Treatment
Approach Considerations
In clinical situations in which renal hypoperfusion or toxic injury is anticipated, therapy with fluids, mannitol, diuretics, and renal-dose dopamine is used to prevent or reverse renal injury. Although these maneuvers do not alter the natural history of acute kidney injury, they are capable of converting the oliguric state to a nonoliguric acute kidney injury, which is more easily managed because it obviates the need for fluid restriction and allows for maximal nutritional support.
Vigorous fluid administration has been successfully used to prevent acute kidney injury following cardiac surgery, cadaveric renal transplantation, hemoglobinuria, myoglobinuria, hyperuricosuria, radiocontrast infusion, and therapy with amphotericin B or cisplatinum.
A trial of intravenous [IV] mannitol or furosemide should be attempted in a patient with oliguria for less than 48 hours who has not responded to adequate hydration [although meta-analysis studies have failed to document a clear benefit that can be associated with the use of either furosemide or mannitol therapy]. [20]
The benefit of renal-dose dopamine therapy is controversial. [21] Current recommendations are that it be considered for use in patients who are adequately hydrated and resistant to furosemide.
Once oliguria is established, mannitol may precipitate congestive heart failure; the risk of ototoxicity from furosemide and adverse hemodynamic changes from dopamine is significant.
Atrial natriuretic peptide
During the past decade, experimental studies in animals and humans have focused on restoration of renal hemodynamics and tubule cell integrity. Atrial natriuretic peptide [ANP] has been shown to improve renal function in animal models of ischemic acute kidney injury, predominantly via afferent arteriolar dilatation. In a large study of adults, ANP reduced the need for dialysis and improved survival in some patients with oliguric acute kidney injury. Further clinical trials with ANP are required to better define its therapeutic profile and optimal target population.
Other ongoing clinical trials include investigations into the role of growth factors such as insulinlike growth factor, nitric oxide inhibitors, antioxidants, and antagonists of endothelin receptors in human acute renal failure. However, in current practice, the efficacy of therapies such as dopamine, fenoldopam, and natriuretic peptides for the treatment of established acute kidney injury remains unproven and their routine use is not recommended.
Considerations in pharmacotherapy
Nephrotoxic agents should be avoided because they may worsen the renal injury and delay recovery of function. Such agents include contrast media, aminoglycosides, and NSAIDs.
Prescribing medication requires knowledge of the route of elimination and adjustments in dose or frequency based on residual renal function. Patients in the early phase with a rising creatinine should be assumed to have a glomerular filtration rate [GFR] of less than 10mL/min, irrespective of the absolute value for serum creatinine.
Consultations
Consult a pediatric nephrologist for management of all cases of oliguria, except in children with prerenal insufficiency from dehydration who have promptly responded to fluid therapy or those with mild nephrotoxic injury who have responded to discontinuation of the drug. Consult a pediatric urologist for the management of obstruction.
Transfer
If the patient with oliguria requires close monitoring of hemodynamic status or if indications for acute dialysis are present, transfer the patient to a center with ICU facilities.
Fluid Management
The major goal of fluid management is to restore and maintain normal intravascular volume. Patients with oliguric acute kidney injury may present with hypovolemia, euvolemia, or volume overload, and an estimation of fluid status is a prerequisite for initial and ongoing therapy. This is accomplished by determination of input and output, body weights, vital signs, skin turgor, capillary refill, peripheral edema, cardiopulmonary examination, serum sodium, and fractional excretion of sodium [FENa].
Children with intravascular volume depletion require prompt and vigorous fluid resuscitation. Initial therapy includes isotonic sodium chloride or lactated Ringer solution at 20mL/kg over 30 minutes, which can be repeated twice if necessary. This therapy should result in increased urine output within 4-6 hours. If oliguria persists [confirmed with bladder catheterization], central venous monitoring may be required to guide further management. Potassium administration is contraindicated until urine flow is established.
Oliguria with volume overload requires fluid restriction and intravenous furosemide. Failure to respond to furosemide suggests the presence of acute tubular necrosis rather than renal hypoperfusion, and fluid removal by dialysis or hemofiltration may be required, especially if signs of pulmonary edema are evident.
