This study aims to classify long-term renal evolution in RA patients via DTW-based clustering. We further compared baseline profiles and disease progression features across these identified groups to uncover key clinical determinants of renal decline.

This single-center prospective cohort study included RA patients (aged ≥18 years, fulfilling the 2010 ACR/EULAR criteria) with at least three serum measurements between January 2015 and December 2024. Patients with missing baseline data or pre-existing renal insufficiency were excluded. eGFR was calculated using the CKD-EPI 2021 creatinine equation. Clinical data, including disease activity (CDAI/DAS28), treatments, and comorbidities, were recorded at months 3, 6, 12, and annually thereafter, with additional visits as clinically indicated. We performed time-series clustering using Dynamic Time Warping (DTW) as the distance metric to identify distinct eGFR trajectories. Annualized eGFR decline rates were compared across clusters using the Mann-Whitney U test.

A total of 1031 RA patients were enrolled with a mean follow-up of 9.9 visits.  Among these patients, the median age was 51 years, 83.6% were women, and the median disease duration was 3.5 years. Based on longitudinal eGFR patterns over a maximum follow-up of 10 years, four distinct trajectory subgroups were identified (Figure 1A): Improving (n=366, 35.5%), Stable (n=273, 26.5%), Fluctuating (n=216, 21.0%), and Rapid Decline (n=176, 17.1%).  The Rapid Decline group, which exhibited a significantly steeper negative annual eGFR slope compared to other clusters (P<0.001， Figure 1B), was characterized by older age (55.5 years), a higher smoking rate (23.3%), and the highest baseline disease burden, including elevated TJC28 (6.0), CDAI (20.0), and HAQ-DI (0.8) scores (all P<0.001). Furthermore, systemic inflammatory markers were most pronounced in the Rapid Decline cluster (ESR: 49.6 mm/h; CRP: 15.4 mg/L) and lowest in the Improving cluster (ESR: 37.0 mm/h; CRP: 7.4 mg/L), reflecting a clear association between baseline inflammation and subsequent renal function deterioration (P=0.003 for ESR, P<0.001 for CRP，Table 1) .

This study identifies four distinct long-term eGFR trajectory patterns in RA patients, highlighting significant heterogeneity in renal function evolution. A high baseline inflammatory burden and advanced disease activity are key indicators of a rapid decline in renal function. These findings emphasize the necessity of early, intensive anti-inflammatory intervention and regular renal monitoring, particularly for patients exhibiting high disease activity at baseline, to mitigate the risk of long-term renal impairment in rheumatoid arthritis