Pediatrics - Acute Kidney Injury

Pediatrics - Acute Kidney Injury

Basics

Description

Acute kidney injury (AKI) is a clinical syndrome characterized by a sudden reduction in kidney function, resulting in impaired filtration of metabolic waste products, disturbances in fluid and electrolyte balance, and abnormalities in acid-base regulation.

According to established Kidney Disease: Improving Global Outcomes (KDIGO) criteria, AKI is identified when at least one of the following occurs:

• An increase in serum creatinine of at least 0.3 mg/dL (26.5 µmol/L) within 48 hours.
• An increase in serum creatinine to at least 1.5 times the baseline value, known or presumed to have occurred within the preceding seven days.
• A reduction in urine output to less than 0.5 mL/kg/hour for at least six hours.

These criteria allow AKI to be recognized through changes in serum creatinine, urine output, or both.

Urine output is variable in children with AKI. Some patients develop anuria, characterized by virtually absent urine production, while others experience oliguria, defined as reduced urine output.

A proportion of children may maintain normal urine output or even develop polyuria despite significant impairment of kidney function.

Consequently, normal urine output does not exclude AKI.

Epidemiology

The epidemiology of pediatric AKI has changed considerably over time.

Historically, AKI was frequently associated with primary kidney diseases. More recently, it has increasingly been recognized as a complication of systemic illness, critical care interventions, infection, hemodynamic instability, and exposure to nephrotoxic medications.

AKI is an important complication among hospitalized children and may affect approximately 10% of pediatric inpatients, although the frequency varies according to the population studied and diagnostic criteria used.

The incidence is substantially higher in children admitted to pediatric intensive care units.

Large observational studies have reported AKI in approximately 27% of critically ill children.

The likelihood of AKI increases with the severity of underlying illness, particularly in patients with shock, sepsis, cardiovascular instability, or multiple organ dysfunction.

AKI is associated with prolonged hospitalization, greater healthcare resource utilization, an increased risk of chronic kidney disease, and higher mortality among critically ill children.

Pathophysiology

The pathogenesis of acute kidney injury is complex and involves several interacting mechanisms that impair renal blood flow, cellular function, and glomerular filtration.

AKI may initially develop because of ischemia, exposure to nephrotoxic substances, inflammation, or other disturbances affecting renal perfusion and cellular integrity.

Renal Ischemia

Reduced renal blood flow may cause inadequate oxygen delivery to kidney tissues.

Persistent or severe hypoperfusion can impair tubular epithelial cell function and contribute to structural kidney injury.

Renal Vasoconstriction

Alterations in the regulation of renal blood vessels may cause vasoconstriction and reduced microvascular perfusion.

These changes can further decrease oxygen delivery to vulnerable regions of the kidney.

Leukocyte Activation And Leukostasis

Inflammatory processes may promote leukocyte activation and accumulation within the renal microcirculation.

This can contribute to endothelial injury, impaired blood flow, and amplification of local inflammation.

Vascular Congestion

Increased venous pressure and renal vascular congestion may reduce effective kidney perfusion.

These mechanisms are particularly relevant in children with cardiac dysfunction, fluid overload, or severe systemic illness.

Cellular Injury And Death

Prolonged ischemia or toxic exposure may damage renal tubular epithelial cells.

Cellular injury can produce impaired tubular transport, loss of epithelial integrity, apoptosis, and, in severe cases, necrosis.

Damaged cells and cellular debris may contribute to tubular obstruction and further impairment of kidney function.

Immune And Inflammatory Responses

Abnormal activation of inflammatory mediators, cytokines, and immune pathways may perpetuate kidney injury.

The interaction between vascular dysfunction, inflammation, and direct cellular damage contributes to the development and progression of AKI.

Etiology

Acute kidney injury has traditionally been classified into three categories: prerenal, intrinsic renal, and postrenal causes.

More recent terminology may describe these categories as functional, structural, and obstructive AKI.

These classifications help organize the causes of AKI, although considerable overlap may occur.

For example, prolonged renal hypoperfusion may initially cause functional impairment but subsequently result in structural tubular injury.

Functional Acute Kidney Injury

Functional AKI occurs when glomerular filtration decreases because of inadequate kidney perfusion without established structural damage to renal tissue.

The reduction in kidney function is often reversible when renal perfusion is promptly restored.

Renal Hypoperfusion

Reduced blood flow to the kidneys may occur because of decreased circulating blood volume or impaired cardiovascular function.

Potential causes include:

• Dehydration.
• Severe vomiting.
• Persistent diarrhea.
• Hemorrhage.
• Shock.
• Sepsis.
• Reduced cardiac output.
• Significant systemic hypotension.

Pathophysiological Mechanism

When effective circulating blood volume decreases, the kidneys activate compensatory mechanisms intended to maintain perfusion and preserve sodium and water.

Despite these responses, severe or persistent hypoperfusion may reduce the glomerular filtration rate.

Reversibility

Functional AKI may improve rapidly when the underlying hemodynamic disturbance is corrected.

However, prolonged hypoperfusion may progress to structural tubular damage.

Structural Acute Kidney Injury

Structural AKI results from direct injury involving renal tubules, glomeruli, blood vessels, or the interstitial compartment.

Unlike purely functional impairment, structural injury may persist after the initial hemodynamic disturbance has resolved.

Acute Tubular Injury

Acute tubular injury may result from prolonged ischemia or direct exposure to nephrotoxic substances.

The term acute tubular necrosis (ATN) has historically been used to describe this form of intrinsic kidney injury.

However, actual tubular necrosis is not always present, and the diagnosis is rarely confirmed histologically because kidney biopsy is usually unnecessary.

Consequently, the term acute tubular injury is often preferred when discussing the broader clinical syndrome.

Glomerular Disorders

Inflammatory diseases involving the glomeruli may impair filtration and cause AKI.

