29 results match your criteria: "Light Chain-Associated Renal Disorders"

Fanconi syndrome in an elderly patient with membranous nephropathy during treatment with the immunosuppressant mizoribine.

CEN Case Rep

February 2023

Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

We report on an 80-year-old man diagnosed with Fanconi syndrome induced by mizoribine after 4 weeks of administration to treat membranous nephropathy. Mizoribine is an oral immunosuppressant that inhibits inosine monophosphate dehydrogenase and is widely used in Japan for the treatment of autoimmune diseases and nephrotic syndrome, as well as after renal transplantation. Acquired Fanconi syndrome is often caused by drugs (antibacterial, antiviral, anticancer, and anticonvulsant drugs) and is sometimes caused by autoimmune diseases, monoclonal light chain-associated diseases, or heavy metal poisoning.

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Renal Expression of Light Chain Binding Proteins.

Front Med (Lausanne)

January 2021

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.

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Monoclonal glomerulopathy with features of cryoglobulinemic glomerulopathy in murine multiple myeloma model.

Ultrastruct Pathol

November 2020

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.

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Paraffin Immunofluorescence Increases Light-Chain Detection in Extra-Renal Light Chain Amyloidosis and Other Light-Chain-Associated Diseases.

Arch Pathol Lab Med

March 2021

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.

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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.

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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.

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Tubular Injury and Dendritic Cell Activation Are Integral Components of Light Chain-Associated Acute Tubulointerstitial Nephritis.

Arch Pathol Lab Med

October 2019

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.

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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.

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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.

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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.

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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.

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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.

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Impaired Lysosomal Function Underlies Monoclonal Light Chain-Associated Renal Fanconi Syndrome.

J Am Soc Nephrol

July 2016

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).

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Article Synopsis
  • * Researchers analyzed 5,410 renal biopsies and found that 2.5% showed signs of kidney damage from these monoclonal chains, with around 46% classified specifically as proximal tubule lesions.
  • * The proximal tubulopathies were categorized into four groups based on their immunomorphological characteristics and clinical scenarios, highlighting the need for better recognition and understanding of these conditions in healthcare.
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Article Synopsis
  • In vitro and ex vivo studies identified how abnormal light chains are processed by mesangial cells to create amyloid fibrils, but these findings have yet to be confirmed in living organisms.
  • To address this, researchers developed a mouse model by injecting them with amyloidogenic light chains from patients with light-chain-associated glomerular amyloidosis, confirming previous findings.
  • This mouse model demonstrates the internalization and trafficking of light chains to lysosomes for fibril formation and allows for long-term study of amyloidogenesis, opening avenues for potential therapies.
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Laser microdissection and proteomic analysis of amyloidosis, cryoglobulinemic GN, fibrillary GN, and immunotactoid glomerulopathy.

Clin J Am Soc Nephrol

June 2013

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

Article Synopsis
  • The study investigates the composition of organized deposits found in various kidney diseases, specifically amyloidosis, fibrillary nephritis, and immunotactoid glomerulopathy, using laser microdissection and mass spectrometry.
  • Key findings show significant differences in protein spectra among these conditions, particularly highlighting apolipoprotein E's abundance in amyloidosis compared to its absence in cryoglobulinemic nephritis.
  • The research concludes that the ratio of apolipoprotein E to other immunoglobulins is critical for understanding the organization of these deposits across different nephropathies.
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[Renal manifestations of light chain associated diseases - epidemiology and prognosis].

Dtsch Med Wochenschr

February 2013

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.

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Screening and differential diagnosis of renal light chain-associated diseases.

Kidney Blood Press Res

June 2012

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.

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Article Synopsis
  • The study analyzed a national sample of end-stage renal disease (ESRD) patients to understand the characteristics and outcomes of nephropathy linked with multiple myeloma/light chain disease (MMN).
  • Out of over 375,000 patients, only 0.88% were found to have MMN, with these patients being predominantly older males, mostly Caucasian, and showing signs of poorer health at the start of dialysis.
  • The findings indicated that MMN patients had a significantly higher two-year mortality rate (58%) compared to other ESRD patients (31%), and were more likely to experience decreased survival after initiating dialysis.
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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.

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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.

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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.

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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.

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