Intrinsic Kidney Pathology Following COVID-19 Infection in Children and Adolescents: A Systematic Review

Introduction: COVID-19 infections resulting in pathological kidney manifestations have frequently been reported in adults since the onset of the global COVID-19 pandemic in December 2019. Gradually, there have been an increased number of COVID-19-associated intrinsic kidney pathologies in children and adolescents reported as well. The pathophysiological mechanisms between COVID-19 and the onset of kidney pathology are not fully known in children; it remains a challenge to distinguish between intrinsic kidney pathologies that were caused directly by COVID-19 viral invasion, and cases which occurred as a result of multisystem inflammatory syndrome due to the infection. This challenge is made more difficult in children, due to the ethical limitations of performing kidney biopsies to reach a biopsy-proven diagnosis. Although previous systematic reviews have summarized the various pathological kidney manifestations that have occurred in adults following acute COVID-19 infection, such reviews have not yet been published for children and adolescents. We describe the results of a systematic review for intrinsic kidney pathology following COVID-19 infection in children and adolescents. Methods: A systematic literature search of published data up until 31 October was completed through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Research articles reporting new-onset or relapsed intrinsic kidney pathology in children or adolescents (≤18 years) following acute COVID-19 infection were included for qualitative review. COVID-19 infection status was defined by a positive result from a RT-PCR, or nuclear antibody testing. Only full-text articles published in the English language were selected for review. Results: Twenty-nine cases from fifteen articles were included in the qualitative synthesis of this systematic review. Nephrotic syndrome, as an umbrella condition, appeared as the most frequently observed presentation (20 cases) with disease remission noted in all cases with steroid treatment. Other cases included numerous glomerulonephritides, such as acute necrotizing glomerulonephritis, MPO vasculitis and collapsing glomerulopathy, and thrombotic microangiopathies, such as aHUS. For patients with transplanted kidneys, T-cell-mediated rejection and mild tubular interstitial infiltration were noted following testing positive for COVID-19. There were no mortalities reported in any of the included cases, although two patients remained dialysis dependent at hospital discharge. Conclusion: This systematic review highlights the various intrinsic pathological kidney manifestations in children and adolescents as a result of acute COVID-19 infection. The clinical timeline and presentation of these cases support the mechanistic hypothesis between COVID-19 infection and the onset of intrinsic kidney pathologies within this context. The progressive introduction of vaccination programs for children and adolescents may hopefully reduce the severity of COVID-19-associated illnesses, and pathological kidney manifestations in this population.

Pneumonia as a cause of chronic kidney disease. Clinical case

In recent years, there has been a change in the clinical picture of chronic kidney disease. Often the patient does not notice any of its manifestations. Identifying a diagnosis becomes an “accidental find.” This fact indicates the “insidiousness” of kidney disease. This was probably influenced by changes in treatment methods. Another problem is diseases that previously “did not cause” kidney pathology. It would seem that ordinary pneumonia does not cause significant disorders of kidney function, but recently, more and more often we see extracellular pathology as the main cause of the development of chronic kidney disease.

PECULIARITIES OF THE CLINICAL COURSE OF NON-ALCOHOLIC STEATOHEPATITIS AND STEATOSIS OF THE LIVER AT COMORBID WITH CHRONIC KIDNEY DISEASE I-III STAGE

