Sophie Chauvet1, Frank Bridoux2, Laure Ecotière1, Vincent Javaugue1, Christophe Sirac3, Bertrand Arnulf4, Antoine Thierry1, Nathalie Quellard5, Serge Milin6, Sébastien Bender3, Jean-Michel Goujon5, Arnaud Jaccard7, Jean-Paul Fermand4, Guy Touchard1. 1. Centre national de référence maladies rares amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, CHU Poitiers, Université de Poitiers, Poitiers, France; Department of Nephrology, Hôpital Jean Bernard, CHU Poitiers, Université de Poitiers, Poitiers, France. 2. Centre national de référence maladies rares amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, CHU Poitiers, Université de Poitiers, Poitiers, France; Department of Nephrology, Hôpital Jean Bernard, CHU Poitiers, Université de Poitiers, Poitiers, France; CNRS UMR 6101, Université de Limoges, Limoges, France. Electronic address: f.bridoux@chu-poitiers.fr. 3. Centre national de référence maladies rares amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, CHU Poitiers, Université de Poitiers, Poitiers, France; CNRS UMR 6101, Université de Limoges, Limoges, France. 4. Department of Immunology and Hematology, Hôpital Saint-Louis AP-HP, Paris, France. 5. Centre national de référence maladies rares amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, CHU Poitiers, Université de Poitiers, Poitiers, France; Department of Pathology, Hôpital Jean Bernard, CHU Poitiers, Université de Poitiers, Poitiers, France. 6. Department of Pathology, Hôpital Jean Bernard, CHU Poitiers, Université de Poitiers, Poitiers, France. 7. Centre national de référence maladies rares amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, CHU Poitiers, Université de Poitiers, Poitiers, France; CNRS UMR 6101, Université de Limoges, Limoges, France; Department of Hematology, CHU Limoges, Université de Limoges, Limoges, France.
Abstract
BACKGROUND: Kidney diseases associated with immunoglobulin M (IgM) monoclonal gammopathy are poorly described, with few data for patient outcomes and renal response. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 35 patients from 8 French departments of nephrology were retrospectively studied. Inclusion criteria were: (1) detectable serum monoclonal IgM, (2) estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m(2) and/or proteinuria with protein excretion > 0.5g/d and/or microscopic hematuria, and (3) kidney biopsy showing monoclonal immunoglobulin deposits and/or lymphomatous B-cell renal infiltration. All patients received chemotherapy, including rituximab-based regimens in 8 cases. PREDICTORS: Patients were classified into 3 groups according to renal pathology: glomerular AL amyloidosis (group 1; n=11), nonamyloid glomerulopathies (group 2; n=15, including 9 patients with membranoproliferative glomerulonephritis), and tubulointerstitial nephropathies (group 3; n=9, including cast nephropathy in 5, light-chain Fanconi syndrome in 3, and isolated tumor infiltration in 1). OUTCOMES: Posttreatment hematologic response (≥50% reduction in serum monoclonal IgM and/or free light chain level) and renal response (≥50% reduction in 24-hour proteinuria or eGFR≥30mL/min/1.73m(2) in patients with glomerular and tubulointerstitial disorders, respectively). RESULTS: Nephrotic syndrome was observed in 11 and 6 patients in groups 1 and 2, respectively. Patients in group 3 presented with acute kidney injury (n=7) and/or proximal tubular dysfunction (n=3). Waldenström macroglobulinemia was present in 26 patients (8, 12, and 6 in groups 1, 2, and 3, respectively). Significant lymphomatous interstitial infiltration was observed in 18 patients (4, 9, and 5 patients, respectively). Only 9 of 29 evaluable patients had systemic signs of symptomatic hematologic disease (2, 5, and 2, respectively). In groups 1, 2, and 3, respectively, hematologic response was achieved after first-line treatment in 3 of 9, 9 of 10, and 5 of 6 evaluable patients, while renal response occurred in 5 of 10, 9 of 15, and 5 of 8 evaluable patients. LIMITATIONS: Retrospective study; insufficient population to establish the impact of chemotherapy. CONCLUSIONS: IgM monoclonal gammopathy is associated with a wide spectrum of renal manifestations, with an under-recognized frequency of tubulointerstitial disorders.
BACKGROUND:Kidney diseases associated with immunoglobulin M (IgM) monoclonal gammopathy are poorly described, with few data for patient outcomes and renal response. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 35 patients from 8 French departments of nephrology were retrospectively studied. Inclusion criteria were: (1) detectable serum monoclonal IgM, (2) estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m(2) and/or proteinuria with protein excretion > 0.5g/d and/or microscopic hematuria, and (3) kidney biopsy showing monoclonal immunoglobulin deposits and/or lymphomatous B-cell renal infiltration. All patients received chemotherapy, including rituximab-based regimens in 8 cases. PREDICTORS: Patients were classified into 3 groups according to renal pathology: glomerular AL amyloidosis (group 1; n=11), nonamyloid glomerulopathies (group 2; n=15, including 9 patients with membranoproliferative glomerulonephritis), and tubulointerstitial nephropathies (group 3; n=9, including cast nephropathy in 5, light-chain Fanconi syndrome in 3, and isolated tumor infiltration in 1). OUTCOMES: Posttreatment hematologic response (≥50% reduction in serum monoclonal IgM and/or free light chain level) and renal response (≥50% reduction in 24-hour proteinuria or eGFR≥30mL/min/1.73m(2) in patients with glomerular and tubulointerstitial disorders, respectively). RESULTS:Nephrotic syndrome was observed in 11 and 6 patients in groups 1 and 2, respectively. Patients in group 3 presented with acute kidney injury (n=7) and/or proximal tubular dysfunction (n=3). Waldenström macroglobulinemia was present in 26 patients (8, 12, and 6 in groups 1, 2, and 3, respectively). Significant lymphomatous interstitial infiltration was observed in 18 patients (4, 9, and 5 patients, respectively). Only 9 of 29 evaluable patients had systemic signs of symptomatic hematologic disease (2, 5, and 2, respectively). In groups 1, 2, and 3, respectively, hematologic response was achieved after first-line treatment in 3 of 9, 9 of 10, and 5 of 6 evaluable patients, while renal response occurred in 5 of 10, 9 of 15, and 5 of 8 evaluable patients. LIMITATIONS: Retrospective study; insufficient population to establish the impact of chemotherapy. CONCLUSIONS: IgM monoclonal gammopathy is associated with a wide spectrum of renal manifestations, with an under-recognized frequency of tubulointerstitial disorders.
Authors: M Vignon; V Javaugue; M P Alexander; K El-Karoui; A Karras; D Roos-Weil; B Royer; B Asli; B Knebelmann; G Touchard; A Jaccard; B Arnulf; F Bridoux; N Leung; J P Fermand Journal: Leukemia Date: 2016-07-20 Impact factor: 11.528
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