Urine Output Monitoring for the Diagnosis of Early- Onset Acute Kidney Injury in Very Preterm Infants

Clin J Am Soc Nephrol. 2022 Jul;17(7):949-956. doi: 10.2215/CJN.15231121 Epub 2022 Jun 28.

De Mul, Aurélie; Parvex, Paloma; Héneau, Alice; Biran, Valérie; Poncet, Antoine; Baud, Olivier; Saint-Faust, Marie; Wilhelm-Bals, Alexandra

Reviewed by: Kate Buttifant and Thomas A Forbes

Background:

Premature neonates are at high risk of acute kidney injury (AKI) due to tubular immaturity, interrupted nephrogenesis and post-natal nephrotoxic insults.(1) AKI in very preterm neonates is associated with increased mortality.(2) AKI is likely to be under-recognised in this age group because of limitations of creatinine rise as a biomarker and an unclear definition of oliguria in this age group.

The current Kidney Disease Improving Global Outcomes (KDIGO) definition for neonatal AKI is extrapolated from adult definitions and is based on creatinine rise and/or oliguria criteria.

Objective:

This study aims to evaluate whether the currently KDIGO neonatal AKI definition might better detect AKI (and its association with mortality) if a higher threshold for oliguria was included.

Study design:

Data was derived from two European neonatal intensive care units. The study examined the diagnostic impact of two alternative oliguria criteria (urine output <1.5mL/kg/hr or <2.0mL/kg/hr) for stage 1 neonatal AKI in very pre-term infants (gestational age 24-30 weeks). Urine output was measured by diaper weight and two serum creatinine levels were taken in the first ten days of life.

Results:

Of 473 very preterm infants, 101 developed AKI based on the current KDIGO definition, with an additional 49 and 116 diagnoses for the <1.5mL/kg/hr and <2mL/kg/hr definitions respectively. Discriminative performance for predicting mortality improved with these adjusted definitions, with areas under the ROC curve of 0.68 (standard definition), 0.73 (<1.5mL/kg/hr) and 0.75 (<2mL/kg/hr).

Both novel criteria demonstrated increased association with mortality compared to the standard KDIGO definition (<1.0ml/kg/hr). Neonatal AKI was associated with a five-fold increase in risk of death with the modified definitions, compared to four-fold with the standard definition.

Implications:

This study highlights ambiguity in the current clinical definition of AKI in neonates. It suggests AKI in premature infants is under-recognised and associated with increased mortality, validating previous findings.(2) Over one quarter of AKI cases had no rise in serum creatinine and were diagnosed solely by urine output criteria, which can be difficult to measure in practice. Future research may consider whether improved awareness of AKI without creatinine rise can attenuate this increased mortality, whether babies with this type of AKI are at risk of chronic kidney disease in adulthood and how this is best followed up. Refinement of the neonatal AKI definition will assist in risk stratification and may improve long term health outcomes for ex-premature patients. Biomarker studies may further improve our visibility and risk stratification of neonatal AKI.

References:

  1. Zappitelli M, Ambalavanan N, Askenazi DJ, Moxey-Mims MM, Kimmel PL, Star RA, et al. Developing a neonatal acute kidney injury research definition: a report from the NIDDK neonatal AKI workshop. Pediatr Res. 2017;82(4):569-73.
  2. Jetton JG, Boohaker LJ, Sethi SK, Wazir S, Rohatgi S, Soranno DE, et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health. 2017;1(3):184-94.