Examples include:

Postinfectious Glomerulonephritis: An immune-mediated glomerular disorder that may develop following certain infections.

Rapidly Progressive Glomerulonephritis: A severe inflammatory glomerular condition that may produce rapid deterioration in kidney function.

Crescentic Glomerulonephritis: A histological pattern associated with severe glomerular injury and rapidly progressive renal dysfunction.

Vascular Disorders

Abnormalities involving the renal vasculature may reduce glomerular blood flow or directly damage small blood vessels.

Hemolytic uremic syndrome (HUS) is an important cause of vascular-associated AKI in children.

It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and kidney injury.

Other vascular disorders, including renal vein thrombosis, may also produce AKI.

Acute Interstitial Nephritis

Acute interstitial nephritis (AIN) is an inflammatory disorder affecting the renal interstitium and tubules.

It is commonly associated with medication exposure.

Potential causative medications include nonsteroidal anti-inflammatory drugs and certain antibiotics.

Other causes include infections, systemic inflammatory conditions, and infiltrative diseases.

AIN may present with kidney dysfunction, sterile pyuria, and occasionally fever, rash, or eosinophilia.

Postrenal Acute Kidney Injury

Postrenal AKI develops when obstruction of urinary drainage increases pressure within the collecting system and impairs glomerular filtration.

Obstruction may be anatomical or functional.

Lower Urinary Tract Obstruction

Obstruction involving the bladder outlet or urethra may impair urine drainage from both kidneys.

Potential causes include posterior urethral valves, urethral abnormalities, or severe bladder dysfunction.

Upper Urinary Tract Obstruction

Obstruction involving the ureters or renal collecting systems may cause AKI when both kidneys are affected.

In children with a solitary functioning kidney, obstruction of that kidney alone may cause significant AKI.

Neonatal Presentation

Obstructive AKI is particularly important in newborns because congenital abnormalities of the urinary tract may present early in life.

Posterior urethral valves and other congenital urinary outflow abnormalities should be considered in neonates with reduced urine output or evidence of urinary tract dilatation.

Reversibility

Prompt relief of obstruction may result in improvement in kidney function.

However, prolonged obstruction may cause persistent structural damage and incomplete recovery.

History

A comprehensive medical history is essential for identifying the underlying cause of AKI and distinguishing functional, structural, and obstructive kidney disorders.

The history should include recent illnesses, fluid losses, medication exposure, underlying medical conditions, urinary symptoms, and potential systemic manifestations.

Previous Infection

A history of recent infection may suggest infection-related kidney disease.

Postinfectious glomerulonephritis may develop following certain bacterial infections, while hemolytic uremic syndrome may occur after gastrointestinal infection, particularly infection with Shiga toxin-producing bacteria.

Systemic infections and sepsis may also cause AKI through hemodynamic disturbances, inflammation, and direct kidney injury.

Preexisting Urinary Tract Abnormalities

Children with neurogenic bladder, congenital urinary tract abnormalities, or a solitary functioning kidney may have an increased risk of obstructive AKI.

A history of recurrent urinary tract infections, urinary retention, or previous urological procedures should be documented.

Medication Exposure

Exposure to nephrotoxic medications is an important cause of AKI in hospitalized and outpatient children.

Potentially nephrotoxic medications include:

Nonsteroidal Anti-Inflammatory Drugs: Medications such as ibuprofen may impair renal perfusion, particularly during dehydration or reduced circulating blood volume.

Beta-Lactam Antibiotics: Certain penicillins and cephalosporins may cause acute interstitial nephritis.

Acyclovir: Intravenous acyclovir may cause kidney injury through crystal precipitation or tubular toxicity, particularly when hydration is inadequate.

Aminoglycosides: Antibiotics such as gentamicin and amikacin may produce dose-related tubular injury.

Amphotericin B: This antifungal medication may cause renal vasoconstriction and tubular dysfunction.

Cisplatin: Cisplatin is a chemotherapeutic agent associated with direct nephrotoxicity.

The medication history should establish the drug, dose, duration of treatment, and timing relative to the onset of kidney dysfunction.

Gross Hematuria

Visible blood in the urine may provide important clues about the underlying kidney disorder.

Tea-Colored Or Cola-Colored Urine: Dark urine may suggest glomerular bleeding, particularly in acute glomerulonephritis.

Bright Red Urine: Fresh red blood may occur with nephrolithiasis, urinary tract injury, or other nonglomerular sources of bleeding.

The appearance of urine is not diagnostic by itself and should be interpreted alongside urinalysis and microscopy.

Trauma

A history of major trauma or crush injury may indicate rhabdomyolysis-associated AKI.

Muscle injury releases myoglobin and other intracellular substances that may contribute to renal tubular injury.

Fever

Fever may suggest infection, systemic inflammation, pyelonephritis, or an immune-mediated renal disorder.

Skin Rash

Rashes may occur with acute interstitial nephritis, vasculitis, or systemic autoimmune disease.

Bloody Diarrhea

A preceding diarrheal illness with visible blood may raise concern for Shiga toxin-associated hemolytic uremic syndrome.

Pallor

Pallor may indicate anemia, including microangiopathic hemolytic anemia associated with hemolytic uremic syndrome.

Severe Vomiting Or Diarrhea

Persistent gastrointestinal fluid losses may cause dehydration, reduced circulating blood volume, and functional AKI.

Abdominal Pain

Abdominal pain may occur with urinary obstruction, nephrolithiasis, hemolytic uremic syndrome, or other systemic diseases associated with AKI.

Hemorrhage And Shock

Significant blood loss or circulatory shock may impair renal perfusion and precipitate AKI.

Reduced Or Absent Urine Output

Oliguria or anuria may indicate significant renal dysfunction or urinary tract obstruction.

Polyuria

Some patients with AKI may present with increased urine output, particularly when tubular concentrating function is impaired.

