Simple clinical and genetic prognostic markers of secondary/renal amyloidosis in rheumatoid arthritis patients

Background: Secondary amyloidosis (SAM) including renal amyloidosis (RAM) is a common severe outcome in rheumatoid arthritis (RA) patients. Some clinical markers were published as risk factors for SA [1]. Objectives: To reveal simple clinical and genentic markers of SAM/RAM in RA patients and to estimate their prognostic value. Methods: In the observational trial of RA patients (n=590: 482 women, 108 men) histologically confirmed secondary amyloidosis (SAM) was revealed in 5.8%, renal amyloidosis (RAM) - in 3.6%. This SAM/RAM frequency was considered as pretest probability. We investigated associations between SAM/RAM and a number of genetic markers (erythrocytic antigens of AB0, MN and Rh0 blood groups, HLA antigens of A, B, C, DR, DQ locuses) and clinical markers (sex, triggers, age of RA onset, early RA variant, RF during the first year of RA, extraarticular manifestations, comorbidity and rapid RA progress. Statistical significance of the revealed association was estimated by Fisher exact test (F). Likelihood ratio of positive (LR+) and negative (LR-) tests and prognostic odds ratio (pOR) as well as SAM/RAM post-test probability (Ppost) were calculated. Results: We revealed no significant difference in SAM /RAM frequency between RA men and women (F, p2-t>0.1). SAM Ppost in RF+ patients during the first 3 years of RA increases 2.5 times vs RF- patients. SAM Ppost in patients with rapid RA progress during the first 3 years (RA severity progression index (DSPI)>+1SD[2]) increases 2.4 times vs patients with DSPI<-1SD. Some co-morbidities were associated with SAM: coronary/cerebral atherosclerosis, gastroduodenal ulcer, cholelithiasis and chronic hepatitis (see table), but they shouldn't be considered as independent SAM predictors because of their moderate pairwise correlation (RG=0.37-0.68). Severe anemia and chronic renal insufficiency increase SAM Ppost up to 35.1% and 55.2% correspondingly. SAM 2.8 times more frequent registered in patients with NSAID adverse drug reactions (ADRs) and 7.7 times more frequent - in patients with glucocorticoids (GK) ADRs vs patients without NSAID/GK ADRs. We revealed distinct negative correlation between methotrexate use and SAM (RG=-0.57, p=0.0002), as well as RAM (RG=-0.79, p<0.0001). SAM Ppost increases 3.3, 2.8, and 2.5 times in the presence of N blood group, HLA B27 and HLA B18 correspondingly. (Table presented).