SERUM CYSTATIN C AS A PREDICTOR OF THE DEVELOPMENT OF ACUTE KIDNEY INJURY IN NEWBORNS WITH HYPOXIC- ISCHEMIC ENCEPHALOPATHY SUBMITTED TO THERAPEUTIC COOLING

Abstract

Assessment of renal function in newborns is extremely important and at the same time challenging due to the unique body structure, increased vulnerability and rapid growth of the latter. However, for the early detection of acute kidney injury (АКI), rational dosing of drugs and safe drug therapy, the identification of early markers of renal dysfunction is essential. The objective is to evaluate the prognostic value of serum biomarkers for the early diagnosis of АКI in newborns with hypoxic-ischemic encephalopathy against the background of therapeutic hypothermia and preventive use of methylxanthines. Materials and Methods. A single-center, prospective, randomized trial involving 44 neonates with АКI requiring therapeutic hypothermia and prophylactically receiving caffeine citrate or theophylline to prevent АКI progression was conducted in from 2019 to 2022 on the basis of the NICU of Zaporizhzhia Regional Clinical Children's Hospital. Laboratory analysis of blood serum samples was performed on day 1, day 3 and 5 from birth, creatinine (Cr) and cystatin C (CysC) levels and their associations with the development of АКI were determined according to the neonatal criteria of the 2012 KDIGO guideline. Statistical analysis was performed using Statistica 13.0 program, TIBCO Software Inc. (license number JPZ804I382130ARCN10-J) and Microsoft Excel 2013 (license number 00331-10000-00001-АА404). The probability of the difference in absolute values of mean values was determined using non-parametric methods of statistical analysis: the Mann-Whitney U-Test for unrelated groups and the Wilcoxon signed-rank t test for related groups. Statistical significance was defined as p < 0.0500. The study was performed in accordance with the moral and ethical standards established by the IGH / GCP guidelines, the World Medical Association Helsinki Declaration, adopted in 1964 and amended in 1975, 1983, 1989, 1996 and 2000, The European Convention of Human Rights and Biomedicine and the legislation of Ukraine. The protocol was approved by the Medical Ethics Commission at Zaporizhzhia State Medical University. The study was performed as part of the research project "Optimization of diagnostics and intensive care of polyetiologic lesions of the brain, gastrointestinal tract, and kidneys in newborns and older children" (State registration number O118U007142) of the Pediatric Surgery and Anesthesiology Department of the State Institution "Zaporizhzhia State Medical University of the Ministry of Health of Ukraine." Results and their discussion. In general, AKI according to KDIGO developed in 5.00 (11.36 %) neonates out of 44.00 (100.00 %), stage 0 was found in 39.00 (88.64 %). 4.00 (9.09%) newborns had stage I, and 1 (2.27%) developed stage II; the data obtained were similar: p = 0.7872; U = 230.00. None of the patients progressed to stage III. In the newborns with preserved renal function during the study there was a decrease in Cr and a predictable, by this marker, increase in GFR. A statistically significant increase in Cr level and decrease in GFR was found in the newborns with renal dysfunction on days 3 and 5 of the study. Cr level progressed from baseline 1.07 (0.87; 1.10) mg/dl to 1.13 (0.86; 1.25) mg/dl on day 3 and to 1.40 (1.15; 1.82) mg/dl on day 5, while GFR decreased from 19.76 (19.07; 22.90) ml/min/1.73m2 to 17.97 (13.84; 24.42) ml/min/1.73m2 on day 3 and was 12.38 (11.12; 17.54) ml/min/1.73m2 on day 5, with p < 0.0500. CysC progressively decreased in the neonates without AKI from 2.50 (2.20; 2.60) ng/ml to 2.25 (2.08; 2.49) ng/ml, p = 0.0095; while in the neonates with AKI the level of this marker did not change and was 2.56 (2.41; 2.70) ng/ml on day 1 and 2.42 (1.89; 2.45) ng/ml on day 5, p = 0.2963. As this marker changed, eGFR (CysC) increased progressively in the cohort of patients without kidney damage but did not change in the other group. The diuresis rates in the newborns of both groups did not differ, being ≥ 1.5 ml/kg/h, which is probably due to methylxanthine therapies, p ≥ 0.0500. Conclusions. CysC assessment did not provide additional information on the development of acute kidney injury in neonates (nAKI) in the first 5 days of life, which would have allowed a quick decision to change the intensive care program. Further studies involving newborns who did not receive prophylactic therapy are needed.

Keywords

• Asphyxia; Hypoxic-ischemic Encephalopathy; Acute Kidney Injury; Creatinine; Cystatine C; Methylxanthines; Newborn; Glomerular Filtration Rate.