PMID- 20588062
OWN - NLM
STAT- MEDLINE
DCOM- 20110113
LR  - 20170118
IS  - 1660-2129 (Electronic)
IS  - 1660-2129 (Linking)
VI  - 116
IP  - 2
DP  - 2010
TI  - Myeloma light chain-induced renal injury in mice.
PG  - e32-41
LID - 10.1159/000317129 [doi]
AB  - We investigated the effects of human light chain (LC) protein-overload in mice 
      kidney to gain further insights into the molecular mechanisms involved in the 
      pathogenesis of myeloma kidney. Intact male C57BL/6, 10- to 12-week-old mice were 
      given daily intraperitoneal (i.p.) injections of 1 ml of human kappa-LCs (1.5 mg/ml, 
      low dose), or (100 mg/ml, high dose) to uninephrectomized mice for 2 weeks. 
      Intact, sham-operated or uninephrectomized control animals were given the same 
      volume (1 ml/day) of saline, human serum albumin (10 mg/ml) or bovine serum 
      albumin (100 mg/ml) i.p. for 2 weeks in place of LCs. The low-dose LC-treated 
      mice had human LCs in their urine and a significant increase in monocyte 
      chemoattractant protein-1 (MCP-1) mRNA in the kidneys. Uninephrectomized mice 
      treated with high-dose kappa-LCs showed tubule casts, and foci of intracytoplasmic 
      rhomboid crystals within the proximal tubules, along with cytoskeletal 
      disruptions and alterations in the brush-border membrane, and high concentrations 
      of human kappa-LC were present in their sera. High-dose LC treatment also led to 
      increases in serum creatinine and tumor necrosis factor-alpha levels, and marked 
      increases in interleukin-6 and MCP-1 expression as well as cellular apoptosis in 
      the kidneys. These studies demonstrate that myeloma LC overload over a range of 
      LC concentrations in mice causes significant functional and morphological kidney 
      injury. The model should be helpful in investigating pathophysiologic mechanisms 
      and exploring therapeutic interventions for myeloma kidney and other 
      LC-associated renal disorders.
CI  - Copyright (c) 2010 S. Karger AG, Basel.
FAU - Khan, Altaf-M
AU  - Khan AM
AD  - Section of Nephrology and Hypertension, Department of Medicine, Tulane University 
      School of Medicine, New Orleans, La 70112, USA.
FAU - Li, Min
AU  - Li M
FAU - Balamuthusamy, Saravanan
AU  - Balamuthusamy S
FAU - Maderdrut, Jerome L
AU  - Maderdrut JL
FAU - Simon, Eric E
AU  - Simon EE
FAU - Batuman, Vecihi
AU  - Batuman V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100629
PL  - Switzerland
TA  - Nephron Exp Nephrol
JT  - Nephron. Experimental nephrology
JID - 101159770
RN  - 0 (Chemokine CCL2)
RN  - 0 (Immunoglobulin kappa-Chains)
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Chemokine CCL2/biosynthesis
MH  - Female
MH  - Humans
MH  - Immunoglobulin kappa-Chains/*toxicity
MH  - Interleukin-6/biosynthesis
MH  - Kidney/metabolism
MH  - Kidney Diseases/*chemically induced/pathology/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Multiple Myeloma/metabolism
MH  - Proteinuria/etiology
EDAT- 2010/07/01 06:00
MHDA- 2011/01/14 06:00
CRDT- 2010/07/01 06:00
PHST- 2009/09/15 00:00 [received]
PHST- 2010/03/09 00:00 [accepted]
PHST- 2010/07/01 06:00 [entrez]
PHST- 2010/07/01 06:00 [pubmed]
PHST- 2011/01/14 06:00 [medline]
AID - 000317129 [pii]
AID - 10.1159/000317129 [doi]
PST - ppublish
SO  - Nephron Exp Nephrol. 2010;116(2):e32-41. doi: 10.1159/000317129. Epub 2010 Jun 
      29.