Cystatin C as a Predictor of Renal Function and Methotrexate-Associated Toxicities in Patients With Rheumatoid...

Methotrexate (MTX) is an anchor drug for most patients with rheumatoid arthritis (RA); however, its use may be limited depending on renal function. Therefore, this study aimed to examine the discrepancy in the estimated glomerular filtration rate (eGFR) using conventional serum creatinine (SCr)-, cystatin C-, and MTX-associated toxicities in patients with RA.

In total, 436 patients were enrolled, and eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on both cystatin C and SCr levels. The CKD and MTX dosing stages were classified according to eGFR. MTX-associated toxicities were also evaluated.

The mean eGFR using CKD-EPI cystatin C (CKD-EPI_cys) was 89.44 mL/min/1.73 m², lower than the eGFR using CKD-EPI SCr (CKD-EPI_SCr) of 95.55 mL/min/1.73 m². After converting eGFR to CKD-EPI_cys by CKD-EPI_SCr, 29.8% of patients were reclassified to a higher stage according to the Kidney Disease: Improving Global Outcomes CKD stage. Also, according to the MTX guidelines, 6.4% of the group with an eGFR > 50 mL/min/1.73 m² were reclassified to eGFR 10-50 mL/1.73 m², requiring dose adjustment. The incidence of MTX-associated toxicities, such as anemia, leukopenia, and nephrotoxicity, was significantly higher in the CKD stage-changed group than in the nonstage-changed group.

Our results showed that eGFR based on SCr was overestimated compared with eGFR based on cystatin C. In addition, we demonstrated that MTX-associated toxicities were significantly increased in the group with a changed stage when the eGFR was converted from CKD-EPI_SCr to CKD-EPI_cys.