Further evidence for tubular dysfunction in insulin dependent diabetes

Abstract

There is evidence that increased excretion of urinary enzymes and low-molecular mass proteins indicate impaired tubular function. The excretion of N-acetyl-beta- d-glucosaminidase (NAG), lysozyme, and ribonuclease in Type I diabetic patients with ( n = 19) and without ( n = 17) persistent proteinuria (urinary protein excretion > 0.5 g/day) was investigated and compared with this exretion in 30 weight- and gender-matched nondiabetic subjects without renal disease. Urinary NAG excretion was significantly higher in diabetic patients with and without persistent proteinuria (1.16 ± 0.09 and 3.19 ± 1.2 Umol/L creatinine, respectively) compared to controls (0.37 ± 0.03 Umol/L creatinine p < 0.01). In addition, the urinary excretion of lysozyme and ribonuclease was significantly increased in diabetic patients. Urinary NAG was found to correlate positively with albuminuria and proteinuria ( r = 0.95 and 0.93, respectively), as well as with ribonuclease and lysozyme ( r = 0.93 and 0.60; p < 0.01) in patients with persistent proteinuria. Furthermore, NAG excretion was significantly related to the duration of diabetes ( r = 0.36; p < 0.05). No relationship existed between urinary NAG and serum creatinine, beta-2-microglobulin, and degree of metabolic control (HbA 7). The lysozyme excretion, but not NAG excretion, was significantly related to hypertension in patients with clinical proteinuria. In conclusion, our results suggest a relationship between the development of tubular dysfunction and the impairment of glomerular function in diabetic nephropathy. An increased excretion of NAG and low-moecular mass proteins may indicate early nephropathy.