Dang Julien, Solignac Justine, Ferlicot Sophie, Mussini Charlotte, Bridoux Frank, Huart Antoine, Essig Marie, Campigli Delphine, Bobot Mickaël, Daniel Laurent, Damy Thibaud, Planté-Bordeneuve Violaine, Sakhi Hamza, Labeyrie Céline, Cauquil Cécile, Echaniz-Laguna Andoni, Kounis Ilias, Moktefi Anissa, Devic Perrine, Mouawad Sarah, Brodin-Sartorius Albane, Snanoudj Renaud, Zaidan Mohamad, Jourde-Chiche Noémie, Audard Vincent
Assistance Publique des Hôpitaux de Paris, Hôpital Ambroise Paré, Service de Néphrologie et Dialyse, Boulogne-Billancourt, France.
Université Versailles-Saint-Quentin, UFR Simone-Veil Santé, INSERM U1179, Montigny-le-Bretonneux, France.
Kidney Int Rep. 2025 Mar 24;10(6):1939-1949. doi: 10.1016/j.ekir.2025.03.029. eCollection 2025 Jun.
Kidney involvement is underestimated in patients with hereditary transthyretin amyloidosis (ATTRv), and few data are available about the renal outcomes of patients treated with targeted therapies.
Patients with ATTRv nephropathy (ATTRv-N) from 6 French referral centers were retrospectively included. The evolution of estimated glomerular filtration rate (eGFR) and proteinuria, and the specific treatments of ATTRv were collected. Renal survival was assessed by using a renal composite end point, including an eGFR decline > 50% from baseline and/or dialysis requirement.
Twenty-three patients (70% female) with a median age at ATTRv-N diagnosis of 50 (interquartile range [IQR]: 37-63) years were included. Baseline eGFR was 60 (39-83) ml/min per 1.73 m. Median urine protein-to-creatinine ratio (UPCR) was 100 (IQR: 20-240) mg/mmol. ATTRv-N was documented by kidney biopsy in 20 of 23 patients (87%). Eleven patients were treated with the transthyretin (TTR) stabilizer, tafamidis; 6 patients with a small interfering RNA (siRNA); 4 with exclusive orthotopic liver transplantation (OLT); whereas 2 received no specific treatment. After a median follow-up of 5.8 (IQR: 3.3-18.6) years, all patients with OLT or no treatment had a progressive eGFR decline, requiring dialysis in 3 of 6 patients. Among patients treated with tafamidis, 8 of 11 (73%) had a progressive eGFR decline, requiring dialysis in 1 patient; and proteinuria was either stable or increasing over time in all patients. All patients who received siRNA therapy had stable or improving eGFR. Renal survival was 44%, 44%, and 100% at 60 months for the patients with exclusive OLT or no treatment, TTR stabilizers, and siRNA, respectively ( = 0.12). Four patients with baseline nephrotic syndrome or high-grade proteinuria, including 3 patients resistant to tafamidis, responded dramatically to siRNA therapy, with a fast, complete, and sustained remission of proteinuria within 1 year.
Our study highlights the underrecognized risk of chronic kidney disease (CKD) and end-stage kidney disease in ATTRv and suggests that siRNA could be a promising therapeutic option for the stabilization of kidney function.
遗传性转甲状腺素蛋白淀粉样变性（ATTRv）患者的肾脏受累情况被低估，关于接受靶向治疗患者的肾脏结局的数据很少。
回顾性纳入来自6个法国转诊中心的ATTRv肾病（ATTRv-N）患者。收集估计肾小球滤过率（eGFR）和蛋白尿的变化情况以及ATTRv的具体治疗方法。通过使用肾脏复合终点评估肾脏生存率，该终点包括eGFR较基线下降>50%和/或需要透析。
纳入23例患者（70%为女性），ATTRv-N诊断时的中位年龄为50岁（四分位间距[IQR]：37 - 63岁）。基线eGFR为60（39 - 83）ml/（min·1.73m²）。尿蛋白与肌酐比值（UPCR）中位数为100（IQR：20 - 240）mg/mmol。23例患者中有20例（87%）通过肾脏活检确诊为ATTRv-N。11例患者接受转甲状腺素蛋白（TTR）稳定剂tafamidis治疗；6例接受小干扰RNA（siRNA）治疗；4例接受单纯原位肝移植（OLT）；2例未接受特异性治疗。中位随访5.8（IQR：3.3 - 18.6）年后，所有接受OLT或未治疗的患者eGFR均进行性下降，6例中有3例需要透析。在接受tafamidis治疗的患者中，11例中有8例（73%）eGFR进行性下降，1例需要透析；所有患者的蛋白尿随时间稳定或增加。所有接受siRNA治疗的患者eGFR稳定或改善。单纯OLT患者、TTR稳定剂治疗患者和siRNA治疗患者在6个月时的肾脏生存率分别为44%、44%和100%（P = 0.12）。4例基线为肾病综合征或重度蛋白尿的患者，包括3例对tafamidis耐药的患者，对siRNA治疗反应显著。蛋白尿在1年内快速、完全且持续缓解。
我们的研究强调了ATTRv患者中未被充分认识的慢性肾脏病（CKD）和终末期肾病风险，并表明siRNA可能是稳定肾功能的一种有前景的治疗选择。
