Purpose To identify urine parameters in type 2 diabetes mellitus (DM2) that predict progression of early nephropathy defined as microalbuminuria (mg albumin-to-g creatinine ratio [alb/cr] in a spot am urine of 20 to 200 mg/g) to advanced nephropathy defined as macroalbuminuria (urine alb/cr > 200 mg/g). We hypothesized that urine indices of increased oxidative stress predict progression of early to advanced DM2 nephropathy.
Methods We recruited 91 DM2 (39 nonsmokers and 52 smokers) with microalbuminuria and estimated GFR (eGFR) > 90 mL/min. Smokers underwent 12 weeks of smoking cessation intervention and 11 of the 52 (21%) quit. Therefore, three groups were compared: nonsmokers (NS, n = 39), smokers who continued smoking (S, n = 41), and smokers who quit (Quit, n = 11). Subjects were prescribed ACE inhibitors and followed 5 years with yearly measurements of urine alb/cr, eGFR, and oxidative stress as urine excretion of 8-iso-PGF2 alpha (8-iso).
Summary At 5 years, urine alb/cr was higher in S (99.2 ± 13.3) than NS (21.2 ± 1.8) and Quit (23.9 ± 2.3), p < .001). At 5 years, 7 of the 41 S subjects but no NS or Quit subjects had macroalbuminuria. Baseline urine 8-iso excretion was greater in S (4.3 ± 0.5 μg/g cr) and Quit (3.8 ± 0.5 μg/g cr) than NS (1.9 ± 0.3 μg/g cr, p < .02, vs S and Quit). Smoking cessation decreased urine 8-iso excretion in Quit ( 3.8 ± 0.5 to 2.0 ± 0.3 μg/g cr, p < .001) but not in S (4.3 ± 0.5 to 4.0 ± 0.5, p = .71). Initial urine 8-iso excretion was greater in 7 of 41 S subjects who developed macroalbuminuria than in the remaining 34 (6.7 ± 0.8 vs 3.6 ± 0.4 μg/g cr, p < .003). These 34 S subjects did not develop macroalbuminuria but nevertheless had higher initial urine 8-iso excretion and higher 5-year urine alb/cr than NS (p < .001) and Quit (p < .03) subjects. Five-year eGFR was not different among groups.
Conclusions The data show that smoking in DM2 is associated with increased oxidative stress as measured by urine 8-iso excretion and that smoking cessation is associated with a reduction in this parameter. Higher levels of urine 8-iso excretion and presumably oxidative stress are associated with progression of DM2 nephropathy.
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