Guideline 7.6 — Neonatal Acute Kidney Injury (AKI)

KEY TAKEAWAYS

Neonatal AKI is common and dangerous — it occurs in ~30% of NICU admissions (higher in ELBW), and any AKI episode roughly triples mortality, with later chronic kidney disease risk.
Use the neonatal modified KDIGO definition — staged by rise in serum creatinine from the lowest prior value AND/OR low urine output, with a neonatal-specific creatinine framework.
Neonatal creatinine is tricky: at birth it reflects the mother's and normally falls over days — a creatinine that fails to fall can signal AKI.
Think in three buckets: prerenal (hypoperfusion — the commonest, and reversible), intrinsic (ATN, nephrotoxins, thrombosis), and postrenal (obstruction — posterior urethral valves).
Management is supportive and cause-directed: restore perfusion, remove/dose-adjust nephrotoxins, manage fluids and hyperkalemia, relieve obstruction, and use kidney support therapy (dialysis — usually peritoneal) for refractory disease.
Prevention matters: nephrotoxin stewardship and careful perfusion/fluid management in at-risk infants.

1. Clinical Overview

Clinical Overview

The neonatal kidney is a work in progress — nephrogenesis completes around 34–36 weeks, glomerular filtration is low at birth and matures over weeks, and the tubules handle sodium, water, and potassium imperfectly. Against this backdrop, acute kidney injury is both common and consequential: it complicates a large fraction of NICU stays, is an independent risk factor for death, and predisposes survivors to chronic kidney disease. For years it lacked a standard definition; the field now uses the neonatal modified KDIGO criteria — a consensus, validated framework based on serum creatinine change and urine output. The clinician's tasks are to recognize AKI (including the subtle sign of a creatinine that doesn't fall), classify the cause (prerenal, intrinsic, postrenal), and manage supportively while treating the underlying problem and protecting the kidneys from further injury.

2. Definitions

Definitions

Neonatal modified KDIGO staging

Stage	Serum creatinine (SCr)	Urine output
1	SCr rise ≥0.3 mg/dL within 48 h, or 1.5–1.9× the lowest previous value	<0.5 mL/kg/h for 6–12 h
2	SCr 2.0–2.9× the lowest previous value	<0.5 mL/kg/h for >12 h
3	SCr ≥3× baseline, or SCr ≥2.5 mg/dL, or receipt of kidney support therapy (dialysis)	<0.3 mL/kg/h for ≥24 h, or anuria ≥12 h

Reference creatinine = the lowest previous value (excluding the first day or two of life).

Term	Meaning
Prerenal AKI	Reduced renal perfusion with intact tubules (reversible with perfusion).
Intrinsic AKI	Parenchymal injury (ATN, nephrotoxins, thrombosis).
Postrenal AKI	Obstruction to urine flow.
Kidney support therapy (KST)	Dialysis/renal replacement (peritoneal dialysis, CRRT, hemodialysis).

3. Pathophysiology & Causes

Pathophysiology & Causes

Prerenal (commonest, reversible): reduced perfusion from hypovolemia, hypotension, sepsis, perinatal asphyxia/HIE, dehydration, blood loss, NEC, or cardiac dysfunction. Tubules are intact — restoring perfusion restores function.

Intrinsic (parenchymal):

Acute tubular necrosis (prolonged ischemia/asphyxia).
Nephrotoxins — aminoglycosides, NSAIDs/indomethacin, vancomycin, amphotericin, acyclovir, contrast.
Sepsis/DIC, renal vein or artery thrombosis (hematuria, thrombocytopenia, flank mass), congenital renal disease.

Postrenal (obstructive): posterior urethral valves, bilateral ureteropelvic/ureterovesical obstruction, neurogenic bladder, or obstruction of a solitary kidney.

Risk factors: prematurity/ELBW, asphyxia/HIE, sepsis, PDA, nephrotoxin exposure, cardiac surgery, low Apgar scores, and maternal factors.

4. Clinical Presentation

Clinical Presentation

Oliguria/anuria (though AKI can be non-oliguric) — measure urine output.
Rising or non-falling creatinine.
Fluid overload (edema, weight gain, worsening respiratory status), electrolyte disturbances (hyperkalemia, hyponatremia, acidosis, hyperphosphatemia, hypocalcemia).
Signs of the underlying cause (sepsis, asphyxia, NEC, obstruction — palpable bladder/flank mass).

