RISK FACTORS AND CLINICAL CORRELATIONS OF URINARY TGF-Β1 IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS AND EARLY KIDNEY FIBROSIS.

The course of juvenile idiopathic arthritis (JIA) is associated with a long-term inflammatory process and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which can cause nephrotoxicity with fibrotic kidney damage in patients with JIA. Regardless of the etiology of joint damage, prolonged inflammation promotes the progression of fibrosis, and renal fibrosis is the final common stage of chronic kidney disease (CKD). Kidney biopsy, which is invasive, risky and underutilized, is generally considered the only clinical method to detect fibrosis. Over the past decade, some progress has been made in the search for minimally invasive biomarkers of early kidney fibrosis, with transforming growth factor-β1 (TGF-β1) playing a key role in the progression of kidney fibrosis, but the significance of TGF-β1 in children with JIA is unknown. Material and Methods: 80 children with JIA were examined. Urinary TGF-β1 levels were determined using a TGF-β1 ELISA kit (DRG International, Inc., Germany, EIA-1864) according to the manufacturer's instructions. Methods of variation statistics were used. Informed consent was obtained from all patients. The study has a positive conclusion of the Commission on Biomedical Ethics of Dnipro State Medical University (Minutes of the meeting of the Commission No. 12 dated December 19, 2002), which decided that the scientific research can be considered in accordance with generally accepted moral standards, the requirements of respecting the rights, interests and personal dignity of study participants, bioethical standards for work with pediatric patients. There is no risk to the research subjects in the performance of the work. The legal representatives of the children involved in the research are informed about all aspects related to the purpose, objectives, methods and expected benefits of the research. Laboratory and instrumental research methods are generally accepted; the drugs to be used are approved for use. No human experiments were performed. Methods of variation statistics were used. Statistical analysis was performed using the STATISTICA 6.1 software package (StatSoft Inc., serial no. AGAR909E415822FA). The work was carried out as part of the research work of the Department of Propaedeutic of Childhood Diseases and Pediatrics 2 of the Dnipro State Medical University «Development of criteria for early diagnosis and prediction of comorbid kidney damage in children with somatic and infectious diseases» (state registration No. 0119U100932, implementation period 01.2019-12.2023). Results. The mean TGF-β1 level in our study was 20.26±16.34 (14.02, 12.5-17.98) pg/ml. Polyarthritis almost quadrupled the probability of pathological changes in TGF-β1. The overwhelming majority of children with elevated TGF-β1 suffered from polyarthritis (80.0 %) - one and a half times more often than those with relatively normal TGF-β1 concentration, p<0.04. If the active stage of the disease lasted at least 4 years, the probability of elevated TGF-β1 increased more than sixfold. The tendency of significant nephrotoxic effect of prolonged active JIA was confirmed by the results of correlation analysis, according to which, in general, the duration of active JIA was directly related to the increase of TGF-β1 (ρ=0.38, p<0.001), and the duration of remission and the total duration of JIA had no significant correlation with it (ρ= -0.19 and ρ=0.18, respectively, p>0.05). The direct dependence of elevated urinary TGF-β1 levels on clinical features such as polyarthritis and the duration of the active phase of JIA has been demonstrated. These clinical features in children with JIA can be considered as risk factors for the development of early renal fibrosis. Against the background of elevated TGF-β1, a reduced GFR according to the Hoek formula (<90 ml/min/1.73 m2) was found in 95 % of cases, i. e. the estimates of the functional state of the kidneys obtained by two different methods were quite clearly the same. In the sample with TGF-β1<17.98 pg/ml, 22.76 % of children received immunobiologic therapy, while in the sample to increase TGF-β1 - only 14.76 %. Immunobiological therapy reduced the risk of increasing this urinary marker by 5.5 times. Conclusions. Elevated levels of the TGF-β1 biomarker were found in 25 % of children with JIA. An association of early renal fibrosis with duration of active phase of JIA ≥ 4 years, increased ESR, polyarthritis, arterial hypertension, and dental caries was observed. Elevated urinary TGF-β1 levels are associated with reduced eGFR and are observed in almost all children with eGFR<90 ml/min/1.73 m2, confirming the importance of early renal fibrosis in the development of renal dysfunction. [ABSTRACT FROM AUTHOR]