Potassium should be withheld until the oliguria improves and serum potassium levels begin to fall.
Monitoring treatment progress
Input and output records, daily weights, physical examination, and serum sodium guide ongoing therapy. When appropriate fluid therapy is administered, the body weight should decrease by 0.5-1.0% daily as a result of caloric deprivation, and the serum sodium concentration should remain steady. A more rapid weight loss and increasing serum sodium indicate inadequate fluid replacement. An absence of weight loss with decreasing serum sodium suggests excess free-water replacement.
Management of Hyperkalemia
In practice, the definitive therapy for significant hyperkalemia accompanying oliguric acute kidney injury frequently includes dialysis. The other forms of therapy outlined in this section serve primarily to tide over the crisis.
Serum potassium levels of 5.5-6.5 mEq/L should be treated by eliminating all sources of potassium from the diet or IV fluids and administration of a cation exchange resin, such as sodium polystyrene sulfonate [Kayexalate]. Kayexalate requires several hours of contact with the colonic mucosa to be effective, and the rectal route of administration is preferred. Complications of this therapy include hypernatremia and constipation.
Emergency treatment of hyperkalemia is indicated when serum potassium exceeds 6.5mEq/L or if peaked T waves are present. In addition to Kayexalate, patients should receive calcium gluconate [with continuous electrocardiographic monitoring] to counteract the effects of hyperkalemia on the myocardium.
Uptake of potassium by cells can be stimulated by infusion of glucose and insulin or by beta-agonists [albuterol by nebulizer]. The efficacy and convenience of nebulized albuterol has been well described in hemodialysis patients with hyperkalemia, but it can cause tachycardia.
Sodium bicarbonate, which also causes a rapid shift of potassium into cells, was the drug of choice in the past. However, the current recommendation is to use this therapy only in the concomitant presence of severe acidosis. Such therapy should be used with caution because it can precipitate hypocalcemia and sodium overload.
Management of Other Electrolytes and Acid-Base Balance
The primary treatment for hyponatremia is free water restriction; however, a serum sodium level of less than 120 mEq/L or accompanied central nervous system [CNS] dysfunction may require 3% sodium chloride infusion.
The management of hyperphosphatemia includes dietary restriction and oral phosphate binders [calcium carbonate or calcium acetate]. Hypocalcemia usually responds to the oral calcium salts used for control of hyperphosphatemia but may require 10% calcium gluconate infusion if severe.
Mild metabolic acidosis is treated with oral sodium bicarbonate or sodium citrate. Severe acidosis [pH < 7.2], especially in the presence of hyperkalemia, requires IV bicarbonate therapy. Recognize that bicarbonate therapy requires adequate ventilation [to excrete the carbon dioxide produced] to be effective, and it may precipitate hypocalcemia and hypernatremia. Patients who cannot tolerate a large sodium load [eg, those with congestive heart failure] may be treated in an ICU setting with IV tromethamine [THAM], with provision of adequate ventilatory support pending institution of dialysis.
Management of Hypertension
Mild hypertension usually responds to salt restriction and diuretics. Moderate, asymptomatic hypertension is most commonly treated with oral or sublingual calcium channel blockers or with IV hydralazine.
For patients with hypertensive encephalopathy, treatment may require continuous sodium nitroprusside infusion with monitoring of thiocyanate levels. Because nitroprusside therapy requires careful drip calculations and administration, other immediate alternatives include a nicardipine drip or labetalol. Once the hypertensive crisis has been controlled, oral long-acting agents can be initiated.
Dialysis
The general goal of dialysis is to remove endogenous and exogenous toxins and to maintain the fluid, electrolyte, and acid-base balance until renal function returns. The indications for acute dialysis are not absolute, and the decision to use this modality depends on the rapidity of onset, duration, and severity of the abnormality to be corrected. Common indications include the following:
Fluid overload that is unresponsive to diuretics or a hindrance to adequate nutrition
Symptomatic acid-base imbalance, electrolyte imbalance, or both [especially hyperkalemia] that is unresponsive to nondialytic management
Refractory hypertension
Symptomatic uremia [CNS symptoms, pericarditis, pleuritis]
The choice between hemodialysis, peritoneal dialysis, and continuous venovenous hemodialysis [CVVH] depends on the overall clinical condition, the availability of technique, the etiology of the renal failure, institutional preferences, and specific indications or contraindications.
