Acute kidney injury and renal failure

Definition and Overview

Acute kidney injury (AKI) in children is defined by the Kidney Disease: Improving Global Outcomes (KDIGO) paediatric adaptation as:

• Rise in serum creatinine (SCr) ≥0.3 mg/dL ($\geq 26.5\,\mu\text{mol/L}$) within 48 hours, OR
• Rise in SCr to $\geq 1.5\times$ baseline within 7 days, OR
• Urine output <0.5 mL/kg/hr for ≥6 hours
• Important paediatric caveat: Neonates and infants have a low baseline SCr (reflecting maternal creatinine initially, then the low muscle mass of the infant); a value that looks "normal" may represent significant GFR impairment.
• Use age-specific reference ranges and trend changes rather than absolute thresholds.

KDIGO AKI staging (paediatric application):

Pathophysiology

Aetiological Classification

AKI in children follows the same prerenal/intrinsic/postrenal framework as adults, but the distribution and causes differ significantly by age.

Prerenal (~40-50% of paediatric AKI):

• Hypovolaemia: gastroenteritis (most common cause in previously healthy children), haemorrhage, burns
• Reduced effective circulating volume: septic shock, cardiac failure, nephrotic syndrome, hepatorenal syndrome
• Drugs reducing renal perfusion: NSAIDs, ACE inhibitors, calcineurin inhibitors

Intrinsic (~40-50%):

• Acute tubular necrosis (ATN): ischaemic (prolonged prerenal state, cardiac surgery, ECMO) or nephrotoxic (aminoglycosides, vancomycin, contrast, myoglobin in rhabdomyolysis)
• Glomerulonephritis: haemolytic uraemic syndrome (HUS, especially Shiga-toxin-producing E. coli), IgA nephropathy, post-streptococcal, SLE nephritis
• Acute interstitial nephritis (AIN): drug-induced (beta-lactams, PPIs), infection
• Vascular: renal vein thrombosis (especially neonates), renal artery thrombosis

Postrenal (~10%):

• Congenital anomalies of the kidney and urinary tract (CAKUT), posterior urethral valves (PUV), bilateral obstructing calculi, neurogenic bladder

Neonatal-Specific Considerations

• Renal blood flow is approximately 15-18% of cardiac output at birth (versus ~25% in adults); GFR is low and tubular function immature
• Renal vein thrombosis presents with haematuria, palpable flank mass, thrombocytopaenia; risk factors: polycythaemia, dehydration, maternal diabetes, central line position
• Perinatal asphyxia and cardiac surgery are the dominant PICU causes of neonatal AKI
• Neonatal SCr reflects maternal level for the first 48-72 hours; serial measurement essential

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

• CAKUT encompass the spectrum of structural abnormalities arising from disrupted embryological development of the kidney and collecting system.
• They are the leading cause of paediatric chronic kidney disease and end-stage renal disease (ESRD).

Classification

Posterior Urethral Valves: PICU Management Points

• Typically male neonate or infant; prenatal ultrasound may show thick-walled bladder, bilateral hydroureteronephrosis, oligohydramnios
• Neonatal presentation: poor urinary stream, sepsis, metabolic acidosis, uraemia, respiratory compromise (pulmonary hypoplasia if severe oligohydramnios)
• Immediate management: urethral catheterisation (decompress bladder) + IV fluid correction of electrolytes; endoscopic valve ablation is definitive
• Long-term bladder dysfunction ("valve bladder") drives secondary renal damage; PICU teams managing these children must be aware of abnormal bladder compliance even post-ablation

Urosepsis in Children

Urosepsis represents urinary tract infection (UTI) causing systemic sepsis; it occurs predominantly in neonates and infants, in children with CAKUT, and in immunocompromised patients.

