Light chains can be toxic to the kidney when they are over produced. The types of pathology one finds are: Cast Nephropathy( usually light chain + uromodulin mediated), AL Amyloidosis( more lambda than kappa mediated), Monoclonal Ig Deposition disease ( LCDD, HCDD, LHCDD)- usually kappa more than lambda. Light Chain Fanconi Syndrome (kappa more than lambda), Cryoglobulinemic GN( polyclonal), Waldenstroms ( IgM kappa or lambda), Immunotactoid GN( igG kappa or lambda), Proliferative GN with monoclonal IgG deposits ( kappa or lambda).
Some key points:
1. 40% more light chains are produced than heavy
chains
2. Around 500mg/day of there FLC are in circulation daily
3. 80% are extravascular
4. 2/3 are kappa and 1/3 are lambda hence a ratio of 1.8:1 ratio in the serum.( function of production and clearance)
5. That ratio showed be the same when in renal injury from other causes to have more kappa than lambda always.
6. FLC are mostly removed by proximal tubule epithelial cells, Kappa is 40% per hour and lambda is 20% per hour, so half lives come out to be 2-4 hours and 3-6 hours respectively.
7. If in renal failure, what gets rid of these FLCS? the reticuloendothelial system does try to do it but the half life can increase to 32 hours
8. Mice injected with FLC from patients with renal lesions developed the SAME renal lesion in those patients suggesting each FLC might act differently in different patients. Hence the primary structure of molecule might be important. A nice article in Kidney International 2011 June summarizes the newest research in LC biology.
image source: aafp.org
Ref:
2. Around 500mg/day of there FLC are in circulation daily
3. 80% are extravascular
4. 2/3 are kappa and 1/3 are lambda hence a ratio of 1.8:1 ratio in the serum.( function of production and clearance)
5. That ratio showed be the same when in renal injury from other causes to have more kappa than lambda always.
6. FLC are mostly removed by proximal tubule epithelial cells, Kappa is 40% per hour and lambda is 20% per hour, so half lives come out to be 2-4 hours and 3-6 hours respectively.
7. If in renal failure, what gets rid of these FLCS? the reticuloendothelial system does try to do it but the half life can increase to 32 hours
8. Mice injected with FLC from patients with renal lesions developed the SAME renal lesion in those patients suggesting each FLC might act differently in different patients. Hence the primary structure of molecule might be important. A nice article in Kidney International 2011 June summarizes the newest research in LC biology.
image source: aafp.org
Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21490587
http://www.ncbi.nlm.nih.gov/pubmed/5666962
http://www.ncbi.nlm.nih.gov/pubmed/1904132
http://www.ncbi.nlm.nih.gov/pubmed/4165739
http://www.ncbi.nlm.nih.gov/pubmed/5666962
http://www.ncbi.nlm.nih.gov/pubmed/1904132
http://www.ncbi.nlm.nih.gov/pubmed/4165739
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