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Front Med (Lausanne) 2020 13;7:609582. Epub 2021 Jan 13.

Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.

Overproduction of human light chains (LCs) and immunoglobulins can result in various forms of renal disease such as cast nephropathy, monoclonal immunoglobulin deposition disease, LC proximal tubulopathy, AL amyloidosis, and crystal storing histiocytosis. This is caused by cellular uptake of LCs and overwhelmed intracellular transport and degradation in patients with high urine LC concentrations. LC kappa and lambda purification was evaluated by sodium dodecyl sulfate gel electrophoresis. Read More

Ultrastruct Pathol 2020 Nov 1;44(4-6):387-394. Epub 2020 Nov 1.

Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina , Charleston, SC, USA.

I and animal models of monoclonal light chain-associated renal diseases are limited. The Vk*MYC transgenic model with multiple myeloma in 50-70 weeks old mice with renal involvement has been reported before, but detailed renal pathologic changes have not been well documented. This study fully investigated pathologic changes in the kidneys of Vk*MYC transgenic model using light microscopy, immunofluorescence stains for kappa and lambda light chains, and electron microscopy. Read More

Arch Pathol Lab Med 2021 03;145(3):352-358

From the Université de Lille, CNRS, Inserm, CHU Lille, Pathology Department, Centre de Biologie Pathologie, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France (Gibier, Gnemmi).

Context.—: Distinguishing the different types of amyloid is clinically important because treatments and outcomes are different. Mass spectrometry is the new gold standard for amyloid typing, but it is costly and not widely available. Read More

Nephron 2020 4;144(4):190-194. Epub 2020 Feb 4.

Department of Nephrology, The Mater Hospital, North Sydney, New South Wales, Australia.

Monoclonal immunoglobulin or free light chains, produced in the setting of plasma cell dyscrasias, are a common cause of kidney injury with a wide variety of disease patterns. Light-chain proximal tubulopathy is a rare form of this disease that is often difficult to diagnose due to its relatively indolent presentation, subtle light microscopic findings, and often negative immunofluorescence using routine laboratory techniques. We report a case of light-chain proximal tubulopathy with cytoplasmic fibrillary inclusions in tubular cells, glomerular endothelial cells, and mesangial cells, which were positive for κ light chains on immunostaining after pronase digestion. Read More

PeerJ 2019 2;7:e7819. Epub 2019 Oct 2.

Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.

Background: Monoclonal overproduction of kappa and/or lambda light chains might result in renal light chain deposition disease. Light chain associated cast nephropathy and renal AL-amyloidosis represent two further pathologies going along with monoclonal gammopathy of renal significance and multiple myeloma. While cast nephropathy often manifests with acute kidney injury, AL-amyloidosis is rather accompanied with chronic kidney disease. Read More

Arch Pathol Lab Med 2019 10 7;143(10):1212-1224. Epub 2019 May 7.

From the Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento (Dr Cheng); and the Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport (Drs Gu, Turbat-Herrera, and Herrera).

Context.—: Light chain-associated acute tubulointerstitial nephritis (LC-ATIN) is a variant of light chain proximal tubulopathy (LCPT). It is characterized by interstitial inflammation with tubulitis and deposition of monoclonal light chains in the tubulointerstitium. Read More

J Nippon Med Sch 2019 ;86(1):2-9

Department of Analytic Human Pathology, Nippon Medical School.

Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum, causing monoclonal gammopathy, which leads to various diseases including renal diseases. Therefore, monoclonal gammopathy is frequently associated with kidney diseases, including glomerular and tubulointerstitial diseases. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease (MIDD), AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), immunotactoid glomerulopathy, and fibrillary glomerulonephritis. Read More

Ann Hematol 2019 May 4;98(5):1095-1100. Epub 2018 Dec 4.

Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Light chain-associated Fanconi syndrome (LCFS) is a disorder of renal proximal tubule due to immunoglobulin light chains. Cases of LCFS are rare and mostly sporadically reported, and treatment of this entity is still controversial. This single-center retrospective study included 22 patients diagnosed with LCFS in Peking Union Medical College Hospital. Read More

Ultrastruct Pathol 2018 May-Jun;42(3):262-288. Epub 2018 Apr 18.

d Departments of Pathology and Translational Pathobiology , Medicine, and Cell Biology and Anatomy, Louisiana State Health Sciences Center , Shreveport , LA , USA.

