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Pediatric Acute Tubular Necrosis Clinical Presentation

  • Author: Prasad Devarajan, MD, FAAP; Chief Editor: Craig B Langman, MD  more...
 
Updated: Jan 19, 2016
 

History

Patients with hospital-acquired acute tubular necrosis (ATN) frequently have no specific symptoms. The diagnosis is, at times, suspected when urine output diminishes and is usually made by the documentation of successive elevations in blood urea nitrogen (BUN) and serum creatinine levels. Careful evaluation of the hospital course usually reveals the cause of ATN. In patients with community-acquired ATN, a thorough history and physical examination are invaluable in pinpointing the etiology.

In children, the most common form is ischemic ATN caused by severe hypovolemia, shock, trauma, sepsis, burns, and major surgery. Nephrotoxic ATN is also common and is caused by various drugs. Their deleterious effect is markedly enhanced by hypovolemia, renal ischemia, or other renal insults.[27]

Conditions resulting in fluid loss

Severe vomiting and/or diarrhea are common causes of renal hypoperfusion in children. Significant fluid loss may also result from hemorrhage or burns. Loss of intravascular volume into the interstitial compartment accompanies major surgery, shock syndromes, and the nephrotic syndrome.

Children with fluid losses may complain of thirst, dizziness, palpitations, and fatigue. A history of acute weight loss and oliguria may be documented; however, ATN resulting from nephrotoxic drugs and from perinatal events are frequently nonoliguric. Refer to the illustration shown below.

Common causes of oliguric versus nonoliguric acute Common causes of oliguric versus nonoliguric acute renal failure in children.

Medication use

In the presence of mild prerenal insufficiency, ingestion of seemingly innocuous medications that impair renal autoregulation can precipitate oliguric ATN; for example, nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the renal synthesis of vasodilator prostaglandins and can precipitate ATN when administered to febrile children with intercurrent dehydration.

Cyclosporine, tacrolimus, and contrast agents are afferent arteriolar constrictors. Their nephrotoxicity is potentiated by preexisting hypovolemia because they inhibit the myogenic response of the afferent arteriole to renal hypoperfusion.

Drugs that induce direct tubule cell damage include aminoglycosides, amphotericin B, cyclosporine, tacrolimus, antineoplastic agents (eg, cisplatin, methotrexate), and contrast agents.

Acyclovir and sulfonamides can precipitate and obstruct the tubular lumens, especially in children with diminished tubular fluid flow.

Conditions associated with release of endogenous tubular toxins

Myoglobinuric ATN may be encountered in various clinical situations, including muscle trauma, prolonged seizures, malignant hyperthermia, snake and insect bites, myositis, severe hypokalemia and hypophosphatemia, and infections such as severe influenza.

Hemoglobinuric ATN can accompany various states of hemolysis, including transfusion reactions, malaria, snake and insect bites, glucose 6-phosphate dehydrogenase deficiency, and mechanical causes such as extracorporeal circulation and cardiac valvular prostheses.

Hyperuricosuric ATN is primarily observed during treatment of lymphoproliferative or myeloproliferative malignancies and presents as tumor lysis syndrome.

Hypoxia

In infants, ATN frequently complicates severe perinatal asphyxia, respiratory distress syndrome, hemorrhage, and cyanotic congenital heart disease. Older children with severe pulmonary or cardiac disease are also prone to ATN.

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Physical Examination

Signs of acute renal failure (ARF) include hypertension, edema, anemia, and signs of heart failure, such as hepatomegaly, gallop rhythm, and pulmonary edema.

Signs of intravascular volume depletion include tachycardia, orthostatic hypotension, decreased skin turgor, dry mucous membranes, and changes in sensorium.

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Complications

Infections develop in 30-70% of patients with ATN. These include infections of the respiratory system, urinary tract, and indwelling catheters. Impaired defenses due to uremia and excessive use of antibiotics and invasive maneuvers may contribute to the high rate of infectious complications.

Cardiovascular complications are primarily a result of fluid and sodium retention. They include hypertension, heart failure, and pulmonary edema. Hyperkalemia results in electrocardiographic (ECG) abnormalities and cardiac arrhythmias.

Other complications include the following:

  • GI (eg, anorexia, nausea, vomiting, ileus, bleeding)
  • Hematologic (eg, anemia, platelet dysfunction)
  • Neurologic (eg, confusion, asterixis, somnolence, seizures)
  • Electrolyte disturbances (eg, hyponatremia, hyperkalemia, hypocalcemia, hyperphosphatemia)
  • Metabolic acidosis
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Contributor Information and Disclosures
Author

Prasad Devarajan, MD, FAAP Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of the Nephrology Fellowship Program, Medical Director of the Kidney Stone Center, Co-Director of the Institutional Office of Pediatric Clinical Fellowships, Director of Clinical Nephrology Laboratory, CEO of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Prasad Devarajan, MD, FAAP is a member of the following medical societies: American Heart Association, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, Society for Pediatric Research

Disclosure: Received none from Coinventor on patents submitted for the use of NGAL as a biomarker of kidney injury for none.

Chief Editor

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, International Society of Nephrology

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Raptor Pharmaceuticals; Eli Lilly and Company; Dicerna<br/>Received grant/research funds from NIH for none; Received grant/research funds from Raptor Pharmaceuticals, Inc for none; Received grant/research funds from Alexion Pharmaceuticals, Inc. for none; Received consulting fee from DiCerna Pharmaceutical Inc. for none.

Acknowledgements

Richard Neiberger, MD, PhD Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group

Disclosure: The Osler Institute Honoraria Speaking and teaching

Adrian Spitzer, MD Professor, Department of Pediatrics, Albert Einstein College of Medicine; Director of NIH Training Program, Children's Hospital at Montefiore Medical Center

Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert Woroniecki, MD Assistant Professor, Department of Pediatrics, Section of Pediatric Nephrology, Albert Einstein College of Medicine, Children's Hospital of Montefiore

Disclosure: Nothing to disclose.

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Common causes of oliguric versus nonoliguric acute renal failure in children.
Metabolic alterations in tubule cells following acute tubular necrosis.
Compensatory mechanisms that maintain glomerular filtration rate despite a reduction in renal perfusion pressure.
Pathogenesis of acute tubular necrosis (macrovascular changes).
Alterations in tubule cell morphology in acute tubular necrosis.
Table. Urinary Indexes in Acute Tubular Necrosis vs Prerenal Failure
  ATN Prerenal
Urine specific gravity 1010 >1020
Urine sodium (mEq/L) >40 < 10
Urine/plasma creatinine < 20 >40
FENa (%) >2 < 1
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