κ Light-chain monoclonal gammopathy and cast nephropathy in a horse with multiple myeloma

2018 ◽  
Vol 253 (9) ◽  
pp. 1177-1183 ◽  
Author(s):  
Christina Eberhardt ◽  
Alexandra Malbon ◽  
Barbara Riond ◽  
Angelika Schoster
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Cast Nephropathy

scholarly journals Crystalglobulinemia in Multiple Myeloma: A Rare Case Report of Survival and Renal Recovery

2020 ◽  
Vol 7 ◽  
pp. 205435812092262
Author(s):  
Angela Chou ◽  
Christopher Long ◽  
Leon Vonthethoff ◽  
Shir-Jing Ho ◽  
Franziska Pettit ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Acute Kidney Injury ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
Rare Complication ◽  
Kidney Injury ◽  
Endothelial Damage ◽  
Cast Nephropathy ◽  
Rare Case Report

Rationale: Crystalglobulinemia is a rare complication of monoclonal gammopathy wherein crystallized immunoglobulins deposit in various organs causing occlusive vasculopathy, endothelial damage, and thrombosis. It should be differentiated from light chain cast nephropathy without crystalline nephropathy through timely diagnosis with a kidney biopsy. Presenting concerns of the patient: We report a case of a 74-year-old female with polyarthralgia, chest pain, petechial rash, and acute kidney injury. Diagnoses: Kidney biopsy revealed eosinophilic casts in the tubular lumen and similar occlusive crystalline deposits within the glomerular vasculature and interlobular arteries. Bone marrow biopsy and serum electrophoresis confirmed immunoglobulin G (IgG) κ multiple myeloma. Interventions: Dialysis was initiated for severe oligoanuric acute kidney injury. The patient was treated with 5 sessions of plasmapheresis and 11 cycles of clone reduction chemotherapy with CyBorD (cyclophosphamide, bortezomib, and dexamethasone). Outcomes: This patient achieved excellent kidney recovery and is no longer dialysis dependent. Teaching points: Crystalglobulinemia should be suspected in patients with rapidly progressive acute kidney injury and monoclonal gammopathy. Timely investigation with kidney biopsy to differentiate this condition from light chain cast nephropathy and initiation of appropriate treatment can lead to remission of disease and excellent recovery of kidney function.

scholarly journals Structural analysis of urinary light chains and proteomic analysis of hyaline tubular casts in light chain associated kidney disorders

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7819 ◽  
Author(s):  
Thomas Reiter ◽  
Daniela Knafl ◽  
Hermine Agis ◽  
Karl Mechtler ◽  
Ludwig Wagner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Proteomic Analysis ◽  
Cathepsin B ◽  
Monoclonal Gammopathy ◽  
Sucrose Gradient ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Cast Nephropathy

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. Methods Urine samples were collected from 17 patients with multiple myeloma or monoclonal gammopathy. The urine sediment was stained for cast morphology by H/E and light chain immunofluorescence. Following micro-selection of casts under microscope, proteomic analysis of casts was performed by mass spectrometry. Sucrose gradient sedimentation was employed and light chain architecture examined by immunoblotting. Uromodulin was measured by ELISA in sucrose gradient fractions. Results Urinary casts were observed of about 30 µm in diameter by H/E staining and under immunofluorescence microscopy. Casts with a diameter of 20 µm were observed as a novel variant. Proteome analysis showed that in addition to the expected light chain variants produced by the malignant clone of plasma cells, also histones such as H2B and cathepsin B were contained. Uromodulin was not detectable in urinary casts of all patients. All eleven patients with lambda light chains showed predominant dimerized light chains in the urine immunoblot. Six patients with kappa light chains presented with predominantly monomeric forms of light chains in the immunoblot. The densitometric evaluated ratio of lambda dimers vs. monomers was significantly higher (2.12 ± 0.75) when compared with the ratio of kappa dimers vs. monomers (0.64 ± 0.47), p = 0.00001. Aggregates of light chains separated in part into denser sucrose fractions. Conclusion This work on urinary casts and light chains demonstrates that hyaline tubular casts represent a complex formation of protein-protein aggregates with histones and cathepsin B identified as novel cast components. Apart from the proteomic composition of the casts, also the formation of the light chains and aggregates is of relevance. Dimerized light chains, which are typical for lambda paraproteins, might be less dialyzable than monomeric forms and may therefore identify patients less responsive to high cut-off dialysis.