Mesangiopathies produced by glomerulopathic monoclonal immunoglobulin light chains (GLCs) acting on the glomerular mesangium produce two characteristic lesions: AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD). In both cases, the pathology is centered in the mesangium, where initial and progressive damage occurs. In AL-Am the mesangial matrix is destroyed and replaced by amyloid fibrils and in LCDD, the mesangial matrix is increased and remodeled. Read More

Pediatr Int 2017 Dec 4;59(12):1281-1282. Epub 2017 Dec 4.

Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.

Biomedica 2016 Dec 1;36(4):498-503. Epub 2016 Dec 1.

Unidad de Nefrología y Trasplante Renal, Hospital Pablo Tobón Uribe, Universidad de Antioquia, Medellín, Colombia.

Light chain-associated kidney compromise is frequent in patients with monoclonal gammopathies; it affects the glomeruli or the tubules, and its most common cause is multiple myeloma. It may develop after a kidney transplant due to recurrence of a preexisting multiple myeloma or it can be a de novo disease manifesting as graft dysfunction and proteinuria. A kidney biopsy is always necessary to confirm the diagnosis. Read More

Leukemia 2017 01 20;31(1):123-129. Epub 2016 Jul 20.

Department of Hematology and Clinical Immunology, INSERM UMR 1126 Institut Universitaire d'Hématologie, Saint Louis University Hospital, Paris, France.

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 m) and tubular proteinuria. Read More

J Am Soc Nephrol 2016 07 27;27(7):2049-61. Epub 2015 Nov 27.

Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Division of Nephrology, UCL Medical School, Brussels, Belgium;

Monoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κLCs (RFS-κLCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κLCs (25 μg/ml). Read More

Arch Pathol Lab Med 2014 Oct;138(10):1365-80

From the Department of Pathology, Louisiana State University, Shreveport.

Context: Lesions associated with monoclonal light and heavy chains display a variety of glomerular, tubular interstitial, and vascular manifestations. While some of the entities are well recognized, including light and heavy chain deposition diseases, AL (light chain) and AH (heavy chain) amyloidosis, and light chain ("myeloma") cast nephropathy, other lesions centered on proximal tubules are much less accurately identified, properly diagnosed, and adequately understood in terms of pathogenesis and molecular mechanisms involved. These proximal tubule-centered lesions are typically associated with monoclonal light chains and have not been reported in patients with circulating monoclonal heavy chains. Read More

Kidney Int 2014 Oct 30;86(4):738-46. Epub 2014 Apr 30.

Department of Pathology, Louisiana State University Health, Shreveport, Louisiana, USA.

In vitro and ex vivo studies have elucidated the step-by-step process whereby some physicochemically abnormal light chains are processed by mesangial cells to form amyloid fibrils. Although crucial steps in the cascade of events have been determined, these findings have not been reproduced in vivo. This has led to some doubts as to the significance and clinical application of the information that has been deciphered. Read More

Clin J Am Soc Nephrol 2013 Jun 14;8(6):915-21. Epub 2013 Feb 14.

Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Background And Objectives: Organized deposits are present in amyloidosis, fibrillary GN, and immunotactoid glomerulopathy. However, the constituents of the deposits are not known.

Design, Setting, Participants, & Measurements: Laser microdissection of glomeruli followed by mass spectrometry was performed to determine the composition of the deposits. Read More

Dtsch Med Wochenschr 2013 Feb 7;138(7):305-12. Epub 2013 Feb 7.

Klinik für Innere Medizin II, Heinrich Braun Klinikum Zwickau.

Background: An impaired renal function in light chain associated disorders may be caused by myeloma cast nephropathy (MCN) but also by AL-amyloidosis (AL-A) and monoclonal immundeposition disease (MIDD).

Patients And Methods: In a monocentric, retrospective analysis, patients suffering from multiple myeloma (MM) (n = 392) requiring medical therapy, AL-A (n = 53) or MIDD (n = 12) diagnosed between 1996 and 2008 were evaluated for renal insufficiency. The different patient cohorts were compared in terms of their clinical course and outcome. Read More

Kidney Blood Press Res 2012 1;35(2):120-8. Epub 2011 Nov 1.

Department of Internal Medicine II, Heinrich Braun Klinikum Zwickau, Zwickau, Germany.

Background: Renal involvement in the light chain-associated diseases multiple myeloma (MM), amyloidosis (AL) and monoclonal immune position disease (MIDD) is common and differential diagnosis usually requires renal biopsy. The aim of this study was to investigate if noninvasive methods are viable to identify and differentiate between the various types of kidney diseases.

