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) $\geq 0.3\,\text{mg/dL}$ ($\geq 26.5\,\mu\text{mol/L}$) within 48 hours, OR
• Rise in SCr to $\geq 1.5\times$ baseline within 7 days, OR
• Urine output $< 0.5\,\text{mL/kg/hr}$ for $\geq 6$ 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 $> 5.5\,\text{mmol/L}$ with ECG changes or $> 6.5\,\text{mmol/L}$ 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 $\text{pH} < 7.1$ 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 $\geq 10\%$ 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 $\geq 8-10\,\text{kg}$ without liver failure; heparin infusion 5-10 units/kg/hr otherwise
• Effluent dose: $20-25\,\text{mL/kg/hr}$ (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 $1-3\,\text{mL/kg/hr}$ 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 $\geq 2$ 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 $1.5-2.5\,\text{g/kg/day}$ 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 $\geq 10\%$ 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)