Effects of pentoxifylline administration on urinary N-acetyl-beta-glucosaminidase excretion in type 2 diabetic patients: a short-term, prospective, randomized study.
BACKGROUND
Tubulointerstitial injury is a major feature of diabetic nephropathy and an important predictor of renal dysfunction. In 45 patients with type 2 diabetes mellitus (DM), we prospectively analyzed urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a marker of tubular renal damage; the potential relationship with urinary protein excretion; and effects of pentoxifylline (PTF) administration.


METHODS
Forty-five patients with type 2 DM initially were compared with 15 healthy controls matched for age and sex. After randomization, PTF (1,200 mg/d) was administered for 4 months to 30 patients and results were compared with data from a control group (n = 15).


RESULTS
Proteinuria and urinary NAG excretion were significantly greater in patients with DM with respect to healthy controls. Before PTF administration, baseline parameters were similar in both groups of patients with DM. At the end of the study, urinary protein excretion and NAG-creatinine ratios decreased in the active group from 920 +/- 522 mg/d and 14.3 +/- 16.9 U/g to 803 +/- 523 mg/d (P < 0.001) and 10.5 +/- 9.3 U/g (P < 0.05), respectively. Conversely, proteinuria and urinary NAG excretion did not change in the control group. Regression analysis showed that urinary NAG excretion was significantly associated with duration of DM (r = 0.61; P < 0.001) and proteinuria (r = 0.51; P < 0.001).


CONCLUSIONS
Urinary NAG excretion is elevated in patients with type 2 DM compared with healthy individuals and increases as nephropathy progresses. PTF administration is effective in reducing proteinuria and urinary NAG excretion in these patients. These findings suggest that PTF may have beneficial effects on tubulointerstitial damage in diabetic kidney disease.
Navarro
Juan F
JF
Nephrology and Biochemistry Services, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Tenerife, Spain. jnavgon@gobiernodecanarias.org
Mora
Carmen
C
Muros
Mercedes
M
Maca
Manuel
M
Garca
Javier
J
D000118:Acetylglucosaminidase / Q000652:urine*; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011507:Proteinuria / Q000201:enzymology / Q000453:epidemiology; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000118:Acetylglucosaminidase; D010431:Pentoxifylline