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 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.
Batuman
V
V
Department of Medicine, Tulane University School of Medicine, New Orleans, La.
Guan
S
S
O'Donovan
R
R
Puschett
J B
JB
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
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009194:Myeloma Proteins; D010710:Phosphates; D005947:Glucose