Urine N-acetyl-beta-D-glucosaminidase - A marker of tubular damage?

Background. Although an indicator of renal tubular dysfunction, an increase d urinary N-acetyl-beta-D-glucosaminidase (NAC) activity might reflect incr eased lysosomal activity in renal tubular cells. Methods. Puromycin aminonucleoside (PAN) was administered to Sprague Dawley rats to induce proteinuria. Total protein, albumin, NAG activity and prote in electrophoretic pattern were assessed in daily urine samples for 33 days . The morphological appearance of the kidneys was examined on days three, f our, six, eight and thirty three and the NAG isoenzyme patterns on days zer o, four, eight and thirty three. Results. Following intravenous PAN urine volume and urine NAC activity incr eased significantly by day two, but returned to normal by day four. After d ay four all treated animals exhibited a marked rise in urine albumin, total protein excretion and NAG activity. Electrophoresis showed a generalised i ncrease in middle and high molecular weight urine proteins from day four on wards. Protein droplets first appeared prominent in tubular cells on day fo ur. Peak urine NAG activity and a change in NAG; isoenzyme pattern coincide d with both the peak proteinuria and the reduction in intracellular protein and NAC droplets (day six onwards). Conclusions. This animal model demonstrates that an increase in lysosomal t urnover and hence urine NAC activity, occurs when increased protein is pres ented to the tubular cells. Urine NAG activity is thus a measure of altered function in the renal tubules and not simply an indicator of damage.