遗传性转甲状腺素蛋白淀粉样变性的短期肾功能下降的自然病程和决定因素：一项法国观察性研究。
Natural course and determinants of short-term kidney function decline in hereditary transthyretin amyloidosis: a French observational study.
机构信息
Service de Néphrologie et Transplantation, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Centre de Référence Maladie Rare 'Syndrome Néphrotique Idiopathique', Fédération Hospitalo-Universitaire 'Innovative Therapy for Immune Disorders', Créteil, France.
Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Equipe "Pathophysiology of Glomerular Diseases", Université Paris-Est Créteil, Créteil, France.
出版信息
Amyloid. 2023 Mar;30(1):38-48. doi: 10.1080/13506129.2022.2098011. Epub 2022 Jul 17.
Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their variants: ATTRV122I (37%), ATTRV30M (29%), and other variants (34%). Median baseline eGFR was 78 ml/min/1.73 m. Seventy-two patients (31%) had an eGFR below 60 ml/min/1.73m and 27/137 patients (20%) had significant proteinuria (urine protein/creatinine ratio ≥30 mg/mmol). Renal biopsy, performed in four cases, found typical Congo red-positive and TTR-labelled amyloid deposits in all cases. Older age (OR 1.07, < .001) and a prior history of hypertension (OR 2.09, = .04) were associated with a higher prevalence of CKD at baseline, whereas higher left ventricular global longitudinal strain (LVGLS) (OR 0.83, < .001) was associated with a lower prevalence. The estimated change in eGFR was -7.12 [-9.61, -4.63] and -8.21 [-10.81, -5.60] ml/min/1.73 m after 12 and 24 months of follow-up, respectively. eGFR decline was independently associated with older age ((67-74], coefficient= -14.35 mL/min/1.73 m, < .01, >74, coefficient = -22.93 mL/min/1.73 m, < .001, versus <56), ATTRV122I (coefficient = -17.17 mL/min/1.73m, < .01, versus ATTRV30M) and LVGLS (coefficient = 1.22, < .01). These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function.
关于遗传性转甲状腺素蛋白（ATTRv）淀粉样变患者肾脏受累的数据很少，该人群慢性肾脏病（CKD）的自然病程尚不清楚。这项观察性研究纳入了法国心脏淀粉样变性参考中心诊断为 ATTRv 淀粉样变性的成年患者，旨在研究肾脏功能结局及其决定因素。多变量逻辑回归模型确定了基线时 CKD 的相关因素。使用多变量线性混合效应模型评估了随访 24 个月时估算肾小球滤过率（eGFR）变化的决定因素。共纳入 232 名 ATTRv 淀粉样变性患者（78 名女性[34%]，平均年龄：64 岁），根据其变体进行分类：ATTRV122I（37%）、ATTRV30M（29%）和其他变体（34%）。中位基线 eGFR 为 78 ml/min/1.73 m。72 名患者（31%）的 eGFR 低于 60 ml/min/1.73 m，27/137 名患者（20%）有明显蛋白尿（尿蛋白/肌酐比值≥30 mg/mmol）。对 4 例患者进行的肾脏活检发现所有病例均存在典型的刚果红阳性和 TTR 标记的淀粉样沉积物。年龄较大（OR 1.07，<0.001）和既往高血压史（OR 2.09，=0.04）与基线时 CKD 患病率较高相关，而左心室整体纵向应变（LVGLS）较高（OR 0.83，<0.001）与较低的患病率相关。随访 12 个月和 24 个月后，eGFR 的估计变化分别为-7.12[-9.61，-4.63]和-8.21[-10.81，-5.60]ml/min/1.73 m。eGFR 下降与年龄较大（67-74 岁，系数=-14.35 ml/min/1.73 m，<0.01，>74 岁，系数=-22.93 ml/min/1.73 m，<0.001，<56 岁）、ATTRV122I（系数=-17.17 ml/min/1.73 m，<0.01，与 ATTRV30M 相比）和 LVGLS（系数=1.22，<0.01）独立相关。这些数据表明，CKD 在 ATTRv 淀粉样变性患者中很常见，并且在评估的第一年 eGFR 下降迅速。年龄较大、LVGLS 较低和 ATTRV122I 与较差的肾脏结局相关。现在需要进一步的研究来评估新型靶向治疗对长期肾功能的影响。
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