Patients (pts) who received methotrexate (MTX) in combination with placebo [PBO] co-therapy to pegloticase fared better in terms of urate-lowering response (71.0% vs. 38.5% during Month 6) and fared better in terms of an infusion reaction (4% vs. 31%), according to the MIRROR randomized controlled study. The effect of pegloticase+MTX co-therapy on renal function is relevant because chronic kidney disease is common among gout patients, and MTX is used with caution in CKD patients. Researchers here provide the results of a MIRROR RCT examining the effects of treatment on eGFR in patients. Patients with uncontrolled gout (serum uric acid [sUA]≥7mg/dL, ULT failure/intolerance, ≥1 gout symptom) were randomly assigned to receive either blinded oral MTX (15mg/wk) or PBO (2:1) after a 2-week MTX tolerance test and 4-week blinded MTX/PBO Run-in (eGFR<40ml/min/1.73m2 excluded). An initial eGFR was taken prior to MTX administration (Wk -6). Treatment and eGFR status (<60 and ≥60ml/min/1.73m2) at baseline were analyzed, together with the mean (SE) change from baseline (CFB) in eGFR. Each randomized patient was analyzed (ITT). Patients were divided into 2 groups: 100 received pegloticase plus MTX (56±13 yrs, 91% men, eGFR=68.9±18.0ml/min/1.73m2), while 52pts received pegloticase plus PBO (53±12 yrs, 85% men, eGFR=71.1±17.6ml/min/1.73m2). After Day 1 of pegloticase medication (MTX/PBO Run-in) and throughout the subsequent treatment period (Days 2-7), eGFR remained steady in both groups. As measured at Wk24, the eGFR CFB in the MTX (N=70; 69 responders) and PBO (N=19; 19 responders) groups were +5.31.3 and +4.32.3ml/min/1.73m2, respectively. No significant difference was found in CFB eGFR at Wk24 between eGFR60 and less than 60 and more than or equal to 60 groups in MTX (+4.1±2.4 [N=27], +6.3±1.7 [N=43] ml/min/1.73m2]) or PBO (+2.5±5.6 [N=7],+7.8±4.1 [N=12] ml/min/1.73m2]) pts (both P≥0.48). When MTX and pegloticase were used together, there was no obvious drop in eGFR after starting oral MTX. Patients with and without an eGFR of less than 60 ml/min/1.73 m2 before therapy had the same results. The results of the MIRROR RCT suggest that the addition of MTX co-therapy did not compromise renal function.