Evaluating innovative metrics for the differential diagnosis of tubular injury in pediatric acute pyelonephritis: A cross-sectional observational study

Background . The COVID-19 pandemic has revealed previously overlooked clinical features of infectious and inflammatory kidney diseases in pediatric patients. The SARS-CoV-2 virus was found to have a direct cytopathic effect on renal tissue, exacerbating pyelonephritis through the development of tubulointerstitial abnormalities and dysregulation of the immune response. In post-COVID-19 pediatric patients, pyelonephritis presents with more pronounced clinical and laboratory manifestations, often taking an atypical course, which hinders timely diagnosis and contributes to the progression of chronic kidney disease. In this connection, it is essential to identify sensitive diagnostic biomarkers and revise therapeutic strategies, taking the post-viral condition into account. Objective : To assess the diagnostic value of biomarkers of tubuloglomerular dysfunction (γ-glutamyltransferase, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1) in children with post-COVID-19 acute pyelonephritis. Methods. A cross-sectional observational study was conducted involving 63 children aged 9–12 years with clinically- and laboratory-confirmed acute pyelonephritis. The pediatric patients were divided into Group 1 (n = 34) and Group 2 (n = 29). The control group (Group 3) comprised 14 age-matched, apparently healthy children (9–12 years old, inclusive), resulting in a total of 77 participants. Clinical evaluation and treatment were conducted in the Nephrology Department of the Samarkand Regional Children’s Multidisciplinary Medical Center (Ministry of Health of the Republic of Uzbekistan). Laboratory and diagnostic procedures were performed at the clinical diagnostic laboratory of the above-mentioned center and the L. M. Isaev Research Institute of Microbiology, Virology, Infectious and Parasitic Diseases (Samarkand). The evaluation was conducted from January 2021 to December 2022. The participants were enrolled upon hospital admission, taking the presence or absence of a history of COVID-19 into account. In order to assess the extent of tubular injury, the urinary excretion of key biomarkers was analyzed: kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, β₂-microglobulin, and γ-glutamyltransferase. Statistical analysis of the data was performed using Excel (Microsoft Office 2016, USA) and StatPlus software (version 7, AnalystSoft Inc., USA). Results. The study results revealed statistically significant increases in the urine concentrations of all studied biomarkers compared to the control group. In Group 1, γ-glutamyltransferase levels were 4.5 times higher than those of the control group; kidney injury molecule-1 levels, 3.9 times higher; the levels of neutrophil gelatinase-associated lipocalin, 25.7 times higher; β₂-microglobulin levels, 7.5 times higher. Group 2 also showed significant differences in these biomarkers, although the changes were less pronounced: the concentrations of γ-glutamyltransferase, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and β₂-microglobulin exceeded control values by 1.4, 1.9, 10.9, and 3.5 times, respectively. The marked increase in these biomarkers, especially neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, indicates proximal and distal tubular injury along with tubulointerstitial inflammation. The elevated levels of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 reflect active processes of cellular injury and inflammation in the renal tubules, which can probably be attributed to the cytopathic effect of SARS-CoV-2 on the epithelium of proximal tubules. Conclusion . In order to monitor latent tubular dysfunction in post-COVID-19 pediatric patients, it is recommended to conduct a screening assessment of urinary biomarker levels: γ-glutamyltransferase, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and β₂-microglobulin. Assessing these concentrations enables the identification of early signs of tubulointerstitial injury, evaluation of pathological activity in renal tubules, and risk stratification for chronic pyelonephritis progression. These findings offer significant clinical utility, providing a basis for early diagnosis, longitudinal monitoring, and development of individualized treatment strategies for children with post-COVID renal dysfunction.

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