Polyuria may also occur during recovery from AKI or after relief of urinary obstruction.

Physical Examination

The physical examination should assess the child’s hemodynamic stability, hydration status, evidence of fluid overload, and manifestations of systemic or renal disease.

General Appearance

The examiner should assess the child’s level of consciousness, overall clinical condition, nutritional status, and evidence of acute illness.

Body Weight

Body weight should be measured accurately and compared with previous measurements when available.

Changes in weight may provide useful information about fluid losses or fluid accumulation.

Serial weight measurements are especially valuable in hospitalized children with AKI.

Hydration Status

Clinical findings such as dry mucous membranes, delayed capillary refill, reduced skin turgor, and tachycardia may suggest volume depletion.

However, hydration assessment should incorporate multiple findings because individual signs may be unreliable.

Shock

Hypotension, poor peripheral perfusion, altered consciousness, and reduced urine output may indicate circulatory shock.

Shock requires urgent recognition and stabilization.

Edema

Peripheral, periorbital, or generalized edema may suggest fluid retention.

The degree of fluid accumulation should be evaluated using serial weights and cumulative fluid balance.

Jaundice

Jaundice may occur in conditions associated with hemolysis, hepatic dysfunction, or multisystem disease.

Lung Examination

Crackles or rales may indicate pulmonary edema resulting from fluid overload.

Increased work of breathing or reduced oxygen saturation may accompany severe pulmonary congestion.

Cardiovascular Examination

A gallop rhythm, tachycardia, or other abnormal cardiac findings may suggest cardiac dysfunction or significant fluid overload.

Blood pressure should be measured using an appropriately sized cuff.

Hypertension may result from impaired sodium and water excretion.

Abdominal And Pelvic Examination

The examination should assess for abdominal masses, bladder distension, flank tenderness, and other findings suggesting urinary tract obstruction.

A palpable enlarged bladder may indicate urinary retention.

Skin Examination

Rashes, petechiae, purpura, and other skin abnormalities may suggest systemic inflammatory, hematologic, or vascular disorders.

Joint Examination

Arthritis or joint swelling may indicate an underlying systemic inflammatory or autoimmune condition associated with kidney injury.

Differential Diagnosis

The evaluation should distinguish true acute kidney injury from chronic kidney dysfunction and conditions that alter serum urea or creatinine concentrations without an equivalent reduction in glomerular filtration.

Chronic Kidney Disease

Chronic kidney disease generally develops over an extended period and may be associated with progressive loss of kidney function.

Clinical findings supporting chronic disease include:

• Poor linear growth.
• Persistent normocytic anemia.
• Secondary hyperparathyroidism.
• Chronic abnormalities in calcium and phosphate metabolism.
• Previous abnormal kidney function measurements.
• Small or abnormal kidneys on imaging in certain conditions.

Acute kidney injury may also occur in children with preexisting chronic kidney disease.

Azotemia Without Equivalent Kidney Injury

Elevated blood urea nitrogen may result from increased protein breakdown or enhanced urea production.

Potential causes include hypercatabolic states, corticosteroid therapy, and upper gastrointestinal bleeding.

An elevated blood urea nitrogen concentration should therefore be interpreted alongside creatinine, hydration status, and the clinical presentation.

Increased Serum Creatinine From Other Causes

Certain conditions or medications may increase serum creatinine without causing a corresponding reduction in glomerular filtration.

Rhabdomyolysis: Muscle injury may increase creatinine generation and can also cause genuine AKI through myoglobin-mediated tubular injury.

Trimethoprim: Trimethoprim may inhibit tubular secretion of creatinine, producing an increase in serum creatinine without a true decline in glomerular filtration.

Cimetidine: Cimetidine may also reduce tubular creatinine secretion and increase the measured serum concentration.

These effects should be considered when interpreting unexpected changes in creatinine.

Diagnostic Tests And Interpretation

All children with suspected AKI should undergo appropriate laboratory evaluation to assess kidney function, electrolyte disturbances, and potential underlying causes.

Initial investigations generally include urinalysis with microscopy, serum chemistry testing, and a complete blood count.

Additional studies should be selected according to the clinical presentation and suspected etiology.

Initial Laboratory Investigations

Urinalysis With Microscopy

Urinalysis provides important information about kidney concentrating ability, protein excretion, hematuria, and the presence of inflammatory or cellular elements.

Urine Specific Gravity

A urine specific gravity greater than approximately 1.020 may indicate preserved urinary concentrating ability and can occur during volume depletion.

However, urine specific gravity alone cannot reliably distinguish functional AKI from structural injury.

Proteinuria

Significant proteinuria may suggest glomerular disease.

Marked proteinuria, particularly when accompanied by hematuria or urinary casts, raises concern for structural kidney injury involving the glomeruli.

Eosinophiluria

Urinary eosinophils have historically been associated with acute interstitial nephritis.

However, eosinophiluria has poor diagnostic sensitivity and specificity and should not be relied upon to confirm or exclude AIN.

Pyuria

The presence of white blood cells in urine may suggest urinary tract infection, pyelonephritis, or interstitial inflammation.

Granular Casts

Granular casts, particularly muddy brown granular casts, may indicate acute tubular injury.

Their presence can support the diagnosis of structural AKI, although they are not present in every case.

Pigmenturia

Urine containing myoglobin or hemoglobin may suggest pigment-associated kidney injury.

This may occur with rhabdomyolysis or significant intravascular hemolysis.

Red Blood Cell Casts

Red blood cell casts strongly suggest bleeding originating within the nephron, particularly glomerulonephritis.

They are less commonly encountered in other inflammatory or structural kidney disorders.

Serum Chemistry

Serum chemistry testing is essential for identifying abnormalities in renal function, electrolyte concentrations, and acid-base balance.

Serum Creatinine

Serum creatinine is commonly used to assess glomerular filtration.

