Cystatin C and Creatinine-Based Estimated GFR and Disease Activity Biomarkers in Rheumatoid Arthritis.

RATIONALE & OBJECTIVE: Creatinine-based estimated glomerular filtration rate (eGFRcr) and cystatin C-based eGFR (eGFRcys) may be inaccurate for patients with rheumatoid arthritis (RA) due to sarcopenia and inflammation. This study characterized changes in eGFRcys and eGFRcr after 2 RA treatment regimens and their association with RA disease activity biomarkers.

STUDY DESIGN: Secondary observational analysis of randomized controlled trial of tumor necrosis factor (TNF) inhibitor plus methotrexate (MTX) versus triple therapy (MTX, sulfasalazine, and hydroxychloroquine).

SETTING & PARTICIPANTS: Patients with active RA enrolled at multiple US institutions into an immunomodulatory treatment trial.

EXPOSURE: RA disease activity biomarkers.

OUTCOME: eGFRcys and eGFRcr at baseline and weeks 6, 18, and 24.

ANALYTICAL APPROACH: Describing eGFRcys and eGFRcr at baseline and during the follow-up period in the overall cohort and by treatment arm. Adjusted mixed-effects linear models to estimate the associations of RA activity biomarkers with eGFR.

RESULTS: The study included 157 eligible trial participants (median age, 58 years; 75% female). At baseline, the mean eGFRcys was lower than the eGFRcr (63.3 vs 84.2; difference, -20.9 mL/min/1.73 m2 [95% CI, -24.7 to -17.0]). Over 24 weeks, neither eGFRcys nor eGFRcr changed overall (1.74 mL/min/1.73 m2 [95% CI, -0.77 to 4.24] and -0.28 mL/min/1.73 m2 [95% CI, -3.71 to 3.15], respectively). Multiple disease activity biomarkers, including vascular cell adhesion protein 1, interleukin 6, tumor necrosis factor receptor 1 (TNFR1), leptin, and resistin, were inversely associated with eGFRcys and/or eGFRcr at baseline in adjusted models. During the follow-up period, only TNF-RI change was inversely associated with eGFRcys change (-2.91 mL/min/1.73 m2 [95% CI, -4.48 to -1.33]) in adjusted models whereas no biomarker change was significantly related to eGFRcr change.

LIMITATIONS: No measured GFR, a relatively short follow-up period, and potential false discovery because of the large number of associations examined.

CONCLUSIONS: Among patients with actively treated RA, eGFRcys is consistently lower than eGFRcr. Overall, neither eGFRcys nor eGFRcr demonstrated a significant change following RA treatments, despite reductions in disease activity biomarkers. Further studies incorporating directly measured GFR are warranted.

PLAIN-LANGUAGE SUMMARY: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can also affect the kidneys. Doctors often check kidney function using blood tests for creatinine or cystatin C, but inflammation and RA medications may influence these tests differently. We studied patients with RA who began either a conventional drug combination (triple therapy) or a tumor necrosis factor (TNF) inhibitor. We measured kidney function and inflammation markers over a 6-month period after the treatment. We found that both cystatin C-based and creatinine-based estimates of kidney function were unchanged overall. An analysis of trial participants who received triple therapy showed an increase in cystatin C-based kidney function, along with a decrease in 1 inflammatory biomarker, TNF receptor 1 (TNFR1); however, the creatinine-based estimates remained unchanged. Understanding how RA treatment and inflammation affect kidney function tests may help develop better ways to monitor kidney function in people with inflammatory diseases.