Patients And Methods: All patients with a light chain-associated disease admitted to our center from 1996 to 2008 were retrospectively evaluated. Read More

Am J Kidney Dis 2006 Apr;47(4):A57, e43-5

Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Clin Nephrol 2001 Sep;56(3):207-10

Nephrology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.

Aims: The patient characteristics and clinical course of nephropathy associated with multiple myeloma/light chain disease (MMN) has not been described for a national sample of end-stage renal disease patients.

Methods: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy between January 1, 1992 and June 30, 1997, and were analyzed in a retrospective registry study of MMN (PDIS=2030A, 2030B, 2030Z, and 203Z).

Results: Of the study population, 3298 (0. Read More

Medicine (Baltimore) 2000 May;79(3):135-54

Service de Néphrologie, Hôpital Tenon, Paris, France.

Fifty-seven cases of Ig light chain-associated Fanconi syndrome (FS) have been reported so far, mostly as isolated reports. The pioneering work by Maldonado and associates (35), who reviewed the first 17 cases in 1975, led to the unifying concept that patients with FS and Bence Jones proteinuria have a special form of plasma cell dyscrasia characterized by slow progression of the tumor and by prominent crystal formation in proximal tubule cells, in the absence of myeloma casts in the distal tubule. We carefully reappraised these characteristics in a series of 11 patients. Read More

Protein Eng 1999 Apr;12(4):363-9

INSERM U25, Laboratoire d'Immunologie Clinique, Hôpital Necker, 161 rue de Sèvres, F-75015 Paris, France.

Plasma cell dyscrasias may be responsible for Fanconi's syndrome, due to the toxicity of a free monoclonal kappa light chain toward kidney proximal tubules. Eight cases of Fanconi's syndrome were analyzed. We compared the structures of VkappaI variability subgroup V domains from five cases of Fanconi's syndrome and one myeloma without renal involvement. Read More

Amyloid 1998 Jun;5(2):117-20

Third Department of Medicine, Kobe University School of Medicine, Japan.

An extracted Bence Jones lambda protein from a Japanese patient with myeloma-associated Fanconi syndrome was found to contain 5 components, including the dimer and the monomer of the entire light-chain, the dimer and the monomer of the constant domain, and monomer of the variable domain. The entire amino acid sequence of this lambda chain was completed. The protein, containing 5 components, was injected intraperitoneally in C3H mice, 20 mg for 13 days and 200 mg for 3 days. Read More

Proc Natl Acad Sci U S A 1994 Apr;91(8):3034-8

Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, IL 60439-4833.

The deposition of certain Bence Jones proteins as tubular casts, basement membrane precipitates, or amyloid fibrils results in the human light-chain-associated renal and systemic diseases--myeloma (cast) nephropathy, light-chain deposition disease, and immunocyte-derived (primary or AL) amyloidosis. To determine if light-chain nephrotoxicity or amyloidogenicity is related to the propensity of these components to form high molecular weight aggregates under physiological conditions, we used a size-exclusion chromatographic system to study 40 different Bence Jones proteins. Each samples was tested over a wide range of protein concentration in three different buffers varying in pH, osmolality, and the presence or absence of low concentrations of urea. Read More

Am J Hematol 1994 Feb;45(2):171-6

Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville 37920.

Primary or AL amyloidosis occurs in patients with monoclonal plasma cell-related disorders and is typically associated with the systemic deposition as amyloid fibrils of the light-chain portion of the immunoglobulin molecule. Recently, the discovery that heavy chains could be involved in amyloid formation led to the designation of this type of disease process as AH amyloidosis. We have now identified a second example of heavy chain-associated amyloidosis in a patient (MAD) who had a serum IgG monoclonal gammopathy and Bence Jones proteinuria. Read More

Curr Top Microbiol Immunol 1992 ;182:261-7

Department of Medicine, Human Immunology, University of Tennessee Medical Center/Graduate School of Medicine.

N Engl J Med 1991 Jun;324(26):1845-51

Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville.

Background: The renal manifestations of diseases associated with the production of monoclonal light chains--myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL--result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. Read More

J Clin Pathol 1991 Mar;44(3):200-4

Department of Pathological of Sciences, University of Manchester.

The amyloid deposits in 21 renal biopsy specimens were subjected to a detailed immunohistochemical analysis using a panel of antibodies against recognised constituents of tissue amyloid. This was a retrospective study of material originally submitted during the investigation of various renal abnormalities and studied by a routine protocol including histochemistry, electron microscopy, and immunofluorescence. The presence of an amyloid was confirmed in all 21 cases. Read More