5. Diagnostic Approach

Diagnostic Approach

Measure urine output (serially — key, and often the earliest sign) and serial serum creatinine (interpret against the falling neonatal trend and the lowest prior value).
Electrolytes, acid-base, phosphate, calcium; CBC/platelets (thrombosis, DIC).
Distinguish prerenal vs intrinsic: response to a perfusion/fluid challenge; fractional excretion of sodium (FENa) (low in prerenal, high in intrinsic) — less reliable in preterm infants (physiologic sodium wasting).
Renal ultrasound — evaluate for obstruction (postrenal), thrombosis, and congenital anomalies; bladder catheterization if obstruction is suspected.
Urinalysis. (Novel biomarkers — NGAL, cystatin C — are emerging but not yet standard.)

5+. Creatinine Reference Values, FeNa and Kidney Support Therapy (Baylor Ed. 33)

Why a "normal" creatinine is not normal here

At birth the serum creatinine is the mother's. In term infants it falls over the first 2 weeks to a nadir of 0.2–0.4 mg/dL. In infants below 32 weeks it may rise slightly after birth — low GFR plus tubular reabsorption of creatinine — then decline slowly over about two months. Judging a preterm creatinine against term values will miss injury.

Age / gestation (below 33 weeks)	50th percentile (mg/dL)	95th percentile (mg/dL)
7 days — 25–27 weeks	0.87	1.23
7 days — 28–29 weeks	0.84	1.18
7 days — 30–33 weeks	0.66	0.95
10–14 days — 25–27 weeks	0.75	1.10
10–14 days — 28–29 weeks	0.69	1.02
10–14 days — 30–33 weeks	0.57	0.84
1 month — 25–27 weeks	0.48	0.72
1 month — 28–29 weeks	0.41	0.64
1 month — 30–33 weeks	0.35	0.57
2 months — 25–27 weeks	0.31	0.51
2 months — 28–29 weeks	0.33	0.58
2 months — 30–33 weeks	0.25	Not available

Fractional excretion of sodium

FeNa = 100 × (serum creatinine × urine sodium) ÷ (serum sodium × urine creatinine), as a percentage. In a term infant, below 2% suggests pre-renal AKI. In a premature infant the test is unreliable — tubular immaturity gives baseline values of 2–6%, so a "high" FeNa there does not establish intrinsic injury.

Scale: using KDIGO, AKI affected 43% of hospitalized neonates below 29 weeks, 18% at 29–36 weeks and 37% above 36 weeks in a large multicentre study, and is independently associated with higher mortality and longer stay. Causes split roughly 80% pre-renal, 10–11% intrinsic and 3–5% post-renal. An infant does not need to meet both the creatinine and urine-output criteria — neonatal AKI is usually non-oliguric.

