ISSN 2415-3060 (print), ISSN 2522-4972 (online)
JMBS
  • 18 of 49
Up
JMBS 2019, 4(4): 115–123
https://doi.org/10.26693/jmbs04.04.115
Clinical Medicine

Interleukin-6 Dynamics as a Predictor of the Renal Dysfunction Formation and a Criterion of the Effectiveness of the Nephroprotective Strategy in Early Rheumatoid Arthritis

Prytkova A. V.
Abstract

Rheumatoid arthritis is one of the most severe chronic human diseases, characterized by pronounced inflammation with proliferation of the synovial membrane of the joints, damage of the internal organs and systems, long-term persistent inflammation activity and gradual destruction of the structure of the joints and periarticular tissues. The purpose of the work was to study the prognostic significance of interleukin-6 over-expression in the formation of nephropathy and to evaluate the adequacy of nephroprotective therapy in the early rheumatoid arthritis. Material and methods. This study included 35 patients aged over 18 with early rheumatoid arthritis. The average age of patients was 50.71 ± 2.25 (from 18 to 76 years), 80% of women, the average duration of the disease at the time of the initial study was 9.21 ± 0.43 months. Results and discussion. The equation for calculating the personal probability of the presence of subclinical renal dysfunction was calculated by using the formula p = 1/1 + e – z, where z – 15.625 + 0.045 IL-6 (the sensitivity of the proposed method was about 83%, which is quite high and indicates clinical approbation of the obtained mathematical model for a qualitative prediction of the risk of nephropathy formation in rheumatoid arthritis). The predicted IL-6 level decreased by 28.24% (p <0.05) compared with the baseline values. Therapy with the drug "Actemra", in addition to a reliable clinical effect, was characterized by high nephroprotective activity. Thus, the decrease in microproteins excretion in the urine were 22.17% and 31.92% for microalbumin and β2-microglobulin, respectively (p<0.05 in all cases). At the same time, a statistically significant increase in the renal functional reserve was observed without a decrease in the initial level of glomerular filtration by endogenous creatinine clearance. We also noted a regression of the glomerular membrane porosity. Increased urinary excretion of albumin in patients with rheumatoid arthritis without concomitant kidney disease was detected in 76% of patients, which far exceeded the general population. The tubulointerstitial involvement was documented in 82% of patients in this group. The increase in the markers of tubular dysfunction is ahead of the increase in the level of the traditional marker of glomerular damage - urinary albumin excretion. As the pathological process progresses, the growth of glomerular and tubular dysfunction runs in parallel. Conclusions. The logistic regression method investigated the dependence of the dichotomous variable (presence or absence of violation of the functional status of the kidneys) from the autonomous regressor, which was considered to be a potential predictor associated with the risk of formation of nephropathy. The obtained data allows to consider IL-6 not only a subclinical predictor of renal function impairment, but also a potential marker for evaluating the nephroprotective effect of therapy in patients with early rheumatoid arthritis.

Keywords: interleukin-6, microalbuminuria, regression, early rheumatoid arthritis (eRA)