A rising creatinine concentration may indicate declining kidney function.

However, creatinine may increase relatively late after kidney injury begins and is influenced by muscle mass, age, hydration, and certain medications.

Blood Urea Nitrogen

Blood urea nitrogen may increase when kidney clearance is impaired.

Its interpretation is affected by hydration, dietary protein intake, catabolism, and gastrointestinal bleeding.

Hyponatremia

Reduced serum sodium may occur because of impaired free-water excretion and excessive water retention.

Metabolic Acidosis

Impaired acid excretion and reduced bicarbonate regeneration may cause metabolic acidosis.

Hyperkalemia

Reduced renal potassium excretion may produce elevated serum potassium concentrations.

Severe hyperkalemia can cause life-threatening cardiac arrhythmias.

Hypocalcemia

Reduced serum calcium may develop because of altered mineral metabolism, hyperphosphatemia, and other disturbances associated with AKI.

Hyperphosphatemia

Impaired phosphate excretion may cause serum phosphate concentrations to increase.

Hyperphosphatemia may contribute to hypocalcemia and other metabolic complications.

Complete Blood Count

A complete blood count may reveal hematologic abnormalities associated with the cause of AKI.

Microangiopathic Hemolytic Anemia

Anemia with fragmented red blood cells may indicate a thrombotic microangiopathic process such as hemolytic uremic syndrome.

Thrombocytopenia

A reduced platelet count accompanying hemolytic anemia and AKI raises concern for hemolytic uremic syndrome.

Eosinophilia

Peripheral eosinophilia may occur with acute interstitial nephritis, particularly when associated with a drug hypersensitivity reaction.

However, eosinophilia is neither sufficiently sensitive nor specific to establish the diagnosis.

Additional Laboratory Investigations

Selected patients require further investigations based on the suspected cause of kidney injury.

Serological Investigations

Serological testing may be useful when acute glomerulonephritis, vasculitis, or systemic autoimmune disease is suspected.

Potential investigations include:

Complement Levels: Reduced C3 or C4 concentrations may occur in certain forms of glomerulonephritis.

Antineutrophil Cytoplasmic Antibodies: ANCA testing may help identify selected small-vessel vasculitides.

Antinuclear Antibodies: ANA testing may be useful when systemic lupus erythematosus is suspected.

Additional testing may include anti-double-stranded DNA antibodies, anti-glomerular basement membrane antibodies, or other targeted investigations.

Hemolysis Investigations

When hemolytic uremic syndrome is suspected, investigations may include a peripheral blood smear, lactate dehydrogenase, bilirubin, and haptoglobin.

Stool testing for Shiga toxin-producing organisms may also be appropriate.

Creatine Kinase

Serum creatine kinase should be considered when rhabdomyolysis or significant muscle injury is suspected.

Fractional Excretion Of Sodium

Fractional excretion of sodium (FENa) estimates the proportion of filtered sodium that is excreted in urine.

It may provide information about tubular sodium handling in selected patients with AKI.

Formula

\mathrm{FENa}(\%) =
\frac{U_{\mathrm{Na}}\times P_{\mathrm{Cr}}}
{P_{\mathrm{Na}}\times U_{\mathrm{Cr}}}
\times100

Where:

• = Urine sodium concentration.
• = Plasma sodium concentration.
• = Urine creatinine concentration.
• = Plasma creatinine concentration.

Interpretation

FENa Below 1%: May suggest increased sodium retention associated with reduced effective renal perfusion.

FENa Above 2%: May suggest impaired tubular sodium reabsorption, as may occur with acute tubular injury.

FENa Between 1% And 2%: Often provides limited diagnostic discrimination.

Limitations

FENa should not be interpreted as a definitive test distinguishing functional from structural AKI.

Diuretic therapy may increase urinary sodium excretion and reduce the reliability of FENa.

A low FENa can also occur despite structural injury, including contrast-associated AKI, pigment nephropathy, and some cases of glomerulonephritis or sepsis-associated AKI.

Neonates may have different urinary sodium handling because of immature tubular function.

Clinical findings, medication exposure, and other laboratory results must be considered alongside FENa.

Fractional Excretion Of Urea

Fractional excretion of urea (FEUrea) estimates the proportion of filtered urea excreted through urine.

It may be useful when diuretic treatment complicates interpretation of urinary sodium measurements.

Formula

\mathrm{FEUrea}(\%) =
\frac{U_{\mathrm{Urea}}\times P_{\mathrm{Cr}}}
{P_{\mathrm{Urea}}\times U_{\mathrm{Cr}}}
\times100

Where:

• = Urine urea concentration.
• = Plasma urea concentration.
• = Urine creatinine concentration.
• = Plasma creatinine concentration.

Interpretation

FEUrea Below 35%: May support reduced renal perfusion with increased tubular urea reabsorption.

FEUrea Above 50%: May suggest impaired tubular function associated with structural kidney injury.

Limitations

FEUrea is generally less affected by loop diuretics than FENa.

However, it remains an imperfect diagnostic test and may be influenced by critical illness, sepsis, altered urea production, and other physiological disturbances.

Neither FEUrea nor FENa should be used in isolation to determine the cause of AKI.

Diagnostic Imaging

Chest Radiography

A chest radiograph may be useful when fluid overload or cardiac dysfunction is suspected.

Potential findings include cardiomegaly, pulmonary vascular congestion, and pulmonary edema.

Renal Ultrasonography

Renal ultrasound is an important noninvasive investigation for assessing kidney size, renal structure, and the urinary collecting system.

It is particularly useful when urinary tract obstruction or congenital anatomical abnormalities are suspected.

Hydronephrosis

Dilatation of the renal collecting system may indicate obstruction of urinary drainage.

Hydronephrosis may involve one or both kidneys depending on the anatomical abnormality.

