91 - Association of urinary biomarkers and chronic kidney disease in extremely low gestational age neonates (ELGANs)

Poster Number: 91
Publication Number: 91.138

Sangeeta Hingorani, University of Washington/Seattle Childrens Hospital, Seattle, WA, United States; Robert H. Schmicker, University of Washington, Seattle, WA, United States; Brian A. Halloran, University of Alabama at Birmingham, Birmingham, AL, United States; Mariana Baserga, University of Utah, Park City, UT, United States; Kaashif A. Ahmad, MEDNAX, Houston, TX, United States; Janine Y. Khan, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Ivan Frantz, Beth Israel Deaconess Medical Center, Boston, MA, United States; tonya Robinson, University of Louisville School of Medicine, Louisville, KY, United States; Edmund F. LaGamma, New York Medical College, Valhalla, NY, United States; Patrick D. Brophy, Golisano Children's Hospital at The University of Rochester Medical Center, Pittsford, NY, United States; Patrick Heagerty, University of Washington, Seattle, WA, United States; Sandra E. Juul, University of Washington, Seattle, WA, United States; Stuart L. Goldstein, Cincinnati Children's Hospital, Cincinnati, OH, United States; David Askenazi, UAB, Birmingham, AL, United States

Background: ELGAN survivors are at increased risk of chronic kidney disease. Urine biomarkers may improve our ability to diagnose disease and shed light on bio-mechanistic pathways. The REPAIReD study examined kidney outcomes of ELGANS enrolled in the PENUT study, a multi-center, randomized placebo-controlled trial of erythropoietin in ELGANS.

Objective: The goal of this study is to evaluate whether known urinary kidney injury biomarkers will predict development of an estimated glomerular filtration rate < 90 mL/min/1.73m2 in ELGANs at 22-26 months corrected gestational age (GA).

Design/Methods: We conducted a case-control study of ELGANs enrolled in PENUT had to have biomarker measurements at 30- and 34 weeks post-menstrual age (PMA) and who survived to 22-26 months corrected age and had a urine and blood sample and BMI available at follow-up. Cases were defined as children with an estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2 using the CKiD cystatin-creatinine equation at follow-up. Up to two controls were chosen per case and matched on sex, GA, and BMI. We evaluated 21 biomarkers chosen based on biological plausibility, and validity as kidney injury biomarkers. Additional biomarkers were associated with rHuEPO induced kidney protection including tubular injury, tubular repair, and inflammation. Urine was collected at 30- and 34-weeks PMA and 22-26 months corrected GA. Samples were prepared as per manufacturer protocol and analyzed on a multiplexing imager, single plate ELISA, and tandem mass spectroscopy (urine creatinine). Samples were run in duplicate, and the average value was used for reporting. Biomarkers are reported in picograms and normalized to urinary creatinine. We used linear mixed models with dummy variables for week and a case x week interaction term. We then used the estimates to predict the point difference (95%CI) of case minus control at each time point.

Results: 40 cases and 79 controls were identified and included in the analysis (Table 1). We found no statistically significant differences between cases and controls in any biomarkers at any of the time points analyzed (Figure 1 and 2). A few biomarkers such as Epo, FGF23, IL15, cystatin C and EGF at 34 weeks warrant further investigation in a larger cohort.Conclusion(s): We did not find significant differences in 21 candidate urine biomarkers measured at 30- and 34 -weeks PMA and at 22-26 months corrected GA between ELGANS with an eGFR < 90 vs > 90 ml /min/1.73m2 at follow-up. Further investigation of some biomarkers and a search for novel biomarkers are needed in ELGANs to predict outcomes and better understand mechanisms of injury.
Figure 1. Forest plots of case minus control estimates at 3 time points for primary urinary biomarkers normalized to urinary creatinineforest1_creatinine.jpeg
Figure1. Forest plots of case minus control estimates at 3 time points for secondary urinary biomarkers normalized to urinary creatinineforest2_creatinine.jpeg