Effect of Myeloma Light Chains on Phosphate and Glucose Transport in Renal Proximal Tubule Cells
Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 µM λ- or χ-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC 50 )...
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Published in | Kidney & blood pressure research Vol. 17; no. 6; pp. 294 - 300 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Basel, Switzerland
01.11.1994
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Subjects | |
Online Access | Get full text |
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Summary: | Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 µM λ- or χ-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC 50 ) of both the λ-and ĸ-light chains on phosphate transport were similar, 34 and 35 µM respectively. The IC 50 of the ĸ-light chain on glucose transport was 360 µM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.0l for the λ-light chain and r = 0.93, p < 0.001 for the χ-light chain, on phosphate transport; and r = 0.93, p < 0.00l for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompet-itive inhibition. The inhibition constant 89 µMfor phosphate uptake derived from the Dixon plot was similar to the IC 50 calculated from the dose-response curves. These findings indicate that light chains, at concentrations found in the tubule fluid of a typical myeloma patient, are potent inhibitors of phosphate and glucose transport in proximal tubular cells, and that direct cell toxicity is a major mechanism of light chain nephrotoxicity. |
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ISSN: | 1420-4096 1011-6524 1423-0143 |
DOI: | 10.1159/000173861 |