Etiologic heterogeneity of acute kidney injury in viral diarrhea in infants: the role of noninvasive biomarkers (NGAL, KIM-1, L-FABP, IL-1)
https://doi.org/10.51793/OS.2026.29.4.005
Abstract
Objective. To conduct a comparative analysis of the incidence of acute kidney injury in infants with rotavirus, norovirus, and COVID-19 associated with gastrointestinal syndrome and to determine its association with clinical predictors and noninvasive biomarkers.
Materials and methods. A total of 148 children aged 1 month to 1 year, hospitalized at the Z. A. Bashlyaeva Children's City Clinical Hospital with a diagnosis of acute infectious gastroenteritis of various etiologies, were examined. Patients were divided into three groups: Group 1: patients with rotavirus infection (RVs, n = 40), Group 2: patients with norovirus infection (NoVs, n = 25), and Group 3: patients with the gastrointestinal form of COVID-19 (n = 83). All patients underwent standard laboratory testing, including urine ELISA testing for NGAL, KIM-1, L-FABP, and IL-1. Clinical symptoms, hospitalization duration, degree of exsiccosis, and clinical predictors of acute kidney injury were assessed.
Results. The risk of developing acute kidney injury in patients with RVs and NoVs was 60% and 52%, respectively, compared to 32.5% for COVID-19 (p < 0.05). Vomiting was the leading symptom of COVID-19. RVs is associated with the most severe diarrhea and significant acid-base balance changes, with a later hospitalization time proving to be a critical factor (p < 0.01). The median NGAL was 40.1 ng/ ml in patients with AKI versus 5.8 ng/ml in patients without AKI (p < 0.001), for KIM-1 it was 0.404 ng/ml versus 0.049 ng/ml, and for L-FABP it was 3.928 ng/ml versus 0.098 ng/ml. IL-1 showed no significant differences (p = 0.250). Elevated NGAL and KIM-1 levels were associated with more severe disease, the degree of exsiccosis, and acidosis. L-FABP and IL-18 also increased in AKI but were less sensitive than NGAL. KIM-1 was a marker of tubular damage in acidosis (pH < 7.30). These results highlight the importance of NGAL and KIM-1 in assessing the risk of developing and the severity of renal injury.
Conclusion. The etiology of viral diarrhea determines the pathogenetic variant of AKI and requires a differentiated approach to its diagnosis. NGAL is a universal early marker of AKI risk, while KIM-1 verifies tubular damage during acidosis later in the disease. The data obtained can be used for personalized patient management depending on the etiology of diarrhea.
Keywords
acute kidney injury,
viral diarrhea,
children,
NGAL,
KIM-1,
L-FABP,
IL-1,
rotavirus,
norovirus,
COVID-19,
early diagnosis,
biomarkers
Supporting agencies: This study was supported by the Autonomous NonCommercial Organization "Association of Graduates and Friends of the International Academy of Postgraduate Education" (Agreement No. 02/24-G-NIR dated August 5, 2024). The sponsor did not participate in the study design, data collection, analysis, or interpretation, or in the writing of the article or the decision to publish it.
About the Authors
Polina Yu. Savinkova
Russian Medical Academy of Continuing Professional Education
Russian Federation
Russian Federation
Polina Yu. Savinkova, Pediatrician, PhD student of the Department of Children's Infectious Diseases,
2/1, b. 1 Barrikadnaya str., Moscow, 125993.
Natalia Yu. Pshenichcnaya
Central Research Institute of Epidemiology; Russian Medical Academy of Continuing Professional Education; Moscow Regional Research Clinical Institute named after M. F. Vladimirsky
Russian Federation
Russian Federation
Natalia Yu. Pshenichnaya, Deputy Director for Clinical and Analytical Work; Head of the Department of Infectious Diseases; Professor, Department of Infectious Diseases,
3a, Novogireevskaya str., Moscow, 111123;
2/1, b. 1, Barrikadnaya str., Moscow, 125993;
61/2, Schepkina str., Moscow, 129110.
Svetlana N. Tuchkova
Russian Medical Academy of Continuing Professional Education; Russian Scientific Center of Surgery named after Academician B. V. Petrovsky, "Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy
Russian Federation
Russian Federation
Svetlana N. Tuchkova, Junior Researcher, Department of Predictive and Prognostic Biomarkers, Research Institute of Molecular and Personalized Medicine; Junior Researcher, Department of Pharmacogenetics and Personalized Therapy, Center for World-Class Genomic Research,
2/1, b. 1, Barrikadnaya str., Moscow, 125993;
2, Abrikosovsky Lane, Moscow, 119991.
Lyudmila N. Mazankova
Russian Medical Academy of Continuing Professional Education
Russian Federation
Russian Federation
Lyudmila N. Mazankova, Honored Doctor of the Russian Federation, Dr. of Sci. (Med.), Professor, Head of the Department of Pediatric Infectious Diseases,
2/1, b. 1, Barrikadnaya str., Moscow, 125993.
References
1. World Health Organization. Diarrhoeal disease. Rotavirus infection 2018. Available at: https://cdn.who.int/media/docs/default-source/immunization/vpd_surveillance/vpd-surveillance-standards-publication/19-whosurveillancevaccinepreventable-19-rotavirus-russianr1.pdf.
2. Samitova E. R. Clinical and Epidemiological Features of COVID-19 in Children in Moscow in 2020-2022. Epidemiologiya I vaktsinoprofilaktika. 2022; 21 (5): 38-48. (In Russ.) https://doi.org/10.31631/20733046-2022-21-5-38-48.
