Association Between Urinary Biomarkers and CKD in Extremely Low Gestational Age Neonates

Am J Kidney Dis. 2023 Nov 4:S0272-6386(23)00893-4. doi: 10.1053/j.ajkd.2023.09.008.

Hingorani, S. et al.

Reviewed by: Caroline Jackson


To explore potential associations between urinary biomarkers and development of CKD in children born at extremely low gestational age (ELGAN) (<28 weeks).

Study Design:

The study includes two analyses. The first is a prospective cohort design comparing urinary biomarkers in ELGAN’s that developed CKD at age 2 to those that did not. The cohort was obtained from within the REPaIReD study cohort.

The second analysis was a matched case-control exploratory study evaluating ten additional urinary biomarkers for potential associations with progression to CKD at age 2. In the matched case control study, forty patients with CKD at 2 years old were matched with 2 controls by gestational age, sex, and BMI.

Patient Characteristics: 

All babies included were born at a PENUT study site hospital between 24 and 27+6 weeks gestation. Babies were excluded if they had other known life-threatening conditions including chromosomal anomalies, congenital infection, twin-twin transfusion syndrome with polycythemia or hydrops fetalis, or DIC.


Of the 327 eligible babies, 15% had CKD at 2 years old. Though there were noted differences between urinary cystatin c and creatinine levels between the cohorts, the only urinary biomarker found to have significantly different levels in the urine of 34-week PMA infants that went on to develop CKD, compared to those that did not was alpha-glutathione S-transferase (αGST). There were higher levels of αGST in babies who later developed CKD.


αGST is a known early marker of tubular dysfunction primarily located in the proximal tubule. The authors propose that elevated urinary αGST levels associated with CKD may reflect an independent role of tubular injury in the development of CKD outside of the previously described relationship between decreased nephron mass and CKD development in ELGANs. As most infants are discharged from the NICU around 34 weeks, detection of elevated αGST could potentially serve as a screening test to guide timing of nephrology follow up for these children.

It was surprising that there was no significant difference in urinary cystatin C, NGAL, or albumin levels between those that did and did not develop CKD at age 2. As these biomarkers are known indicators of kidney injury and CKD in other settings, the lack of association identified in this study may further suggest the existence of an independent tubular etiology for kidney injury in ELGANs that may one day serve as a more sensitive screening test for CKD risk.