Recognition

• Neonates and young infants: fever, hypothermia, poor feeding, jaundice (urinary-source sepsis is a key cause of late-onset neonatal jaundice), hypoglycaemia
• Older children: fever, rigors, flank pain, costovertebral tenderness; may progress rapidly to septic shock
• Obstructed and infected kidney (pyonephrosis) is a urological emergency: fever + ipsilateral pain + hydronephrosis = urgent decompression

Causative Organisms

• Escherichia coli (most common, all ages)
• Klebsiella spp. Enterococcus spp. Pseudomonas (in instrumented/obstructed urinary tracts)
• Group B Streptococcus (GBS): neonates
• Extended-spectrum beta-lactamase (ESBL)-producing organisms: increasing prevalence; relevant for empiric antibiotic selection in recurrent or healthcare-associated UTI

Management of Urosepsis

1. Recognise sepsis early; apply paediatric sepsis definitions (age-specific vital-sign thresholds)
2. Obtain blood culture + urine culture (catheter specimen in neonates/young infants) before antibiotics
3. Empiric antibiotics within 1 hour of recognition of septic shock:
   • Neonates: ampicillin 50 mg/kg IV + gentamicin 4-5 mg/kg IV (once-daily, with therapeutic drug monitoring)
   • Infants and children: IV cephalosporin (ceftriaxone 50-100 mg/kg/day, max 2 g; or cefotaxime 50 mg/kg/dose 6-hourly) or piperacillin-tazobactam 100 mg/kg/dose 8-hourly if complicated/obstructed
   • Adjust for local ESBL prevalence and patient risk factors; use meropenem 20 mg/kg/dose 8-hourly if ESBL suspected
4. Urgent imaging: renal ultrasound to exclude obstruction and collection; CT or MRI if equivocal
5. Urgent urological decompression (percutaneous nephrostomy or ureteric stent) if obstructed pyonephrosis
6. Haemodynamic resuscitation per paediatric septic shock algorithm (fluid boluses 10-20 mL/kg isotonic crystalloid, reassess after each bolus; escalate to vasoactive infusions if fluid-refractory)

Investigations

Management

General Principles

• Identify and reverse the primary cause promptly
• Optimise fluid status: avoid both volume overload and ongoing hypovolaemia; fluid overload >10% of body weight is independently associated with worse outcomes in PICU
• Monitor fluid balance meticulously: input/output charting by weight (g/hr in neonates)
• Restrict nephrotoxins: aminoglycosides with TDM, NSAIDs off, contrast minimisation, withhold ACE inhibitors/ARBs/diuretics in volume-depleted states

Electrolyte and Metabolic Emergencies

Hyperkalaemia ($K^+ > 6.0\,\text{mmol/L}$ in neonates or >5.5 mmol/L with ECG changes or >6.5 mmol/L any age):

1. Calcium gluconate 10% 0.5-1 mL/kg IV over 5-10 min (cardiac membrane stabilisation; repeat if ECG changes persist)
2. Sodium bicarbonate 1-2 mmol/kg IV (if acidotic; transcellular shift)
3. Salbutamol nebulised 2.5-5 mg (weight-independent for transcellular shift) or IV 4 mcg/kg over 20 min
4. Insulin-dextrose: insulin 0.1 units/kg + dextrose 0.5 g/kg (25% dextrose 2 mL/kg) IV over 30 min; monitor BSL 30-minutely
5. Sodium polystyrene sulfonate (Resonium) 0.5-1 g/kg oral/rectal (elimination; avoid in neonates due to colonic necrosis risk)
6. Dialysis if refractory or anuric with ongoing rise

Metabolic acidosis: Sodium bicarbonate supplementation if pH <7.1 or $\text{HCO}_3^- < 10\,\text{mmol/L}$, prioritising RRT in refractory or hypernatraemia-risk cases.

Hypertension: Fluid overload and renin-driven hypertension are common; initial management with amlodipine 0.1-0.3 mg/kg/dose oral or hydralazine 0.1-0.5 mg/kg IV for acute crises.

Fluid overload: Target euvolaemia; cautious use of furosemide 1-2 mg/kg IV to maintain urine output but do not delay RRT if oliguria is established ATN.

