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Acute Tubular Necrosis Treatment & Management

  • Author: Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
Updated: Dec 21, 2015

Approach Considerations

The main goal of treatment of acute tubular necrosis (ATN) is to prevent further injury to the kidney. Extracellular fluid (ECF) volume should be assessed promptly, either on clinical grounds or by invasive means (Swan-Ganz catheter), and repletion of any deficit should be initiated promptly. The 2011 UKRA guidelines recommend optimizing hemodynamic status by appropriate fluid therapy, giving vasopressors and/or inotropes and treating any underlying sepsis.[3]

All possible nephrotoxic drugs should be stopped. In addition, doses of all medications that are eliminated by the kidney should be adjusted.

Any complications that develop must be aggressively treated.

Visit the Pediatric Acute Tubular Necrosis article for additional information.


Correction of Oliguria

Despite some controversy in the literature, in general, if oliguria is present, make an attempt to increase urine output using intravenous loop diuretics. Use diuretics only if ECF volume and cardiac function are first carefully assessed and found adequate.

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 administered slowly because high doses can lead to hearing loss. If no response occurs, the treatment should be discontinued.

Dopamine, a selective renal vasodilator, has also been used to increase urine output, but this treatment has little benefit and is no longer recommended.



In general, there is no clear consensus on when or how often to perform hemodialysis in the setting of acute kidney injury (AKI). Some studies have suggested that early initiation may be beneficial, but in one prospective trial, aggressive dialysis did not improve recovery or survival rates. However, hemodialysis is still considered standard therapy in severe AKI. In addition, continuous hemodialysis (continuous venovenous hemodiafiltration [CVVHD] and continuous arteriovenous hemofiltration with dialysis [CAVHD]) and peritoneal dialysis are also available.

The 2011 UKRA AKI guidelines recommend starting renal replacement therapy (hemodialysis, CVVHD, CAVHD, or peritoneal dialysis) once AKI is firmly established but before overt complications arise.[3] .

No compelling studies suggest that one mode of dialysis is better than another. In general, patients with multiorgan failure and hemodynamic instability may benefit from a continuous mode because it is typically less hemodynamically taxing. The 2011 UKRA AKI guidelines recommend lowering the threshold for starting dialysis in the case of multiorgan failure.[3]

Some studies suggest that the use of biocompatible membranes instead of cuprophane membranes may improve the recovery rate and decrease the mortality rate in AKI. The 2011 UKRA AKI guidelines recommend using synthetic or modified cellulosic membranes rather than unmodified celluloid membranes if a choice is available. In addition, UKRA guidelines recommend bicarbonate as the preferred buffer for dialysate and replacement fluid in continuous dialysis.[3]

According to the 2011 UKRA guidelines, regardless of whether dialysis is performed intermittently or continuously, the prescribed dose should be assessed at each hemodialysis session.[3]

The 2011 UKRA guidelines recommend venovenous access rather than arteriovenous access for dialysis. Access should be placed by an experienced or supervised staff member, using real-time ultrasound as a guide to placement.[3]


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, where they may reduce the vasoconstrictive action of the drug. However, their use is typically avoided because of possible hypotension.


Dietary Measures

Aggressive and early nutritional support improves survival rates. Adequate protein and caloric intake is essential because marked increase in protein catabolism is often observed, especially in patients with shock, sepsis, or rhabdomyolysis. The risks of this catabolism include malnutrition and an impaired immune system. According to the 2011 UKRA AKI guidelines, patients with AKI who are receiving dialysis should be referred to a dietician for individual evaluation. The UKRA also recommends nutritional support with 25-35 kcal/kg/day, and up to1.7 g amino acids/kg/day, for patients receiving dialysis who are hypercatabolic.[3]


Prevention of Acute Tubular Necrosis

The approach to prevention differs with ischemic ATN and nephrotoxic ATN.

Prevention of ischemic acute tubular necrosis

Be attentive to optimizing cardiovascular function as well as to maintaining intravascular volume, especially in patients with preexisting risk factors or those taking nephrotoxic medications. Medicines that reduce systemic resistance (eg, afterload reducers) may cause renal vasoconstriction or affect the kidney’s autoregulatory response (eg, angiotensin-converting enzyme [ACE] inhibitors, cyclooxygenase [COX] inhibitors) and also should be used with caution.

Prevention of nephrotoxic acute tubular necrosis

Prevention of nephrotoxic ATN depends on the possible nephrotoxin under consideration.

With aminoglycosides, studies have demonstrated that once-daily dosing decreases the incidence of nephrotoxicity. In one study, 24% of patients receiving 3 daily doses developed clinical nephrotoxicity, compared to only 5% of patients receiving 1 daily dose. However, other studies comparing a single daily dose to 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 ECF 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 less nephrotoxic intrinsically.