3. Mazankova L. N., Luzan P. Y. Early diagnosis and predicting of acute kidney injury in children with viral gastroenteritis of various agents (Literature review). Detskie infektsii. 2023; 22 (3): 55-61. (In Russ.) DOI: 10.22627/2072-8107-202322-3-55-61.
4. Bradshaw C., Han J., Chertow G. M., et al. Acute Kidney Injury in Children Hospitalized With Diarrheal Illness in the United States. Hosp Pediatr. 2019; 9 (12): 933-941. DOI: 10.1542/hpeds.2019-0220.
5. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012.2.1.138.
6. Khwaja A. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Nephron Clin Pract. 2012; 120: c179-c184. DOI: 10.1159/000339789.
7. Sutherland S. M., Byrnes J. J., Kothari M., et al. AKI in hospitalized children: comparing the pRIFLE, AKIN, and KDIGO definitions. Clin J Am Soc Nephrol. 2015; 10 (4): 554-561. DOI: 10.2215/CJN.01900214.
8. Bazargani B., Ataei N., Hosseini M., et al. New Biomarkers in Early Diagnosis of Acute Kidney Injury in Children. Avicenna J Med Biotechnol. 2022; 14 (4): 264-269.
9. Nguyen M. T., Devarajan P. Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol. 2008; 23 (12): 2151-2157. DOI: 10.1007/s00467-0070470-x.
10. Singhal N., Kumar S., Saha A., et al. Bedside biomarkers in pediatric cardio renal injuries in emergency. Int J Crit Illn Inj Sci. 2014; 4 (3): 238-246. DOI: 10.4103/2229-5151.141457.
11. Ganda I. J., Lihawa N., Utiarahman S., et al. Kidney injury molecule type-1, interleukin-18, and insulin-like growth factor binding protein 7 levels in urine to predict acute kidney injury in pediatric sepsis. Front Pediatr. 2022; 10: 1024713. DOI: 10.3389/fped.2022.1024713.
12. Bennett M. R., Nehus E., Haffner C., et al. Pediatric reference ranges for acute kidney injury biomarkers. Pediatr Nephrol. 2015; 30 (4): 677-685. DOI: 10.1007/s00467-014-2989-y.
13. Yamamoto T., Noiri E., Ono Y., et al. Renal L-type fatty acidbinding protein in acute ischemic injury. J Am Soc Nephrol. 2007; 18 (11): 2894-2902. DOI: 10.1681/ASN.2007010097.
14. Yokoyama T., Kamijo-Ikemori A., Sugaya T., et al. Urinary excretion of liver type fatty acid-binding protein accurately reflects the degree of tubulointerstitial damage. Am J Pathol. 2009; 174 (6): 2096-2106. DOI: 10.2353/ajpath.2009.080780.
15. Liang X. L., Liu S. X., Chen Y. H., Yan L. J., Li H., Xuan H. J., Liang Y. Z., Shi W. Combination of urinary kidney injury molecule-1 and interleukin-18 as early biomarker for the diagnosis and progressive assessment of acute kidney injury following cardiopulmonary bypass surgery: a prospective nested case-control study. Biomarkers. 2010; 15 (4): 332-9. DOI: 10.3109/13547501003706558. PMID: 20233133.
16. Rivetti G., Gizzone P., Petrone D., et al. Acute Kidney Injury in Children: A Focus for the General Pediatrician. Children (Basel). 2024; 11 (8): 1004. DOI: 10.3390/children11081004.
17. Kellum J. A., Lameire N., KDIGO AKI Guideline Work Group. Diagnosis, Evaluation, and Management of Acute Kidney Injury: A KDIGO Summary (Part 1). Crit Care. 2013; 17 (1): 204. DOI: 10.1186/cc11454.
18. Parfenchik I. V. Kidney damage in children with severe forms of acute intestinal infections Journal of GrGMU. 2018; 3. (In Russ.) URL: https://cyberleninka.ru/article/n/porazhenie-pochek-u-detey-s-tyazhelymi-formami-ostryhkishechnyh-infektsiy.
19. Deep A., Bansal M., Ricci Z. Acute kidney injury and special considerations during renal replacement therapy in children with coronavirus disease-19: perspective from the critical care nephrology section of the European Society of Paediatric and Neonatal Intensive Care. Blood Purification. 2021; 50 (2): 150-160. DOI: 10.1159/000509677.
20. Armaly Z., Kinaneh S., Skorecki K. Renal manifestations of Covid-19: physiology and pathophysiology. Journal of Clinical Medicine. 2021; 10 (6): 1216. DOI: 10.3390/jcm10061216.
21. Goldstein S. L., Krallman K. A., Roy J. P., et al. Derivation and validation of an optimal neutrophil gelatinase-associated lipocalin cutoff to predict stage 2/3 acute kidney injury (AKI) in critically ill children. Kidney International Reports. 2024; 9 (8): 2443-2452. DOI: 10.1016/j.ekir.2024.05.010.
22. Vaidya V. S., Ozer J. S., Dieterle F., et al. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nature Biotechnology. 2010; 28 (5): 478-485. DOI: 10.1038/nbt.1623.
23. Bugarski M., Ghazi S., Polesel M., et al. Changes in NAD and lipid metabolism drive acidosis-induced acute kidney injury. Journal of the American Society of Nephrology. 2021; 32 (2): 342-356. DOI: 10.1681/ASN.2020071003.
Review
For citations:
Savinkova P.Yu., Pshenichcnaya N.Yu., Tuchkova S.N., Mazankova L.N. Etiologic heterogeneity of acute kidney injury in viral diarrhea in infants: the role of noninvasive biomarkers (NGAL, KIM-1, L-FABP, IL-1). Lechaschi Vrach. 2026;(4):42-49. (In Russ.) https://doi.org/10.51793/OS.2026.29.4.005
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