AB1720 CORRELATION BETWEEN THE CLINICAL FEATURES, COMORBIDITY FACTORS AND TREATMENT SCHEME OF JUVENILE IDIOPATHIC ARTHRITIS IN CHILDREN AND EARLY BIOMARKERS OF KIDNEY DAMAGE
Authors: S. Samsonenko
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The course of juvenile idiopathic arthritis (JIA) is associated with a prolonged inflammatory process and long-term symptomatic use of NSAIDs, which not only help control the inflammatory symptoms of JIA, but also cause nephrotoxic effects that can cause fibrotic kidney damage in patients with JIA. The hypothesis of the risk of early development of kidney fibrosis in children with JIA looks quite logical, and the need for timely correction of chronic kidney disease (CKD) raises the issue of non-invasive diagnosis of CKD using renal biomarkers. <h3>Objectives:</h3> To determine the relationship between the levels of early biomarkers of kidney damage (TGF-β1 and KIM-1) in urine with the features of the clinical course of JIA, comorbidity factors and treatment scheme. <h3>Methods:</h3> Were examined 80 children with JIA. Urinary TGF-β1 and KIM-1 levels were determined using a ELISA kit according to the manufacturer's instructions. Methods of variation statistics were used. <h3>Results:</h3> Increased levels of biomarkers KIM-1 and TGF-β1 in urine were found in 25% of children with JIA. Factor analysis of the level of urinary tubular marker KIM-1 depending on the features of the clinical course of JIA revealed 12 factors, 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. To analyze the frequency of elevation of transforming growth factor-β1, which is a noninvasive biomarker of early renal fibrosis, we formed a sample of patients who had a TGF-β1 level not less than the upper quartile of the variation range we studied (17.98 pg/mL) and conducted a comparative analysis with a sample of patients with a TGF-β1 level &lt;17.98 pg/mL. Factor tables of frequency distribution of all features of the clinical course of JIA depending on the content of TGF-β1 in the urine were studied. Based on the results of this analysis the following factors were significantly associated with high TGF-β1 levels: total duration of the active stage of more than 4 years, duration of the disease of more than 6 years, elevated ESR, polyarthritis, as well as hypertension and dental caries. The results of the examination of renal markers depending on the characteristics of therapy showed the following. When using short courses of NSAIDs in children receiving methotrexate, only a tendency to increase KIM-1 in the urine was found. At the same time prolonged use of NSAIDs had a negative effect on the level of KIM-1. 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. <h3>Conclusion:</h3> Structural damage to the renal tubules in children with JIA is observed in 25% of patients. Risk factors for tubular kidney damage include high activity of JIA, arthritis of ≥ 6 joints, arthritis of the hip joints, and arterial hypertension. The duration of concomitant therapy with methotrexate and NSAIDs is likely to significantly correlate with the level of structural kidney damage. Immunobiological therapy reduces the risk of impaired tubular structure, and the chance of early renal fibrosis in children with JIA. <h3>REFERENCES:</h3> [1] Gicchino MF, Di Sessa A, Guarino S, Miraglia Del Giudice E, Olivieri AN, Marzuillo P. Prevalence of and factors associated to chronic kidney disease and hypertension in a cohort of children with juvenile idiopathic arthritis. Eur J Pediatr. 2021;180(2):655-661. DOI:10.1007/s00431-020-03792-4. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>