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Neonatal acute kidney injury: Evaluation, management, and prognosis

Neonatal acute kidney injury: Evaluation, management, and prognosis
Literature review current through: Jan 2024.
This topic last updated: Aug 31, 2021.

INTRODUCTION — Acute kidney injury (AKI), formerly referred to as acute renal failure, is defined as an acute reduction in kidney function due to a decline in glomerular filtration rate leading to retention of urea and other nitrogenous waste products, and loss of fluid, electrolyte, and acid-base regulation. AKI is an important contributing factor to the morbidity and mortality of critically ill neonates.

The diagnostic evaluation, management, and prognosis of neonatal AKI are presented in this topic review. The pathogenesis, etiology, presentation, and diagnosis of neonatal AKI are presented separately. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis".)

IDENTIFYING THE UNDERLYING CAUSE

Overview — Once the diagnosis of neonatal AKI is made, further evaluation is focused towards identifying the underlying etiology so that management can be directed towards reversing the underlying cause if possible (table 1).

The evaluation consists of a directed history and physical examination including evaluation of the fluid status, renal imaging, and the use of a fluid challenge as a diagnostic and therapeutic measure. Laboratory tests such as serum potassium, bicarbonate, and phosphorus are not as useful in neonates compared with older patients, because of the variable range of values due to functional and developmental immaturity of the neonatal kidney, which is affected by gestational age (GA) and postnatal age. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Normal neonatal kidney function'.)

Our general approach to the diagnostic evaluation encompasses the following (algorithm 1):

Renal ultrasound to identify patients with congenital anomalies of the kidney and urinary tract (CAKUT), particularly those associated with obstructive uropathy and patients with renal vascular disease. (See "Fetal hydronephrosis: Etiology and prenatal management", section on 'Prenatal kidney and urologic ultrasound examination' and "Identifying newborns with critical congenital heart disease", section on 'Prenatal diagnosis'.)

Except for infants with clear evidence of systemic or pulmonary fluid overload or obstructive uropathy on ultrasonography, a fluid challenge is administered to differentiate patients with prerenal AKI due to hypovolemia (positive response) from those with intrinsic kidney disease.

Further evaluation for those who failed to respond to the fluid challenge includes a review of nephrotoxic exposure, history of perinatal asphyxia or severe/prolonged renal hypoperfusion, and presence of concomitant conditions (eg, sepsis, nephrotic syndrome, congenital heart disease) associated with intrinsic kidney disease.

History — The history is directed towards uncovering an obvious risk factor or cause for neonatal AKI.

Prenatal ultrasound demonstrating bilateral hydronephrosis or unilateral hydronephrosis in a solitary kidney is indicative of postrenal AKI due to obstructive uropathy. (See "Postnatal evaluation and management of hydronephrosis", section on 'Postnatal ultrasound'.)

History of potentially nephrotoxic drugs administered either pre- or postnatally is suggestive of intrinsic kidney injury [1]. These include aminoglycosides, prostaglandin synthesis inhibitors (eg, indomethacin), amphotericin B, vancomycin, and acyclovir.

Prenatal administration of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers.

History of perinatal asphyxia. (See "Perinatal asphyxia in term and late preterm infants", section on 'Acute kidney injury'.)

Prematurity – Very preterm infants (GA less than 32 weeks) are at a higher risk for AKI. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Incidence'.)

History of excessive fluid loss (eg, bleeding, diarrhea, or increased insensible loss) that are not adequately replaced is suggestive of prerenal AKI due to hypovolemia.

Family history of congenital nephrotic syndrome or cystic kidney disease is suggestive of an underlying chronic condition resulting in chronic kidney disease (CKD). (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Differential diagnosis'.)

Prenatal history of oligohydramnios caused by decreased urine output is suggestive of an underlying chronic congenital condition resulting in CKD. (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Amniotic fluid'.)

Physical examination — The physical examination should include measurement of blood pressure, and assessment of hydration status (eg, hypovolemia or hypervolemia) including weight changes or signs of heart failure. It is important to identify infants with systemic or pulmonary fluid overload (edema, weight gain, elevated blood pressure, diaphoresis, and tachypnea) as a fluid challenge is contraindicated for patients with these findings because it may exacerbate their symptoms.

The presence of the following physical findings often points to a specific underlying etiology.

Weight changes:

Hypovolemia and prerenal AKI is suggested by excessive weight loss.

Hypervolemia is suggested by excessive weight gain due to impaired water excretion resulting in fluid retention. This may be seen in patients with either intrinsic or postrenal AKI.

Vital signs and perfusion:

Hypovolemia and prerenal AKI is often accompanied by increased heart rate and decreased peripheral perfusion (prolonged capillary refill).