Peritoneal dialysis
In general, peritoneal dialysis is a gentler continuous method that was a more preferred technique in children in the past. It is not the treatment of choice for acute, severe fluid overload or hyperkalemia, however, because the onset of action is slower. Specific contraindications include abdominal wall defects, bowel distention, perforation or adhesions, and communications between the chest and abdominal cavities.
Hemodialysis
Hemodialysis requires vascular access, heparinization, a large extracorporeal blood volume, and skilled personnel, but it has the advantage of rapid correction of fluid, electrolyte, and acid-base imbalances. This therapy may be difficult to accomplish in hypotensive patients with multiorgan damage
CVVH
CVVH has emerged as an alternative therapy for children who require fluid removal in an unstable, critically ill setting. The major advantage of these techniques is in their potential ability to remove fluid, even in a hypotensive child in whom hemodialysis may be contraindicated and peritoneal dialysis may be inefficient. However, patients require the presence of trained personnel and specialized equipment that are available only at select tertiary care centers.
Management of Urologic Obstruction
Patients with oliguria secondary to obstruction frequently require urologic care. The site of obstruction determines the primary therapy.
Obstruction of the bladder neck due to posterior urethral valves should be immediately relieved by gentle insertion of a fine urethral catheter. Foley catheters should not be used because the balloon may become lodged in the dilated prostatic urethra, resulting in incomplete bladder emptying.
The subsequent management of choice is endoscopic ablation of the valves. A temporary cutaneous vesicostomy may be required in a small infant whose urethra may not accept an endoscope or when hydronephrosis and renal function do not improve after catheterization.
Relief of obstruction is often followed by postobstructive diuresis. The resultant polyuria, hypokalemia, and hyponatremia should be managed with vigorous fluid replacement guided by frequent determinations of urinary flow rate, urinary electrolytes, and serum electrolytes.
Diet
Children with oliguric acute kidney injury are frequently in a highly catabolic state; therefore, aggressive nutritional support is important. Adequate calories should be provided to allow for maintenance requirements, and supplements should be provided to combat excessive catabolism. Children should be administered at least 150% of maintenance caloric intake and at least 3 g/kg/d of daily protein intake.
Protein of high biologic value should be administered in amounts that are sufficient to maintain neutral nitrogen balance, reflected by steady BUN levels.
Oral feeding is the preferred route. Infants should be placed on a low-phosphorus formula [Similac PM 60/40], and older children should be fed a low-phosphorus/low-potassium diet.
Additional calories may be supplied by fortifying foods with Polycose and medium-chain triglycerides.
Children who are nauseous or anorexic may benefit from enteral feedings. If these are not possible, central IV hyperalimentation may be used to deliver concentrated dextrose [25%] and lipids [20%].
If adequate nutrition cannot be achieved because of fluid restriction, early institution of ultrafiltration or dialysis should be considered.
Cerda J. Oliguria: an earlier and accurate biomarker of acute kidney injury?. Kidney Int. 2011 Oct. 80[7]:699-701. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012. 120 [4]:c179-84. [QxMD MEDLINE Link].
Bianchi NA, Stavart LL, Altarelli M, Kelevina T, Faouzi M, Schneider AG. Association of oliguria with acute kidney injury diagnosis, severity assessment, and mortality among patients with critical illness. JAMA Netw Open. 2021 Nov 1. 4 [11]:e2133094. [QxMD MEDLINE Link]. [Full Text].
Devarajan P. Acute kidney injury: Acute kidney injury: still misunderstood and misdiagnosed. Nat Rev Nephrol. 2017 Mar. 13 [3]:137-8. [QxMD MEDLINE Link].
