My Patient with Monoclonal Gammopathy of Undetermined Significance has a Kidney Problem

2017 ◽  
Vol 1 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Nelson Leung
Keyword(s):  
Kidney Disease ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Lymphoproliferative Disorder ◽  
Kidney Diseases ◽  
Organ Damage ◽  
Renal Diseases ◽  
Premalignant Condition ◽  
Definition Of ◽  
Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition signifying the presence of a B-cell lymphoproliferative disorder. By connotation, it should not meet the definition of multiple myeloma, Waldenström macroglobulinemia, or lymphoma. In addition, it cannot be responsible for any end-organ damage. Similar to polyclonal immunoglobulins (Ig), monoclonal gammopathy has been increasingly recognized as an important cause of kidney disease. The recent introduction of the term “monoclonal gammopathy of renal significance” (MGRS) highlights this importance. MGRS is similar to MGUS in which the B-cell lymphoproliferative disorder has not reached a state considered to be malignant, but differentiates itself by the presence of a monoclonal gammopathy related kidney disease. This distinction is important since it separates MGRS, which is not benign, from the MGUS condition, which is benign. It also allows for a better classification of kidney diseases caused by monoclonal gammopathies. There are many renal diseases and lesions that have been identified to be secondary to MGRS. In addition, MGRS-associated renal diseases can mimic polyclonal Ig mediated kidney diseases. Kidney biopsy with immunofluorescence is the key for diagnosing MGRS-related kidney diseases. Once the diagnosis is made, a specific evaluation is needed for the diagnosis and treatment of MGRS-related kidney diseases that differs from the polyclonal Ig counterparts.

scholarly journals Dysproteinemias and Glomerular Disease

2017 ◽  
Vol 13 (1) ◽  
pp. 128-139 ◽  
Author(s):  
Nelson Leung ◽  
Maria E. Drosou ◽  
Samih H. Nasr
Keyword(s):  
Kidney Disease ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Kidney Diseases ◽  
Substantial Reduction ◽  
Cell Lineage ◽  
Monoclonal Protein ◽  
Major Mechanism ◽  
Malignant State ◽  
Monoclonal Proteins

Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein–related kidney diseases.

scholarly journals Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 438
Author(s):  
Jean Harb ◽  
Nicolas Mennesson ◽  
Cassandra Lepetit ◽  
Maeva Fourny ◽  
Margaux Louvois ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Coat Proteins ◽  
Chronic Stimulation ◽  
B Cell Epitopes ◽  
Monoclonal Immunoglobulins ◽  
Self Antigen ◽  
Coxsackievirus B1 ◽  
Undetermined Significance

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

scholarly journals Therapeutic Approaches Targeting Proteostasis in Kidney Disease and Fibrosis

2021 ◽  
Vol 22 (16) ◽  
pp. 8674
Author(s):  
Jia-Huang Chen ◽  
Chia-Hsien Wu ◽  
Chih-Kang Chiang
Keyword(s):  
Kidney Disease ◽  
Er Stress ◽  
Kidney Diseases ◽  
Trigger Factor ◽  
Renal Diseases ◽  
Therapeutic Approaches ◽  
Adaptive Process ◽  
Unfolded Protein ◽  
Molecular Signals ◽  
The Relationship

Pathological insults usually disturb the folding capacity of cellular proteins and lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which leads to so-called “ER stress”. Increasing evidence indicates that ER stress acts as a trigger factor for the development and progression of many kidney diseases. The unfolded protein responses (UPRs), a set of molecular signals that resume proteostasis under ER stress, are thought to restore the adaptive process in chronic kidney disease (CKD) and renal fibrosis. Furthermore, the idea of targeting UPRs for CKD treatment has been well discussed in the past decade. This review summarizes the up-to-date literature regarding studies on the relationship between the UPRs, systemic fibrosis, and renal diseases. We also address the potential therapeutic possibilities of renal diseases based on the modulation of UPRs and ER proteostasis. Finally, we list some of the current UPR modulators and their therapeutic potentials.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

scholarly journals The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Mingxuan Chi ◽  
Kuai Ma ◽  
Jing Wang ◽  
Zhaolun Ding ◽  
Yunlong Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Renal Diseases

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

scholarly journals The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal Diseases

2018 ◽  
Vol 29 (7) ◽  
pp. 1810-1823 ◽  
Author(s):  
Sanjeev Sethi ◽  
S. Vincent Rajkumar ◽  
Vivette D. D’Agati
Keyword(s):  
Renal Disease ◽  
B Cell ◽  
B Lymphocytes ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
Organ Damage ◽  
Renal Tissue ◽  
Renal Diseases ◽  
Malignant Neoplasms ◽  
Cast Nephropathy

Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a “benign” hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.

scholarly journals SP161PREVALENCE OF KIDNEY DISEASE IN MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Wenceslao Adrian Aguilera-Morales ◽  
Fabiola Alonso-Garcia ◽  
Javier Burgos-Martin ◽  
Kamila Klimek ◽  
Marina Almenara-Tejederas ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Monoclonal Gammopathy ◽  
Undetermined Significance

scholarly journals Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 28-38
Author(s):  
Olga Martinez-Arroyo ◽  
Ana Ortega ◽  
Josep Redon ◽  
Raquel Cortes
Keyword(s):  
Kidney Disease ◽  
Extracellular Vesicles ◽  
Renal Damage ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Cell Types ◽  
Organ Damage ◽  
Renal Diseases ◽  
Biological Processes ◽  
Potential Use

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

scholarly journals Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Amir Taherkhani ◽  
Reyhaneh Farrokhi Yekta ◽  
Maede Mohseni ◽  
Massoud Saidijam ◽  
Afsaneh Arefi Oskouie
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iga Nephropathy ◽  
Focal Segmental Glomerulosclerosis ◽  
Membranous Glomerulonephritis ◽  
Renal Diseases ◽  
Segmental Glomerulosclerosis ◽  
Therapeutic Procedures ◽  
Definition Of ◽  
End Stage

AbstractChronic Kidney Disease (CKD) is a global health problem annually affecting millions of people around the world. It is a comprehensive syndrome, and various factors may contribute to its occurrence. In this study, it was attempted to provide an accurate definition of chronic kidney disease; followed by focusing and discussing on molecular pathogenesis, novel diagnosis approaches based on biomarkers, recent effective antigens and new therapeutic procedures related to high-risk chronic kidney disease such as membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy, which may lead to end-stage renal diseases. Additionally, a considerable number of metabolites and proteins that have previously been discovered and recommended as potential biomarkers of various CKDs using ‘-omics-’ technologies, proteomics, and metabolomics were reviewed.

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