Hypervolemia is suggested by elevated blood pressure, diaphoresis, and tachypnea.

Palpable kidneys may be an indication of renal vein thrombosis, severe hydronephrosis, or cystic kidney disease.

Palpable enlarged bladder may be an indication of urethral obstruction (eg, posterior urethral valves) or neurogenic bladder.

Congenital anomalies that are associated with kidney disease include:

Ambiguous genitalia

Undescended testicles

Prune belly – Deficient abdominal wall musculature and undescended nonpalpable testes

Outer ear anomalies

Renal ultrasound

Prenatal ultrasound — Prenatal ultrasonography is a common procedure in many countries and is able to detect CAKUT and in other organs (eg, congenital heart disease). (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Antenatal screening' and "Identifying newborns with critical congenital heart disease", section on 'Prenatal diagnosis'.)

Severe bilateral fetal hydronephrosis is indicative of postrenal AKI due to obstructive uropathy. Postrenal AKI may also be associated with severe unilateral hydronephrosis in a solitary kidney. In males, the most common diagnosis is posterior urethral valves with additional findings of a dilated bladder and posterior urethra (image 1). (See "Fetal hydronephrosis: Etiology and prenatal management", section on 'Prenatal kidney and urologic ultrasound examination' and "Clinical presentation and diagnosis of posterior urethral valves".)

Other kidney malformations that can be detected antenatally include renal cystic disease and renal hypodysplasia, which are associated with CKD. (See "Prenatal sonographic diagnosis of cystic kidney disease" and "Renal hypodysplasia", section on 'Antenatal presentation'.)

Postnatal imaging — Renal ultrasound examination is the initial postnatal imaging study to evaluate all newborns with AKI (algorithm 1). It is used to document the presence of one or two kidneys, and delineates kidney size and shape. The absence of bilateral hydronephrosis and hydroureter or unilateral findings in a solitary kidney, and a normal size bladder with normal emptying typically rules out urinary tract obstruction (postrenal AKI). Simultaneous Doppler examination allows assessment of renal blood flow and helps diagnose occlusion of the major renal vessels (eg, renal arterial or venous thrombosis). (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Postrenal disease' and "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Renal vasculature disease'.)

Renal ultrasound also can differentiate AKI from CKD by detecting findings (eg, cysts, hypoplasia) that are consistent with congenital or genetic conditions. (See "Kidney cystic diseases in children" and "Autosomal dominant polycystic kidney disease (ADPKD) in children", section on 'Kidney manifestations' and "Renal hypodysplasia", section on 'Ultrasound findings' and "Autosomal recessive polycystic kidney disease in children", section on 'Imaging'.)

Fluid challenge — A fluid challenge is of diagnostic as well as therapeutic value. This intervention is used to identify infants with prerenal AKI due to hypovolemia. It should be administered to all infants with AKI and oliguria except those with hypertension or other clinical signs of intravascular volume overload (heart failure, respiratory distress, or edema) (algorithm 1).

The fluid challenge consists of an intravenous (IV) administration of 10 to 20 mL/kg of isotonic saline given over one to two hours. Saline is effective as a fluid challenge and avoids complications associated with colloid administration, including the risk of infection and leakage of protein into the lungs leading to pulmonary edema [2]. We do not infuse colloid such as albumin or fresh frozen plasma, except when clearly indicated (eg, fresh frozen plasma for a bleeding diathesis or albumin for hypoalbuminemia with increased risk for third spacing).

A positive response is any urine output in an anuric patient, an increase in urine output to ≥1 mL/kg per hour in an oliguric patient, or improvement of serum creatinine (SCr) (table 2), is indicative of a prerenal cause due to hypovolemia (see "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Serum creatinine' and "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Prerenal disease'). For infants who respond, continued efforts are focused on achieving and maintaining adequate hydration by replacing deficits and ongoing losses. (See 'Fluid management' below.)

For patients who develop clinical signs of fluid overload (elevated blood pressure, respiratory rate, and/or heart rate), the evaluation should focus on evidence of cardiac disease or intrinsic renal AKI. Respiratory symptoms may occur in conditions that cause altered distribution of fluid from the vascular space into the interstitium referred to as third spacing. Neonatal conditions associated with third spacing include nephrotic syndrome, hepatic failure, sepsis, hypoalbuminemia, and hydrops fetalis.

The fluid challenge should be repeated in infants who do not respond to the initial infusion and do not have clinical signs of fluid overload. Absence of a response to a repeated challenge generally indicates intrinsic kidney disease. For this subset of patients, a comprehensive review for evidence of nephrotoxin exposure, prenatal asphyxia, or hyporenal perfusion, and an evaluation for sepsis should be performed. Conservative treatment, including fluid restriction, careful monitoring of fluid balance and serum electrolytes, and renal replacement therapy (RRT) are provided for these patients. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Intrinsic renal disease' and "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Postrenal disease'.)

