We showed that eGFR-Cr was more than 20% higher than eGFR-CysC in 18.9% of our cohort of RA patients. Furthermore, an overestimation of renal function when using eGFR-Cr was significantly related to lower BMI, lower Hb, lower CK, no NSAID use, diabetes mellitus, and Steinbrocker radiological stage 4.
An overestimation of renal function may occur when using eGFR-Cr for evaluation of renal function in patients with RA. In our study, a significant positive correlation was observed between eGFR-Cr and eGFR-CysC. However, 13.8% of patients with eGFR-Cr ≥ 60 ml/min/1.73 m2 showed eGFR-CysC < 60 ml/min/1.73 m2. Therefore, these patients may be at risk of having chronic kidney disease (CKD) overlooked and being treated as patients with normal renal function. This may lead to unexpected adverse effects when renally excreted drugs are used.
Lin et al. (19) reported that myopenia (sarcopenia) is very common in RA patients and associated with functional limitations and joint disorders. Torii et al. (20) found myopenia to be independently associated with age, long duration of illness, joint destruction, and malnutrition in RA. In our study, lower BMI and Steinbrocker stage 4 were identified as independent factors relevant to Group A, suggesting that Group A included more patients with myopenia. Umegaki et al. (21) and Scott et al. (22) reported that diabetic patients frequently had sarcopenia. In our study, diabetes mellitus was related to Group A, suggesting an association with sarcopenia. In recent years, the treatment of RA has progressed dramatically with the advent of bDMARDs and tsDMARDs, and the number of RA patients with myopenia has decreased. Nevertheless, our study documented a possible overestimation of renal function by more than 20% with eGFR- Cr in about 19% of RA patients, which was likely attributable to the presence of myopenia/sarcopenia. Flahault et al. (23) reported that low serum CK levels in CKD patients reflected loss of muscle mass and malnutrition and were associated with high mortality. In our study, low CK was found to be an independent factor relevant to Group A. This low CK was also considered to be associated with sarcopenia.
Some studies have reported that chronic inflammation causes renal dysfunction in RA patients. Kochi et al. (24) showed that persistently elevated CRP was related to CKD. Sumida et al. (25) reported that the use of bDMARDs reduced the risk of developing CKD, and suggested that controlling chronic inflammation might contribute to prevention of CKD. On the other hand, Couderc et al. (26) studied the risk factors of eGFR < 60 ml/min/1.73 m2 in 931 RA patients retrospectively, and reported that disease duration and disease activity (DAS28-ESR) were not related factors. In our study, univariate analysis showed Group A to have higher DAS28-ESR, CRP, and ESR than Group B, but multivariate analysis did not find them significant factors. Alternatively, our multivariate analysis indicated that anemia was associated with Group A. Masson et al. (27) reported hepcidin and interleukin-6 to be important relevant factors for anemia in RA. Thus, in our analysis, though disease activity and inflammatory markers were not found to be independent relevant factors, anemia, which could be caused by inflammation, was related to the discrepancy between eGFR-Cr and eGFR-CysC. It was suggested that disease activity and inflammatory markers may promote muscle mass reduction mediated by inflammation.
Nozawa et al. (28) noted that eGFR-CysC appeared to be lower when ≥ 10 mg/day prednisolone was administered, while not being affected by < 10 mg. In our study, Group A used prednisolone ≤ 10 mg/day (3 patients administered 10 mg/day prednisolone), and thus it was considered to have a negligible effect on eGFR-CysC.
Less frequent administration of NSAIDs was found to be related to Group A. Even though serum Cr values were similar, as Group A had higher serum CysC and BUN levels, they were judged to have clinical impairment of renal function. Thus, MTX and NDAIDs were less used in Group A. It was unlikely that medication for RA affected directly the discrepancy between eGFR-Cr and eGFR-CysC.
This study showed that 23.9% of the patients had eGFR-Cr < 60 ml/min/1.73 m2, and 41.6% had absolute eGFR-Cr < 60 ml/min. Saisho et al. (29) examined eGFR-Cr of 7135 RA patients in the Ninja study from Japan, and reported that the values of EGFR-Cr from 60 to 30, 30 to 15, and < 15 ml/min/1.73 m2 were 17.5%, 0.8%, and 0.2%, respectively. Furthermore, Mori et al. (30) reported from Japan that eGFR-Cr < 60 ml/min/1.73 m2 and absolute eGFR-Cr < 60 ml/min in RA patients were 18.6% and 33.8%, respectively. The results of these previous reports were consistent with ours with respect to BSA-indexed eGFR and absolute eGFR.
Our study had the following limitations. First, the numbers of patients might not have been sufficient. Second, outpatients with relatively stable disease control do not represent the entire RA population in terms of disease activity. Third, it was a temporary cross-sectional study.