Bladder Abnormalities

A thickened or trabeculated bladder may suggest chronic bladder outlet obstruction or abnormal bladder function.

Increased Renal Echogenicity

Increased renal cortical echogenicity may occur with several structural kidney disorders.

Potential causes include acute tubular injury, acute interstitial nephritis, glomerulonephritis, and hemolytic uremic syndrome.

However, increased echogenicity is nonspecific and must be interpreted in the clinical context.

Doppler Ultrasonography

Doppler imaging may be useful for assessing renal blood flow and detecting selected vascular abnormalities.

Renal vein thrombosis is one condition that may be identified through Doppler evaluation.

Diagnostic Procedures

Renal Biopsy

Kidney biopsy is not routinely required in most children with AKI.

It may be considered when kidney dysfunction is prolonged, unexplained, or suspected to result from a specific inflammatory or structural disorder.

Indications For Renal Biopsy

Possible indications include:

• Persistent AKI without an established cause.
• Suspected rapidly progressive glomerulonephritis.
• Possible crescentic glomerulonephritis.
• Certain immune-mediated kidney disorders requiring tissue diagnosis.
• Unexplained structural AKI when histological findings may alter treatment.

The decision should be made in consultation with a pediatric nephrologist.

Treatment

General Principles

Management of acute kidney injury focuses on identifying and correcting the underlying cause, maintaining adequate renal perfusion, preventing further kidney damage, and treating complications.

The choice of treatment depends on the severity of AKI, the child’s hemodynamic condition, fluid status, electrolyte abnormalities, and associated systemic illness.

Supportive care is the foundation of treatment, although some patients require specific interventions such as relief of urinary obstruction, immunosuppressive therapy, or kidney replacement therapy.

Medication

Adjustment Of Drug Dosing

Reduced kidney function may impair the elimination of medications and their active metabolites.

Drugs primarily cleared through the kidneys may accumulate and produce toxicity when usual doses are continued.

Medication doses and administration intervals should therefore be reviewed according to kidney function, changes in serum creatinine, and the patient’s clinical condition.

Therapeutic drug monitoring may be necessary for medications with narrow therapeutic ranges.

Avoidance Of Nephrotoxic Medications

Potentially nephrotoxic medications should be discontinued, substituted, or minimized whenever clinically feasible.

Examples include NSAIDs, aminoglycosides, amphotericin B, and selected other medications.

When nephrotoxic treatment is essential, dosing and drug concentrations should be carefully monitored.

Dopamine

Low-dose dopamine, previously referred to as renal-dose dopamine, does not improve kidney recovery or prevent progression of AKI.

It should not be administered solely to increase urine output or improve renal function.

Loop Diuretics

Loop diuretics, such as furosemide, increase urinary sodium and water excretion when sufficient renal tubular function remains.

They may be useful for managing fluid overload in selected patients.

However, loop diuretics do not reverse the underlying kidney injury or improve renal recovery.

They should not be used routinely to prevent AKI or convert oliguric AKI into nonoliguric AKI.

Osmotic Diuretics

Mannitol has historically been used in selected circumstances involving renal injury.

However, routine mannitol administration has not been shown to improve AKI outcomes and may be harmful, particularly when significant oliguria, anuria, or fluid overload is present.

Sodium Bicarbonate

Sodium bicarbonate may be considered in selected patients with severe metabolic acidosis.

Urinary alkalinization with bicarbonate has also historically been used in rhabdomyolysis-associated AKI.

However, routine bicarbonate administration specifically to prevent kidney injury in rhabdomyolysis is not supported by strong evidence.

Treatment should prioritize appropriate fluid resuscitation, correction of electrolyte abnormalities, and management of the underlying condition.

Prevention Of Contrast-Associated Kidney Injury

N-acetylcysteine and intravenous sodium bicarbonate have previously been used in attempts to prevent contrast-associated AKI.

However, more recent evidence has not demonstrated consistent benefit from N-acetylcysteine prophylaxis.

Sodium bicarbonate has not shown clear superiority over isotonic saline.

Prevention in high-risk patients should focus on appropriate assessment of kidney function, avoidance of unnecessary nephrotoxic exposure, and individualized intravenous hydration when indicated.

N-acetylcysteine is not recommended as routine prophylaxis for intravenous iodinated contrast administration.

Additional Therapies

Supportive Management

Supportive care is essential for preventing progression of AKI and managing associated complications.

Avoidance Of Further Kidney Injury

Potentially nephrotoxic medications should be avoided whenever possible.

Hemodynamic instability, severe dehydration, and other reversible causes of reduced renal perfusion should be corrected promptly.

Electrolyte Monitoring

Serum electrolytes should be monitored regularly, with the frequency determined by the severity of kidney dysfunction.

Particular attention should be given to potassium, sodium, calcium, phosphate, and bicarbonate concentrations.

Potassium Restriction

In children with oliguria, anuria, or hyperkalemia, excessive potassium administration should be avoided.

Potassium-containing intravenous fluids, medications, supplements, and dietary sources should be reviewed.

Dietary restrictions should be individualized according to serum potassium concentrations and nutritional requirements.

Hyponatremia

Hyponatremia in AKI may result from impaired free-water excretion and excessive water retention.

Management often involves restricting unnecessary free-water intake and addressing the underlying cause.

Hypertonic Saline

Hypertonic saline may be required for severe symptomatic hyponatremia, particularly when seizures or significant neurological manifestations are present.

It should not be used routinely for mild or asymptomatic hyponatremia.

Correction must be carefully monitored to avoid excessively rapid changes in serum sodium concentration.

Fluid Management

Fluid management is one of the most important components of AKI treatment.

The approach depends on the child’s hemodynamic condition, intravascular volume status, urine output, and degree of fluid accumulation.

Management can be organized into three phases.

Phase 1: Fluid Resuscitation And Repletion

The initial objective is to restore adequate circulating blood volume and end-organ perfusion.

