Original Investigations
Cigarette smoking predicts faster progression of type 2 established diabetic nephropathy despite ACE inhibition,☆☆,

https://doi.org/10.1053/ajkd.2002.30559Get rights and content

Abstract

Blood pressure reduction and angiotensin-converting enzyme (ACE) inhibitors slow but do not stop progressive decline of renal function in established diabetic nephropathy (DN), but predictors of this decline in patients undergoing these interventions are unknown. We prospectively examined patients to determine whether age, sex, ethnicity, mean blood pressure, plasma creatinine, urine protein excretion, and cigarette smoking predict renal function decline in type 2 DN treated toward the recommended mean blood pressure goal of 92 mm Hg (about 125/75 mm Hg) with antihypertensives including ACE inhibitors. Thirty-three DN patients with initial plasma creatinine less than 1.4 mg/dL were followed 64.0 ± 1.1 months. After correcting for differences in follow-up time, demographic variables, and other relevant variables, plasma creatinine increased, indicating renal function decline despite mean blood pressure reduction to 92 ± 1 mm Hg and administration of ACE inhibitors. Regression analysis showed that smoking was the only examined parameter that significantly predicted renal function decline. Smokers (n = 13) and nonsmokers (n = 20) had similar follow-up (61.4 ± 2.1 months versus 65.7 ± 1.1 months), mean blood pressure (91 ± 1 mm Hg versus 92 ± 1 mm Hg), and initial plasma creatinine (1.05 ± 0.08 mg/dL versus 1.08 ± 0.03 mg/dL). Nevertheless, follow-up plasma creatinine was higher in smokers than nonsmokers (1.78 ± 0.20 mg/dL versus 1.32 ± 0.04 mg/dL). The data show that renal function declines faster in smokers than nonsmokers with type 2 DN undergoing treatment to improve blood pressure including ACE inhibitors. Cigarette smoking remains a risk factor for renal function decline in type 2 DN despite currently recommended therapy. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Materials and methods

Patients eligible for this study were diabetics referred to the Texas Tech University Health Sciences Center (TTUHSC) nephrology clinic for evaluation and management of urine dipstick-positive proteinuria (≥1+). Study subjects were recruited in 1995 to be followed until the end of 2000. Patients were determined to have diabetes by their primary care physician and must have had at least one documented fasting blood glucose level greater than 126 mg/dL before beginning hypoglycemic therapy. All

Results

Table 1 shows initial patient characteristics and after 64.0 ± 1.1 months of follow-up.

. Entry and Follow-Up Characteristics of Study Patients (n = 33)

Age (y)Sex (% M)Body Weight (kg)Ethnicity (% B/W/H)Systolic BP (mm Hg)Diastolic BP (mm Hg)Mean BP (mm Hg)Hemoglobin A1c (%)Plasma Albumin (mg/dL)Plasma Creatinine (mg/dL)Calculated GFR (mL/min)Smoke? (% Yes)Urine Protein-to-Creatinine Ratio
Initial
45.5 ± 2.05583.9 ± 2.024.2/30.3/45.5145.1 ± 3.086.6 ± 2.1106.1 ± 2.210.6 ± 0.93.6 ± 0.21.06 ± 0.03

Discussion

Patients with DN progress inexorably toward ESRD, albeit more slowly with improved BP and ACE inhibitor therapy.3, 4, 5, 6 We prospectively examined clinical factors that predict progression of type 2 DN in patients with initially well-preserved renal function and treated as currently recommended.2 Cigarette smoking was the only examined factor that predicted DN progression, and the rate in smokers was twice that of nonsmokers. These studies show that smoking is a risk factor for DN progression

Acknowledgements

We are thankful to Kay T. Kimball, PhD, and Ronald B. Harrist, PhD, for expert statistical analysis. We also thank the nursing and clerical staff of the Internal Medicine Clinic of the Department of Internal Medicine at Texas Tech University Health Sciences Center, for their valuable assistance.

References (30)

  • S Klahr et al.

    The effects of dietary protein restriction and blood-pressure control on the progression chronic renal disease

    N Engl J Med

    (1994)
  • CC Cowie et al.

    Disparities in incidence of incidence of diabetic end-stage renal disease according to race and type of diabetes

    N Engl J Med

    (1989)
  • HH Parving et al.

    Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy

    Lancet

    (1983)
  • TV Perneger et al.

    Projections of hypertension-related renal disease in middle-aged residents of the United States

    JAMA

    (1993)
  • JS Christiansen

    Cigarette smoking and the prevalence of microangiopathy in juvenile-onset insulin-dependent diabetes mellitus

    Diabetes Care

    (1978)
  • Cited by (0)

    Supported by Texas Tech University Health Sciences Center.

    ☆☆

    Address reprint requests to Donald E. Wesson, MD, Texas Tech University Health Sciences Center, 3601 Fourth Street, Lubbock, TX 79430. E-mail: [email protected]

    0272-6386/02/3902-0018$35.00/0

    View full text