title: Effect of myeloma light chains on phosphate and glucose transport in renal proximal tubule cells.
abstract: Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 microM lambda- or kappa-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 (IC50) of both the lambda- and kappa-light chains on phosphate transport were similar, 34 and 35 microM respectively. The IC50 of the kappa-light chain on glucose transport was 360 microM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.01 for the lambda-light chain and r = 0.93, p < 0.001 for the kappa-light chain, on phosphate transport; and r = 0.93, p < 0.001 for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompetitive inhibition. The inhibition constant 89 microM for phosphate uptake derived from the Dixon plot was similar to the IC50 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.
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, La.
authors.forename: V
authors.initials: V
authors.lastname: Batuman
authors.forename: S
authors.initials: S
authors.lastname: Guan
authors.forename: R
authors.initials: R
authors.lastname: O'Donovan
authors.forename: J B
authors.initials: JB
authors.lastname: Puschett
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000494:pharmacology; D007146:Immunoglobulin lambda-Chains / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009101:Multiple Myeloma; D009194:Myeloma Proteins / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D051437:Renal Insufficiency
chemical_list: D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009194:Myeloma Proteins; D010710:Phosphates; D005947:Glucose