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group

2010 ◽  
Vol 28 (33) ◽  
pp. 4976-4984 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Evangelos Terpos ◽  
Asher Chanan-Khan ◽  
Nelson Leung ◽  
Heinz Ludwig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Light Chain ◽  
Renal Injury ◽  
High Dose ◽  
Acute Renal Injury ◽  
High Dose Dexamethasone ◽  
Cast Nephropathy ◽  
High Dose Melphalan

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

scholarly journals Resolution of cast nephropathy following free light chain removal by haemodialysis in a patient with multiple myeloma: a case report

2008 ◽  
Vol 2 (1) ◽  
Author(s):  
Kolitha Basnayake ◽  
Colin Hutchison ◽  
Dia Kamel ◽  
Michael Sheaff ◽  
Neil Ashman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Light Chain ◽  
Free Light Chain ◽  
Cast Nephropathy

Monoclonal immunoglobulin–mediated kidney disease: What is beyond amyloidosis in real practice?

2019 ◽  
Vol 3 (3) ◽  
pp. 105-112 ◽  
Author(s):  
Elena V Zakharova ◽  
Tatyana A Makarova ◽  
Ekaterina S Stolyarevich ◽  
Olga A Vorobyeva
Keyword(s):  
Kidney Disease ◽  
B Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Monoclonal Immunoglobulin ◽  
B Cell Malignancies ◽  
Cast Nephropathy ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

Background:Monoclonal immunoglobulin–mediated kidney disease with various patterns of damage may occur in patients with B-cell malignancies and non-malignant monoclonal gammopathies, and the latter are actually merged under the umbrella of monoclonal gammopathy of renal significance. Amyloidosis is the most well-known monoclonal immunoglobulin–related kidney damage. We focused on the rarer conditions and aimed to evaluate the non-amyloid spectrum of monoclonal immunoglobulin–mediated patterns of renal damage in real clinical practice.Methods:A single-center non-interventional retrospective study included 45 patients with pathology-proven non-amyloid monoclonal immunoglobulin–mediated kidney disease, followed during 2002–2018. Disease duration, proteinuria, serum creatinine, need for dialysis at the time of kidney biopsy, clinical diagnosis, and kidney pathology findings were analyzed.Results:No significant differences in the median age, disease duration at the time of biopsy, or main clinical presentation of kidney disease were found between patients with monoclonal gammopathy of renal significance and patients with B-cell malignancies. Pathology patterns like proliferative glomerulonephritis with monoclonal immunoglobulin deposits, membranous nephropathy, C3 glomerulopathy, cryoglobulinemic glomerulonephritis, and combinations of light chain proximal tubulopathy with monoclonal immunoglobulin deposition disease, and of C3 glomerulopathy with light chain proximal tubulopathy were found in monoclonal gammopathy of renal significance setting only. In contrast, light chain proximal tubulopathy alone, anti-glomerular basement glomerulonephritis, and combinations of cast nephropathy with light chain proximal tubulopathy, and cast nephropathy with monoclonal immunoglobulin deposition disease were associated with multiple myeloma only. Monoclonal immunoglobulin deposition disease, intracapillary monoclonal immunoglobulin M deposits, and cast nephropathy alone were seen in both settings.Conclusion:The presence of monoclonal gammopathy in patients with proteinuria and/or impaired kidney function demands kidney biopsy. Neither duration of kidney disease nor its clinical presentation allows differentiating malignant and non-malignant causes of monoclonal immunoglobulin–mediated renal damage. Several pathology patterns, even cast nephropathy, can be found both in cases of monoclonal gammopathy of renal significance and in cases of B-cell malignancies. Dual patterns of damage, including combinations of organized and non-organized deposits, or organized deposits with monoclonal immunoglobulin–induced damage without monoclonal immunoglobulin deposition, constitute up to 9%, mostly in multiple myeloma cases.