Laboratory evaluation — Laboratory evaluation is not as helpful in identifying the etiology of AKI in neonates as it is in older infants, children, and adults. This is due to the functional and developmental immaturity of the neonatal kidney, especially in preterm infants.

Urine tests

The utility of the urinalysis in neonates is limited by the following:

Proteinuria, which is used to indicate intrinsic kidney disease in older patients, is commonly a normal finding in newborns, especially in very preterm infants [3]. The degree of proteinuria increases with decreasing GA.

Microscopic hematuria may be a common finding, especially in specimens obtained by catheterization.

Glucosuria is common in preterm infants born before 34 weeks gestation and is not indicative of kidney injury [4].

Limited urinary volume may preclude a satisfactory microscopic examination.

Urinalysis is relatively normal in cases of prerenal disease (most common cause of neonatal AKI) and most cases of postrenal disease.

The presence of muddy brown granular casts and epithelial cell casts is highly suggestive of acute tubular necrosis (ATN) (picture 1 and picture 2). However, the absence of these urinary findings does not exclude the diagnosis.

Urine osmolality and sodium used in older children and adults are not helpful tests to differentiate between prerenal and intrinsic neonatal renal AKI, especially in extremely preterm infants (GA less than 28 weeks) because of their limited urine concentrating ability and a lower renal tubular sodium reabsorption. In addition, urine-specific gravity is not useful, because proteinuria and glycosuria are commonly observed in neonates. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Tubular function'.)

Serum/plasma sodium — Changes in serum or plasma sodium (PNa) reflect changes in water balance.

Rise in sodium levels is usually due to excessive free water losses that have not been replenished. It is a common finding in preterm infants with insufficient water intake and increased insensible losses due to increased body surface area, body size, thinness of the skin dermis, and the frequent use of radiant heaters and some phototherapy units. The increase in sodium in AKI is usually accompanied by loss of body weight.

Decrease in sodium levels in spite of adequate intake is due to retention of water due to impaired water excretion. The decrease in sodium is often accompanied by an increase in body weight and/or evidence of fluid overload (eg, edema).

Fractional excretion of sodium — The fractional excretion of sodium (FENa) is the most commonly used laboratory test to differentiate between prerenal AKI and intrinsic disease due to ATN. However, the ability to use FENa in neonates is limited due to a lower renal tubular sodium reabsorption, especially in extremely preterm infants [3]. (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury".)

FENa is calculated from measured concentrations of urinary sodium (UNa) and creatinine (UCr), and plasma sodium (PNa) and plasma creatinine (PCr):

FENa, percent = ((Una × SCr) ÷ (SNa × UCr)) × 100

Calculators are available for FENa expressed using either standard units (calculator 1) or SI (international system) units (calculator 2).

FENa is a direct measurement of renal tubular handling of the filtered sodium, but sodium reabsorption is decreased in neonates [3]. As a result, the FENa cutoff values differentiating prerenal AKI and ATN in neonates are higher to minimize the overlap between neonates with and without AKI [5,6]. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Tubular function'.)

In term infants, the FENa is usually below 2 percent in prerenal AKI and usually greater than 2.5 percent in ATN [7].

In preterm infants, FENa cutoff values increase with decreasing GA as the threshold for sodium reabsorption decreases with decreasing GA. Limited data suggest the use of the following to differentiate intrinsic from prerenal AKI (value below 2 percent) [3,8]:

FENa >3 percent in preterm infants >31 weeks GA

FENa >6 percent in preterm infants 29 to 30 weeks GA

Because of overlap, the FENa is not used in infants <28 weeks GA

PREVENTION — Neonates are more vulnerable to AKI than older individuals due to functional and developmental immaturity of the neonatal kidney that affects glomerular filtration and tubular function (eg, concentrating ability), hemodynamic changes that occur at delivery, and risk of hypovolemia due to large insensible water losses. As a result, prevention of AKI is challenging.

Preventive measures — Although there is limited evidence demonstrating effectiveness in neonates, the following preventive measures are used:

Adjusting the administration of renally excreted drugs (eg aminoglycosides), which are potentially nephrotoxic based on glomerular filtration rates that vary based on gestational and postnatal age [9]. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Glomerular filtration rate'.)

Ongoing surveillance for exposure to nephrotoxic drugs [10]. If possible, discontinue any medication that is nephrotoxic.

