AB0053 THE ROLE OF ANGIOPOIETIN-LIKE PROTEINS TYPES 3 AND 4 IN THE DEVELOPMENT OF RENAL DYSFUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS

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Background:Rheumatoid arthritis (RA) often contributes to the development of kidney disease. Angiopoietin-like proteins can be target markers for studying cardiorenal complications of RA [1].Objectives:Assessment of the correlation of serum concentrations of angiopoietin-like proteins types 3 and 4 (ANGPTL 3 and 4) with the progression of renal dysfunction in RA patients.Methods:114 patients with reliable RA (90.4% of women, 9.6% of men) aged 21 to 80 years (mean age 55.4 ± 11.2 years old), disease duration - 11.18 ± 9.03 years, positive for rheumatoid factor (RF-IgM) - 63.2%, positive for anti-citrullinated protein antibody (ACPA) - 59.7%) were examined. 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 we used the calculated glomerular filtration rate (GFR) according to the CKD-EPI formula [2], taking into account the height and weight of a particular patient without indexing by body surface area. GFR values <60 ml / min / 1.73 m2 were regarded as a certain decrease, and GFR values from 60 to 89 ml / min / 1.73 m2 - as a slight decrease in global kidney function.Results:The concentration of ANGPTL3 in the blood serum of RA patients (n = 158) was 641.9 ± 224.5 ng / ml, and that of ANGPTL4 (n = 158) - 3.15 [0.77; 12.1] ng / ml. 74.7% (n = 118) were considered positive for the presence of ANGPTL3; 49.4% (n = 78) of RA patients were recognized as positive for the presence of ANGPTL4. The average glomerular filtration rate in RA patients was 74.0 ± 18.6 ml / min. More than а half of the examined RA patients had GFR ranging from 89 to 60 ml / min / 1.73 m2 (C1 - 21.5%; C2 - 58.9%; C3 - 19.6%). No sharp reduce of renal function (GFR <30 ml / min / 1.73 m2) corresponding to CKD C4-5 stages was recorded. Negative correlations of average strength were found between GFR and the level of ANGPTL 3 (r = -0.32, p <0.001) and ANGPTL 4 (rS = -0.31, p <0.001), as well as with age (rS = -0.28, p <0.001), the duration of RA (rS = -0.22, p = 0.005) and blood pressure increase (rS = -0.25, p = 0.001). On the basis of GFR measurements, patients were divided into three groups: group I - optimal renal function (> 90 ml / min); group II - a slight decrease in renal function (89-60 ml / min); group III - reduced renal function (<59 ml / min).Table 1.Content of ANGPTL 3 and 4 in RA patients with different GFR, ng / mlGroup I (n=34)Group II (n=93)Group III (n=31)ANGPTL 3533,4±161,7 I-III650,0±223,9733,2±244,1ANGPTL 40,77 [0,28;3,6] I-II, I-III3,3 [0,93;12,1]6,48 [1,52;19,3]Note: upper case indicates intergroup differences at p <0.05.There was a significant difference in the content of ANGPTL3 in patients of the first group and the patients of the third group (H-test = 6.55, p = 0.032) and ANGPTL4 in the group of patients with normal renal function (group I) and groups of RA patients with decreased GFR (group I- II: H-test = 10.7, p = 0.001; groups I-III: H-test = 20.1, p <0.001). ANGPTL4 indices also had intergroup differences (groups II-III: H-test = 7.2, p = 0.007) with GFR less than 90 ml / min.Conclusion:Chronic rheumatoid inflammation potentiates the development of renal dysfunction according to our data in 78.5% of patients. It is also accompanied by an increase in the content of ANGPTL types 3 and 4 in the blood of RA patients. A better understanding of the actions and mechanisms of ANGPTL may be of paramount importance for the development of effective ways of treatment for cardiorenal complications in RA.