The dissertation is devoted to the improvement of early diagnosis of comorbid kidney damage in children with juvenile idiopathic arthritis (JIA). The problem of JIA is determined by the significant prevalence, chronic course of the disease, the severity of clinical manifestations of erosive-destructive arthritis, as well as comorbid damage to vital organs and systems, which greatly aggravates the course of the underlying disease and worsens its prognosis.
Among 80 patients with JIA the following disease variants were identified (according to ILAR criteria): systemic arthritis - 9 (11.25%) children, polyarthritis - 47 (58.75%), persistent oligoarthritis - 24 (30%) children. Children were stratified according to the JADAS-27 scale: remission - 60 (75.0%), low activity of JIA - 14 (17.5%), high activity - 6 (7.5%); the duration of the active stage of JIA: active stage <4 years - 59 (73.75%) and ≥4 years - 21 (26.25%).
The results of the correlation analysis showed a direct correlation between serum cystatin C level and disease activity according to the JADAS-27 scale with the assessment of VAS by the doctor and the patient, the number of active joints and ESR. An inverse association was found between the duration of remission and cystatin C levels. The level of GFR varied depending on the activity of JIA. A decrease in GFR was noted in all children with high activity and in 71 % - with low activity. In remission a decrease in GFR was noted in a quarter of cases and a low risk of a decrease in this indicator was established (according to the Hoek formula).
To determine the factors of formation of structural kidney disorders, a study of non-invasive biomarkers of early renal fibrosis KIM-1 and TGF-β1 in urine was conducted. Elevated levels of KIM-1 and TGF-β1 biomarkers in urine were found in 25% of children with JIA. The increase in the level of these markers occurred when the disease activity was maintained for more than 4 years, the total duration was more than 6 years, and there was a reduced GFR and polyarthritis. A significant frequency of increased renal biomarkers in children with JIA in the presence of hypertension syndrome was noteworthy.
Factor analysis of the level of urinary tubular marker KIM-1 depending on the features of the clinical course of JIA revealed 12 factors (disease debut, disease duration, duration of the active stage of JIA, duration of remission, form of JIA, JADAS-27 activity, children's health status according to the CHAQ scale, groups and number of affected joints, number of joints with impaired function, blood pressure, GFR by Schwartz formula and Hoek formula) 7 most significant factors were identified: high JIA activity, ≥ 6 joints affected during the examination period, arthritis of small joints of the hands, arthritis of the wrists, arthritis of the hips, hypertension, and a GFR below normal by the Hoek formula, which are associated with high levels of KIM-1 in the urine. The highest risk of tubular kidney damage in children with JIA was noted in the case of high disease activity, hip arthritis, and the presence of hypertension. Elevated urinary KIM-1 levels are associated with decreased GFR, which suggests that renal dysfunction in children with JIA is the result of combined damage of the tubular and glomerular renal apparatus.
The use of a combination of methotrexate and NSAIDs led to an increase in TGF-β1 levels and quadrupled the chances of increasing this marker of early renal fibrosis. In patients with a combination of methotrexate and immunobiological therapy low levels of renal biomarkers and no risk of increased TGF-β1 were observed.
According to the odds ratio analysis the risk factors for the development of structural and functional renal impairment in children with JIA are high disease activity, a significant duration of the active stage (more than 4 years), polyarthritis, hip arthritis, as well as the use of NSAIDs, hypertension, and dental caries. The use of immunobiological therapy has a positive effect on kidney function due to the effective suppression of JIA activity