For infants cared for in the neonatal intensive care unit, avoiding hypovolemia by ensuring balanced fluid and electrolyte intake and output. Appropriate readjustment of fluid intake is based on the assessment of accurate measurements of intake and output (urinary volume), weight (at least daily and sometimes more frequently), and serum sodium concentration [11]. (See "Fluid and electrolyte therapy in newborns", section on 'Monitoring tools' and "Fluid and electrolyte therapy in newborns", section on 'Fluid and electrolyte management'.)

Carefully enforcing fluid restriction when needed, as may be the case for newborn infants with patent ductus arteriosus, postcardiac surgery, intracranial hemorrhage, bronchopulmonary dysplasia, or who are oliguric or anuric.

Monitoring of renal function, including serum creatinine (SCr) measurements and urine output for at-risk patients with the following [11,12]:

Prematurity with a gestational age (GA) <32 weeks

Exposure nephrotoxic medication [10]

Critical congenital heart disease

Perinatal asphyxia

Sepsis

Polycythemia

Hydrops fetalis

Unproven measures

Dopamine — Although dopamine infused at low doses (1 to 3 mcg/kg per minute) increases renal blood flow and can raise urinary output, there is at present no evidence for a renal protective effect in critically ill newborns and potential harm from adverse effects [13]. However, dopamine beginning at 5 mcg/kg per min is used to manage infants with distributive shock who do not adequately respond to fluid resuscitation. (See "Renal actions of dopamine".)

Theophylline and perinatal asphyxia — Several studies have shown that theophylline, a nonspecific adenosine receptor antagonist that inhibits the renal vasoconstriction produced by adenosine, reduces the risk of kidney dysfunction in asphyxiated full-term infants [14-20]. These data show that prophylactic theophylline administration (dosing from 5 to 8 mg/kg) compared with placebo was associated with a reduction in severe kidney dysfunction. However, we do not suggest prophylactic theophylline be given, because there is lack of information regarding long-term kidney and neurodevelopmental outcome. More importantly, these trials were conducted prior to the use of hypothermia therapy, and these data cannot be used to predict the effect of prophylactic theophylline on kidney outcome in infants undergoing hypothermia therapy, which is the recommended intervention for infants with severe perinatal asphyxia. But if hypothermia therapy is not available, prophylactic theophylline should be considered to reduce the risk of severe kidney dysfunction. (See "Clinical features, diagnosis, and treatment of neonatal encephalopathy", section on 'Therapeutic hypothermia' and "Perinatal asphyxia in term and late preterm infants".)

MANAGEMENT — The general management of neonatal AKI includes:

Specific treatment of the underlying cause, if available

Fluid management

Electrolyte management

Nutritional support

Review and adjustment of drug therapy

Kidney replacement therapy (KRT)

Directed therapy based on etiology — Specific interventions for neonatal AKI based on the underlying etiology include (see "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Pathogenesis and etiology'):

Hypovolemia – As noted above, fluid resuscitation (challenge) restores renal perfusion and function for infants with prerenal AKI due to hypovolemia. (See 'Fluid challenge' above.)

Cardiac disease and reduced renal perfusion – Directed therapy for the underlying cardiac condition restores renal perfusion and function. Examples include:

Administration of prostaglandin E1 for a ductal-dependent critical congenital heart defect. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Specific congenital heart disease measures'.)

Cardiac pacing for infants with complete heart block, which is most commonly seen in patients with neonatal lupus. (See "Bradycardia in children", section on 'Acute management of patients with poor perfusion' and "Neonatal lupus: Management and outcomes", section on 'Infants and children at risk for complete heart block'.)

Sepsis – Antibiotic therapy. (See "Management and outcome of sepsis in term and late preterm neonates", section on 'Antibiotic therapy' and "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Antibiotic therapy'.)

Hypoalbuminemia or capillary leak – Judicious intravenous (IV) administration of albumin infusion and furosemide for symptomatic patients with edema due to low oncotic pressure. (See "Evaluation and management of edema in children", section on 'Intravenous albumin infusion'.)

Obstructive uropathy – Decompression and drainage of the urinary tract should be performed. In most instances, temporary drainage is performed by placement of a catheter in the bladder. Surgical drainage, if needed, should be performed after stabilization of the patients, including medical therapy to correct electrolyte abnormalities, particularly hyperkalemia. (See "Management of posterior urethral valves", section on 'Postnatal management'.)

Renal vascular thrombosis – For neonates with severe renal vascular thrombosis and AKI, thrombolytic therapy should be considered. (See "Neonatal thrombosis: Management and outcome", section on 'Treatment based on thrombus location'.)

Nephrotoxin exposure – Any nephrotoxic medication should be either discontinued or dose adjusted for the severity of kidney failure.

