Medicine
®
OBSERVATIONAL STUDY
Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease A Retrospective Study of 10 Cases Maxime Dauvergne, MD, Anissa Moktefi, MD, Marion Rabant, MD, PhD, Ce´cile Vigneau, MD, PhD, Tomek Kofman, MD, Stephane Burtey, MD, PhD, Christophe Corpechot, MD, PhD, Thomas Stehle´, MD, Dominique Desvaux, MD, Nathalie Rioux-Leclercq, MD, Philippe Rouvier, MD, PhD, Bertrand Knebelmann, MD, PhD, Jean-Jacques Boffa, MD, PhD, Thierry Frouget, MD, Eric Daugas, MD, PhD, Mathieu Jablonski, MD, Karine Dahan, MD, Isabelle Brocheriou, MD, PhD, Philippe Remy, MD, Philippe Grimbert, MD, PhD, Philippe Lang, MD, PhD, Oliver Chazouilleres, MD, PhD, Dil Sahali, MD, PhD, and Vincent Audard, MD, PhD
Abstract: The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.
Editor: Sanket Patel. Received: May 8, 2015; revised: June 17, 2015; accepted: July 2, 2015. From the Service de Ne´phrologie et Transplantation (MD, TK, TS, PR, PG, PL, DS, VA), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Centre de re´fe´rence maladie rare Syndrome Ne´phrotique Idiopathique, Institut Francilien de recherche en Ne´phrologie et Transplantation (IFRNT), DHU VIC (Virus-Immunite´-Cancer), AP-HP (Assistance Publique–Hoˆpitaux de Paris), Universite´ Paris Est Cre´teil (UPEC), Cre´teil, France; Equipe 21 (MD, AM, TK, TS, DD, PG, PL, DS, VA), INSERM Unite´ 955, Universite´ Paris Est Cre´teil, Cre´teil, France; De´partement de Pathologie (AM, DD), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, AP-HP, UPEC, Cre´teil, France; Service d’Anatomie pathologique (MR), Hoˆpital Necker - Enfants Malades, AP-HP, Universite´ Paris Descartes, Paris, France; CHU Pontchaillou (CV, TF), Service de Ne´phrologie, Universite´ de Rennes, Rennes, France; Service de Ne´phrologie et de Transplantation Re´nale (SB), Hoˆpital de la Conception, AP-HM, Aix-Marseille Universite´, Marseille, France; Centre de Re´fe´rence Maladies Rares des Maladies Inflammatoires des Voies Biliaires & Service d’He´patologie (CC, OC), Hoˆpital SaintAntoine, Centre de Re´fe´rence Maladies Rares des Maladies Inflammatoires des Voies Biliaires & Service d’He´patologie; Inserm, UMR-S 938, Centre de Recherche Saint-Antoine; AP-HP, Sorbonne Universite´s, Universite´ Pierre et Marie Curie (UPMC), Paris, France; CHU Pontchaillou (N R-L), Service d’Anatomie Pathologie, Universite´ de Rennes, Rennes, France; Service d’Anatomie pathologique (PR), Hoˆpital de la Pitie´-Salpe´trie`re, APHP, UPMC, Paris, France; Service de Ne´phrologie et Dialyse (BK), Hoˆpital Necker-Enfants Malades, AP-HP, Universite´ Paris Descartes, Paris, France; Service de Ne´phrologie et Dialyses (J-J B, KD), Hoˆpital Tenon, AP-HP, UMPC, Paris, France; Service de Ne´phrologie (ED, MJ), Groupe hospitalier Bichat/Claude-Bernard, AP-HP, Universite´ Paris Diderot, Paris, France; Service d’Anatomie pathologique (IB), Hoˆpital Tenon, AP-HP, UPMC, Paris, France. Correspondence: Vincent Audard, Department of Nephrology and Transplantation, Henri Mondor Hospital, AP-HP, Institut Francilien de Recherche en Ne´phrologie et Transplantation (IFRNT), Universite´ Paris Est Cre´teil, Cre´teil F-94010, France (e-mail: [email protected]). MD and AM contributed equally to this work. The authors have no funding and conflicts of interest to disclose. Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000001243
Medicine
Volume 94, Number 30, July 2015
We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens. The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was 18 years) were retrospectively identified. Demographic, clinical, biological, and histological data were assessed for each patient at the time of MN diagnosis.
