Acute Kidney Injury in Children: Classification, Recognition and Treatment Principles
Abstract
:1. Introduction
2. Classifications
3. Clinical Diagnostic Evaluation
4. Basic Principles of Pediatric AKI Treatment
5. Long-Term Implications of Pediatric AKI
6. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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AKI Stage | Serum Creatinine | Urine Output |
---|---|---|
1 | Increase in serum creatinine by ≥0.3 mg/dL from baseline (≥26.5 µmol/L) within 48 h or increase in serum creatinine to ≥ 1.5 times baseline within prior 7 days | Urine volume ≤ 0.5 mL/kg/h for six hours |
2 | Increase in serum creatinine to 2–2.9 times from baseline | Urine volume < 0.5 mL/kg/h for 12 h |
3 | Increase in serum creatinine to > 3 times from baseline or creatinine concentration > 353.6 µmol/L (4 mg/dL) or initiation of RRT or estimated GFR < 35 mL/min/1.73 m2 | Urine volume < 0.3 mL/kg/h for 24 h or anuria for at least 24 h |
Causes of AKI | Main Characteristics | |
---|---|---|
Anatomical location of the initial injury | Prerenal disease | The most common form of AKI in children |
Volume-responsive or functional AKI | ||
Decreased renal perfusion due to hypovolemia (bleeding, GI, urinary or cutaneous losses) or decreased effective circulation (heart failure, septic shock and cirrhosis) | ||
Reduced GFR and normal renal tubular function with increased reabsorption of Na+ and water, causing oliguria | ||
Urine flow and GFR return to normal after correction of renal perfusion | ||
Intrinsic kidney disease | Structural damage to the renal parenchyma | |
Most commonly due to prolonged hypoperfusion, sepsis, nephrotoxins or severe glomerular diseases | ||
Postrenal disease | Usually due to congenital or acquired anatomic obstructions to the lower urinary tract | |
Clinical setting or circumstance | Community-acquired AKI | Associated with a single predominant insult, such as volume depletion |
Often reversible | ||
Hospital-acquired AKI | Usually in the critical care setting | |
Multifactorial and part of multiorgan failure | ||
Profoundly complicates treatment and outcome | ||
Urine output | Anuria | No urine output |
Oliguria | <1 mL/kg/h in infants <0.5 mL/kg/h in children and adults > 6 h | |
Nonoliguria | >1 mL/kg/h in infants >0.5 mL/kg/h in children and adults > 6 h | |
Polyuria | >3 mL/kg/h, often in patients with ATN and nephrotoxic AKI, with impaired urinary concentrating defect |
Laboratory Test | Main Characteristics of Specific Findings |
---|---|
Urinalysis | Muddy brown granular casts and epithelial cell casts suggest intrinsic AKI or ATN |
Red cell casts suggest glomerulonephritis, especially when associated with dysmorphic red cells and marked proteinuria; white cells and white cell casts may be present | |
Pyuria with white cell, granular or waxy casts indicate tubulointerstitial disease or UTI | |
A positive test for heme on a urine dipstick without red blood cells in the sediment suggest hemolysis or rhabdomyolysis | |
Usually normal in cases with prerenal AKI | |
Patients with ATN have σ < 1.010 and urine osmolality (more accurate measure of concentrating ability) < 350 mosmol/kg while those with prerenal AKI have σ > 1.020 and urine osmolality > 500 mosmol/kg | |
Fractional excretion of Na+ | FENa < 1 (<2 in neonates): prerenal AKI, majority of the filtered Na+ is reabsorbed as a response to reduced perfusion |
FENa > 2 (>2.5 in neonates): indicates ATN | |
FENa 1–2: inconclusive | |
Limitations of FENa: fluid administration prior to measurement, diuretic use and AKI due to contrast nephropathy or pigment nephropathy |
Types of Nephrotoxins | Special Features |
---|---|
Pharmaceuticals | Many drugs (prescription or over the counter) have a side effect profile with potential for kidney injury |