Purpose - to establish clinical peculiarities of the clinical course of the liver nonalcoholic steatosis (NALS) and steatohepatitis (NASH) at comorbidity with chronickidney disease (CKD) (chronic pyelonephritis) I-III stage.Material and methods. We have examined 444 patients: 84 patients with non-alcoholicadipose liver disease (NAALD) with obesity I degree (I group), containing 2 subgroups -32 patients with NALS and 52 patients with NASH; 270 NAALD patients with comorbidobesity I degree and CKD I-III stages (group 2), including 110 patients with NALS and160 patients with NASH. The control group consisted of 90 patients with CKD I-III stagewith normal body weight.Results. Clinical peculiarities of the liver non-alcoholic steatosis at comorbidity withCKD are a significant prevalence, in comparison with the clinical course without kidneypathology, of the frequency of manifestation of astheno-vegetative (70,9% to 40,6%),dyspeptic (33,6% to 18,8%), cholestatic (30,9% to 15,6%) syndromes, hepatomegaly(97,3% - 71,8%), predominance of steatosis II and III degree (47,2% and 31,8% to 25,0% and 15, 6% at NALS without kidney pathology). High frequency of asthenovegetative(98,1% to 61,5%) syndrome, dyspepsia (79,4% to 59,6%), discomfort in the rightsubcostal area (84,4% to 32,7%), cholestasis (37,5% to 17,3%), hepatomegaly (100,0%to 86,5%), prevalence of steatosis II and III degree (58,1% and 26,3% to 32,7% and11,5% at NASH without kidney pathology) is peculiar for non-alcoholic steatohepatitisclinical course at comorbidity with CKD as compared to the course without kidneypathology.Conclusions. Thus, the clinical course of nonalcoholic steatosis and steatohepatitis atcomorbidity with obesity and chronic kidney disease (CKD) is characterized by higherfrequency and intensity of the clinical and biochemical syndromes.

ЭТИОЛОГИЯ И ОСОБЕННОСТИ ТЕЧЕНИЯ ХБП У ДЕТЕЙ ПРИ ПАТОЛОГИИ МОЧЕВЫДЕЛИТЕЛЬНОЙ СИСТЕМЫ

This article presents data on the development of (chronickidney disease) CKD in children.In particular, with the pathology of the urinary system in children of different age groups.We analyzed the main clinical characteristics and laboratory parameters in children with pathology of the urinary system.The main parameters of the functional state of the kidneys were considered, the glomerular filtration rate (GFR) was calculated using the CKD EPI formula.The chronic pathology of the urinary systemin children was also analyzed.The course of CKD in children with various clinical nosological forms of kidney pathology was studied.

Urinary Kidney Biomarker Panel Detects Preclinical Antisense Oligonucleotide-Induced Tubular Toxicity

Sensitive kidney safety assessment is important for successful drug development in both preclinical and clinical stages. The Food and Drug Administration recently qualified a composite measure of 6 urine creatinine-normalized biomarkers, such as clusterin, cystatin C, kidney injury molecule 1 (KIM-1), N-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, for monitoring kidney toxicity in early clinical trials. The qualification was based on small molecule drugs in humans, and the full panel has not been assessed in other species or for other drug modalities. This study evaluated the effects on these biomarkers for a constrained ethyl antisense oligonucleotide (tool ASO) with demonstrated kidney toxicity in mice compared to a control ASO of the same chemistry. Dosing 50 mg/kg of the tool ASO resulted in mild proximal tubular pathology and elevations in KIM-1, clusterin, NGAL, and cystatin C. A lower dose resulted in milder histopathology and lower biomarker increases. Unexpectedly, the control ASO induced mild elevations in KIM-1, NGAL, and cystatin C, despite the lack of pathology. Both KIM-1 and clusterin were most closely associated with kidney pathology and increased with the severity of injury. Altogether, our data suggest that a biomarker panel is a sensitive tool for the detection of preclinical ASO-induced kidney pathology.

DIAGNOSIS OF CONGENITAL KIDNEY DISEASE IN YOUNG CHILDREN

An algorithm for diagnosing congenital kidney disease in the antenatal and early postnatal period was developed, and the management of these patients depending on the nature of the detected pathology was determined. The article presents the results of diagnostics of congenital kidney disease in 126 children. Of these, 70 children showed signs of kidney pathology in the antenatal period during ULTRASOUND examination of the kidneys in the fetus. The criteria for detected congenital pathology in the antenatal and early postnatal period are determined.