Children with hypovolemia may require prompt administration of isotonic intravenous fluids.

Commonly used solutions include 0.9% sodium chloride and appropriate balanced crystalloid solutions.

Fluid boluses should be individualized according to the child’s age, weight, perfusion, and underlying condition.

Assessment After Fluid Administration

The response to resuscitation should be evaluated through:

• Heart rate.
• Blood pressure.
• Capillary refill time.
• Mental status.
• Peripheral perfusion.
• Urine output.
• Evidence of pulmonary or peripheral fluid overload.

Additional fluid administration should be based on repeated clinical assessment.

Children with cardiac dysfunction or established fluid overload may require a more cautious approach.

Phase 2: Fluid Balance Maintenance

Once adequate renal perfusion and circulating volume have been established, fluid management should focus on balancing ongoing intake with fluid losses.

Fluid Intake

Sources of fluid intake include:

• Intravenous maintenance fluids.
• Blood products.
• Intravenous medications.
• Enteral feeds.
• Parenteral nutrition.
• Oral fluids.

Fluid Output

Sources of fluid loss include:

• Urine.
• Gastrointestinal losses.
• Drainage from tubes or surgical sites.
• Insensible losses through the skin and respiratory tract.

Fluid Restriction

Fluid restriction may be necessary when urine output remains low and the child begins to accumulate fluid.

The prescribed fluid allowance should be individualized according to the patient’s clinical status and ongoing losses.

Fluid Overload

Positive fluid balance may lead to edema, pulmonary congestion, hypertension, and impaired cardiovascular function.

Increasing degrees of fluid overload have been associated with worse clinical outcomes in critically ill children with AKI.

Fluid overload at the time kidney replacement therapy is initiated is also associated with increased mortality.

Calculation Of Percentage Fluid Overload

Fluid overload may be estimated using cumulative fluid intake, cumulative output, and the patient’s admission weight.

\%FO =
\frac{\text{Cumulative Fluid Intake (L)}-\text{Cumulative Fluid Output (L)}}{\text{Admission Body Weight (kg)}}\times100

This calculation assumes that one liter of accumulated fluid weighs approximately one kilogram.

A positive value indicates net fluid accumulation.

Clinical Importance

Serial fluid balance assessment helps identify patients who may benefit from fluid restriction, diuretic therapy, or kidney replacement therapy.

The percentage of fluid overload should be interpreted alongside body weight changes, physical findings, respiratory status, and hemodynamic stability.

Phase 3: Fluid Removal And Recovery

When kidney function begins to recover, urine output may increase and previously retained fluid may be eliminated.

However, some children remain unable to excrete sufficient fluid despite appropriate conservative management.

Diuretic Therapy

Loop diuretics may be used to promote fluid removal in selected patients who retain sufficient kidney function.

The response should be closely monitored.

Kidney Replacement Therapy

When fluid overload remains severe or refractory to medical management, kidney replacement therapy may be necessary.

This is particularly important when excessive fluid accumulation compromises oxygenation, cardiovascular function, or the ability to provide essential nutrition and medications.

Recovery Phase

As kidney function improves, fluid and electrolyte management should be adjusted according to changing urine output.

Some patients develop substantial polyuria during recovery and may require careful replacement of fluid and electrolyte losses.

Kidney Replacement Therapy

Kidney replacement therapy (KRT), also called renal replacement therapy (RRT), may be required when severe AKI causes complications that cannot be adequately controlled through medical treatment.

Indications For Kidney Replacement Therapy

Important indications include:

Refractory Fluid Overload: Significant fluid accumulation that cannot be controlled using fluid restriction or appropriate diuretic therapy.

Severe Hyperkalemia: Elevated serum potassium that remains dangerous despite emergency medical treatment.

Refractory Metabolic Acidosis: Severe acidosis that does not respond to appropriate treatment or continues to worsen.

Symptomatic Uremia: Clinical manifestations of toxin accumulation, including encephalopathy, pericarditis, or bleeding associated with platelet dysfunction.

Other Severe Metabolic Disturbances: Persistent or life-threatening biochemical abnormalities that cannot be controlled medically.

Intermittent Hemodialysis

Intermittent hemodialysis provides relatively rapid removal of metabolic waste products and correction of selected electrolyte abnormalities.

It is generally more suitable for patients who can tolerate the associated fluid and hemodynamic changes.

Continuous Kidney Replacement Therapy

Continuous kidney replacement therapy provides gradual removal of fluid and solutes over an extended period.

It is often preferred for critically ill children with significant hemodynamic instability or a need for precise fluid management.

Selection Of Treatment Modality

The choice between intermittent hemodialysis, continuous therapy, and other available modalities depends on the child’s age, size, cardiovascular stability, clinical condition, and available expertise.

The decision should be made in consultation with pediatric nephrology and intensive care specialists.

Nutritional Management

Adequate nutrition is essential in children with AKI.

Critically ill children are at increased risk of malnutrition because of metabolic stress, reduced intake, gastrointestinal intolerance, and increased nutritional requirements.

Energy Requirements

Energy intake should be sufficient to support normal metabolic processes, tissue repair, and growth.

Protein Intake

Protein restriction solely to delay kidney replacement therapy is not recommended.

Insufficient protein intake may contribute to muscle breakdown, impaired healing, and worsening nutritional status.

Electrolyte Content

Dietary potassium, phosphate, and sodium intake may need to be adjusted according to serum concentrations and clinical findings.

Fluid Requirements

Nutritional plans should account for fluid restrictions when urine output is severely reduced or fluid overload is present.

Specialist Nutritional Support

Dietitian involvement may be beneficial, particularly in critically ill children or those requiring kidney replacement therapy.

Specific Treatment According To Etiology

The underlying cause of AKI should be identified and treated whenever possible.

