Effect of Myeloma Light Chains on Phosphate and Glucose Transport in Renal Proximal Tubule Cells

• Published in: Kidney & blood pressure research Vol. 17; no. 6; pp. 294 - 300
• Main Authors: Batuman, Vecihi, Guan, Shangbo, O’Donovan, Richard, Puschett, Jules B.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.11.1994
• Subjects: Animals; Biological Transport - drug effects; Cells, Cultured; Glucose - metabolism; Immunoglobulin kappa-Chains - pharmacology; Immunoglobulin lambda-Chains - pharmacology; Ion Transport - drug effects; Ion Transport - physiology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Male; Multiple Myeloma; Myeloma Proteins - pharmacology; Original Paper; Phosphates - metabolism; Rats; Renal Insufficiency; Cell culture; Bence-Jones proteins; Light chains; Multiple myeloma; Glucose transport; Nephrotoxicity; Phosphate transport
• ISSN: 1420-4096; 1011-6524; 1423-0143
• DOI: 10.1159/000173861

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.