Smoking might affect response to ACE inhibitor in chronic kidney disease

 

CHICAGO – Smoking appears to be a modifiable risk factor for progression of chronic kidney disease associated with primary hypertension in patients treated with ACE inhibitors, Bethany Roehm, MD, reported at a meeting sponsored by the American Society of Nephrology.

Significantly increased albuminuria was noted in patients with chronic kidney disease who continued to smoke after initiating ACE inhibitor therapy, based on results from a 5-year follow-up study of 108 patients who smoked cigarettes at study entry – 25 of whom quit smoking within the first year of the study – and 108 patients who never smoked.

Further, smokers who were able to quit had improvements in measures of kidney function, said Dr. Roehm, of Tufts Medical Center, Boston, who presented the study findings.

It’s important that “we motivate our patients to stop smoking even though this can be challenging in the outpatient setting, she said. “More studies are needed to further investigate the relationship between the kidney protective effects of ACE inhibitors and the impact cigarette smoking may have on these effects.”

In addition to primary hypertension, study subjects had an estimated glomerular filtration ratio (eGFR) of 60 to 89 mL/min per 1.73 m², and a urine albumin–to-creatinine ratio (UACR) greater than 200 mg/g. At baseline, the 108 smokers had at least a 1-year history of smoking more than a pack of cigarettes daily. They were matched with 108 people who had never smoked.

The smokers received smoking cessation information and guidance; 25 quit smoking. The nonsmokers, continued smokers, and quitters were comparable at baseline. The three groups were followed for 5 years after starting treatment with an ACE inhibitor, usually enalapril.

At 5 years, average eGFR was lower (P less than .01) in continued smokers (54.9 mL/min) than in nonsmokers (66.8 mL/min) and quitters (64.1 mL/min).

Baseline levels of urine (mcg)-to-creatinine (g) isoprostane 8-isoprostaglandin F2-alpha (8-iso/cr), an indicator of lipid peroxidation, were higher in smokers than in nonsmokers. In those who quit smoking, the level had declined at 1 year and remained at a level almost identical to that seen in the nonsmokers. One-year mean urine 8-iso/cr was higher in continued smokers (3.6) than in nonsmokers (1.6, P less than .01) and quitters (1.6, P less than .01).

Systolic blood pressure declined similarly in all three groups over the follow-up.

“The smokers had a faster decline in kidney function over time than the nonsmokers and the subjects who quit smoking ... [and] our continued smokers actually had an increase in albuminuria despite being placed on an ACE inhibitor,” Dr. Roehm said in an interview. Continued smoking appeared to interfere with the decrease in urinary protein excretion that typically accompanies ACE inhibitor therapy. “Higher urine 8-iso excretion, consistent with higher oxidative stress, was present in continued smokers, suggesting oxidative stress as a factor.”

The findings need to be confirmed in larger studies and in patients with CKD due to a wider variety of causes, Dr. Roehm said. Funding for the study was provided by pharmaceutical company support to Texas Tech University, Lubbock, and the Larry and Jane Woirhaye Memorial Endowment in Renal Research. Dr. Roehm reported having no financial disclosures.

 

CHICAGO – Smoking appears to be a modifiable risk factor for progression of chronic kidney disease associated with primary hypertension in patients treated with ACE inhibitors, Bethany Roehm, MD, reported at a meeting sponsored by the American Society of Nephrology.

Significantly increased albuminuria was noted in patients with chronic kidney disease who continued to smoke after initiating ACE inhibitor therapy, based on results from a 5-year follow-up study of 108 patients who smoked cigarettes at study entry – 25 of whom quit smoking within the first year of the study – and 108 patients who never smoked.

Further, smokers who were able to quit had improvements in measures of kidney function, said Dr. Roehm, of Tufts Medical Center, Boston, who presented the study findings.

It’s important that “we motivate our patients to stop smoking even though this can be challenging in the outpatient setting, she said. “More studies are needed to further investigate the relationship between the kidney protective effects of ACE inhibitors and the impact cigarette smoking may have on these effects.”

In addition to primary hypertension, study subjects had an estimated glomerular filtration ratio (eGFR) of 60 to 89 mL/min per 1.73 m², and a urine albumin–to-creatinine ratio (UACR) greater than 200 mg/g. At baseline, the 108 smokers had at least a 1-year history of smoking more than a pack of cigarettes daily. They were matched with 108 people who had never smoked.

The smokers received smoking cessation information and guidance; 25 quit smoking. The nonsmokers, continued smokers, and quitters were comparable at baseline. The three groups were followed for 5 years after starting treatment with an ACE inhibitor, usually enalapril.

