Smoking and Adverse Outcomes in Patients With CKD: The Study of Heart and Renal Protection (SHARP)

Abstract

Background: The absolute and relative importance of smoking to vascular and nonvascular outcomes in people with chronic kidney disease (CKD), as well its relevance to kidney disease progression, is uncertain.

Study design: Observational study.

Setting & participants: 9,270 participants with CKD enrolled in SHARP.

Predictor: Baseline smoking status (current, former, and never).

Outcomes: Vascular events, site-specific cancer, ESRD, rate of change in estimated glomerular filtration rate (eGFR), and cause-specific mortality.

Results: At baseline, 1,243 (13%) participants were current smokers (median consumption, 10 cigarettes/day); 3,272 (35%), former smokers; and 4,755 (51%), never smokers. Median follow-up was 4.9 years. Vascular event rates were 36% higher for current than never smokers (2,317 events; relative risk [RR], 1.36; 95% CI, 1.19-1.55), reflecting increases in both atherosclerotic (RR, 1.49; 95% CI, 1.26-1.76) and nonatherosclerotic (RR, 1.25; 95% CI, 1.05-1.50) events. Cancer was 37% higher among current smokers (632 events; RR, 1.37; 95% CI, 1.07-1.76), with the biggest RRs for lung (RR, 9.31; 95% CI, 4.37-19.83) and upper aerodigestive tract (RR, 4.87; 95% CI, 2.10-11.32) cancers. For 6,245 patients not receiving dialysis at baseline, ESRD incidence did not differ significantly between current and never smokers (2,141 events; RR, 1.02; 95% CI, 0.89-1.17), nor did estimated rate of change in eGFR (current smokers, -1.77±0.14 [SE]; never smokers, -1.70±0.07mL/min/1.73m(2) per year). All-cause mortality was 48% higher among current smokers (2,257 events; RR, 1.48; 95% CI, 1.30-1.70), with significant increases in vascular (RR, 1.35; 95% CI, 1.07-1.69) and nonvascular (RR, 1.60; 95% CI, 1.34-1.91) causes of death, especially cancer (RR, 2.32; 95% CI, 1.58-3.40) and respiratory (RR, 2.25; 95% CI, 1.51-3.35) mortality.

Limitations: Smoking status not assessed during follow-up.

Conclusions: In this study of patients with CKD, smoking significantly increased the risks for vascular and nonvascular morbidity and mortality, but was not associated with kidney disease progression. The associations with vascular and neoplastic disease are in keeping with those observed in the general population and are likely modifiable by cessation.

Keywords: Cigarette smoking; Study of Heart and Renal Protection (SHARP); cancer; cause-specific mortality; chronic kidney disease (CKD); disease progression; end-stage renal disease (ESRD); estimated glomerular filtration rate (eGFR); risk factor; tobacco; vascular events; vascular morbidity.

Figure 1

Relevance of baseline smoking status to vascular outcomes, (A) overall and (B) separately by history of cardiovascular disease (CVD) or diabetes. Relative risks are adjusted for age, sex, ethnicity, country, education, and for (A) only, prior disease (prior CVD and diabetes) and are quoted above the squares. Numbers of events in each group are quoted below the squares. Abbreviation: CI, confidence interval.

Figure 2

Relevance of baseline smoking status to (A) cancer incidence and (B) site-specific cancer. All relative risks (RRs) and annual event rates are adjusted for age, sex, ethnicity, country, education, and prior disease (prior cardiovascular and diabetes). In (A), RRs are quoted above the squares with numbers of events quoted below the squares. Abbreviations: CI, confidence interval; py, per year.

Figure 3

Relevance of baseline smoking status to renal progression among 6,245 patients not on dialysis therapy at randomization. Relative risks are adjusted for age, sex, ethnicity, country, education, and prior disease (prior cardiovascular and diabetes) and are quoted above the squares with the number of events quoted below the squares. Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease.

Figure 4

Relevance of baseline smoking status to cause-specific mortality, (A) overall and (B) separately by history of cardiovascular disease (CVD) or diabetes. Relative risks are adjusted for age, sex, ethnicity, country, education, and for (A) only, prior disease (prior CVD and diabetes) and are quoted above the squares. Numbers of events in each group are quoted below the squares. Abbreviation: CI, confidence interval.