Hyperuricemia and gout are associated with poor outcomes in kidney transplant (KT) recipients, including graft failure. The PROspective sTudy of pEglotiCase in Transplant patients (PROTECT) trial showed high urate-lowering efficacy of pegloticase in immunosuppressed KT recipients with uncontrolled gout. Here, we report serial dual-energy computed tomography (DECT) findings in PROTECT participants.
KT recipients with uncontrolled gout (serum urate [SU] ≥7 mg/dL, refractory to/intolerant of oral urate-lowering therapy, and symptoms [≥2 flares per year, tophi, and/or gouty arthritis]) and serial DECT imaging were included. Patients were required to have an estimated glomerular filtration rate ≥15 mL/min/1.73 m ² >1 y posttransplant. All patients received pegloticase for ≤24 wk (8 mg infusion every 2 wk) and underwent imaging (screening, week 14, week 24). DECT images were acquired with standard protocols and postprocessed for monosodium urate (MSU) volume (V _MSU ) using default settings. Regions (bilateral hands/wrists, feet/ankles, knees) with paired screening/week 24 images and screening V _MSU ≥0.5 cm ³ (minimized DECT-artifact influence) were included.
Eight patients underwent DECT imaging (all men; age: 52.3 ± 11.2 y, time since KT: 18.7 ± 6.9 y, estimated glomerular filtration rate: 45.6 ± 12.4 mL/min/1.73 m ² , SU: 10.4 ± 2.1 mg/dL). Six patients (75%) completed the study and received 24 wk of pegloticase therapy, and 2 prematurely discontinued because of COVID-exposure concerns. Of the 6 patients, 4 met imaging inclusion criteria and were included in the analysis. All 4 patients had sustained SU-lowering during month 6 with marked V _MSU reduction at week 24 (mean change in V _MSU : -98.9%±1.7% [5 imaging regions]). Numerous bone erosions were present in all patients with MSU-adjacent, unknown mineral deposit-adjacent, and deposit-independent erosions. Imaging suggested osteopenia/osteomalacia in 5 patients (83%). After pegloticase treatment, MSU-adjacent erosions decreased in size in a single patient with no DECT evidence of osteopenia/osteomalacia.
Consistent with prior studies in nontransplant populations, marked depletion of deposited MSU occurred in KT recipients with uncontrolled gout after pegloticase therapy. However, unlike transplant-naive patients, subsequent bone erosion remodeling was not widely observed in urate-adjacent erosions, perhaps due to overall poor bone health in this patient population.
ClinicalTrials.gov: NCT04087720.