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Rheumatoid arthritis (RA) is a systemic inflammatory disease, with impacts beyond the affected joints. The association of RA with chronic kidney disease (CKD) is common yet often overlooked, limiting clinicians鈥� efforts to manage progressive renal dysfunction in these patients.

In light of this, a new study conducted by researchers in the U.S. and Japan examined the relationship between level of RA disease activity and progressive impairments in renal function. Their findings were recently published in the journal Annals of the Rheumatic Diseases.¹

Tracking RA disease activity

Participants in the study were identified using CorEvitas RA registry data, which includes information on disease characteristics, disease activity, treatment and adverse events, patient demographics, and comorbidities.¹ Data collection from this prospective observational cohort started at enrollment in October 2001 (with follow-up visits, usually every 6 months) and continued through last visit or until September 2022. In total, 31,129 patients with 鈮�2 recorded visits and complete data were included.

RA disease activity was scored on the time-averaged Clinical Disease Activity Index (CDAI), which was updated at each visit to determine cumulative disease activity, using standard cutoffs of 鈮�2.8 for remission, >2.8 to 10.0 for low disease activity, >10.0 to 22.0 for moderate disease activity, and >22.0 for high disease activity.

The investigators also assessed disease activity using the Disease Activity Score C-Reactive Protein (DAS-CRP), averaged over time. On this measure, activity was scored as in remission (鈮�2.6), low (>2.6 to 3.2), moderate (>3.2 to 5.1), or high (>5.1). Data were adjusted for demographics, disease duration, and estimated glomerular filtration rate (eGFR) at baseline.

Factors that could change over time were updated at every visit and included body mass index (BMI), comorbidities, treatment regimens, and smoking status. Multivariable mixed-effect linear regression was used to estimate the primary outcome鈥攃hange in eGFR from enrollment鈥攁nd subgroup analyses of demographics and other factors. Kaplan-Meier survival analyses and Cox proportional hazard regressions were used for the secondary outcome: development of Kidney Disease: Improving Global Outcomes (KDIGO) CKD stage 3a or worse (eGFR <60 mL/min/1.73 m2 for more than 3 months) and stage 3b or worse (eGFR <45 mL/min/1.73 m2 for more than 3 months).

The details

The main analysis included patients with any level of disease activity whose eGFR was 鈮�60 mL/min/1.73 m2 at enrollment (median age 58 years, 76.3% female, 82.3% White). From the total patient population, 6647 were in remission, 10,028 had low disease activity, 8548 had moderate disease activity, and 5906 had high disease activity, using CDAI definitions. Patients with higher levels of disease activity tended to have more comorbidities鈥攊ncluding hypertension鈥攁nd to be using slightly more treatments, including biologics and Janus kinase (JAK) inhibitors, at the time of study enrollment.

Longitudinal change in eGFR from enrollment was calculated using the CKD Epidemiology Collaboration (CKD-EPI) equation, which is independent of race and recommended by the National Kidney Foundation.^1,2 Over time, patients with higher levels of RA disease activity had a more acute slope of decline in eGFR.¹ Compared with patients who were in remission at baseline, the incremental additive mean rate of decline per year with high disease activity was 鈥�0.18 (95% confidence interval [CI] 鈥�0.27 to 鈥�0.08). For those with moderate disease activity, the decline was 鈥�0.17 (95% CI 鈥�0.23 to 鈥�0.10); for patients with low disease activity, it was 鈥�0.09 (95% CI 鈥�0.15 to 鈥�0.03).

Subgroup analyses were similar in that higher disease activity correlated with more eGFR decline, across variables including age, sex, BMI, baseline eGFR, disease duration, and type of therapy, leading the study authors to note that 鈥淩A disease activity itself may be associated with accelerated kidney function decline.鈥�¹

In terms of secondary outcomes, patients with higher disease activity again were more likely to progress to more severe CKD. With a median follow-up time of 3.5 years, the likelihood of progression to KDIGO stage 3a in patients with high disease activity versus remission was 1.27 (95% CI 1.05 to 1.52); for KDIGO Stage 3b, it was 1.93 (95% CI 1.16 to 3.20). Patients with moderate or low disease activity also were more likely to progress compared with patients in remission.

Limitations and conclusions

Despite these intriguing findings, the study was limited in some respects. For one, the investigators didn鈥檛 collect data on the severity of comorbidities, which may have introduced residual confounding. The same could be said for the types, doses, and frequency of use of nonsteroidal anti-inflammatory drugs. And, as the authors stated, 鈥渟ince our registry does not collect data on urinalyses and kidney biopsies, the cause and structural correlates of the decline in eGFR, as well as the longitudinal association of RA activity with albuminuria, cannot be determined.鈥�¹

So, what should clinicians take away from this large prospective observational study? The bottom line is that patients with any level of RA disease activity are at increased risk for more-rapid declines in eGFR or progression to KDIGO stage 3a or 3b CKD. In fact, one of the more interesting findings was that the effect of RA disease activity on eGFR was more pronounced in those with unimpaired kidney function at baseline than in those with established CKD, suggesting the importance of early intervention to control RA disease activity.

As the authors succinctly concluded, 鈥淭his study suggests that controlling disease activity may potentially contribute to preserving kidney function in patients with RA.鈥�¹ As such, they recommend further studies to elucidate the role of different therapies and treatment strategies in kidney function preservation. 

Published: October 24, 2024