Acute Tubular Necrosis Treatment & Management

Updated: Dec 19, 2018
  • Author: Nikhil A Shah, MBBS, DNB(Neph); Chief Editor: Vecihi Batuman, MD, FASN  more...
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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. [26]




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.



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 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. 


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 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.



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 of nephrotoxic acute tubular necrosis

Strategies for prevention of nephrotoxic ATN vary with different nephrotoxins.

With aminoglycosides, studies have demonstrated that once-daily dosing decreases the incidence of nephrotoxicity. In one study, 24% of patients receiving 3 daily doses of gentamicin developed clinical nephrotoxicity, compared with only 5% of patients receiving 1 daily dose. [30] However, other studies comparing a single daily dose with multiple daily doses have failed to find a difference in the incidence of nephrotoxicity. Therapeutic efficacy is not diminished by single daily dosing.

With amphotericin B, efforts should be made to minimize the use of the drug and ensure that extracellular fluid volume is adequate. By saline loading, maintenance of a high urine flow rate has been shown to be helpful. Likewise, various lipid formulations of amphotericin B have been developed, namely, amphotericin B colloid dispersion (ABCD), amphotericin B complex (ABLC), and liposomal amphotericin B; these lipid formulations are believed to be intrinsically less nephrotoxic.

Whereas amphotericin B is suspended in bile salt deoxycholate, which has a detergent effect on cell membranes, the lipid formulations do not contain deoxycholate. The lipid formulations also bind more avidly to fungal cell wall ergosterol as opposed to the cholesterol in human cell membranes. Liposomal amphotericin B is preferred in patients with renal insufficiency or evidence of renal tubular dysfunction.

With cyclosporine and tacrolimus (calcineurin inhibitors), regular monitoring of blood levels can help maintain therapeutic levels and prevent nephrotoxicity. Usually, renal insufficiency is easily reversed by a reduction of the dosage. On the other hand, persistent injury can lead to interstitial fibrosis.

With cisplatin, the key to preventing renal injury is volume loading with saline. Some investigators advocate the use of amifostine, a thiol donor that serves as an antioxidant. Others prefer using carboplatin, a less nephrotoxic alternative.

Prevention of contrast-induced nephropathy

For contrast-induced nephropathy (CIN) from the use of radiocontrast dye, isotonic sodium chloride solution infusion has proven benefits as a preventive measure. [31]  Typically, isotonic sodium chloride solution (0.9%) administered at a rate of 1 mL/kg/h 12 hours before and 12 hours after the administration of the dye load is most effective, especially in the setting of prior renal insufficiency and diabetes mellitus. This has been shown to be superior to half normal saline infusions.

A single-center, randomized, controlled trial demonstrated that isotonic sodium bicarbonate (3 mL/kg/h given 1 h prior to the contrast-requiring procedure and then continued at 1 mL/kg/h for 6 h post procedure) may offer even greater protection than isotonic sodium chloride. [32]  The postulated mechanism is being attributed to the inhibition of oxidant injury by the administered alkali.

Nonionic contrast media are also protective in patients with diabetic nephropathy and renal insufficiency. In susceptible patients, the use of nonionic, low-osmolar contrast media reduces the likelihood of clinical nephrotoxicity.

Some investigators recommend the avoidance of contrast-requiring procedures, if at all possible. Magnetic resonance imaging (MRI) studies usually necessitate the use of gadolinium as a contrast agent, which, in several studies, has been shown to be less nephrotoxic than conventional contrast media. Using the lowest possible amount of contrast media in the procedure is also recommended.

To date, several interventions have been suggested to decrease the risk of CIN, such as furosemide, mannitol, dopamine, and fenoldopam, but none of these agents have been shown to be significantly effective.

The use of N-acetylcysteine (NAC) as a prophylactic agent has gained popularity, on the basis of the theory that contrast media cause direct renal tubular epithelial cell toxicity via exposure to reactive oxygen species (ROS), and NAC is believed to have antioxidant properties that potentially counteract the effects of ROS. [33]  Studies have also suggested that pretreatment with oral NAC (600 mg or 1200 mg bid on the day before and the day of the contrast-requiring procedure) acts as an antioxidant, scavenging ROS and thereby reducing the nephrotoxicity of contrast media.

Based on what is currently known, making a strong, evidence-based recommendation for the use of NAC in the prevention of CIN is not possible. Recognizing that NAC is inexpensive and is not associated with significant complications, in the absence of other effective pharmacologic therapy, its use in clinical practice is not entirely inappropriate. Additional large randomized, controlled trials of NAC are needed to better define its proper role in preventing CIN. The recently published PRESERVE trial demonstrated no benefit of either sodium bicarbonate or NAC for prevention of CIN, compared to saline hydration. [34]

Theophylline, an adenosine antagonist with a similar mechanism of action as NAC, is viewed as another potential agent to prevent CIN, the main difference being the lower risk profile associated with the latter. Its use is based on the idea that contrast media cause local release of adenosine, a known vasoconstrictor considered by some to have a potential role in the pathogenesis of CIN, and theophylline is a known adenosine antagonist. Although theophylline appears to be promising, further randomized trials are required to confirm its benefit in the prevention of CIN.

Aside from the recommended prophylactic medications discussed above, other guidelines recommend withholding potential nephrotoxic agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs).

In patients with underlying volume depletion, withholding ACE inhibitors and/or angiotensin receptor blockers (ARBs) may even be necessary. The use of ACE inhibitors and ARBs is limited by the tendency to cause prerenal failure, especially in patients who are considered to be at high risk; risk factors include advanced age, underlying renovascular disease, concomitant use of diuretics or vasoconstrictors (eg, NSAIDs, COX-2 inhibitors, and calcineurin inhibitors), and elevated baseline serum creatinine.

Metformin should be withheld at least 48 hours before a contrast imaging procedure and if AKI develops.

Prevention of rhabdomyolysis

Preventive strategies for rhabdomyolysis include aggressive volume resuscitation with normal saline at 1000-1500 mL/h with a goal urine output of 300 mL/h. Caution should be exercised to avoid producing a compartment syndrome, especially in those patients who remain oligoanuric despite infusions of large volumes of fluid.

In the presence of sufficient urine output, urine alkalinization to achieve a urine pH of greater than 6.5 is recommended to increase the solubility of the heme proteins within the tubules. This has also been shown to reduce the generation of ROS. Mannitol has not been shown to be more efficacious than volume expansion with normal saline alone.


Long-Term Monitoring

AKI in hospital inpatients has long-term implications after discharge. A meta-analysis of 13 cohort studies showed that patients with AKI had higher risk for developing chronic kidney disease (CKD) (hazard ratio [HR] 8.8, 95% confidence index [CI] 3.1-25.5), end-stage renal disease (HR 3.1, 95%CI 1.9-5.0) and mortality (HR 2.0, 95% CI 1.3 - 3.1). [35] AKI was also independently associated with risk of cardiovascular disease and congestive heart failure. Patients with AKI whose kidney function does not return to 25% of baseline have higher risk of mortality and renal outcomes. [36]

KDIGO guidelines recommend a 3-month follow-up after an AKI to determine whether the patient has experienced renal recovery or new-onset or progressive CKD. [24] Longer followup may benefit all patients, but may be especially valuable in patients with higher risk of poor outcomes. Higher-risk features are as follows [37] :

  • AKI requiring dialysis
  • Pre-existing CKD
  • Failure of kidney function to return to baseline
  • History of diabetes, heart failure, or cancer