Renal Replacement Therapy (RRT) in Children

Indications (AEIOU mnemonic):

• Acidosis refractory to medical management
• Electrolyte imbalance refractory to treatment (particularly hyperkalaemia)
• Intoxication (overdose of dialysable substance)
• Oliguria/anuria causing fluid overload ≥10% body weight
• Uraemia with symptoms (encephalopathy, pericarditis, coagulopathy)

Modality selection by size and haemodynamic status:

CRRT prescription key points:

• Anticoagulation: citrate regional anticoagulation preferred in children ≥8-10 kg without liver failure; heparin infusion 5-10 units/kg/hr otherwise
• Effluent dose: 20-25 mL/kg/hr (prescribe higher to achieve this delivered dose, as downtime and filter clotting reduce actual delivery)
• Fluid balance: prescribe net negative balance in fluid-overloaded patients: typically 1-3 mL/kg/hr net ultrafiltration, guided by haemodynamic monitoring
• Calcium supplementation mandatory with citrate CRRT; monitor ionised calcium 4-hourly
• Phosphate depletion common with CRRT; supplement via dialysate or IV to maintain $\text{PO}_4 > 0.8\,\text{mmol/L}$

Specific Conditions

Haemolytic Uraemic Syndrome (HUS)

• Most common cause of AKI requiring dialysis in previously healthy children
• Stx-HUS (STEC-HUS): follows bloody diarrhoea from E. coli O157:H7 or O111; triad of microangiopathic haemolytic anaemia, thrombocytopaenia, AKI
• Avoid antibiotics in Stx-HUS (increases Shiga-toxin release); avoid antimotility agents
• Atypical HUS (complement-mediated): eculizumab 600 mg IV (dose by weight) is indicated early; urgent haematology/nephrology review
• Indications for dialysis in HUS: oligoanuria, hyperkalaemia, severe fluid overload, hypertensive encephalopathy

Neonatal AKI

• Definition adjusted: SCr rise $\geq 26.5\,\mu\text{mol/L}$ within 48 hours or stage by modified KDIGO neonatal criteria
• Common causes: perinatal asphyxia (hypoxic-ischaemic injury), sepsis, cardiac surgery, nephrotoxins (gentamicin, indomethacin, vancomycin), renal vein thrombosis
• Fluid management: strict input/output by weight; avoid fluid overload, which worsens pulmonary outcome in the asphyxiated neonate
• Peritoneal dialysis is first-line RRT in neonates; CRRT requires experienced nursing and specialised circuits

Complications and Long-Term Considerations

• Acute: hyperkalaemia (life-threatening arrhythmia), severe acidosis, fluid overload (pulmonary oedema, impaired ventilation), hypertensive emergency, uraemic encephalopathy, bleeding (uraemic platelet dysfunction)
• Recovery phase: polyuric phase after ATN may cause significant electrolyte losses; careful replacement required
• Long-term: children with AKI have a significant risk of CKD progression, hypertension, and proteinuria regardless of apparent renal recovery; requires nephrology follow-up for ≥2 years post-episode
• CAKUT and ESRD: ARPKD, severe bilateral renal dysplasia, and PUV are the principal paediatric causes of ESRD; PICU teams should maintain awareness of transplant evaluation needs and the trajectory toward renal replacement in long-term care planning
• Nutritional support: AKI is a hypercatabolic state; enteral nutrition should be initiated early; protein restriction is not routinely recommended in children receiving RRT (target 1.5-2.5 g/kg/day protein); phosphate and potassium content of feeds must be monitored

PICU Viva Framing

Key discriminators the examiner will probe:

• FE$_{\text{Na}}$ interpretation in neonates: physiological tubular immaturity causes higher sodium wasting; thresholds differ from older children and adults
• HUS antibiotic avoidance: know the evidence and mechanism
• Fluid overload as an outcome driver: fluid overload ≥10% body weight is an independent mortality risk; RRT should not be withheld waiting for "absolute" indications if fluid overload is escalating
• CRRT circuit priming: blood prime is required in infants where the extracorporeal volume exceeds 10-15% of the child's blood volume; failure to do so causes haemodynamic instability and haemodilution
• PUV recognition: any male neonate with bilateral hydronephrosis, poor urinary stream, metabolic acidosis, and a thick-walled bladder on ultrasound needs urgent urological assessment and catheterisation
• Urosepsis empiric regimen: justify gentamicin use (excellent gram-negative coverage, once-daily dosing with TDM is safe) and know when to escalate to carbapenem (recurrent UTI, prior ESBL, healthcare-associated infection)