Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer Therapies
Introduction: 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. Methods: Patients with ATTRv nephropathy (ATTRv-N) from 6 French referral centers were re...
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Elsevier
2025-06-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S246802492500172X |
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| author | Julien Dang Justine Solignac Sophie Ferlicot Charlotte Mussini Frank Bridoux Antoine Huart Marie Essig Delphine Campigli Mickaël Bobot Laurent Daniel Thibaud Damy Violaine Planté-Bordeneuve Hamza Sakhi Céline Labeyrie Cécile Cauquil Andoni Echaniz-Laguna Ilias Kounis Anissa Moktefi Perrine Devic Sarah Mouawad Albane Brodin-Sartorius Renaud Snanoudj Mohamad Zaidan Noémie Jourde-Chiche Vincent Audard |
| author_facet | Julien Dang Justine Solignac Sophie Ferlicot Charlotte Mussini Frank Bridoux Antoine Huart Marie Essig Delphine Campigli Mickaël Bobot Laurent Daniel Thibaud Damy Violaine Planté-Bordeneuve Hamza Sakhi Céline Labeyrie Cécile Cauquil Andoni Echaniz-Laguna Ilias Kounis Anissa Moktefi Perrine Devic Sarah Mouawad Albane Brodin-Sartorius Renaud Snanoudj Mohamad Zaidan Noémie Jourde-Chiche Vincent Audard |
| author_sort | Julien Dang |
| collection | DOAJ |
| description | Introduction: 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. Methods: 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. Results: 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 m2. 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 (P = 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. Conclusion: 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. |
| format | Article |
| id | doaj-art-73eff0412efb48b9b9adcb959510bb82 |
| institution | DOAJ |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-73eff0412efb48b9b9adcb959510bb822025-08-20T03:21:15ZengElsevierKidney International Reports2468-02492025-06-011061939194910.1016/j.ekir.2025.03.029Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer TherapiesJulien Dang0Justine Solignac1Sophie Ferlicot2Charlotte Mussini3Frank Bridoux4Antoine Huart5Marie Essig6Delphine Campigli7Mickaël Bobot8Laurent Daniel9Thibaud Damy10Violaine Planté-Bordeneuve11Hamza Sakhi12Céline Labeyrie13Cécile Cauquil14Andoni Echaniz-Laguna15Ilias Kounis16Anissa Moktefi17Perrine Devic18Sarah Mouawad19Albane Brodin-Sartorius20Renaud Snanoudj21Mohamad Zaidan22Noémie Jourde-Chiche23Vincent Audard24Assistance 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; AP-HP, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, France; Correspondence: Julien Dang, AP-HP, Université Versailles-Saint-Quentin, Hôpital Ambroise Paré, Service de Néphrologie et Dialyse, 9, avenue Charles de Gaulle, 92100 Boulogne-Billancourt, France.Aix-Marseille Université, C2VN, INSERM, INRAE, Marseille, France - AP-HM, Hôpital de la Conception, Service de Néphrologie et Transplantation rénale, Marseille, FranceAP-HP, Hôpital de Bicêtre, Service d’Anatomie Pathologique, Le Kremlin-Bicêtre, FranceAP-HP, Hôpital de Bicêtre, Service d’Anatomie Pathologique, Le Kremlin-Bicêtre, FranceHôpital de Poitiers, Service de Néphrologie, Hémodialyse et Transplantation rénale, Poitiers, FranceService de Néphrologie et Transplantation d’organes, Hôpital Rangueil, Toulouse, FranceAssistance 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, FranceAix-Marseille Université, C2VN, INSERM, INRAE, Marseille, France - AP-HM, Hôpital de la Conception, Service de Néphrologie et Transplantation rénale, Marseille, FranceAix-Marseille Université, C2VN, INSERM, INRAE, Marseille, France - AP-HM, Hôpital de la Conception, Service de Néphrologie et Transplantation rénale, Marseille, FranceService d’Anatomie Pathologique, Hôpital de la Conception, Marseille, FranceService de Cardiologie, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, FranceService de Neurologie, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, FranceService de Néphrologie et Transplantation, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Université Paris Est-Créteil, INSERM U955, Institut Mondor de recherche Biomédicale, Créteil, FranceService de Neurologie, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, FranceService de Neurologie, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, FranceService de Neurologie, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, FranceCentre Hépato-Biliaire, AP-HP, Hôpital Paul-Brousse, Villejuif, FranceService d’Anatomie Pathologique, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, FranceService de Neurologie, Hospices Civils de Lyon, Hôpital Lyon Sud, Lyon, FranceAP-HP, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, FranceAP-HP, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, FranceAP-HP, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, FranceAP-HP, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, FranceAix-Marseille Université, C2VN, INSERM, INRAE, Marseille, France - AP-HM, Hôpital de la Conception, Service de Néphrologie et Transplantation rénale, Marseille, FranceService de Néphrologie et Transplantation, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Université Paris Est-Créteil, INSERM U955, Institut Mondor de recherche Biomédicale, Créteil, FranceIntroduction: 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. Methods: 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. Results: 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 m2. 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 (P = 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. Conclusion: 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.http://www.sciencedirect.com/science/article/pii/S246802492500172Xgene silencinggenetic kidney diseaseglomerular diseasehereditary transthyretin amyloidosisnephrotic syndromesystemic amyloidosis |
| spellingShingle | Julien Dang Justine Solignac Sophie Ferlicot Charlotte Mussini Frank Bridoux Antoine Huart Marie Essig Delphine Campigli Mickaël Bobot Laurent Daniel Thibaud Damy Violaine Planté-Bordeneuve Hamza Sakhi Céline Labeyrie Cécile Cauquil Andoni Echaniz-Laguna Ilias Kounis Anissa Moktefi Perrine Devic Sarah Mouawad Albane Brodin-Sartorius Renaud Snanoudj Mohamad Zaidan Noémie Jourde-Chiche Vincent Audard Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer Therapies Kidney International Reports gene silencing genetic kidney disease glomerular disease hereditary transthyretin amyloidosis nephrotic syndrome systemic amyloidosis |
| title | Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer Therapies |
| title_full | Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer Therapies |
| title_fullStr | Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer Therapies |
| title_full_unstemmed | Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer Therapies |
| title_short | Kidney Outcomes in Patients With Hereditary Transthyretin Amyloid Nephropathy Treated With Transthyretin Stabilizers And Gene-Silencer Therapies |
| title_sort | kidney outcomes in patients with hereditary transthyretin amyloid nephropathy treated with transthyretin stabilizers and gene silencer therapies |
| topic | gene silencing genetic kidney disease glomerular disease hereditary transthyretin amyloidosis nephrotic syndrome systemic amyloidosis |
| url | http://www.sciencedirect.com/science/article/pii/S246802492500172X |
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