POS0546 RENAL DYSFUNCTION AND METABOLIC CHANGES IN PATIENTS WITH RHEUMATOID ARTHRITIS ARE ASSOCIATED WITH ANGIOPOIETIN-LIKE PROTEIN TYPE 4
Authors: V. Aleksandrov, A. Aleksandrov
Journal: Annals of the Rheumatic Diseases (2021)

Background: Along with chronic inflammation, the development of renal damage in rheumatoid arthritis (RA) is promoted by the presence of metabolic syndrome (MS), which may be an independent risk factor for the progression of chronic kidney disease. Objectives: To establish a correlation between serum angiopoietin-like protein type 4 (ANGPTL4) and the presence of renal dysfunction and metabolic disorders in RA patients. Methods: We examined 158 patients with RA (91.8% - women and 8.2% - men) aged 21 to 80 years old with an average duration of the disease - 9 [4; 15] years. The majority of patients were seropositive for RF-IgM (57.6%) and for anti-citrullinated protein antibody (ACPA) (60.1%), with an advanced clinical stage (45.6%) and moderate activity (3.2 &lt;DAS28 ≤ 5.1) of the pathological process (58.2%). The laboratory examination included the determination of serum concentrations of angiopoietin-like protein type 3 (Human Angiopoietin-like Protein 3 ELISA, Bio Vendor, Czech Republic) and type 4 (RayBio Human ANGPTL4 ELISA Kit; RayBiotech, USA). To assess renal function in RA patients, the estimated glomerular filtration rate (GFR) was used according to the 2009 CKD-EPI formula. On the basis of GFR measurements, the patients were divided into three groups: I - optimal renal function (&gt; 90 ml / min); II - a slight decrease in renal function (89-60 ml / min); III - reduced renal function (&lt;59 ml / min). A combination of the increased blood pressure (≥140 / 90 mmHg), the increased triglyceride levels (≥1.7 mmol / L), and the impaired carbohydrate metabolism (increased fasting plasma glucose ≥6.1 mmol / L) with a background of central obesity (waist circumference&gt; 94 cm in men and&gt; 80 cm in women) served as the basis for inclusion into the group of RA patients with signs of MS. Results: A multivariate analysis of variance was performed comparing ANGPTL indices depending on GFR in the groups of RA patients without signs of MS and RA patients with MS. It was revealed that there are significant differences in the level of both ANGPTL3 (F = 8.86, p = 0.0034) and ANGPTL4 (F = 29.6, p &lt;0.001) between RA patients with varying severity of metabolic disorders. The study of the influence of several factors (MS and renal dysfunction) on the content of ANGPTL in RA patients showed that the presence of metabolic disorders had an insignificant effect on the parameters of ANGPTL3 in the groups of patients with optimal and slightly reduced GFR, acquiring significance only with a more intense decrease in GFR (&lt;59 ml / min / 1.73 m2). These factors and their interactions explain the insignificant share of the variability in ANGPTL3 (R 2 = 0.11), which indicates a low quality of the model. There was a more pronounced difference in the level of ANGPTL4 in the presence of metabolic disorders in the groups of RA patients with varying degrees of renal dysfunction. The factors under consideration and their interactions do not make this model significant (p = 0.1), although they can explain a significant proportion of the variability in ANGPTL4 (R 2 = 0.32). We differentiated RA patients into patients with high or optimal GFR (≥89 ml / min) and patients with reduced GFR (&lt;89 ml / min) when combining groups of RA patients with varying degrees of renal dysfunction (group II and group III). Multivariate analysis of variance using the new characteristics showed a significant increase in ANGPTL 4 in the blood serum of RA patients with reduced GFR (F = 18.5, p &lt;0.001) and severe metabolic changes (F = 24.2, p &lt;0.001). Thus, the concentration of ANGPTL4 in RA patients is directly influenced by two factors (renal dysfunction and the presence of MS), which can describe the variability of this sign in more than 30% of cases. The squared multiple correlation coefficient (R 2 ) in this model is 0.33. Conclusion: ANGPTL type 4 should be considered as a key factor linking the development of the renal dysfunction in RA patients and the metabolic changes caused by rheumatoid inflammation. Disclosure of Interests: None declared