Fluid management — Meticulous fluid management is needed to avoid fluid overload and its potential respiratory morbidity, especially in infants with AKI. In a retrospective multicenter study of critically ill term and near-term infants, positive fluid balance in the first week of life was independently associated with an increased risk of mechanical ventilation, and infants with AKI were more likely to have a positive fluid balance than infants without AKI [21].

All infants with AKI should be weighed every 12 hours and fluid administration adjusted according to weight changes and a review of the infant's intake and output. In addition, serum sodium may be useful in assessing changes in water balance and readjusting fluid intake. Fluids containing potassium should be discontinued or minimized. (See 'Serum/plasma sodium' above and 'Electrolyte and acid-base management' below.)

Fluid management is based on the underlying cause of AKI and the fluid status of the infant based on weight and balance between fluid input and output.

For infants with prerenal AKI due to hypovolemia (those who responded to a fluid challenge), fluid resuscitation is continued until the infant is judged to be euvolemic based on weight, serum sodium concentration, and urinary volume. Fluid therapy is then readjusted to maintain the euvolemic status with ongoing close monitoring. (See "Fluid and electrolyte therapy in newborns", section on 'Monitoring tools' and "Fluid and electrolyte therapy in newborns", section on 'Fluid and electrolyte management'.)

For patients with prerenal AKI due to reduced arterial effective circulation, fluid management is individualized based on the clinical status of the patient and directed therapy towards the underlying etiology. As noted below, a trial of furosemide may be administered.

For infants with intrinsic AKI, especially those who present with oliguria or anuria, fluid administration is limited to estimated insensible water losses plus the urine output.

Daily insensible loss in newborns increases with decreasing birth weight as follows [22-24]:

>2500 g – 15 to 25 mL/kg

1500 to 2500 g – 15 to 35 mL/kg

<1500 g – 30 to 60 mL/kg

The insensible fluid requirement for infants cared for under radiant warmers rather than incubators may increase by 25 to 100 percent. In addition, the daily fluid increment may be increased for some infants receiving phototherapy.

During the diuretic phase of intrinsic AKI, the fluid requirement increases. Ongoing monitoring of urine output with adjustment in fluid administration is necessary.

For infants with postrenal AKI, fluid management is dictated by the clinical status of the infant, as the urinary output generally increases once the underlying obstruction is relieved.

Furosemide — Loop diuretic therapy does not alter the natural course of AKI. The dissociation between increasing the urine output and not shortening the course of AKI with diuretic therapy probably reflects the ability of the diuretic to enhance the urine output in a few functioning nephrons. However, there is no effect on nonfunctioning nephrons, and as a result, there is no effect on the course of the kidney failure and recovery.

For patients with signs of fluid overload (edema, tachypnea, tachycardia, or elevated blood pressure), a trial of furosemide (1 to 2 mg/kg) can be administered to induce a diuresis to improve the patient's fluid status. In some cases, a higher dose of 3 mg/kg can be used. In addition, furosemide may be given to convert AKI from an oliguric to a nonoliguric form, which may help for nutrition.

Ototoxicity is a complication due to accumulation of furosemide in an infant with AKI. The risk of ototoxicity increases with concomitant administration of aminoglycosides.

Medications — Drug management includes:

Avoidance, if possible, of nephrotoxic drugs, as they may worsen kidney injury and delay recovery of kidney function.

Readjustment of dosing of renally excreted drug based on the infant's estimated glomerular filtration rate. Monitoring of drug levels, if available, is also useful to optimize dosing.

Nutrition — Nutritional support is essential for infants with AKI, with a goal of providing a minimum of 100 kcal/kg per day.

Enteral nutrition – For infants who are able to take enteral feedings, human milk should be given. If not available, a formula that has a low renal solute load and low phosphate content (eg, Similac PM 60/40) can be used, and can also supplement breast milk when the mother's milk supply is low. Fluid restriction makes it difficult to meet the caloric needs of an oliguric infant using nonsupplemental human milk or standard formula. As a result, the caloric density of human milk can be increased to 24 cal/oz by the addition of a low renal solute and phosphate formula powder. The caloric density of both human milk and standard formula can be increased further to a maximum of 30 cal/oz with the use of carbohydrate (eg, Polycose) or lipid (medium-chain triglycerides oil) modulators. Human milk fortifiers should not be used as they contain high amounts of calcium and phosphorus.