Mehrazma M, Hooman N, Otukesh H. Prognostic value of renal pathological findings in children with atypical hemolytic uremic syndrome. Iran J Kidney Dis. 2011 Nov. 5[6]:380-5. [QxMD MEDLINE Link].
Adragna M, Balestracci A, García Chervo L, Steinbrun S, Delgado N, Briones L. Acute dialysis-associated peritonitis in children with D+ hemolytic uremic syndrome. Pediatr Nephrol. 2012 Apr. 27 [4]:637-42. [QxMD MEDLINE Link].
Bunchman TE, McBryde KD, Mottes TE, et al. Pediatric acute renal failure: outcome by modality and disease. Pediatr Nephrol. 2001 Dec. 16[12]:1067-71. [QxMD MEDLINE Link].
Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001. Am J Kidney Dis. 2005 Jan. 45[1]:96-101. [QxMD MEDLINE Link].
Bailey D, Phan V, Litalien C, et al. Risk factors of acute renal failure in critically ill children: A prospective descriptive epidemiological study. Pediatr Crit Care Med. 2007 Jan. 8[1]:29-35. [QxMD MEDLINE Link].
Schneider J, Khemani R, Grushkin C, Bart R. Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. Crit Care Med. 2010 Mar. 38[3]:933-9. [QxMD MEDLINE Link].
Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, AWARE Investigators. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med. 2017 Jan 5. 376 [1]:11-20. [QxMD MEDLINE Link].
Symons JM, Chua AN, Somers MJ, et al. Demographic characteristics of pediatric continuous renal replacement therapy: a report of the prospective pediatric continuous renal replacement therapy registry. Clin J Am Soc Nephrol. 2007 Jul. 2[4]:732-8. [QxMD MEDLINE Link].
Goldstein SL, Devarajan P. Pediatrics: Acute kidney injury leads to pediatric patient mortality. Nat Rev Nephrol. 2010 Jul. 6[7]:393-4. [QxMD MEDLINE Link].
Goldstein SL, Devarajan P. Acute kidney injury in childhood: should we be worried about progression to CKD?. Pediatr Nephrol. 2011 Apr. 26[4]:509-22. [QxMD MEDLINE Link].
Garg AX, Suri RS, Barrowman N, et al. Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA. 2003 Sep 10. 290[10]:1360-70. [QxMD MEDLINE Link].
Askenazi DJ, Feig DI, Graham NM, Hui-Stickle S, Goldstein SL. 3-5 year longitudinal follow-up of pediatric patients after acute renal failure. Kidney Int. 2006 Jan. 69[1]:184-9. [QxMD MEDLINE Link].
Krawczeski CD, Goldstein SL, Woo JG, et al. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011 Nov 22. 58[22]:2301-9. [QxMD MEDLINE Link]. [Full Text].
Siew ED, Ware LB, Ikizler TA. Biological markers of acute kidney injury. J Am Soc Nephrol. 2011 May. 22[5]:810-20. [QxMD MEDLINE Link].
Cantarovich F, Rangoonwala B, Lorenz H, et al. High-dose furosemide for established ARF: a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Am J Kidney Dis. 2004 Sep. 44[3]:402-9. [QxMD MEDLINE Link].
Gambaro G, Bertaglia G, Puma G, D'Angelo A. Diuretics and dopamine for the prevention and treatment of acute renal failure: a critical reappraisal. J Nephrol. 2002 May-Jun. 15[3]:213-9. [QxMD MEDLINE Link].
Onder AM, Rosen D, Mullett C, Cottrell L, Kanosky S, Grossman OK, et al. Comparison of Intraoperative Aminophylline Versus Furosemide in Treatment of Oliguria During Pediatric Cardiac Surgery. Pediatr Crit Care Med. 2016 Aug. 17 [8]:753-63. [QxMD MEDLINE Link].
Abuelo JG. Normotensive ischemic acute renal failure. N Engl J Med. 2007 Aug 23. 357[8]:797-805. [QxMD MEDLINE Link].
American Society of Nephrology. American Society of Nephrology Renal Research Report. J Am Soc Nephrol. 2005 Jul. 16[7]:1886-903. [QxMD MEDLINE Link]. [Full Text].
