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Unformatted text preview: tly b/c of differences in distal nephron NaCl concentration & b/c of variable affinity of the immunoglobulin light chains to the binding site on the THP) % change in turbidity (from co­precipitation) v. % change in turbidity (from co­precipitation) v. NaCl concentration for in vitro solutions of THP w/ various low molecular weight proteins (Sanders 1990) Pathogenesis of cast nephropathy: Pathogenesis of cast nephropathy: in vivo rat data (Sanders 1992) • Obstruction occurred in the distal nephron only & • • • showed direct BJP­concentration dependence Obstruction took significantly longer to develop in rats given volume infusion at high rates Obstruction developed more rapidly with increasing furosemide concentrations Colchicine prevented obstruction by decreasing tubular secretion & carbohydrate content of THP Change in turbidity of in vitro solutions of rat Change in turbidity of in vitro solutions of rat THP +/­ colchicine w/ increasing concentrations of furosemide (Sanders 1992) Compounding factors… Compounding factors… • • • • • • Hypercalcemia Hyperuricemia Infection Volume depletion or loop diuretics Nephrotoxic drugs, IV contrast Proximal tubular injury from light chain reabsorption & interference w/ lysosomal function; cycle whereby dysfunction further decrease in light chain reabsorption Treatment of cast nephropathy Treatment of cast nephropathy • Vol...
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