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.[14] 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 of body weight/h given 1 h prior to the contrast-requiring procedure and then continued at 1 mL/kg of body weight/h for 6 h post procedure) may offer even greater protection than isotonic sodium chloride.[15] 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.[16] Studies have also suggested that pretreatment with oral NAC (600 mg or 1200 mg bid on the day prior to and on the day of the contrast-requiring procedure) acts as an antioxidant, scavenging ROS, thereby reducing the nephrotoxicity of contrast media.

Based on what is known now, 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.

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. 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, theophylline is a known adenosine antagonist. Although theophylline appears to be promising, further randomized trials are required to show any proven 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) and COX-2 inhibitors. In those patients with underlying volume depletion, withholding ACE inhibitors and/or angiotensin receptor blockers (ARBs) may even be necessary. Metformin should be withheld at least 48 hours before the procedure and until CIN has been ruled out.

Angiotensin II and prostaglandins play central roles in the maintenance of the glomerular filtration rate (GFR) in the face of volume depletion. ACE inhibitors and ARBs have gained popularity not only as antihypertensive agents but also as renoprotective agents that either slow or halt the progression of diabetic and nondiabetic kidney disease. They have also been shown in several studies to have a role in chronic heart failure as well as ventricular remodeling.

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.

Serum creatinine and electrolytes, especially potassium, should be measured before and at least 1 week after starting or changing the dose of the medication. A threshold for discontinuation of therapy has been suggested to be (1) an increase in serum creatinine of more than 0.5 mg/dL if the initial serum creatinine is less than 2.0 mg/dL or (2) an increase in serum creatinine of more than 1.0 mg/dL if the baseline serum creatinine is greater than 2.0 mg/dL.

An increase in serum creatinine of up to 30% is acceptable, but a continued rise of over 30% should prompt immediate discontinuation of the medication. Alternatively, discontinuation of ACE inhibitor or angiotensin receptor blocker therapy is not necessary if smaller increases in serum creatinine occur.

If and when prerenal AKI does develop, one should commence looking for underlying heart disease, volume depletion, hypotension, concomitant use of vasoconstrictors, or renovascular disease.

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.

Contributor Information and Disclosures

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF Clinical Professor of Medicine, Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine; Research Director, Internal Medicine Training Program, Advocate Christ Medical Center; Consulting Staff, Associates in Nephrology, SC

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF is a member of the following medical societies: American Heart Association, American Medical Association, American Society of Hypertension, American Society of Nephrology, Chicago Medical Society, Illinois State Medical Society, National Kidney Foundation, Society of General Internal Medicine

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Otsuka, Mallinckrodt, ZS Pharma<br/>Author for: UpToDate, ACP Smart Medicine.


Mahendra Agraharkar, MD, MBBS, FACP FASN, Clinical Associate Professor of Medicine, Baylor College of Medicine; President and CEO, Space City Associates of Nephrology

Mahendra Agraharkar, MD, MBBS, FACP is a member of the following medical societies: American College of Physicians, American Society of Nephrology, National Kidney Foundation

Disclosure: Received ownership interest/medical directorship from South Shore DaVita Dialysis Center for other; Received ownership/medical directorship from Space City Dialysis /American Renal Associates for same; Received ownership interest from US Renal Care for other.

Brent Kelly, MD Assistant Professor, Department of Dermatology, University of Texas Medical Branch, Galveston, Texas

Brent Kelly, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.


George R Aronoff, MD Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation

Disclosure: Nothing to disclose.

F John Gennari, MD Associate Chair for Academic Affairs, Robert F and Genevieve B Patrick Professor, Department of Medicine, University of Vermont College of Medicine

F John Gennari, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Federation for Medical Research, American Heart Association, American Physiological Society, American Society for Clinical Investigation, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Lee HT, Kim JY, Kim M, Wang P, Tang L, Baroni S, et al. Renalase protects against ischemic AKI. J Am Soc Nephrol. 2013 Feb. 24(3):445-55. [Medline]. [Full Text].

  2. Verghese E, Ricardo SD, Weidenfeld R, et al. Renal primary cilia lengthen after acute tubular necrosis. J Am Soc Nephrol. 2009 Jul 16. [Medline]. [Full Text].

  3. [Guideline] Lewington A, Kanagasundaram S, UK Renal Association. Clinical Practice Guidelines: Acute Kidney Injury. 5th Edition. The Renal Association. Available at 2011; Accessed: Dcember 16, 2015.

  4. Izzedine H, Escudier B, Rouvier P, Gueutin V, Varga A, Bahleda R, et al. Acute tubular necrosis associated with mTOR inhibitor therapy: a real entity biopsy-proven. Ann Oncol. 2013 Sep. 24(9):2421-5. [Medline].

  5. Foley RN, Sexton DJ, Reule S, Solid C, Chen SC, Collins AJ. End-stage renal disease attributed to acute tubular necrosis in the United States, 2001-2010. Am J Nephrol. 2015. 41 (1):1-6. [Medline].