Parenteral nutrition – Infants with AKI are often critically ill and require parenteral nutrition. Such infants should receive amino acids up to a maximum of 1.5 g/kg per day, which can be increased by an additional 1.5 g/kg per day for those infants who receive renal replacement therapy (RRT). IV lipid solution is provided up to a maximum of 2 g/kg per day. The concentration of glucose and solutes such as sodium, potassium, calcium, and phosphorus depend upon the infant's weight, serum electrolyte concentrations, the severity of the kidney failure, and whether or not the patient is receiving RRT. Generally, potassium and phosphate supplementation are initially avoided in total parenteral nutrition because of a high risk of hyperkalemia and/or hyperphosphatemia. If needed, these can be given separately and can be added to the total parenteral nutrition once kidney function is more stable. (See 'Kidney replacement therapy' below.)

Electrolyte and acid-base management — Electrolyte abnormalities are common complications of AKI. In general, electrolyte disturbances are asymptomatic, and require a high index of suspicion and routine monitoring for early detection. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Presentation due to other laboratory abnormalities'.)

General measures to reduce or prevent electrolyte abnormalities in neonates with AKI include:

No administration of potassium or phosphorus unless there is confirmed hypokalemia or hypophosphatemia.

Typically, infants do not receive sodium supplementation in the first day of life, as newborns are volume-expanded with an expected water and electrolyte loss. After the first day of life, usual sodium requirements are 1 to 2 mEq/kg per day.

Hyperkalemia — Hyperkalemia is one of the most common complications of AKI. Depending upon the severity and the rate of onset, hyperkalemia can be mild and asymptomatic or so severe as to constitute a medical emergency due to potentially life-threatening disturbances in cardiac conduction. A plasma potassium concentration above 7 mEq/L is potentially life-threatening. Immediate therapy is warranted if electrocardiographic changes are present, regardless of the degree of hyperkalemia (algorithm 2). Electrocardiographic findings associated with hyperkalemia consist of peaked T waves, which typically are the earliest change, followed by flattened P waves, increased PR interval, and widening of the QRS complex. Muscle weakness is another potential manifestation that is challenging to ascertain in critically ill neonates. (See "Management of hyperkalemia in children".)

Metabolic acidosis — The most effective intervention for neonatal metabolic acidosis is treating the underlying cause because it remains unclear whether IV bicarbonate therapy is effective and safe. We do not use sodium bicarbonate routinely to correct acidosis in preterm infants. If bicarbonate therapy is to be given in preterm infants (severe acidosis that has not responded to directed medical management of the underlying cause), it should be administered as a slow infusion over 30 minutes to minimize fluctuations in cerebral hemodynamics [25,26]. Bicarbonate can be given to replace ongoing excessive kidney and gastrointestinal losses.

In the neonate, bicarbonate therapy has been associated with intraventricular hemorrhage, myocardial injury, deterioration of cardiac function, and worsening of intracellular acidosis [25]. The adverse effects and lack of efficacy of bicarbonate therapy were illustrated in an observational study of 775 very low birth weight infants born between 2002 and 2006 who were admitted to a single level III neonatal intensive care unit [27]. Sodium bicarbonate was administered to 21 percent of patients within the first seven days of life. After adjusting for potential confounders (eg, gestational age [GA], birth weight, severity of illness, and serum sodium concentrations), sodium bicarbonate infusion was associated with an increased risk of death (38.6 versus 10.8 percent) and intraventricular hemorrhage (58.4 versus 13.1 percent). Although sodium bicarbonate administration increased serum bicarbonate levels, it did not alter the degree of acidosis, as blood gas pH remained the same before and after bicarbonate infusion (mean pH 7.23 versus 7.24).

These results suggest that sodium bicarbonate was not beneficial in correcting acidosis and was associated with significant adverse effects. As a result, sodium bicarbonate should not be used routinely to correct acidosis in preterm infants.

Hypocalcemia — Hypocalcemia generally is not treated with IV calcium gluconate unless the patient is symptomatic or the hypocalcemia is severe. (See "Neonatal hypocalcemia".)

Hyperphosphatemia — Among patients who are hyperphosphatemic, lowering the serum phosphate concentration will also tend to raise the serum calcium, which is often low. Phosphorus intake should be restricted, which, in infants taking enteral feedings, can be accomplished by using a formula low in phosphorus or human milk, which also has a low phosphate concentration. Oral phosphate binders such as calcium carbonate can be used to decrease intestinal absorption if needed. (See "Pediatric chronic kidney disease-mineral and bone disorder (CKD-MBD)", section on 'Phosphate binders'.)

Hyponatremia — Hyponatremia in newborns is almost always due to dilution that results from the excessive water intake that cannot be excreted. This is often accompanied with an increase in weight. Therapy generally consists of restricting free water intake, which usually results in a gradual return of the serum sodium to normal levels. However, if neurologic signs such as seizures or lethargy develop or if the serum sodium concentration is extremely low (<115 mEq/L), urgent partial correction is needed with hypertonic saline.