Kidney support therapy: who qualifies, and on which machine

Indications: fluid overload refractory to diuretics; hyperkalaemia or metabolic acidosis unresponsive to medical therapy; inability to tolerate fluid restriction because of medications, blood products or nutrition; uraemic encephalopathy or pericarditis; removal of a dialysable toxin; and hyperammonaemia from an inborn error of metabolism.
Size thresholds: peritoneal dialysis above 2 kg, CRRT above 2.5 kg, haemodialysis above 3 kg — between 2 and 3 kg the choice is made case by case with nephrology. High-frequency ventilation is not a contraindication.
Peritoneal dialysis is the gentlest modality and the one of choice for neonatal end-stage disease. Allow about 2 weeks after catheter placement before use where possible, to let the site heal and limit leaking. Contraindicated by diaphragmatic hernia or defect, intra-abdominal surgery, NEC, gastroschisis, bladder exstrophy, or any compromised peritoneum. Watch for peritonitis (fever or cloudy fluid — send cell count and culture), leaking, hernia, and a pleuro-peritoneal connection, suspected when a chest drain output rises, a new effusion appears, or the drain volume falls below the fill volume.
Haemodialysis needs a dual-lumen 7 or 7.5 Fr catheter, preferably right internal jugular, and the smallest circuit is about 70 mL, so blood priming is necessary. Fluid restriction is set by the maximum removal the treatment can achieve — exceeding it produces significant hypotension. Contraindicated when access cannot be established or the infant needs multiple inotropes or vasopressors.
CRRT: the CARPEDIEM system is designed for 2.5–10 kg and is usually preferred in the NICU; its smallest circuit is 32 mL. Access is the same 7–7.5 Fr dual-lumen catheter, or paired 3–4 Fr PICC lines in a femoral vein and the right IJ in very small infants. CRRT solutions contain no phosphate, so hypophosphataemia is expected and supplementation needed. Anticoagulation is most often prostacyclin — contraindicated by platelets below 20,000, active bleeding, or more than two vasoactive agents — or regional citrate, which demands close calcium monitoring. A low-dose heparin infusion of 5–10 units/kg/h is often run to protect the catheter; it needs no monitoring or titration and continues even when the circuit is disconnected. Routine circuit changes are daily on CARPEDIEM and every 72 hours on Prisma.
Starting a circuit: hypotension is common at initiation and at every circuit change, so the renal and the NICU clinician must both be at the bedside with a time-out. Have IV calcium chloride, saline or 5% albumin, and a vasoactive agent ready — set the vasoactive in line if the infant is not already on one. Keep the infant warm to reduce bradycardia. If the pressure drops: calcium first if hypocalcaemic or on citrate, then a 5–10 mL/kg bolus of saline or 5% albumin, then start or titrate a vasopressor.
Nutrition: do not restrict protein in AKI — these infants must still meet their minimum protein intake — and a neonate on CRRT needs at least 2.5 g/kg of protein to cover circuit losses. Renal replacement removes water-soluble vitamins, which need replacing, and a renal dietitian should set the targets.
Afterwards: monitor renal function weekly until it returns to baseline, more often with further illness or nephrotoxin exposure, since susceptibility rises after one episode. KDIGO recommends nephrology review of AKI survivors within 3 months to check for resolution or evolving chronic kidney disease.

6. Management

Management

Supportive and cause-directed — there is no specific "cure"; protect the kidneys and treat the underlying problem.

Treat the cause / restore perfusion

Prerenal: restore perfusion/volume (careful fluid resuscitation), support blood pressure, treat sepsis.
Postrenal: relieve obstruction (bladder catheter; urology — e.g., posterior urethral valves).
Intrinsic: remove or dose-adjust nephrotoxins; manage thrombosis; supportive care through ATN recovery.

Fluid & electrolyte management

Careful fluid balance — avoid overload (match insensible losses + urine output; restrict in oliguric overload); track daily weight.
Hyperkalemia (an emergency): ECG monitoring; calcium (membrane stabilization), insulin/glucose, salbutamol, cation-exchange resin, and dialysis if refractory.
Manage hyponatremia (usually dilutional → restrict water), metabolic acidosis, hyperphosphatemia, and hypocalcemia.
Diuretics (furosemide) may increase urine output but don't change the course — avoid in obstruction/hypovolemia.

Kidney support therapy (dialysis)

Indications: refractory fluid overload, hyperkalemia, acidosis, or uremia.
Modalities: peritoneal dialysis (often preferred in neonates), CRRT, or hemodialysis (newer devices exist for small infants).

Supportive

Adjust all drug dosing for renal function; optimize nutrition; involve nephrology; arrange long-term follow-up (CKD risk).

7. Monitoring

Monitoring

Serial urine output and creatinine, electrolytes, acid-base, weight/fluid balance.
Blood pressure (acute and long-term — hypertension risk).
Response to therapy and recovery of function.
Long-term renal follow-up (blood pressure, proteinuria, renal function) — AKI survivors are at risk of CKD.

8. Complications

Complications

Fluid overload (pulmonary edema, worsening respiratory status), life-threatening hyperkalemia, acidosis, uremia.
Increased mortality (independent risk factor).
Chronic kidney disease and hypertension in survivors.
Nephrotoxic drug accumulation if dosing isn't adjusted.

9. Safety Warnings

Safety Warnings

⚠️ Measure urine output — non-oliguric AKI is missed if you only watch creatinine, and oliguria is often the earliest sign.
⚠️ A creatinine that fails to fall may be AKI — interpret against the normal neonatal decline.
⚠️ Hyperkalemia is an emergency — monitor ECG and treat aggressively.
⚠️ Remove/dose-adjust nephrotoxins (aminoglycosides, NSAIDs, vancomycin, etc.).
⚠️ Rule out obstruction (renal ultrasound; posterior urethral valves) — it's reversible.
⚠️ Adjust all renally-cleared drug doses and arrange CKD follow-up.