  6. Nagler EV, Vanmassenhove J, van der Veer SN, Nistor I, Van Biesen W, Webster AC, et al. Diagnosis and treatment of hyponatremia: a systematic review of clinical practice guidelines and consensus statements. BMC Med. 2014 Dec 11. 12:1. [Medline].

  7. Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, Thiessen-Philbrook H, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014 Aug. 60(2):622-32. [Medline]. [Full Text].

  8. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004 Aug. 8(4):R204-12. [Medline]. [Full Text].

  9. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007. 11(2):R31. [Medline]. [Full Text].

  10. American College of Radiology. ACR Appropriateness Criteria: Renal Failure. Available at Accessed: September 10, 2010.

  11. Perdiz LB, Furtado GH, Linhares MM, et al. Incidence and risk factors for surgical site infection after simultaneous pancreas-kidney transplantation. J Hosp Infect. 2009 Aug. 72(4):326-31. [Medline].

  12. Mattoso R, Khouri N, de Jesus L, et al. Risk factors for graft dysfunction in the late period of renal transplantation. Transplant Proc. 2009 Jun. 41(5):1594-8. [Medline].

  13. Devarajan P. Emerging biomarkers of acute kidney injury. Contrib Nephrol. 2007. 156:203-12. [Medline].

  14. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med. 2002 Feb 11. 162(3):329-36. [Medline].

  15. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 May 19. 291(19):2328-34. [Medline].

  16. Tepel M, van der Giet M, Schwarzfeld C, et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000 Jul 20. 343(3):180-4. [Medline].

  17. Wijewickrama ES, Gooneratne L, De Silva C, Lanarolle RL. Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria. Saudi J Kidney Dis Transpl. 2013 Jan. 24(1):105-8. [Medline].

  18. Dent CL, Ma Q, Dastrala S, et al. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care. 2007. 11(6):R127. [Medline].

  19. du Cheyron D, Daubin C, Poggioli J, et al. Urinary measurement of Na+/H+ exchanger isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF. Am J Kidney Dis. 2003 Sep. 42(3):497-506. [Medline].

  20. Han WK, Bailly V, Abichandani R, et al. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002 Jul. 62(1):237-44. [Medline].

  21. Hirsch R, Dent C, Pfriem H, et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol. 2007 Dec. 22(12):2089-95. [Medline].

  22. Mishra J, Dent C, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005 Apr 2-8. 365(9466):1231-8. [Medline].

  23. Mishra J, Ma Q, Kelly C, et al. Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol. 2006 Jun. 21(6):856-63. [Medline].

  24. Mishra J, Mori K, Ma Q, et al. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol. 2004 Dec. 15(12):3073-82. [Medline].

  25. Parikh CR, Jani A, Melnikov VY, et al. Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis. 2004 Mar. 43(3):405-14. [Medline].

  26. van Timmeren MM, Vaidya VS, van Ree RM, et al. High urinary excretion of kidney injury molecule-1 is an independent predictor of graft loss in renal transplant recipients. Transplantation. 2007 Dec 27. 84(12):1625-30. [Medline]. [Full Text].

  27. Wagener G, Jan M, Kim M, et al. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006 Sep. 105(3):485-91. [Medline].

  28. Zhou H, Hewitt SM, Yuen PS, et al. Acute kidney injury biomarkers - needs, present status, and future promise. Nephrol Self Assess Program. 2006 Mar. 5(2):63-71. [Medline]. [Full Text].

  29. Hickson LJ, Chaudhary S, Williams AW, Dillon JJ, Norby SM, Gregoire JR, et al. Predictors of outpatient kidney function recovery among patients who initiate hemodialysis in the hospital. Am J Kidney Dis. 2015 Apr. 65 (4):592-602. [Medline].

A photomicrograph of renal biopsy shows renal medulla, which is composed mainly of renal tubules. Patchy or diffuse denudation of the renal tubular cells is observed, suggesting acute tubular necrosis (ATN) as the cause of acute kidney injury (AKI).
Acute tubular necrosis (ATN). Flattening of the renal tubule cells due to tubular dilation.
Acute tubular necrosis. Intratubular cast formation.
Acute tubular necrosis. Intratubular obstruction due to the denuded epithelium and cellular debris. Note that the denuded tubular epithelial cells clump together due to rearrangement of intercellular adhesion molecules (ICAM).
Sloughing of cells, which is responsible for the formation of granular casts, a feature of acute tubular necrosis (ATN).
Table. Laboratory Findings Used to Differentiate Prerenal Azotemia From ATN
Finding Prerenal Azotemia ATN and/or Intrinsic Renal Disease
Urine osmolarity


>500 < 350
Urine sodium


< 20 >40
Fractional excretion of sodium (FENa)


< 1 >2
Fractional excretion of urea


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