ImportanceTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined.ObjectiveTo assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM.Design, Setting, and ParticipantsThis retrospective, observational, single-center cohort study evaluated patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK who underwent an eGFR baseline assessment and a follow-up assessment at 1 year between January 2000 and April 2024. Data analysis was performed in June 2024.Main Outcomes and MeasuresThe primary outcome was the risk of all-cause mortality associated with decline in kidney function (defined as a decrease in eGFR >20%).ResultsAmong 2001 patients, mean (SD) age was 75.5 (8.4) years, and 263 patients (13.1%) were female. The median (IQR) change in eGFR was −5 mlL/min/1.73 m2 (−12 to 1), and 481 patients (24.0%) experienced decline in kidney function. Patients who experienced decline in kidney function more often had the p.(V142I) genotype than patients with stable kidney function (99 [20.6%] vs 202 [13.3%]; P < .001) and had a more severe cardiac phenotype at baseline, as evidenced by higher median (IQR) concentrations of serum cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290]; P < .001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; P < .001), while baseline median (IQR) kidney function was similar between the 2 groups (eGFR: 63 mL/min/1.73 m2 [51-77] vs 61 mL/min/1.73 m2 [49-77]; P = .41). Decline in kidney function was associated with a 1.7-fold higher risk of mortality (hazard ratio [HR], 1.71; 95% CI, 1.43-2.04; P < .001), with a similar risk across the 3 genotypes (wild type: HR, 1.64; 95% CI, 1.31-2.04; p.(V142I): HR, 1.70; 95% CI, 1.21-2.39; non-p.(V142I): HR, 1.51; 95% CI, 0.87-2.61) (P for interaction = .93) and the 3 NAC disease stages (stage 1: HR, 1.69; 95% CI, 1.22-2.32; stage 2: HR, 1.69; 95% CI, 1.30-2.18; stage 3: HR, 1.61; 95% CI, 1.11-2.35) (P for interaction = .97). Decline in kidney function remained independently associated with mortality after adjusting for increases in NT-proBNP and outpatient diuretic intensification (HR, 1.48; 95% CI, 1.23-2.76; P < .001).Conclusions and RelevanceIn this retrospective cohort study, decline in kidney function was frequent in patients with ATTR-CM and was consistently associated with an increased risk of mortality, even after adjusting for established markers of worsening ATTR-CM. eGFR decline represents an independent marker of ATTR-CM disease progression that could guide treatment optimization in clinical practice.

中文翻译：

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转甲状腺素蛋白淀粉样变性心肌病的肾脏结局


重要性转甲状腺素蛋白淀粉样变性心肌病 （ATTR-CM） 是一种进行性心肌病，通常伴有慢性肾病。慢性肾功能不全与较差的结局相关，但肾功能随时间变化的预后价值尚未确定。目的评估估计肾小球滤过率 （eGFR） 下降在大型患者队列中 ATTR-CM.Design、环境和参与者的预后重要性这项回顾性、观察性、单中心队列研究评估了在英国国家淀粉样变性中心 （NAC） 诊断为 ATTR-CM 的患者，这些患者在 2000 年 1 月至 2024 年 4 月期间接受了 eGFR 基线评估和 1 年时的随访评估。数据分析于 2024 年 6 月进行。主要结局和措施主要结局是与肾功能下降相关的全因死亡风险（定义为 eGFR 降低 >20%).结果2001 例患者中，平均 （SD） 年龄为 75.5 （8.4） 岁，其中 263 例患者 （13.1%） 为女性。eGFR 的中位 （IQR） 变化为 -5 mlL/min/1.73 m2 （-12 至 1），481 例患者 （24.0%） 出现肾功能下降。肾功能下降的患者比肾功能稳定的患者更常具有 p.（V142I） 基因型 （99 [20.6%] vs 202 [13.3%];P < .001），基线时具有更严重的心脏表型，血清心脏生物标志物的中位 （IQR） 浓度较高（N 末端 B 型利钠肽前体 [NT-proBNP]：2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290];P < .001;肌钙蛋白 T：0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074];P < .001），而两组之间的基线中位肾功能 （IQR） 相似（eGFR：63 mL/min/1.73 m2 [51-77] vs 61 mL/min/1.73 m2 [49-77];P = .41）。肾功能下降与死亡风险增加 1.7 倍相关 （风险比 [HR]，1.71;95% CI，1.43-2.04;P < .001），在 3 种基因型中具有相似的风险（野生型：HR，1.64;95% CI，1.31-2.04;p.（V142I）：HR，1.70;95% CI，1.21-2.39;非 p.（V142I）：心率，1.51;95% CI，0.87-2.61）（交互作用 P = .93）和 3 个 NAC 疾病阶段（第 1 阶段：HR，1.69;95% CI，1.22-2.32;第 2 阶段：HR，1.69;95% CI，1.30-2.18;第 3 阶段：HR，1.61;95% CI，1.11-2.35）（交互作用 P = .97）。在调整了 NT-proBNP 的增加和门诊利尿剂强化后，肾功能下降仍然与死亡率独立相关 （HR，1.48;95% CI，1.23-2.76;P < .001）。结论和相关性在这项回顾性队列研究中，ATTR-CM 患者的肾功能下降很常见，并且始终与死亡风险增加相关，即使在调整了 ATTR-CM 恶化的既定标志物之后也是如此。eGFR 下降是 ATTR-CM 疾病进展的独立标志物，可指导临床实践中的治疗优化。