10. Common Mistakes

Common Mistakes

Not measuring urine output and missing non-oliguric AKI.
Interpreting creatinine without the falling-neonatal-trend context.
Continuing nephrotoxins at full dose.
Fluid overloading an oliguric infant.
Missing postrenal obstruction (no ultrasound).
Under-treating hyperkalemia.
Failing to arrange long-term renal follow-up.

11. Clinical Pearls

Clinical Pearls

💡 Creatinine should fall after birth — if it doesn't, think AKI.
💡 Urine output is the early warning — measure it in at-risk infants.
💡 Prerenal is common and reversible — restore perfusion first.
💡 Always exclude obstruction — posterior urethral valves are fixable.
💡 Kidneys hate the usual suspects — aminoglycosides, NSAIDs, vancomycin.
💡 AKI isn't over at discharge — CKD risk means lifelong follow-up.

12. Summary Table

Summary Table

Domain	Bottom line
Definition	Neonatal modified KDIGO — SCr rise (from lowest prior value) and/or low urine output
Creatinine caveat	Reflects maternal at birth; normally falls — non-falling = concern
Buckets	Prerenal (perfusion — commonest/reversible), intrinsic (ATN/nephrotoxins/thrombosis), postrenal (obstruction)
Workup	Urine output + serial SCr; electrolytes/acid-base; FENa (unreliable preterm); renal ultrasound
Management	Restore perfusion; remove/adjust nephrotoxins; fluid balance; treat hyperkalemia; relieve obstruction
Dialysis	Refractory overload/hyperkalemia/acidosis/uremia → peritoneal dialysis / CRRT
Outcomes	↑Mortality; CKD/hypertension risk → long-term follow-up

13. Step-by-Step Bedside Algorithm

AT-RISK NEONATE (preterm/ELBW, asphyxia/HIE, sepsis, PDA, nephrotoxins) → MEASURE URINE OUTPUT + serial SCr
        │
        ▼
AKI by neonatal KDIGO? (SCr rise from lowest prior value and/or low UO; or SCr not falling)
        │ Yes
        ▼
CLASSIFY THE CAUSE
   ├─ PRERENAL (hypoperfusion) → restore perfusion/volume, support BP, treat sepsis
   ├─ POSTRENAL → RENAL ULTRASOUND + bladder catheter → relieve obstruction (urology; PUV)
   └─ INTRINSIC (ATN/nephrotoxin/thrombosis) → REMOVE/ADJUST NEPHROTOXINS; supportive
        │
        ▼
SUPPORTIVE MANAGEMENT
   • fluid balance (match losses; restrict if oliguric overload); daily weight
   • HYPERKALEMIA emergency → ECG + calcium + insulin/glucose + salbutamol (± resin/dialysis)
   • manage hyponatremia (restrict water), acidosis, phosphate, calcium
   • adjust ALL renally-cleared drug doses; optimize nutrition
        │
        ▼
Refractory overload / hyperkalemia / acidosis / uremia?
        │ Yes → KIDNEY SUPPORT THERAPY (peritoneal dialysis / CRRT) + nephrology
        ▼
Recovery → monitor function/BP → LONG-TERM RENAL FOLLOW-UP (CKD risk)

14. References to Verify

Confirm each against the primary source before clinical or published use.

1.Definition: Jetton JG, Askenazi DJ. Neonatal modified KDIGO definition of AKI (2012) and subsequent consensus. (Verify staging.)
2.Epidemiology: Jetton JG, et al. Incidence and Outcomes of Neonatal AKI (AWAKEN). Lancet Child Adolesc Health. 2017. (~30% incidence; mortality — verify.)
3.Management reviews: contemporary neonatal AKI reviews (fluid/electrolyte management, dialysis modalities). (Verify.)
4.Nephrotoxin stewardship: "Baby NINJA" and related nephrotoxin-monitoring programs. (Verify.)
5.Long-term: evidence linking neonatal AKI to later CKD/hypertension. (Verify.)

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Chapter 7.6 — Neonatal Acute Kidney Injury (AKI)