AB0668 PROGRESSION OF CHRONIC KIDNEY DISEASE IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH METHOTREXATE
Authors: I. Hajime, H. Hanaoka, K. Hiramoto, J. Kikuchi, M. Akiyama, S. Saito, Y. Kondo, Y. Kaneko
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with rheumatoid arthritis (RA) have a high prevalence of chronic kidney disease (CKD), which is associated with chronic inflammation, immune-mediated glomerular injury, micro-vasculopathy, and treatment-related nephrotoxicity [1,2]. Elevation of C-reactive protein (CRP) and disease activity are associated with CKD progression in patients treated with biological disease modifying anti-rheumatic drugs (bDMARDs) [3]. Meanwhile, methotrexate (MTX) has mild nephrotoxicity and shows dose-dependent renal impairment [4]. Therefore, in patients treated with MTX, there may be a contradictory relationship between treatment intensity and disease activity. <h3>Objectives:</h3> To identify factors associated with progression of CKD in patients with RA treated MTX. <h3>Methods:</h3> We reviewed consecutive patients with RA who were treated with MTX with stable RA condition for more than five years from 2018 to 2023. Patients who had CKD or started concomitant bDMARDs were excluded. We collected clinical characteristics including CDAI, CRP levels, erythrocyte sedimentation rates, estimated glomerular filtration rate, MTX dose, glucocorticoid use, and concomitant conventional synthetic DMARDs. CKD progression was defined as eGFR level &lt;60 ml/min/1.73m<sup>2</sup> at two measurements more than 90 days apart. <h3>Results:</h3> A total of 115 patients were included in the study. The mean age was 62 years, female was 100 (87%), and the mean eGFR at MTX initiation was 84 ml/min/1.73m<sup>2</sup>. During 5 years of observation, 22 patients (19.1%) progressed to CKD. Patients in the CKD progression group were older, (71 years vs 60 years, p&lt;0.001), used other concomitant csDMARDs more frequently (p=0.020), and showed lower eGFR (73 vs 86 ml/min/1.73m<sup>2</sup>, p=0.010) at MTX initiation. Moreover, the mean CDAI levels over 5 years in the CKD progression group was significantly higher than the non-CKD progression group (5.8 vs 2.4, p=0.006). Then, we focused on 83 patients who were treated with MTX monotherapy for more than five years. The mean age was 63 years, and 72 (87%) were female. The mean dose of methotrexate was 8.1 mg/week, and the mean CDAI during 5 years was 2.6. During the 5-year observation period, 12 patients (14.6%) progressed to CKD. Patients in the CKD progression group were older (76 years vs 60 years, p&lt;0.010) and were more frequently complicated with hypertension (33% vs 8.4%, p=0.030). Again, the mean CDAI during 5 years in the CKD progression group was significantly high (6.5 vs 1.9, p=0.010). The dose was not different between the two groups (8.5 vs 8.0 mg/week, p=0.700). Multivariable analysis revealed that eGFR at MTX initiation (odds ratio [OR] 0.58, p=0.002) and mean CDAI levels for five years (OR 1.86, p=0.001) are independently associated with CKD progression. A receiver operating characteristic curve identified 3.9 as a cut-off value of CDAI and 75 ml/min/1.73m<sup>2</sup> of eGFR at MTX initiation to discriminate patients with CKD progression from those without. <h3>Conclusion:</h3> Mild decrease in eGFR at MTX initiation and strict control of disease activity were crucial to prevent progression to CKD in patients with RA who were treated with MTX, while the MTX dose are not relevant with progression of CKD. <h3>REFERENCES:</h3> [1] Scott DL. Rheumatoid arthritis. <i>Lancet</i>. 2010;376(9746):1094-1108. [2] Sihvonen S. <i>Neohron Clin Pract</i> 2004; 96: c107-c114 [3] Hironari H. Clin Kidney J. 2022 Jan 31;15(7):1373-1378. [4] Hayashi K. Sci Rep. 2020 Oct 30;10(1):18715. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Inokuchi Hajime: None declared, Hironari Hanaoka: None declared, Kazuoto Hiramoto: None declared, Jun Kikuchi: None declared, Mitsuhiro Akiyama: None declared, Shuntaro Saito: None declared, Yasushi Kondo: None declared, Yuko Kaneko She has received research funding from Pfizer.