Cigarette smoking exacerbates and its cessation ameliorates renal injury in type 2 diabetes

Background: Patients with type 2 diabetes and macroalbuminuria generally experience progressive glomerular filtration rate (GFR) decline despite angiotensin-converting enzyme inhibition (ACEI) and blood pressure (BP) control but this therapy generally stabilizes GFR in those without macroalbuminuria. Cigarette smoking exacerbates GFR decline in patients with type 2 diabetes and macroalbuminuria despite ACEI and BP control; whether this therapy prevents nephropathy progression in nonmacroalbuminuric type 2 diabetic smokers is unknown. Methods: We determined the course of urine excretion of indices of renal injury that distinguished patients with type 2 diabetes with and without macroalbuminuria but with normal plasma creatinine who were prospectively followed 6 months while receiving ACEI and BP control. We compared this course in nonsmokers and smokers with normo-, micro-, and macroalbuminuria (n = 157) and in response to smoking cessation in a separate cohort (n = 80) with microalbuminuria. Results: Urine excretion of transforming growth factor beta-1 (UTGFbetaV) increased in macroalbuminuric but not in nonmacroalbuminuric nonsmokers and UTGFbetaV rate was higher in smokers than nonsmokers within each albuminuria group. In the separate microalbuminuric cohort, the rate of UTGFbetaV change for quitting smokers was not different from nonsmokers (0.093 versus -0.123 ng/g of creatine/week, P = not significant) but that for nonquitting smokers (0.970) was higher than nonsmokers (P = 0.017). Conclusions: Patients with type 2 diabetes who are at high risk compared with low risk for nephropathy progression have progressive renal injury as measured by increasing UTGFbetaV, Cigarette smoking exacerbates renal injury in type 2 diabetes despite BP control and ACEI, but its cessation in those with microalbuminuria ameliorates the progressive renal injury caused by continued smoking.