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Cigarette Smoking Enhances Increased Urine Albumin Excretion as a Risk Factor for Glomerular Filtration Rate Decline in Primary Hypertension

Background:Subjects with severe compared with mild primary hypertension are at greater risk for decline in glomerular filtration rate (GFR), but additional risk factors are poorly defined. Methods:Seventy-five subjects referred for assistance with blood pressure control (“severe”) and 150 not-referred hypertensive subjects (“mild”) were prospectively followed for 7 years. The primary outcome was the change in calculated GFR during follow-up as predicted by various clinical parameters, including urine albumin excretion measured as urine albumin (mg)-to-creatinine (g) (alb/cr) ratio. Results:Calculated GFR declined faster (more negative slope) in patients with severe hypertension than in those with mild hypertension (-0.188 ± 0.025 versus -0.120 ± 0.008 mL/min/month; P = 0.010), despite similar follow-up systolic blood pressure (133.4 ± 1.2 versus 131.9 ± 0.8 mm Hg). Severe subjects had higher entry alb/cr (241.3 ± 29.1 versus 11.4 ± 0.5) and a greater proportion of cigarette smokers than mild subjects (56 versus 19%). Regression analysis comparing GFR decline to alb/cr showed that GFR changed minimally for alb/cr up to 200 but declined at a progressively faster rate as alb/cr increased above 200. GFR declined faster (more negative slope) in smokers than in nonsmokers (-0.231 ± 0.023 versus -0.102 ± 0.008 mL/min/month; P < 0.001). Cigarette smoking increased the risk for GFR decline in subjects with alb/cr <200 and in those with alb/cr >200, but the effect was much more robust for subjects with alb/cr >200. Conclusions:Urine alb/cr >200 increases the risk for subsequent GFR decline in primary hypertension, and this risk is enhanced by cigarette smoking.