Prevalence of Light-Chain Monoclonal Gammopathy of Undetermined Significance (LC-MGUS) among Olmsted County, Minnesota Residents Aged 50 Years or Greater.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5060-5060
Author(s):  
S. Vincent Rajkumar ◽  
Robert Kyle ◽  
Matthew Plevak ◽  
Raynell Clark ◽  
Dirk Larson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
General Population ◽  
Natural History ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Olmsted County ◽  
Serum Samples ◽  
Geographic Population ◽  
History Of ◽  
Undetermined Significance

Abstract Background: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that carries a 1% per year risk of progression to multiple myeloma (MM) or related malignancy. The prevalence and natural history of MGUS, in which by definition intact immunoglobulin heavy chain (IgH) is expressed, has been well described. However, up to 20% of myeloma (MM) is characterized by complete lack of IgH expression (Light-chain MM); the prevalence of a corresponding precursor entity, light chain MGUS (LC-MGUS) has not been determined. We report the first prevalence estimates of LC-MGUS in the general population from a large, well-defined geographic population using modern laboratory techniques. Methods: The cohort for this study was derived from one previously assembled by us to estimate the prevalence of MGUS (N Engl J Med2006;354:1362-9). The original cohort used to estimate the prevalence of MGUS consisted of 21,463 of the 28,038 enumerated residents aged 50 or over of Olmsted County Minnesota as of January 1, 1995. The sensitive serum free light chain (FLC) assay (The Binding Site Limited, Birmingham, U.K.) was performed on stored serum samples from these 21,463 persons. IgH expression was determined by immunofixation on all FLC results that had an abnormal kappa/lambda ratio (<0.26 or >1.65). LC-MGUS was defined as the presence of an abnormal FLC ratio and a negative immunofixation for IgH expression. Results: Adequate stored serum samples were available in 20,733 (97%) of the 21,463 persons. To date, the FLC assay has been performed and results were available for analysis on samples from 16,637 persons. An abnormal FLC ratio was observed in 572 persons. IgH expression was detected in 255 of these cases on immunofixation; these persons are considered as having MGUS, and were excluded from the estimation of LC-MGUS prevalence. This resulted in 317 persons out of 16,637 who had an abnormal FLC ratio without evidence of IgH expression, resulting in an estimated prevalence of LC- MGUS of 2%. Of the 317 cases of LC-MGUS identified in this study, 217 were kappa and 100 were lambda; in 35 cases the presence of the corresponding monoclonal light chain was apparent on immunofixation. The median age of the cohort of LC-MGUS was 62 years; males=151, females =166. The involved FLC level ranged from 0.118–270.0 mg/dL. The FLC ratio ranged from 0.014–0.253 (lambda) and 1.67–511.01 (kappa). So far, progression to multiple myeloma has occurred in 4 patients, a rate much higher than what is expected based on the prevalence of myeloma in the general population. Two additional patients have developed CLL. Conclusions: LC-MGUS is prevalent in 2% of the general population aged 50 years of age or older. The natural history of this disorder needs to be determined.

24: Resolution of Cast Nephropathy Following Free Light Chain Removal by Hemodialysis in a Patient with Multiple Myeloma

2008 ◽  
Vol 51 (4) ◽  
pp. B33
Author(s):  
Kolitha Basnayake ◽  
Colin Hutchison ◽  
Dia Kamel ◽  
Michael Sheaff ◽  
Neil Ashman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Free Light Chain ◽  
Cast Nephropathy
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