Residency · Residency · Medicine Pediatrics
Acute Kidney Injury in Pediatric and Adult Patients
Overview
Acute kidney injury (AKI) is defined by an abrupt decline in kidney function, leading to retention of waste products, fluid overload, and electrolyte derangements. Staging systems differ between pediatric and adult practice, and etiologies shift dramatically by age. The Med-Peds physician must understand the nuances of AKI diagnosis, management, and the emerging role of novel biomarkers across the lifespan.
Definitions and Staging
KDIGO Staging (Universal Standard)
| Stage | Serum Creatinine Criteria | Urine Output Criteria |
|---|---|---|
| 1 | 1.5-1.9x baseline OR ≥0.3 mg/dL increase within 48h | <0.5 mL/kg/hr for 6-12 hours |
| 2 | 2.0-2.9x baseline | <0.5 mL/kg/hr for ≥12 hours |
| 3 | ≥3.0x baseline OR ≥4.0 mg/dL OR initiation of RRT | <0.3 mL/kg/hr for ≥24 hours or anuria ≥12 hours |
Stage 1: serum creatinine 1.5-1.9x baseline OR increase >=0.3 mg/dL within 48 hours; urine output <0.5 mL/kg/hr for 6-12 hours. Stage 2: serum creatinine 2.0-2.9x baseline; urine output <0.5 mL/kg/hr for >=12 hours. Stage 3: serum creatinine >=3.0x baseline OR increase to >=4.0 mg/dL OR initiation of RRT; urine output <0.3 mL/kg/hr for >=24 hours or anuria for >=12 hours.
Pediatric-Specific Staging (pRIFLE)
Modified for children using estimated creatinine clearance (Schwartz formula) Risk: eCCl decrease >=25%; UO <0.5 mL/kg/hr for 8 hours. Injury: eCCl decrease >=50%; UO <0.5 mL/kg/hr for 16 hours. Failure: eCCl decrease >=75% OR eCCl <35 mL/min/1.73m2; UO <0.3 mL/kg/hr for 24 hours or anuria for 12 hours. Loss: persistent failure >4 weeks. ESRD: persistent failure >3 months.
Challenges in Pediatric AKI Diagnosis
Baseline creatinine often unknown (no prior labs in healthy children) Creatinine varies by age, muscle mass, and sex; neonatal creatinine reflects maternal levels in the first 48-72 hours. Neonatal creatinine normally rises briefly then falls as maternal creatinine is cleared and neonatal GFR matures. Small absolute creatinine changes in children with low baseline values represent proportionally larger GFR changes.
Epidemiology
Pediatric AKI: 25-30% of critically ill children develop AKI; associated with increased mortality, length of stay, and CKD risk. Adult AKI: occurs in 10-15% of hospitalized adults, up to 50% of ICU patients. Neonatal AKI: 18-40% of NICU admissions; risk factors include prematurity, perinatal asphyxia, sepsis, nephrotoxic medications. AWARE study: 26.9% incidence of AKI in pediatric ICU patients worldwide.
Etiology by Age
Prerenal (Most Common Across All Ages)
Pediatric: dehydration (gastroenteritis most common cause of AKI in children worldwide), hemorrhage, sepsis, burns, cardiac failure. Adult: hypovolemia, sepsis, cardiorenal syndrome, hepatorenal syndrome, medications (ACEi/ARB, NSAIDs, diuretics)
Intrinsic Renal
Pediatric-Predominant Causes
Hemolytic uremic syndrome (HUS): classic (typical) HUS from Shiga toxin-producing E. coli (STEC-HUS); diarrhea prodrome, microangiopathic hemolytic anemia, thrombocytopenia, AKI; peak age 6 months - 5 years. Atypical HUS: complement-mediated; genetic mutations in complement regulatory proteins; may present at any age; treated with eculizumab. Nephrotoxic medications: aminoglycosides, vancomycin, amphotericin B, NSAIDs, chemotherapy (cisplatin, methotrexate) Acute glomerulonephritis: post-streptococcal GN (PSGN), IgA nephropathy, lupus nephritis, ANCA vasculitis. Acute interstitial nephritis (AIN): drug-induced (antibiotics, NSAIDs, PPIs) Tumor lysis syndrome: leukemia and lymphoma; hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia. Congenital anomalies: obstructive uropathy (posterior urethral valves), bilateral renal agenesis/dysplasia.
