title: Current anti-myeloma therapies in renal manifestations of monoclonal light chain-associated Fanconi syndrome: a retrospective series of 49 patients.
abstract: We retrospectively reviewed 49 patients with light chain (LC) Fanconi syndrome (FS). Patients presented with chronic kidney disease (median estimated glomerular filtration rate (eGFR) of 33 ml/min/1.73 m2) and tubular proteinuria. All patients tested had elevated fractional excretion of phosphate, uric acid, generalized aminoaciduria and/or normoglycemic glycosuria. Thirty-eight patients had monoclonal gammopathy of renal significance and eleven patients had an overt hematological malignancy. The monoclonal LC isotype was kappa in 46/49 cases. Kidney biopsy in 39 patients showed various proximal tubular lesions and characteristic LC intracytoplasmic crystalline inclusions in 24 patients. Forty-two patients received chemotherapy. Patients with plasma cell proliferation (n=38) received bortezomib-based regimens (n=11), immunomodulatory agents (n=7) or alkylating agents (n=6). High-dose melphalan (HDM) followed by autologous stem cell transplantation was performed in 14 patients. Hematological response was obtained in 90% of evaluable patients, assessed on serum free light chains (FLC). GFR remained stable as long as hematological response was maintained and declined when serum FLC level rebounded. Improvement in proximal tubule function occurred in 13 patients. In patients with LC-associated FS, chemotherapy using HDM and/or new generation anti-myeloma agents can stabilize renal function and improve proximal tubule function. Serum FLC should be used to assess the hematological response, related to renal outcome.
authors.affiliation: Department of Hematology and Clinical Immunology, INSERM UMR 1126 Institut Universitaire d'Hématologie, Saint Louis University Hospital, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Vignon
authors.affiliation: Department of Nephrology, Dialysis and Renal Transplantation, Centre de référence amylose AL et autres maladies par dépôts d'immunoglobuline monoclonales, University Hospital of Poitiers, Poitiers, France.
authors.forename: V
authors.initials: V
authors.lastname: Javaugue
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Alexander
authors.affiliation: Department of Nephrology, Necker University Hospital, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: El-Karoui
authors.affiliation: Department of Nephrology, Georges Pompidou University Hospital, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Karras
authors.affiliation: Department of Hematology, Pitié-Salpétrière University Hospital, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Roos-Weil
authors.affiliation: Department of Hematology, University Hospital of Amiens, Amiens, France.
authors.forename: B
authors.initials: B
authors.lastname: Royer
authors.affiliation: Department of Hematology and Clinical Immunology, INSERM UMR 1126 Institut Universitaire d'Hématologie, Saint Louis University Hospital, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Asli
authors.affiliation: Department of Nephrology, Necker University Hospital, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Knebelmann
authors.affiliation: Departments of Nephrology and Ultrastructural Pathology, Centre national de référence amylose AL et autres maladies par dépôts d'immunoglobulines monoclonales, University Hospital of Poitiers, Poitiers, France.
authors.forename: G
authors.initials: G
authors.lastname: Touchard
authors.affiliation: Department of Hematology, Centre national de référence amylose AL et autres maladies par dépots d'immunoglobulines monoclonales, University Hospital of Limoges, Limoges, France.|Department of Immunology, National Center for Scientific Research, Joint Research Unit 7276, University of Limoges, Centre de référence de l'amylose AL et des autres maladies par dépôts d'immunoglobuline monoclonale, Limoges, France.
authors.forename: A
authors.initials: A
authors.lastname: Jaccard
authors.affiliation: Department of Hematology and Clinical Immunology, INSERM UMR 1126 Institut Universitaire d'Hématologie, Saint Louis University Hospital, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Arnulf
authors.affiliation: Department of Nephrology, Dialysis and Renal Transplantation, Centre de référence amylose AL et autres maladies par dépôts d'immunoglobuline monoclonales, University Hospital of Poitiers, Poitiers, France.|Department of Immunology, National Center for Scientific Research, Joint Research Unit 7276, University of Limoges, Centre de référence de l'amylose AL et des autres maladies par dépôts d'immunoglobuline monoclonale, Limoges, France.
authors.forename: F
authors.initials: F
authors.lastname: Bridoux
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: N
authors.initials: N
authors.lastname: Leung
authors.affiliation: Department of Hematology and Clinical Immunology, INSERM UMR 1126 Institut Universitaire d'Hématologie, Saint Louis University Hospital, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Fermand
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005198:Fanconi Syndrome / Q000628:therapy*; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007147:Immunoglobulin Light Chains; D007674:Kidney Diseases; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007147:Immunoglobulin Light Chains