Serum cystatin C as a marker of renal dysfunction in children with juvenile idiopathic arthritis




juvenile idiopathic arthritis, renal dysfunction


An accurate assessment of the estimated glomerular filtration rate (eGFR) is important for early detection of chronic kidney disease, control of nephrotoxicity, and dose adjustment of drugs. To date, there has been only one cohort retrospective study of the prevalence of chronic kidney disease in children with juvenile idiopathic arthritis (JIA).

Purpose - to determine the level of serum cystatin C and, on its basis, the state of eGFR depending on the form of the clinical course, degree of activity, methods of treatment of JIA in children.

Materials and methods. 80 children with JIA were examined. The content of serum cystatin C was determined by enzyme-linked immunosorbent assay. The Hoek formula was used to calculate eGFR based on the level of cystatin C in blood serum.

Results. A decrease in eGFR below 90 ml/min/1.73m2 to 63.08 ml/min/1.73m2 based on serum cystatin C was found in 41.3% of children with JIA. The variant of the clinical course of JIA does not affect the concentration of serum cystatin С and the level of eGFR. Meanwhile, a high degree of risk of developing a decrease in eGFR in children with polyarthritis was established - 72.7% versus 48.9% (OR=2.78; CI: 1.07-7.24; p<0.04). Elevated serum cystatin С levels and decreased eGFR are associated with the degree of JIA activity and its duration. A decrease in eGFR is observed in all children with high activity of JIA, 71.4% - with low activity, 28.3% - in remission. A low risk of developing a decrease in eGFR in children in remission of JIA was established - 51.5% versus 91.5% (OR=0.10; CI: 0.03-0.34; p<0.001). The duration of the active stage of JIA ≥4 years negatively affects the level of eGFR, which leads to a high risk of developing a decrease in eGFR - 39.4% versus 17% (OR=3.17; CI: 1.13-8.9; p<0.04). A high risk of developing a decrease in eGFR was established in children with JIA who received non-steroidal anti-inflammatory drugs (NSAIDs) at the time of the examination - 54.5% versus 8.5% (OR=12.9; CI: 3.76-44.25; p<0.001). The use of immunobiological therapy is associated with a low risk of developing a decrease in eGFR - 9.1% versus 46.8% (OR=0.11; CI: 0.03-0.42; p<0.001).

Conclusions. Renal dysfunction was found in 41.3% of children with JIA. Its development is affected by high activity of JIA, duration of the active stage of JIA ≥4 years, and treatment with NSAIDs.

The study was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution specified in the work. Informed consent was obtained from the parents of the children for the research.

No conflict of interests was declared by the authors.


Conkar S, Mir S, Karaslan FN, Hakverdi G. (2018). Comparing different estimated glomerular filtration rate equations in assessing glomerular function in children based on creatinine and cystatin C. J Clin Lab Anal. 32 (6): e22413.; PMid:29484708 PMCid:PMC6817194

Gicchino MF, Di Sessa A, Guarino S et al. (2021). Prevalence of and factors associated to chronic kidney disease and hypertension in a cohort of children with juvenile idiopathic arthritis. Eur J Pediatr. 180 (2): 655-661.; PMid:32860100

Hickson LJ, Crowson CS, Gabriel SE et al. (2014). Development of reduced kidney function in rheumatoid arthritis. Am J Kidney Dis. 63 (2): 206-213.; PMid:24100126 PMCid:PMC3944015

Hoek FJ, Kemperman FA, Krediet RT. (2003). A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant. 18 (10): 2024-2031.; PMid:13679476

Kandasamy Y, Rudd D. (2021). Cystatin C: A more reliable biomarker of renal function in young infants? A longitudinal cohort study. Acta Paediatr. 110 (4): 1341-1345.; PMid:32799396 PMCid:PMC7984386

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. (2013). KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International Supplements. 3 (1): 1-50. URL:

Kochi M, Kohagura K, Shiohira Y et al. (2016). Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis. PLoS One. 11 (8): e0160225.; PMid:27537204 PMCid:PMC4990299

Kushnirenko SV. (2019). Cystatin C - based evaluation of the estimated glomerular filtration rate in children with chronic kidney disease 1-3 st. (3а and 3b). Modern Pediatrics. Ukraine. 6 (102): 12-17.

Mangge H, Liebmann P, Tanil H et al. (2000). Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis. Clin Chim Acta. 300 (1-2): 195-202.

Mian AN, Schwartz GJ. (2017). Measurement and Estimation of Glomerular Filtration Rate in Children. Adv Chronic Kidney Dis. 24 (6): 348-356.; PMid:29229165 PMCid:PMC6198668

Miyamae T, Tani Y, Kishi T et al. (2020). Updated version of Japanese Childhood Health Assessment Questionnaire (CHAQ). Mod Rheumatol. 30 (5): 905-909.; PMid:31441680

Nakashima A, Horita S, Matsunaga T et al. (2021). Factors contributing to discrepant estimated glomerular filtration values measured by creatinine and cystatin C in patients with rheumatoid arthritis. Sci Rep. 11 (1): 9884.; PMid:33972623 PMCid:PMC8110572

Nordal EB, Zak M, Berntson L et al. (2011). Juvenile Arthritis Disease Activity Score (JADAS) based on CRP; validity and predictive ability in a Nordic population-based setting. Pediatr Rheumatol Online J. 9 (1): 155.; PMCid:PMC3194508

Ringold S, Angeles-Han ST, Beukelman T et al. (2019). 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken). 71 (6): 717-734.; PMid:31021516 PMCid:PMC6561125

Sato H, Kuroda T, Tanabe N et al. (2010). Cystatin C is a sensitive marker for detecting a reduced glomerular filtration rate when assessing chronic kidney disease in patients with rheumatoid arthritis and secondary amyloidosis. Scand J Rheumatol. 39 (1): 33-37.; PMid:20132068

Targońska-Stepniak B, Majdan M. (2011). Cystatin C concentration is correlated with disease activity in rheumatoid arthritis patients. Scand J Rheumatol. 40 (5): 341-346.; PMid:21619490