Adult-Predominant Causes
Acute tubular necrosis (ATN): ischemic (prolonged prerenal state) or nephrotoxic (contrast-induced, aminoglycosides, cisplatin, rhabdomyolysis) Contrast-induced AKI: rising creatinine 24-72 hours after contrast administration; prevention with IV hydration. Rhabdomyolysis: crush injury, statins, seizures, extreme exertion; CK >5000 IU/L; myoglobin is directly nephrotoxic. Acute interstitial nephritis: PPIs most common drug cause in adults. Glomerulonephritis: ANCA vasculitis, anti-GBM disease, lupus nephritis, IgA nephropathy. Thrombotic microangiopathy: TTP (ADAMTS13 deficiency), HUS, malignant hypertension, scleroderma renal crisis.
Postrenal (Obstructive)
Pediatric: posterior urethral valves (most common congenital obstructive cause in boys), ureteropelvic junction obstruction, neurogenic bladder, urolithiasis, tumor (Wilms) Adult: urolithiasis, BPH (most common in older men), malignancy (cervical, prostate, bladder), retroperitoneal fibrosis, neurogenic bladder.
Evaluation
Laboratory
Serum creatinine (serial measurements), BUN, electrolytes (potassium, phosphorus, calcium) Urinalysis with microscopy: muddy brown granular casts (ATN), RBC casts (GN), WBC casts (AIN/pyelonephritis), eosinophiluria (AIN) Urine sodium and FENa: prerenal (<1%) vs. intrinsic (>2%); FEUrea if on diuretics (<35% prerenal, >50% intrinsic) CBC with smear: schistocytes (TMA/HUS/TTP), thrombocytopenia. LDH, haptoglobin, reticulocyte count: hemolysis workup. CK: rhabdomyolysis. Complement levels (C3, C4): post-streptococcal GN (low C3), lupus nephritis (low C3 and C4), aHUS. ANCA, anti-GBM, ANA, anti-dsDNA: glomerulonephritis workup. ADAMTS13 activity: TTP evaluation. Stool STEC culture/PCR: if HUS suspected.
Imaging
Renal ultrasound: assess kidney size, hydronephrosis, echogenicity, blood flow (Doppler) Must rule out obstruction in all AKI cases (especially in children with unknown anatomy) CT without contrast: renal calculi if suspected. Voiding cystourethrogram (VCUG): posterior urethral valves in neonatal boys with bilateral hydronephrosis.
Novel Biomarkers
NGAL (neutrophil gelatinase-associated lipocalin): rises 2-4 hours after kidney injury (vs. creatinine which rises 24-48 hours later); available in urine and serum. Cystatin C: less affected by muscle mass than creatinine; useful in children, elderly, and patients with low muscle mass. KIM-1 (kidney injury molecule-1): tubular injury marker. TIMP-2 x IGFBP7 (NephroCheck): FDA-approved for AKI risk assessment in adults. [FUROSEMIDE STRESS TEST]: 1-1.5 mg/kg IV furosemide; urine output <200 mL in 2 hours predicts progression to Stage 3 AKI or need for RRT in adults.
Management
General Principles (All Ages)
Identify and treat the underlying cause; Optimize volume status: fluid resuscitation for prerenal AKI; fluid restriction for oliguric intrinsic AKI with volume overload. Discontinue nephrotoxic agents; Adjust medication doses for decreased GFR; Monitor electrolytes frequently (potassium, phosphorus, calcium); Monitor fluid balance (strict I&O, daily weights).
Fluid Management
Prerenal AKI: isotonic crystalloid bolus (20 mL/kg in children, 250-500 mL in adults); reassess and repeat as needed. Volume overload: loop diuretics (furosemide 1-2 mg/kg IV in children, 40-80 mg IV in adults); if resistant, continuous infusion or addition of metolazone/chlorothiazide. Fluid overload >10%: associated with increased mortality; consider early RRT.
Electrolyte Management
Hyperkalemia: see detailed protocol (cardiac stabilization with calcium, shift with insulin/dextrose and albuterol, elimination with diuretics/kayexalate/RRT) Hyperphosphatemia: dietary restriction, phosphate binders (calcium carbonate, sevelamer) Hypocalcemia: correct only if symptomatic or before treating hyperkalemia. Metabolic acidosis: sodium bicarbonate if pH <7.1 or bicarbonate <12 mEq/L.
Nephrotoxin Stewardship
NINJA (Nephrotoxic Injury Negated by Just-in-time Action) program: automated surveillance of nephrotoxic medication exposure in hospitalized children. Reduces AKI rates by 25-40% through daily creatinine monitoring in exposed patients and prompting medication review. Applicable concept for adult hospitalists as well.
