Conformational mediated renal selectivity towards albumin in diabetes mellitus

In an attempt to define the nature of renal selectivity in diabetes mellitus, we have determined the free sulfhydryl (SH) groups of serum and urinary albumin in 9 normal subjects and 24 diabetic patients with various grades of renal involvement, as defined by their urinary excretion rates of albumin (alb. UER): 8 with alb. UER less than 10 micrograms/min (Group A), 6 with alb. UER between 10 and 30 micrograms/min (Group B), 5 with alb. UER between 30 and 200 micrograms/min (Group C) and 5 with alb. UER greater than 200 micrograms/min (Group D). The free SH group content of urinary albumin was three to four fold increased in comparison with its serum homologue in normal subjects and in diabetics with normal or slightly increased alb. UERs (Groups A and B). Diabetics in Group C showed a two-fold increase in free SH groups of urinary albumin compared to serum albumin and diabetics with clinical nephropathy (Group D) showed no increase at all. The SH group content of urinary albumin correlated in all diabetics with the concentration of glycosyl albumin and the of urinary/serum albumin SH groups ratio was inversely correlated with alb. UER. From these observations concerning the selectivity properties of the renal filter in normal and diabetic subjects, it is concluded that the mechanism for progression of diabetic nephropathy may be the hyperfiltration of albumin with an altered conformational state.