Nephrotoxicity of low molecular weight serum proteins: physicochemical interactions between myoglobin, hemoglobin, bence-jones proteins and tamm-horsfall mucoprotein.

Three types of low molecular weight serum proteins, myoglobin, hemoglobin and BENCE-JONES proteins, are associated clinically with acute renal failure. All have isoelectric points which render them anionic at blood pH but cationic in the distal nephron under conditions of aciduria. Experiments in which these proteins were mixed with TAMM-HORSFALL mucoprotein in vitro and the pH lowered with lN HCl showed co-precipitation of proteins at pH levels of 5.5 and below. In vivo experiments in which 11 different BENCE-JONES proteins of pl ranging from 5.2 to 6.6 were injected into aciduric, hydropenic rats showed an acute rise in serum urea nitrogen and creatinine concentrations with BENCE-JONES proteins of pl greater than 5.7 compared with little change in rats injected with BENCE-JONES proteins of pl less than 5.7. These data suggest that protein pl and urine pH are important in determining nephrotoxicity; a mechanism by which these low molecular weight serum proteins and TAMM-HORSFALL proteins interact in the distal nephron to initiate acute renal failure in postulated.