Renal Replacement Therapy (RRT)
Indications (same across ages): refractory hyperkalemia, severe metabolic acidosis, fluid overload not responsive to diuretics, uremia (encephalopathy, pericarditis, bleeding), toxic ingestion (methanol, ethylene glycol, lithium, aspirin) Modalities: Peritoneal dialysis (PD): particularly useful in neonates and small infants; simpler, no anticoagulation needed. Continuous renal replacement therapy (CRRT): preferred in hemodynamically unstable patients (children and adults); slower solute and fluid removal. Intermittent hemodialysis (IHD): hemodynamically stable patients; more rapid correction. Pediatric considerations: vascular access challenges in small children, smaller circuit volumes (risk of hypothermia and hemodynamic instability with priming), specialized pediatric equipment.
HUS: A Pediatric-Predominant Emergency
Typical (STEC-HUS)
Prodrome: bloody diarrhea 5-7 days before onset. Triad: microangiopathic hemolytic anemia (schistocytes, elevated LDH, low haptoglobin), thrombocytopenia, AKI. Peak age: 6 months - 5 years. Management: supportive care (fluids, transfusion, RRT as needed); NO antibiotics for STEC infection (may increase HUS risk); NO anti-motility agents. Prognosis: 60-70% recover completely; 25% have long-term renal sequelae; 3-5% mortality in developed countries.
Atypical HUS (aHUS)
Complement-mediated TMA; genetic mutations (CFH, CFI, MCP, C3, CFB) Presents at any age; may be triggered by infection, pregnancy, or medications. Treatment: eculizumab (anti-C5 monoclonal antibody) -- dramatically improves outcomes; ravulizumab (long-acting anti-C5) Plasma exchange/plasmapheresis: as bridging therapy.
<image>A diagnostic flowchart for AKI across ages, starting with elevated creatinine or decreased urine output. The chart branches into prerenal, intrinsic, and postrenal categories based on clinical context, urinalysis findings, and FENa. Each branch shows age-specific etiologies: pediatric-predominant causes (HUS, posterior urethral valves, tumor lysis syndrome) in blue and adult-predominant causes (contrast nephropathy, rhabdomyolysis, BPH) in red. Key diagnostic studies are shown at each decision node (renal ultrasound for obstruction, urine microscopy for casts, complement levels for HUS).</image>
<image>A comparison of AKI staging systems side by side: KDIGO (universal), pRIFLE (pediatric), and AKIN (adult). Each system is shown as a table with staging criteria based on creatinine changes and urine output thresholds. Color-coded severity bands (green for Stage 1/Risk, yellow for Stage 2/Injury, red for Stage 3/Failure) visually link corresponding stages across systems. An annotation highlights the challenge of establishing baseline creatinine in children without prior laboratory data.</image>
<image>An infographic on hemolytic uremic syndrome showing the pathogenesis and clinical course of typical STEC-HUS. A timeline shows the progression from STEC infection (contaminated food), through bloody diarrhea prodrome (days 1-5), to HUS onset (days 5-10) with the triad of microangiopathic hemolytic anemia, thrombocytopenia, and AKI. Peripheral blood smear showing schistocytes is illustrated. The management panel contrasts typical HUS (supportive care only, NO antibiotics) with atypical HUS (eculizumab, complement pathway diagram showing C5 blockade).</image>
Clinical Pearls
In pediatric AKI, baseline creatinine is often unknown -- small absolute changes in creatinine represent proportionally larger changes in GFR in children with low muscle mass. Dehydration is the most common cause of AKI in children worldwide -- oral and IV rehydration is the most important intervention globally. NEVER give antibiotics for confirmed STEC (Shiga toxin E. coli) infection -- antibiotics may increase the risk of developing HUS. The NINJA program (nephrotoxin stewardship) reduces AKI in hospitalized children by 25-40% -- advocate for similar programs in your institution. FENa <1% suggests prerenal azotemia; FENa >2% suggests intrinsic renal disease -- but diuretics invalidate FENa (use FEUrea instead) Fluid overload >10% in AKI is independently associated with increased mortality -- early RRT should be considered. Cystatin C and NGAL are emerging biomarkers that detect AKI earlier than creatinine, which is a lagging indicator. In neonates, the first 48-72 hours of creatinine reflect maternal creatinine -- do not diagnose neonatal AKI based on immediate postnatal creatinine values. Always obtain a renal ultrasound in AKI to rule out obstruction -- it is the one reversible cause that must not be missed.
References
- Kellum JA, Lameire N, et al. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1-138.
- Kaddourah A, Basu RK, Bagshaw SM, et al. Epidemiology of acute kidney injury in critically ill children and young adults (AWARE study). N Engl J Med. 2017;376(1):11-20.
- Goldstein SL, Kirkendall E, Nguyen H, et al. Electronic health record identification of nephrotoxin exposure and associated acute kidney injury (NINJA). Clin J Am Soc Nephrol. 2013;8(8):1283-1290.
- Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073-1086.
- Ostermann M, Bellomo R, Burdmann EA, et al. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020;98(2):294-309.
