Document Detail


The pathogenesis of acute kidney impairment in patients with multiple myeloma.
MedLine Citation:
PMID:  22920637     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Acute kidney injury in myeloma, a serious complication associated with poor prognosis, is generally mediated by the toxic and inflammatory effects of monoclonal free light chains (FLCs) on kidney proximal tubule cells and by the formation of intratubular casts through interaction with Tamm-Horsfall proteins. Production of excessive quantities of FLCs is seen in most cases of FLC-associated kidney injury, although a direct relation between quantity and nephrotoxicity does not exist, indicating variable toxicity among light chain species. Toxic effects of FLCs include inhibition of transport functions, Fanconi syndrome, generation of reactive oxygen species, cytoskeletal abnormalities, and apoptosis and necrosis in proximal tubule cells. Excessive endocytosis of FLCs in proximal tubule cells also induces cell stress responses that result in stimulation of inflammatory pathways through activation of nuclear transcription factors κB and mitogen-activated protein kinases, induction of proinflammatory cytokines, and epithelial to mesenchymal transition. The mechanisms of nephrotoxicity of FLC described here explain the basis of acute kidney injury seen in patients with multiple myeloma and provide the rationale for eliminating or reducing the FLC burden in myeloma patients with renal involvement. The inflammatory pathways that are activated as a result of FLC toxicity also show clearly how severe chronic tubulointerstitial nephritis can occur in patients with myeloma kidney and identify several attractive opportunities for novel therapeutic interventions.
Authors:
Vecihi Batuman
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Advances in chronic kidney disease     Volume:  19     ISSN:  1548-5609     ISO Abbreviation:  Adv Chronic Kidney Dis     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101209214     Medline TA:  Adv Chronic Kidney Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  282-6     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
Affiliation:
Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA; and Southeast Louisiana Veterans Health Care System, Medicine Service, New Orleans, LA.
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