Examples of these drugs: ACE inhibitors, NSAIDs, aminoglycosides, analgesic combinations, pentostatin, anti-angiogenesis medications, phenacetin, antivirals (such as acyclovir), ARBs, calcineurin inhibitors, hydroxyethyl starch, topiramate, ifosfamide, vancomycin, mTOR inhibitors, immunotherapies, zonisamide, ambisome, pamidronate disodium, amphotericin B, indomethacin, iodixanol (Visipaque), piperacillin/tazobactam, mesalamine, methotrexate, vancomycin, foscarnet, mitomycin, zoledronic acid, nafcillin, etc. | |
Naturally occurring nephrotoxins | Animal and insect venoms |
Kidney injury via various mechanisms: hemodynamic changes, microvascular thrombosis, AIN and direct cellular toxicity | |
Botanicals cause kidney injury by intentional consumption as a food (usually in excess) or as part of traditional healing methods | |
Examples: aristolochic acid, datura species, ephedra species, mefenamic acid, melamine, phenylbutazone, etc. | |
Environmental nephrotoxins | Daily threat, associated with many deaths worldwide |
Exposure through contaminated ground water, traditional medicines and soil remains a global health problem | |
Exposure to heavy metals can cause tubular dysfunction acutely and progressive CKD with further exposure | |
Drugs of abuse have nephrotoxic potential, including synthetic cannabinoids, MDMA, heroin and cocaine | |
Other nephrotoxins: bismuth, cadmium, copper, hydrocarbons, lead, mercury, ethylene glycol poisoning from antifreeze ingestion, etc. |
Mechanism of Nephrotoxicity | Special Features |
---|---|
Pseudo-nephrotoxicity | A fraction of serum creatinine is eliminated through active tubular secretion via several transporters, including OCT2 |
Example: the drug trimethoprim, an OCT2 inhibitor, inhibits tubular secretion of creatinine, increasing its serum concentrations without direct injury to the kidney | |
Indirect nephrotoxicity | Medications (not directly nephrotoxic) contribute to systemic disease, causing kidney damage, such as hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) |
Example: rhabdomyolysis is a systemic syndrome that results in AKI due to vasoconstriction, direct ischemic injury, the proliferation of free radicals and tubular obstruction associated with myoglobinuria | |
Vascular complications | The kidney receives about 25% of the cardiac output and is sensitive to factors that influence systemic hemodynamics |
Excessive exogenous fluid administration may increase venous pressure in the kidney, leading to interstitial edema, which can reduce RBF and the GFR and lead to additional salt and water retention; fluid overload in critically ill children worsens outcomes | |
Iatrogenic intravascular volume depletion (with drugs such as norepinephrine) due to excessive diuresis may decrease effective circulating arterial blood volume and compromise kidney perfusion, especially in patients with reduced baseline kidney perfusion | |
Acute interstitial nephritis | Cell-mediated immune response: drugs may act as haptens to modify the endogenous response to native renal proteins or induce an autoimmune reaction to the tubular basement membrane through molecular mimicry |
Drugs may also trigger systemic immune activation that leads to the deposition or sequestration of immune complexes in the kidney interstitium | |
Interstitial infiltration by lymphocytes, macrophages, eosinophils and mast cells leads to inflammation and, eventually, fibrosis | |
Kidney biopsy reveals interstitial inflammation, edema and tubulitis | |
Drugs associated with AIN include beta-lactam antibiotics, rifampin, sulfonamides, NSAIDs, proton pump inhibitors and immune checkpoint inhibitors | |
Glomerular disease | Several drugs are associated with immune-mediated glomerular disease through the production of autoantibodies, such as ANCA-associated vasculitis with pauci-immune glomerulonephritis or drug-induced lupus |
Examples of these drugs: hydralazine, propylthiouracil, methimazole, cocaine, allopurinol and procainamide | |