MN Diagnosis All patients included in this study underwent a renal biopsy for a nephrotic syndrome (NS) or a significant proteinuria (albumin excretion rate of >0.3 g/d). Immunofluorescence (IF) on renal biopsies was performed using monoclonal antibodies specific for IgG1, IgG2, IgG3, and IgG4 (SigmaAldrich : Saint Louis, MO, USA; 1 in 30 dilution). IF staining intensity was graded on a scale of 0 to 3þ by one observer (A.M.). In one case with interstitial nephritis associated with glomerular lesions, IgG4 labeling was performed by immunohistochemistry (monoclonal antibody against human IgG4, binding site; 1:200 dilution). Reduced kidney function was defined as a permanent (at least 3 months) decrease of
2
| www.md-journal.com
Volume 94, Number 30, July 2015
estimated glomerular filtration rate (eGFR) to
®
OBSERVATIONAL STUDY
Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease A Retrospective Study of 10 Cases Maxime Dauvergne, MD, Anissa Moktefi, MD, Marion Rabant, MD, PhD, Ce´cile Vigneau, MD, PhD, Tomek Kofman, MD, Stephane Burtey, MD, PhD, Christophe Corpechot, MD, PhD, Thomas Stehle´, MD, Dominique Desvaux, MD, Nathalie Rioux-Leclercq, MD, Philippe Rouvier, MD, PhD, Bertrand Knebelmann, MD, PhD, Jean-Jacques Boffa, MD, PhD, Thierry Frouget, MD, Eric Daugas, MD, PhD, Mathieu Jablonski, MD, Karine Dahan, MD, Isabelle Brocheriou, MD, PhD, Philippe Remy, MD, Philippe Grimbert, MD, PhD, Philippe Lang, MD, PhD, Oliver Chazouilleres, MD, PhD, Dil Sahali, MD, PhD, and Vincent Audard, MD, PhD
Abstract: The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.
Editor: Sanket Patel. Received: May 8, 2015; revised: June 17, 2015; accepted: July 2, 2015. From the Service de Ne´phrologie et Transplantation (MD, TK, TS, PR, PG, PL, DS, VA), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Centre de re´fe´rence maladie rare Syndrome Ne´phrotique Idiopathique, Institut Francilien de recherche en Ne´phrologie et Transplantation (IFRNT), DHU VIC (Virus-Immunite´-Cancer), AP-HP (Assistance Publique–Hoˆpitaux de Paris), Universite´ Paris Est Cre´teil (UPEC), Cre´teil, France; Equipe 21 (MD, AM, TK, TS, DD, PG, PL, DS, VA), INSERM Unite´ 955, Universite´ Paris Est Cre´teil, Cre´teil, France; De´partement de Pathologie (AM, DD), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, AP-HP, UPEC, Cre´teil, France; Service d’Anatomie pathologique (MR), Hoˆpital Necker - Enfants Malades, AP-HP, Universite´ Paris Descartes, Paris, France; CHU Pontchaillou (CV, TF), Service de Ne´phrologie, Universite´ de Rennes, Rennes, France; Service de Ne´phrologie et de Transplantation Re´nale (SB), Hoˆpital de la Conception, AP-HM, Aix-Marseille Universite´, Marseille, France; Centre de Re´fe´rence Maladies Rares des Maladies Inflammatoires des Voies Biliaires & Service d’He´patologie (CC, OC), Hoˆpital SaintAntoine, Centre de Re´fe´rence Maladies Rares des Maladies Inflammatoires des Voies Biliaires & Service d’He´patologie; Inserm, UMR-S 938, Centre de Recherche Saint-Antoine; AP-HP, Sorbonne Universite´s, Universite´ Pierre et Marie Curie (UPMC), Paris, France; CHU Pontchaillou (N R-L), Service d’Anatomie Pathologie, Universite´ de Rennes, Rennes, France; Service d’Anatomie pathologique (PR), Hoˆpital de la Pitie´-Salpe´trie`re, APHP, UPMC, Paris, France; Service de Ne´phrologie et Dialyse (BK), Hoˆpital Necker-Enfants Malades, AP-HP, Universite´ Paris Descartes, Paris, France; Service de Ne´phrologie et Dialyses (J-J B, KD), Hoˆpital Tenon, AP-HP, UMPC, Paris, France; Service de Ne´phrologie (ED, MJ), Groupe hospitalier Bichat/Claude-Bernard, AP-HP, Universite´ Paris Diderot, Paris, France; Service d’Anatomie pathologique (IB), Hoˆpital Tenon, AP-HP, UPMC, Paris, France. Correspondence: Vincent Audard, Department of Nephrology and Transplantation, Henri Mondor Hospital, AP-HP, Institut Francilien de Recherche en Ne´phrologie et Transplantation (IFRNT), Universite´ Paris Est Cre´teil, Cre´teil F-94010, France (e-mail: [email protected]). MD and AM contributed equally to this work. The authors have no funding and conflicts of interest to disclose. Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000001243
Medicine
Volume 94, Number 30, July 2015
We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens. The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was 18 years) were retrospectively identified. Demographic, clinical, biological, and histological data were assessed for each patient at the time of MN diagnosis.
MN Diagnosis All patients included in this study underwent a renal biopsy for a nephrotic syndrome (NS) or a significant proteinuria (albumin excretion rate of >0.3 g/d). Immunofluorescence (IF) on renal biopsies was performed using monoclonal antibodies specific for IgG1, IgG2, IgG3, and IgG4 (SigmaAldrich : Saint Louis, MO, USA; 1 in 30 dilution). IF staining intensity was graded on a scale of 0 to 3þ by one observer (A.M.). In one case with interstitial nephritis associated with glomerular lesions, IgG4 labeling was performed by immunohistochemistry (monoclonal antibody against human IgG4, binding site; 1:200 dilution). Reduced kidney function was defined as a permanent (at least 3 months) decrease of
2
| www.md-journal.com
Volume 94, Number 30, July 2015
estimated glomerular filtration rate (eGFR) to