Full text: PDF (Ukr) 254K

References
  1. Mota LM. Laurindo IM, Santos Neto LL. Early rheumatoid arthritis: concept. Rev Assoc Med Bras. 2010; 56: 227-9. https://doi.org/10.1590/S0104-42302010000200024
  2. Escalas C, Dalichampt M, Combe B, Fautrel B, Guillemin F, Durieux P, et al. Effect of adherence to European treatment recommendations on early arthritis outcomes: data from the ESPOIR cohort. Ann Rheum Dis. 2012; 71(11): 1803-8. https://www.ncbi.nlm.nih.gov/pubmed/22563026. https://doi.org/10.1136/annrheumdis-2011-200761
  3. Verhoeven MMA, Welsing PMJ, Bijlsma JWJ, van Laar JM, Lafeber FPJG, Tekstra J, et al. Effectiveness of Remission Induction Strategies for Early Rheumatoid Arthritis: a Systematic Literature Review. Curr Rheumatol Rep. 2019 Apr 23; 21(6): 24. https://doi.org/10.1007/s11926-019-0821-1
  4. Huang Y, Zheng S, Wang R, Tang C, Zhu J, Li J. CCL5 and related genes might be the potential diagnostic biomarkers for the therapeutic strategies of rheumatoid arthritis. Clin Rheumatol. 2019 Apr 22. https://www.ncbi.nlm.nih.gov/pubmed/31011897. https://doi.org/10.1007/s10067-019-04533-1
  5. Liu X, Zhu Y, Zheng W, Qian T, Wang H, Hou X. Antagonism of NK-1R using aprepitant suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes. Artif Cells Nanomed Biotechnol. 2019 Dec; 47(1): 1628-34. https://www.ncbi.nlm.nih.gov/pubmed/31010320. https://doi.org/10.1080/21691401.2019.1573177
  6. Shostak HA, Muradyants AA. Ranniy revmatoidnyy artrit: algoritmy diagnostika i lecheniya [Early rheumatoid arthritis: diagnostic and treatment algorithms]. Farmateka. 2011; 11: 61-6. [Russian]
  7. Sorokin EV. Serdechno-sosudistye zabolevaniya, mikroalbuminuriya i statiny: ozhidaetsya li novyy proryv? [Cardiovascular diseases, microalbuminuria and statins: is a new breakthrough expected?]. Russkiy meditsinskiy zhurnal. 2010; 18(22): 1327-31. [Russian]
  8. Tyapkina MA. Vzaimosvyaz albuminurii i kardiovaskulyarnogo riska u bolnykh s revmatoidnym artritom [The relationship of albuminuria and cardiovascular risk in patients with rheumatoid arthritis]. Byulleten meditsinskikh Internet-konferentsiy. 2013; 3(3): 514. [Russian]
  9. Batyushin MM, Vystavkina EA. Klinicheskie proyavleniya i faktory riska porazheniya pochek pri revmatoidnom artrite [Clinical manifestations and risk factors for kidney damage in rheumatoid arthritis]. Fundamentalnye issledovaniya. 2012; 5: 249-52. [Russian]
  10. Benucci M, Saviola G, Manfredi M, Sarzi-Puttini P, Atzeni F. Cost effectiveness analysis of disease-modifying antirheumatic drugs in rheumatoid arthritis. A sustemic review literature. Int J Rheumatol. 2011; 22: 845-9. https://www.ncbi.nlm.nih.gov/pubmed/22162693. https://www.ncbi.nlm.nih.gov/pmc/articles/3228304. https://doi.org/10.1155/2011/845496
  11. Moura RA, Cascão R, Perpétuo I, Canhão H, Vieira-Sousa E, Mourão AF, et al. Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival. Rheumatolog. 2011; 50(2): 278-82. https://www.ncbi.nlm.nih.gov/pubmed/21047805. https://doi.org/10.1093/rheumatology/keq338
  12. Fransen J, Stucki G, van Reil PLCM. Rheumatoid arthritis measures. Arthr Rheum. 2003; 49: 214-24. https://doi.org/10.1002/art.11407
  13. Reneses, S, Pestana L, Garcia A. Comparison of the 1987 ACR criteria and the 2010 ACR/EULAR criteria in an inception cohort of patients with recent-onset inflammatory polyarthritis. Clin Exp Rheumatol. 2012; 30(3): 417-20. https://www.ncbi.nlm.nih.gov/pubmed/22704895
  14. Tian S, Yan Y, Qi X, Li X, Li Z. Treatment of Type II Collagen-Induced Rat Rheumatoid Arthritis Model by Interleukin 10 (IL10)-Mesenchymal Stem Cells (BMSCs). Med Sci Monit. 2019 Apr 21; 25: 2923-34. https://www.ncbi.nlm.nih.gov/pubmed/31005957. https://www.ncbi.nlm.nih.gov/pmc/articles/6489530. https://doi.org/10.12659/MSM.911184
  15. Moura RA, Weinmann P, Pereira PA, Caetano-Lopes J, Canhão H, Sousa E, et al. Alterations on peripheral blood B-cell subpopulations in very early arthritis patients. Rheumatology. 2010; 49(6): 1082-92. https://www.ncbi.nlm.nih.gov/pubmed/20211867. https://doi.org/10.1093/rheumatology/keq029
  16. McCoy SS, Crowson CS, Maradit-Kremers H, Therneau TM, Roger VL, Matteson EL, et al. Longterm outcomes and treatment after myocardial infarction in patients with rheumatoid arthritis. J Rheumatol. 2013 May; 40(5): 605-10. https://www.ncbi.nlm.nih.gov/pubmed/23418388. https://www.ncbi.nlm.nih.gov/pmc/articles/3895921. https://doi.org/10.3899/jrheum.120941
  17. Poppelaars PB, van Tuyl LHD, Boers M. Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up. Ann Rheum Dis. 2019 May; 78(5): 586-9. https://www.ncbi.nlm.nih.gov/pubmed/30808623. https://doi.org/10.1136/annrheumdis-2018-214618
  18. Stepanova AA, Savenkova ND, Novik GA, Dementeva EA, Gurina OP. Diagnosticheskoe znachenie kontsentratsii tsitokinov IL-1β, IL-6, TNF-α i belka-predshestvennika amiloida SAA v krovi u patsientov s yuvenilnym revmatoidnym artritom [Diagnostic value of the concentration of cytokines IL-1β, IL-6, TNF-α and amyloid precursor protein SAA in the blood of patients with juvenile rheumatoid arthritis]. Rossiyskiy vestnik perinatologii i pediatrii. 2015; 5: 85-91. [Russian]
  19. Jones G. Tocilizumab monotherapy is superior to methotrexate monotherapy in reducing disease activity in patients with rheumatoid arthritis: The AMBITION study. Presented at EULAR, 13 June 2008.
  20. Emery P. Tocilizumab significantly improves disease outcomes in patients with rheumatoid arthritis whose anti-TNF therapy failed: The RADIATE study. Presented at EULAR, 13 June 2008.