May also be due to direct cellular toxicity at the level of the podocyte, the endothelial cell or the mesangial cell that is caused by interferon, anabolic steroids, bisphosphonates and sirolimus | |
Direct tubular toxicity | Drugs or their metabolites may directly damage tubular cells via mitochondrial injury, oxidative stress or DNA damage, which can lead to apoptosis and necrosis |
Examples of these drugs: cisplatin, aminoglycosides, cidofovir, foscarnet, tenofovir and radiocontrast agents | |
Osmotic nephrosis | Drugs such as mannitol, hydroxyethyl starch, immunoglobulins and dextrans may lead to osmotic nephrosis through pinocytosis and cellular accumulation, leading to cell swelling, vacuolation and obstruction of the tubular lumen |
Crystalluria/nephrolithiasis | Some medications or their metabolites are insoluble in the urine and can result in crystalline nephropathy and renal calculi formation |
Exacerbated by volume depletion, reduced urinary flow rates, high drug doses, rapid drug infusion rates and altered urine pH | |
Examples of these drugs: acyclovir, methotrexate, sulfamethoxazole, indinavir, atazanvir, triamterene, ciprofloxacin and ethylene glycol | |
Systemic conditions, such as tumor lysis syndrome, may also lead to crystal deposition in the kidney | |
Altered electrolyte handling | Drugs may alter kidney’s handling of phosphate, glucose, magnesium, potassium, sodium or water |
Specific patterns: SIADH, diabetes insipidus or acquired Fanconi syndrome | |
Drugs causing this type of kidney dysfunction include lithium, ifosfamide, selective-serotonin reuptake inhibitors, anti-epileptics and vincristine |
Parameter | Special Conditions | Description of Therapeutic Measures |
---|---|---|
Fluid volume | Hypovolemia | Immediate i.v. fluid administration in order to restore renal function and prevent progression to intrinsic AKI |
Euvolemia | Fluid losses (insensible fluid and urine GI losses) must be balanced with the given fluids | |
Hypervolemia | Fluid removal/restriction needed | |
Oliguric AKI: consider furosemide to convert AKI to nonoliguric form | ||
Early consideration for RRT in critically ill child | ||
Electrolytes | Oliguria/anuria | Restriction of potassium and phosphorus |
Hyperkalemia is the most common electrolyte complication and is potentially life-threatening due to cardiac arrhythmia | ||
Therapy according to severity of hyperkalemia | ||
Sodium | Intake restriction to 2–3 mEq/kg/day to prevent fluid retention and hypertension | |
Polyuria | Replacement of electrolyte losses | |
Acid–base balance | Metabolic acidosis | Common abnormality of AKI |
NaHCO3 indicated in life-threatening situations despite possible adverse effects | ||
Hypertension | Common complication of AKI | |
Therapy according to the severity and cause of hypertension | ||
Nutrition | AKI is associated with catabolism | |
Nutritional support needed to enhance the recovery | ||
Normal nutritional maintenance requirements and supplemental calories to address the catabolic needs | ||
Caloric intake: at least 120 Kcal/kg/day in infants and at least 150% of maintenance needs in older children | ||
Drugs | Avoidance of nephrotoxic agents | |
Dosing adjustment of renally excreted drugs according to renal function |
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Kopač, M. Acute Kidney Injury in Children: Classification, Recognition and Treatment Principles. Children 2024, 11, 1308. https://doi.org/10.3390/children11111308
Kopač M. Acute Kidney Injury in Children: Classification, Recognition and Treatment Principles. Children. 2024; 11(11):1308. https://doi.org/10.3390/children11111308
Chicago/Turabian StyleKopač, Matjaž. 2024. "Acute Kidney Injury in Children: Classification, Recognition and Treatment Principles" Children 11, no. 11: 1308. https://doi.org/10.3390/children11111308
APA StyleKopač, M. (2024). Acute Kidney Injury in Children: Classification, Recognition and Treatment Principles. Children, 11(11), 1308. https://doi.org/10.3390/children11111308