Dalbeth Nicola, Abdellatif Abdul, Botson John K, Saag Kenneth G, Kumar Ada, Padnick-Silver Lissa, Vranic Zana, Marder Brad A, Becce Fabio
Department of Medicine, University of Auckland, Auckland, New Zealand.
Division of Nephrology, Kidney Hypertension Transplant Clinic, Baylor College of Medicine, Houston, TX.
Transplant Direct. 2025 May 12;11(6):e1803. doi: 10.1097/TXD.0000000000001803. eCollection 2025 Jun.
BACKGROUND: 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. METHODS: 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 >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) using default settings. Regions (bilateral hands/wrists, feet/ankles, knees) with paired screening/week 24 images and screening V ≥0.5 cm (minimized DECT-artifact influence) were included. RESULTS: 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, 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 reduction at week 24 (mean change in V: -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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04087720.
背景：高尿酸血症和痛风与肾移植（KT）受者的不良预后相关，包括移植失败。移植患者聚乙二醇化尿酸酶前瞻性研究（PROTECT）试验显示，聚乙二醇化尿酸酶对免疫抑制的痛风未控制的KT受者具有较高的降尿酸疗效。在此，我们报告PROTECT参与者的系列双能计算机断层扫描（DECT）结果。 方法：纳入痛风未控制（血清尿酸[SU]≥7mg/dL，对口服降尿酸治疗难治/不耐受，且有症状[每年≥2次发作、痛风石和/或痛风性关节炎]）且进行系列DECT成像的KT受者。患者需在移植后>1年时估计肾小球滤过率≥15mL/min/1.73m²。所有患者接受聚乙二醇化尿酸酶治疗≤24周（每2周静脉输注8mg）并接受成像检查（筛查、第14周、第24周）。使用标准方案采集DECT图像，并使用默认设置对尿酸单钠（MSU）体积（V）进行后处理。纳入具有配对筛查/第24周图像且筛查V≥0.5cm³（最小化DECT伪影影响）的区域（双侧手/腕、足/踝、膝）。 结果：8例患者接受了DECT成像（均为男性；年龄：52.3±11.2岁，KT后时间：18.7±6.9年，估计肾小球滤过率：45.6±12.4mL/min/1.73m²，SU：10.4±2.1mg/dL）。6例患者（75%）完成研究并接受了24周的聚乙二醇化尿酸酶治疗，2例因担心接触新冠病毒而提前停药。在这6例患者中，4例符合成像纳入标准并纳入分析。所有4例患者在第6个月时SU持续降低，第24周时V显著降低（V的平均变化：-98.9%±1.7%[5个成像区域]）。所有患者均存在大量与MSU相邻、与未知矿物质沉积相邻以及与沉积无关的骨侵蚀。5例患者（83%）成像提示存在骨质减少/骨软化。聚乙二醇化尿酸酶治疗后，1例患者与MSU相邻的侵蚀面积减小，且无DECT证据显示存在骨质减少/骨软化。 结论：与既往在非移植人群中的研究一致，聚乙二醇化尿酸酶治疗后，痛风未控制的KT受者体内沉积的MSU明显减少。然而，与未接受过移植的患者不同，在尿酸盐相邻的侵蚀中未广泛观察到随后的骨侵蚀重塑，这可能是由于该患者群体总体骨骼健康状况较差。 临床试验注册：ClinicalTrials.gov：NCT04087720。
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