At 5 years, average eGFR was lower (P less than .01) in continued smokers (54.9 mL/min) than in nonsmokers (66.8 mL/min) and quitters (64.1 mL/min).

Baseline levels of urine (mcg)-to-creatinine (g) isoprostane 8-isoprostaglandin F2-alpha (8-iso/cr), an indicator of lipid peroxidation, were higher in smokers than in nonsmokers. In those who quit smoking, the level had declined at 1 year and remained at a level almost identical to that seen in the nonsmokers. One-year mean urine 8-iso/cr was higher in continued smokers (3.6) than in nonsmokers (1.6, P less than .01) and quitters (1.6, P less than .01).

Systolic blood pressure declined similarly in all three groups over the follow-up.

“The smokers had a faster decline in kidney function over time than the nonsmokers and the subjects who quit smoking ... [and] our continued smokers actually had an increase in albuminuria despite being placed on an ACE inhibitor,” Dr. Roehm said in an interview. Continued smoking appeared to interfere with the decrease in urinary protein excretion that typically accompanies ACE inhibitor therapy. “Higher urine 8-iso excretion, consistent with higher oxidative stress, was present in continued smokers, suggesting oxidative stress as a factor.”

The findings need to be confirmed in larger studies and in patients with CKD due to a wider variety of causes, Dr. Roehm said. Funding for the study was provided by pharmaceutical company support to Texas Tech University, Lubbock, and the Larry and Jane Woirhaye Memorial Endowment in Renal Research. Dr. Roehm reported having no financial disclosures.

 

CHICAGO – Smoking appears to be a modifiable risk factor for progression of chronic kidney disease associated with primary hypertension in patients treated with ACE inhibitors, Bethany Roehm, MD, reported at a meeting sponsored by the American Society of Nephrology.

Significantly increased albuminuria was noted in patients with chronic kidney disease who continued to smoke after initiating ACE inhibitor therapy, based on results from a 5-year follow-up study of 108 patients who smoked cigarettes at study entry – 25 of whom quit smoking within the first year of the study – and 108 patients who never smoked.

Further, smokers who were able to quit had improvements in measures of kidney function, said Dr. Roehm, of Tufts Medical Center, Boston, who presented the study findings.

It’s important that “we motivate our patients to stop smoking even though this can be challenging in the outpatient setting, she said. “More studies are needed to further investigate the relationship between the kidney protective effects of ACE inhibitors and the impact cigarette smoking may have on these effects.”

In addition to primary hypertension, study subjects had an estimated glomerular filtration ratio (eGFR) of 60 to 89 mL/min per 1.73 m², and a urine albumin–to-creatinine ratio (UACR) greater than 200 mg/g. At baseline, the 108 smokers had at least a 1-year history of smoking more than a pack of cigarettes daily. They were matched with 108 people who had never smoked.

The smokers received smoking cessation information and guidance; 25 quit smoking. The nonsmokers, continued smokers, and quitters were comparable at baseline. The three groups were followed for 5 years after starting treatment with an ACE inhibitor, usually enalapril.

At 5 years, average eGFR was lower (P less than .01) in continued smokers (54.9 mL/min) than in nonsmokers (66.8 mL/min) and quitters (64.1 mL/min).

Baseline levels of urine (mcg)-to-creatinine (g) isoprostane 8-isoprostaglandin F2-alpha (8-iso/cr), an indicator of lipid peroxidation, were higher in smokers than in nonsmokers. In those who quit smoking, the level had declined at 1 year and remained at a level almost identical to that seen in the nonsmokers. One-year mean urine 8-iso/cr was higher in continued smokers (3.6) than in nonsmokers (1.6, P less than .01) and quitters (1.6, P less than .01).

Systolic blood pressure declined similarly in all three groups over the follow-up.

“The smokers had a faster decline in kidney function over time than the nonsmokers and the subjects who quit smoking ... [and] our continued smokers actually had an increase in albuminuria despite being placed on an ACE inhibitor,” Dr. Roehm said in an interview. Continued smoking appeared to interfere with the decrease in urinary protein excretion that typically accompanies ACE inhibitor therapy. “Higher urine 8-iso excretion, consistent with higher oxidative stress, was present in continued smokers, suggesting oxidative stress as a factor.”

The findings need to be confirmed in larger studies and in patients with CKD due to a wider variety of causes, Dr. Roehm said. Funding for the study was provided by pharmaceutical company support to Texas Tech University, Lubbock, and the Larry and Jane Woirhaye Memorial Endowment in Renal Research. Dr. Roehm reported having no financial disclosures.