Renal Hypoperfusion

Children with dehydration or reduced circulating blood volume require restoration of adequate renal perfusion.

Treatment may include isotonic fluid resuscitation and correction of the underlying cause of fluid loss.

Urinary Tract Obstruction

Obstructive AKI requires prompt identification and relief of urinary outflow obstruction.

Possible interventions include bladder catheterization, urinary drainage, or other urological procedures.

The type of intervention depends on the anatomical location and cause of obstruction.

Acute Interstitial Nephritis

When medication-induced AIN is suspected, the causative medication should be discontinued whenever clinically feasible.

Corticosteroids may be considered in selected patients with persistent or severe immune-mediated interstitial nephritis following specialist assessment.

Acute Glomerulonephritis

Treatment of glomerulonephritis depends on the specific underlying disorder.

Some forms require supportive care, while others may need corticosteroids or additional immunosuppressive treatment.

Rapidly progressive glomerulonephritis requires urgent pediatric nephrology assessment.

Hemolytic Uremic Syndrome

Management generally involves supportive care, careful fluid and electrolyte regulation, and treatment of associated complications.

Kidney replacement therapy may be necessary in severe cases.

The treatment approach varies according to whether the condition is associated with Shiga toxin infection, complement dysregulation, or another underlying cause.

Admission, Inpatient, And Nursing Considerations

Children with clinically significant AKI often require hospital admission for close observation, management of fluid and electrolyte disturbances, and treatment of the underlying disorder.

The level of care depends on AKI severity and associated systemic complications.

Initial Management Of Hypovolemia

Hypovolemic children require prompt restoration of circulating blood volume.

Isotonic crystalloid solutions, such as 0.9% sodium chloride or an appropriate balanced crystalloid, may be administered intravenously.

The quantity and rate of fluid administration should be guided by hemodynamic status and repeated clinical assessment.

Prevention Of Fluid Overload

Excessive fluid administration should be avoided once adequate perfusion has been restored.

Children with persistent oliguria after correction of hypovolemia may require fluid restriction rather than additional fluid boluses.

Management Of Severe Hyperkalemia

Hyperkalemia is one of the most urgent complications of AKI because it can cause life-threatening cardiac conduction abnormalities and arrhythmias.

A serum potassium concentration above approximately 6.5 mmol/L requires urgent clinical assessment, particularly when kidney function is impaired.

The urgency of treatment also depends on the rate of potassium increase, ECG findings, associated symptoms, and overall clinical condition.

Initial Assessment

Management should include:

• Immediate clinical assessment.
• Electrocardiography.
• Continuous cardiac monitoring for moderate or severe hyperkalemia.
• Discontinuation of potassium-containing fluids or medications.
• Repeat serum potassium measurement when appropriate to exclude sample hemolysis or laboratory error.

Treatment should not be delayed for repeat laboratory confirmation when significant hyperkalemia is strongly suspected and the child is clinically unstable.

Intravenous Calcium Gluconate

Intravenous calcium is used to stabilize the cardiac membrane in patients with life-threatening hyperkalemia, particularly when ECG changes are present.

Calcium does not reduce the serum potassium concentration.

A pediatric emergency protocol may use 10% calcium gluconate at a dose of approximately 0.5–0.7 mL/kg intravenously, subject to protocol-specific maximum doses.

Administration requires continuous cardiac monitoring and careful attention to infusion rate and vascular access.

Insulin And Glucose

Intravenous insulin promotes movement of potassium from the extracellular fluid into cells.

Glucose is administered to reduce the risk of insulin-induced hypoglycemia.

A commonly used emergency regimen includes short-acting insulin at approximately 0.1 unit/kg intravenously, with a maximum dose of 10 units, accompanied by an appropriate intravenous glucose dose.

An example glucose dose is 0.5 g/kg.

The precise regimen, concentration, and administration method should follow the local pediatric hyperkalemia protocol.

Blood glucose must be monitored frequently after insulin administration because delayed hypoglycemia may occur.

Nebulized Salbutamol

Salbutamol, also known as albuterol, stimulates beta-2 adrenergic receptors and promotes intracellular potassium uptake.

It may be used alongside insulin and glucose to produce additional potassium reduction.

The dose should be selected according to the child’s weight and local emergency protocol.

Tachycardia and other adrenergic adverse effects should be monitored.

Sodium Bicarbonate

Intravenous sodium bicarbonate may be considered when severe hyperkalemia occurs with significant metabolic acidosis.

Its potassium-lowering effect is less reliable than insulin and beta-2 agonists.

Bicarbonate should not be administered routinely for hyperkalemia in the absence of an appropriate indication.

Serum calcium and acid-base status should be monitored because bicarbonate administration may reduce ionized calcium and worsen hypocalcemia.

Potassium-Binding Resins

Sodium polystyrene sulfonate has historically been used to promote gastrointestinal potassium elimination.

However, its onset is delayed and its effectiveness in emergency treatment is limited.

It is not appropriate as the sole treatment for life-threatening hyperkalemia.

Sodium polystyrene sulfonate may also cause serious gastrointestinal adverse effects, including intestinal injury and necrosis.

Sorbitol-containing preparations are particularly concerning and should generally be avoided.

Potassium-binding therapies should be considered only when appropriate for the patient’s clinical condition and local treatment protocol.

Furosemide

Furosemide may promote urinary potassium excretion when the patient has sufficient residual kidney function and is producing urine.

It is unlikely to be effective in patients with severe anuria.

The patient’s volume status should be considered before administration.

Kidney Replacement Therapy

Urgent dialysis or continuous kidney replacement therapy may be required when severe hyperkalemia persists despite appropriate emergency treatment.

It may also be necessary when hyperkalemia is associated with advanced kidney dysfunction and insufficient potassium excretion.

Emergency Monitoring

Children receiving treatment for severe hyperkalemia require repeated potassium measurements, continuous cardiac monitoring, and careful assessment of blood glucose and other electrolytes.

