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 mu M 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 mu M respectively. The IC50 of the kappa-light chain on glucose transport was 360 mu M. 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 Lineweaver-Burk plot analyses were characteristic for noncompetitive inhibition. The inhibition constant 89 mu M 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.