Origin and significance of urinary N-acetyl-beta,D-glucosaminidase (NAG) in renal patients with proteinuria

In patients with proteinuria, indices of tubular damage are unreliable since filtered plasma enzymes could contribute to tubular enzymuria. Previous work has suggested the existence of various forms of the 'A' isoenzyme of N-acetyl-beta,D-glucosaminidase (NAG), one of which could be kidney specific and thus a useful marker of renal tubular damage. By using fast protein liquid chromatography, two forms of the 'A' isoenzyme, 'A1' and 'A2' were separated in human urine, plasma and kidney tissue. The isoenzyme profile in pathological urine resembled that seen in kidney tissue, the 'A2' isoenzyme predominating. The ratio A2/A1 in the urine of renal patients was significantly greater than in the plasma of renal patients, end-stage renal failure patients and healthy volunteers. There was no difference in the plasma ratios of the three groups studied. The clearances of total NAG, 'A1' and 'A2' isoenzymes were all greater than that of the lower molecular weight protein transferrin. This indicates that the origin of urinary NAG in patients with proteinuria is from the kidney itself. Thus, analysis of urinary NAG and its isoenzymes may be of benefit as an early predictor of renal tubular damage and may also be useful as a non-invasive indicator of disease progression.