In patients with a sodium deficit, correction with supplemental sodium is warranted. (See "Fluid and electrolyte therapy in newborns", section on 'Hyponatremia'.)

Hypertension — Approximately 10 to 20 percent of infants with AKI have hypertension usually due to fluid overload. Treatment is focused on correcting the fluid overload with fluid restriction, and possibly, a trial of furosemide to enhance diuresis. Criteria for pharmacologic measures are the same as hypertensive infants without AKI. (See "Etiology, clinical features, and diagnosis of neonatal hypertension", section on 'Acquired kidney parenchymal diseases' and "Management of hypertension in neonates and infants".)

Kidney replacement therapy — KRT should be considered if appropriate fluid and electrolyte balance and adequate nutrition cannot be maintained, because of persistent oliguria or anuria. Early referral to a center with an experienced and knowledgeable clinical team and resources is important as it takes time to assemble the appropriate personnel and equipment.

We consider KRT despite appropriate medical therapy for infants who have:

Severe acidosis (serum bicarbonate concentration <12 mEq/L).

Hyperkalemia (plasma potassium concentration ≥8 mEq/L or rapidly rising potassium levels) refractory to medical management.

Hyponatremia (serum sodium concentration ≤120 mEq/L).

Volume overload with heart failure, pulmonary edema – RRT is performed rarely in patients with severe hypertension that is not responsive to medications and is associated with central nervous system signs, such as seizures, or with heart failure.

Provide nutrition for infants who are anuric, oliguric, or who require fluid restriction that is inadequate to meet their caloric needs.

The question of whether to institute KRT in a newborn with no expectation of recovery of kidney function or with severe multisystem failure is difficult. Decisions should be made after considerable discussion with the neonatologist, nephrologist, other consultants as needed, and the family/caregiver.

The choice of modality is influenced by the clinical presentation and potential for recovery, the presence or absence of multisystem failure, the indication for RRT, and the availability of staff and appropriate equipment for the neonatal patient [28]. In neonates, peritoneal dialysis and continuous KRT (CKRT) are the two most commonly used modalities. (See "Pediatric acute kidney injury: Indications, timing, and choice of modality for kidney replacement therapy", section on 'Modality'.)

Peritoneal dialysis is generally preferred in newborns because it is safe, effective, and technically simpler and less expensive than hemodialysis (HD) and hemofiltration, requiring only minimal equipment [29,30]. Peritoneal dialysis can be initiated immediately after the dialysis catheter is placed and can be performed as soon as three days after major abdominal surgery [31]. It is less efficient in altering blood solute composition and in fluid removal than the other modalities, but it can be applied continuously and is therefore well tolerated by hemodynamically unstable patients. Unlike HD and hemofiltration, systemic heparinization is not required.

Morbidity and mortality are high in newborns undergoing peritoneal dialysis and are related to the infant's underlying diagnosis and clinical condition [32]. Complications include peritonitis, obstruction of the dialysis catheter, leaking dialysate, and inguinal or umbilical hernias.

CKRT – CKRT (continuous hemofiltration with or without dialysis) allows more precise fluid and metabolic control and nutritional support than peritoneal dialysis. For infants who are hemodynamically unstable, CKRT may be preferable to HD as fluid shifts are more gradual with CKRT. In patients with inborn errors of metabolism, clearance of ammonia and branched-chain amino acids are similar for CKRT and HD. Like HD, CKRT needs a vascular access but it is a better option as compared with HD in hemodynamically unstable patients.

HD offers a rapid change in plasma solute composition and rapid removal of excessive body water. However, this may not be tolerated by hemodynamically unstable patients and is technically challenging in newborns. Most centers do not have staff and equipment to perform HD in the neonate.

PROGNOSIS — AKI increases the risk of mortality and morbidity for neonates [12,33,34]. In particular, high mortality rates and significant morbidity (neurodevelopment impairment and chronic kidney disease [CKD]) due to AKI are seen in the following subset of neonates:

Very low birth weight infants (birth weight <1500 g) [35,36] and extremely preterm infants (gestational age [GA] <28 weeks) [37]

Neonates undergoing cardiac surgery [38,39]

Neonates supported by extracorporeal membrane oxygenation [40,41]

Perinatal asphyxia [42]

Follow-up care is required for infants with AKI as they are at risk for CKD or elevated blood pressure [12]. (See "Chronic kidney disease in children: Clinical manifestations and evaluation".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute kidney injury in children".)

