenous needles.
Anemia
Anemia may develop from many possible causes. Erythropoiesis is reduced in AKI. Patients
with ATN-related uremia may have platelet dysfunction and subsequent hemorrhage leading
to anemia. In addition, volume overload may lead to hemodilution, and red cell survival time
may be decreased. Anemia can be corrected with blood transfusions.
Diet
KDIGO guidelines for AKI/ATN suggests the following dietary measures, although
most are supported with limited evidence [24] :
 Total energy intake of 20–30 kcal/kg/d
 Avoid restriction of protein intake
 Administer 0.8–1.0 g/kg/d of protein in noncatabolic AKI patients without
need for dialysis and 1.0–1.5 g/kg/d in patients with AKI on renal replacement
and up to a maximum of 1.7 g/kg/d in patients on continuous renal
replacement therapy (CRRT) and in hypercatabolic patients.
 Entreral nutrition is preferential than parenteral

Prevention

Prevention includes the following:

 Maintaining euvolemia and renal perfusion in critically ill patients

 Avoiding nephrotoxic drugs when possible

 Closely monitoring renal function when nephrotoxic drugs must be used

 Taking measures to prevent contrast nephropathy

 Among patients with diabetes, controlling blood glucose levels

There is no evidence that loop diuretics, mannitol, or dopamine helps prevent or alter the
course of established acute tubular necrosis.

Prognosis
For patients with ATN, the in-hospital survival rate is approximately 50%, with
about 30% of patients surviving for 1 year. Factors associated with an increased
mortality rate include the following:
 Poor nutritional status
 Male sex
 Oliguria
 Need for mechanical ventilation
 Acute myocardial infarction
 Stroke
 Seizures
The mortality rate in patients with ATN is probably related more to the severity of
the underlying disease than to ATN itself. For example, the mortality rate in
patients with ATN after sepsis or severe trauma is much higher (about 60%) than
the mortality rate in patients with ATN that is nephrotoxin related (about 30%). The
mortality rate is as high as 60-70% with patients in a surgical setting. If multiorgan
failure is present, especially severe hypotension or acute respiratory distress
syndrome, the mortality rate ranges from 50 to 80%.
Patients with oliguric ATN have a worse prognosis than patients with nonoliguric
ATN. This probably is related to more severe necrosis and more significant
disturbances in electrolyte balance. In addition, a rapid increase in serum creatinine
(ie, >3 mg/dL) probably also indicates a poorer prognosis. Again, this probably
reflects a more serious underlying disease.