Analysis of the dependence of the levels of markers of early kidney damage — cytokines KIM-1 and TGF-β1 in children with juvenile idiopathic arthritis

Abstract

Background. Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characte­rized by chronic joint inflammation in children under the age of 16 years. Kidney damage in JIA ranges from asymptomatic proteinuria to severe glomerulonephritis that can lead to chronic kidney disease. Given the above data, the assumption of an increased risk of early development of kidney damage in children with JIA is reasonable. The purpose was to analyze the risk factors for structural tubular lesions by studying the level of kidney injury molecule-1 (KIM-1) and transforming growth factor β1 (TGF-β1) in children with JIA, depending on the characteristics of the clinical course of the disease and the treatment received. Materials and methods. Eighty children with JIA who were undergoing inpatient treatment at the Regional Medical Center for Family Health of the State Regional Health Department were examined. A retrospective analysis of medical documentation was conducted to assess the child’s age at the onset of JIA, the duration of its course, clinical features, and treatment. Further, during the work, a clinical examination, assessment of the health of children, general clinical, biochemical, immunoenzymatic and immunological studies, ultrasound examination of joints and kidneys were performed. Structural tubular markers KIM-1 and TGF-β1 were measured in urine samples. Results. The average KIM-1 level was 0.9970 ± 0.1662 (0.98; 0.90–1.12) ng/ml, TGF-β1 — 20.26 ± 16.34 (14.02; 12.5–17.98) pg/ml. The average KIM-1 values varied depending on the form of JIA and the degree of disease activity. At the same time, with high JIA activity, the KIM-1 level was statistically significantly higher (1.1510 ± 0.0806 ng/ml, p < 0.05 compared to remission). A similar trend was observed when analyzing TGF-β1 levels. Elevated KIM-1 was associated with high JIA activity, involvement of ≥ 6 joints at the time of examination, and lesions of small joints of the hands and wrist joints. Elevated TGF-β1 was statistically significantly associated with polyarthritis, JIA duration of ≥ 6 years, and active disease stage of ≥ 4 years. Conclusions. Our study revealed a statistically significant relationship between the levels of KIM-1 and TGF-β1 biomarkers and the degree of JIA activity. The antinuclear antibodies status in patients with JIA did not affect the levels of KIM-1 and TGF-β1. Elevated content of KIM-1 and TGF-β1 in urine indicate the risk of structural kidney damage in patients with JIA. Risk factors are high JIA activity, significant joint involvement, prolonged active stage, the presence of hypertension, and NSAIDs treatment. The combination of NSAIDs with methotrexate increased the levels of KIM-1 and TGF-β1, which indicated a nephrotoxic effect, while the combination of methotrexate with immunobiological drugs decreased the levels of biomarkers.