SUMMARY AND RECOMMENDATIONS

Introduction – Acute kidney injury (AKI) is defined as an acute reduction in kidney function due to a decline in glomerular filtration rate, which recovers over days to weeks. (See 'Introduction' above.)

Evaluation – Once a diagnosis of neonatal AKI is made, evaluation is performed to determine the underlying cause (algorithm 1). Elements of the evaluation include:

History – Directed history to uncover an obvious risk factor or cause for neonatal AKI. This includes reviewing the results of a prenatal ultrasound if available, and a history for nephrotoxic exposure, perinatal asphyxia, or hypovolemia. (See 'History' above.)

Physical examination – Key findings that may be associated with AKI include edema, elevated pressure, palpable kidneys suggesting enlargement, distended bladder, and other nonrenal anomalies associated with AKI (eg, critical congenital heart disease). Excessive weight loss is suggestive of hypovolemia and prerenal AKI, whereas excessive weight gain suggests impairment of water excretion seen in patients with intrinsic and postrenal disease. (See 'Physical examination' above.)

Imaging – A renal ultrasound is obtained to document the presence of one or two kidneys, the shape and size of the kidney(s), and detects congenital anomalies or vascular abnormalities. In particular, severe bilateral hydronephrosis or severe unilateral hydronephrosis in a solitary kidney is suggestive of postrenal disease due to obstructive uropathy. A renal ultrasound also identify patients with chronic congenital disease (eg, cystic renal disease, renal hypodysplasia) who present in a similar manner to neonates with AKI. (See 'Renal ultrasound' above.)

Fluid challenge – Administration of a fluid challenge can identify patients with prerenal disease due to hypovolemia. (See 'Fluid challenge' above.)

Laboratory testing – Laboratory evaluation is not as helpful in identifying the etiology of AKI in neonates due to the functional and developmental immaturity of the neonatal kidney, especially in preterm infants. (See 'Laboratory evaluation' above.)

Prevention – Preventive measures include (see 'Prevention' above):

Dose adjustment of renally excreted drugs that are potentially nephrotoxic based on the infant's kidney function.

Renal function (serum creatinine [SCr]) is monitored for patients at risk for AKI.

Careful attention to fluid management to avoid hypovolemia and hypervolemia. For patients cared for in the neonatal intensive care unit, fluid and electrolyte management is readjusted by changes in the infant's fluid status determined by frequent measurement of weight, accurate intake and output, and serum sodium.

Management

Specific treatment of the underlying cause. (See 'Directed therapy based on etiology' above.)

Fluid therapy is determined by the underlying cause of the AKI and the fluid status of the infant. Fluid administration is adjusted based on weight changes (obtained every 12 hours), a review of the infant's intake and output, and changes in serum sodium. (See 'Fluid management' above.)

Furosemide, a loop diuretic, is ototoxic and does not alter the course of neonatal AKI. Furosemide may be given as a trial to induce a diuresis in neonates with AKI who have signs of fluid overload. (See 'Furosemide' above.)

Drug management includes avoiding nephrotoxic drugs if possible and readjusting the dose of renally excreted drugs based on the infant's estimated glomerular filtration rate. (See 'Medications' above.)

The nutritional intake is targeted to provide a minimum of 100 kcal/kg per day. For infants who are able to take enteral feedings, human milk or formula that has a low renal solute load and phosphate content is recommended. For infants who receive parenteral nutrition, the daily recommended intake of amino acids is up to a maximum of 1.5 g/kg per day and intravenous (IV) lipid solution up to a maximum of 2 g/kg per day.

Electrolyte abnormalities are common complications of AKI. They include hyperkalemia, metabolic acidosis, hypocalcemia, hyperphosphatemia, hyponatremia. (See 'Electrolyte and acid-base management' above.)

Hypertension is a common in neonates with AKI, primarily due to fluid overload. The indications and approach for initiation of pharmacologic therapy are the same as those used for infants without AKI. (See "Management of hypertension in neonates and infants", section on 'Who should be treated?'.)

Indications for kidney replacement therapy (KRT) include clinically significant fluid overload; hyperkalemia, hyponatremia, metabolic acidosis that are unresponsive to medical therapy; and to provide adequate nutrition for anuric or oliguric patients. Available modalities for the neonates include hemodialysis (HD), peritoneal dialysis, and hemofiltration (with or without dialysis). (See 'Kidney replacement therapy' above.)

Outcome – AKI increases the risk of mortality and morbidity for neonates. Neonates at increased risk include very low birth weight infants (birth weight <1500 g), those who undergo cardiac surgery, infants supported by extracorporeal membrane oxygenation, or infants who were exposed to perinatal asphyxia. (See 'Prognosis' above.)

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Topic 111976 Version 21.0

References

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