Andreoli SP. Acute kidney injury in children. Pediatr Nephrol. 2009 Feb. 24[2]:253-63. [QxMD MEDLINE Link]. [Full Text].
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012 Aug 25. 380 [9843]:756-66. [QxMD MEDLINE Link].
Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011 Nov. 121[11]:4210-21. [QxMD MEDLINE Link]. [Full Text].
Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005 Nov. 16[11]:3365-70. [QxMD MEDLINE Link].
Devarajan P. Cellular and molecular derangements in acute tubular necrosis. Curr Opin Pediatr. 2005 Apr. 17[2]:193-9. [QxMD MEDLINE Link].
Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006 Jun. 17[6]:1503-20. [QxMD MEDLINE Link].
Devarajan P, Goldstein SL. Acute renal failure. Kher KK, Schnaper HW, Makker SP. Clinical Pediatric Nephrology. Second Edition. Oxon, UK: Informa Healthcare; 2007. 3770390.
Goldstein SL. Pediatric acute kidney injury: it's time for real progress. Pediatr Nephrol. 2006 Jul. 21[7]:891-5. [QxMD MEDLINE Link].
Goldstein SL. Pediatric acute renal failure: demographics and treatment. Contrib Nephrol. 2004. 144:284-90. [QxMD MEDLINE Link].
Gouyon JB, Guignard JP. Management of acute renal failure in newborns. Pediatr Nephrol. 2000 Sep. 14[10-11]:1037-44. [QxMD MEDLINE Link].
Lameire NH, De Vriese AS, Vanholder R. Prevention and nondialytic treatment of acute renal failure. Curr Opin Crit Care. 2003 Dec. 9[6]:481-90. [QxMD MEDLINE Link].
Mehta RL, Chertow GM. Acute renal failure definitions and classification: time for change?. J Am Soc Nephrol. 2003 Aug. 14[8]:2178-87. [QxMD MEDLINE Link]. [Full Text].
Mehta RL, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004 Oct. 66[4]:1613-21. [QxMD MEDLINE Link].
Siegel NJ, Van Why SK, Devarajan P. Pathogenesis of acute renal failure. Avner ED, Harmon WE, Niaudet P, eds. Pediatric Nephrology. Philadelphia, PA: Lippincott Williams & Wilkins; 2004. 1223.
Pathogenesis of prerenal failure
Compensatory mechanisms for preventing a fall in glomerular filtration rate [GFR] in the presence of prerenal failure
Mechanisms of intrinsic acute renal failure.
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:
Serve[d] as a director, officer, partner, employee, advisor, consultant or trustee for: Consultant for Reata, Dicerna, Alnylam
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 Tenured Professor of Pediatrics, The First Isaac A Abt, MD, Professor of Kidney Diseases [Emeritus], Northwestern University, The Feinberg School of Medicine; Staff Nephrologist, 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 Federation for Clinical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Pediatric Nephrology, Association of Clinical Scientists, Cochrane Collaboration, International Bone and Mineral Society, International Conferences on Calcium Regulating Hormones, International Pediatric Nephrology Association, International Society of Nephrology, International Society of Renal Nutrition and Metabolism, Midwest Society for Pediatric Research, Pediatric Academic Societies, ROCK [Research on Calculus Kinetics] Society, Society for Pediatric Research
Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Horizon Pharmaceuticals]; ; Dicerna Pharmaceuticals
Incyte Pharmaceuticals; Eli Lilly for: Federation bio; Dicerna pharmaceuticals.
Acknowledgements
Laurence Finberg, MD Clinical Professor, Department of Pediatrics, University of California, San Francisco, School of Medicine and Stanford University School of Medicine
Laurence Finberg, MD is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.
Luther Travis, MD Professor Emeritus, Departments of Pediatrics, Nephrology and Diabetes, University of Texas Medical Branch School of Medicine
Luther Travis, MD is a member of the following medical societies: Alpha Omega Alpha, American Federation for Medical Research, International Society of Nephrology, and Texas Pediatric Society
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.