Emergency medication doses and infusion preparation must be verified against the institutional pediatric protocol because medication errors can cause serious harm.

Ongoing Care

Follow-Up Recommendations

Long-term follow-up is important because AKI may resolve completely or result in persistent abnormalities of kidney function.

Even children whose serum creatinine returns to normal may have an increased risk of subsequent kidney disease.

Assessment Of Renal Recovery

Follow-up should evaluate:

• Serum creatinine.
• Estimated glomerular filtration rate.
• Urinalysis.
• Proteinuria or albuminuria.
• Blood pressure.
• Growth and development.
• Recurrence of kidney-related symptoms.

Children With Complete Recovery

Children who appear to recover fully may still benefit from reassessment of kidney health after the acute episode.

A follow-up evaluation within approximately three months is commonly recommended.

Children With Severe Acute Kidney Injury

Children who experienced severe AKI, required kidney replacement therapy, or had incomplete recovery should undergo earlier and more comprehensive assessment.

A kidney health evaluation within one to three months after discharge is appropriate for many high-risk patients.

Long-Term Surveillance

Children with persistent kidney abnormalities, recurrent AKI, hypertension, proteinuria, or reduced glomerular filtration may require ongoing pediatric nephrology care.

Follow-up strategies should be individualized according to the severity of the original episode and the degree of recovery.

Prognosis

The prognosis of acute kidney injury depends on the underlying cause, severity and duration of kidney dysfunction, associated illnesses, and response to treatment.

Complete Recovery

Some children experience full recovery of kidney function after correction of the underlying cause.

This is particularly likely when transient renal hypoperfusion is recognized and treated promptly.

Incomplete Recovery

Other patients may experience persistent reductions in glomerular filtration, proteinuria, or hypertension.

These findings may indicate residual kidney injury.

Progression To Chronic Kidney Disease

AKI is associated with an increased long-term risk of chronic kidney disease.

The likelihood of persistent impairment is greater in patients with severe or recurrent AKI, prolonged kidney dysfunction, or preexisting renal abnormalities.

Kidney Failure

In severe cases, kidney function may fail to recover adequately, resulting in persistent kidney failure requiring long-term kidney replacement therapy.

Mortality

The risk of death increases when AKI occurs alongside severe systemic illness or multiple organ dysfunction.

Among critically ill children, AKI is independently associated with increased mortality.

The underlying severity of illness, extent of organ dysfunction, and development of complications strongly influence the outcome.

Complications

Postobstructive Diuresis

A marked increase in urine output may occur after relief of urinary tract obstruction.

This phenomenon is known as postobstructive diuresis.

Although increased urine output may indicate restoration of urinary drainage, excessive diuresis can lead to dehydration, hypotension, and electrolyte disturbances.

Careful monitoring of urine output and appropriate fluid replacement may be necessary.

Fluid Overload

Impaired sodium and water excretion may cause excessive fluid accumulation.

Fluid overload can lead to edema, pulmonary congestion, hypertension, and cardiovascular dysfunction.

Congestive Heart Failure

Severe fluid retention may increase cardiac workload and contribute to heart failure, particularly in children with underlying cardiac disease.

Hypertension

Excessive fluid accumulation and altered renal regulation of blood pressure may result in systemic hypertension.

Dilutional Hyponatremia

Retention of free water may reduce serum sodium concentrations.

Severe hyponatremia can produce neurological complications.

Hyperkalemia

Hyperkalemia is a potentially life-threatening complication of AKI.

Reduced urinary potassium excretion may cause progressive elevation of serum potassium.

Cardiac Arrhythmias

Severe hyperkalemia can interfere with cardiac electrical conduction.

Possible manifestations include peaked T waves, prolonged conduction intervals, widened QRS complexes, bradyarrhythmias, and ventricular arrhythmias.

Untreated severe hyperkalemia may lead to cardiac arrest.

Uremia

Accumulation of nitrogenous waste products and other uremic toxins may produce systemic complications.

Neurological Manifestations

Uremia may cause fatigue, lethargy, altered mental status, and encephalopathy.

Severe cases may be associated with seizures or reduced consciousness.

Bleeding Tendency

Uremia may impair platelet function and increase the risk of bleeding.

Infection Risk

Children with severe kidney dysfunction or critical illness may be more susceptible to infection because of associated immune dysfunction, invasive devices, and underlying systemic disease.

Uremic Pericarditis

Severe uremia may cause inflammation of the pericardium.

This is an important indication for urgent kidney replacement therapy.

Metabolic Acidosis

AKI may impair the kidneys’ ability to excrete hydrogen ions and regenerate bicarbonate.

The resulting metabolic acidosis may become severe when kidney dysfunction is advanced or associated with shock or tissue hypoperfusion.

Severe acidosis can impair cardiovascular function and contribute to further physiological instability.

Hypocalcemia

Reduced serum calcium may occur because of abnormalities in phosphate metabolism and other disturbances associated with kidney dysfunction.

Neuromuscular Manifestations

Significant hypocalcemia may cause muscle cramps, paresthesias, and increased neuromuscular excitability.

Tetany

Severe hypocalcemia may cause tetany, characterized by involuntary muscle contractions and spasms.

Seizures And Cardiac Effects

Marked hypocalcemia may occasionally contribute to seizures or cardiac conduction abnormalities.

Long-Term Kidney Dysfunction

Children who survive AKI may develop persistent renal abnormalities.

Possible long-term consequences include:

• Chronic kidney disease.
• Persistent proteinuria.
• Hypertension.
• Reduced glomerular filtration.
• Increased susceptibility to subsequent episodes of AKI.
• Kidney failure requiring long-term replacement therapy in severe cases.

Early recognition, appropriate treatment, and structured follow-up are important for reducing the risk of these complications.