Smoking Counteracts the Benefit of Medications for Kidney Disease

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Smoking may partly counteract the benefits of treatment with angiotensin converting enzyme inhibitors (ACE inhibitors) for patients with chronic kidney disease (CKD), according to a study presented at Kidney Week 2016.

Smoking has been linked to worsening kidney decline, but the exact mechanisms are unclear, according to lead author Bethany Roehm, MD, of Tufts Medical Center in Boston.

“The importance of smoking as a renal risk factor is highlighted by the fact that its negative effects have been shown in subjects of the general population and in patients with primary or secondary renal disease,” said Stephan R. Orth, MD, PhD, FASN, of the Dialysis Center in Bad Aibling, Germany (Hallan SI and Orth SR. Kidney Int 2011; 80:516–523).

One of the reasons it is difficult to pinpoint how smoking contributes to kidney disease exacerbation is that cigarette smoke is made up of more than 4000 chemicals, Orth said, but it is “sensible to assume that several of these components act as nephrotoxic potpourri.”

To further study smoking’s effects, Roehm and her colleagues enrolled 216 patients with early CKD who were taking ACE inhibitors; 108 were smokers and 108 were nonsmokers. All of the smokers were given a smoking cessation intervention, but 83 continued to smoke and 25 quit. All of the patients were followed for 5 years after starting ACE inhibitors. At enrollment, patients in all groups had comparable estimated glomerular filtration rate (eGFR) and systolic and diastolic blood pressures. But urinary 8-Iso/cr was higher in the continuing smokers and those who later quit.

Those who never smoked and those who quit had slower worsening of their kidney function, according to Dr. Roehm and her colleagues. After 1 year of taking ACE inhibitors, the nonsmokers had lowered their alb/cr to 395 ± 143 compared with 420 ± 148 (p<0.01) at initiation. In quitters these levels didn’t change significantly from their entry levels, (356 ± 178 vs. 367 ± 160, p=0.15). But continuing smokers saw increases in alb/cr (453 ± 152 vs 426 ±138, p<0.01). Continuing smokers also had higher urinary 8-iso/cr (3.6 ± 0.8) than nonsmokers (1.6 ± 0.3, p<0.01) and quitters (1.6 ± 0.3, p<0.01). At 5 years, eGFRs were also lower in the continued smokers (54.9 ± 5.6 mL/min) than in the nonsmokers (66.8 ± 5.8 mL/min) and quitters (64.1 ± 5.6 mL/min) with a p value <0.01.

Dr. Roehm and her colleagues concluded that ongoing smoking was counteracting the typical decrease in protein excretion seen in patients treated with ACE inhibitors likely owing to oxidative stress.

“It has practically become dogma that if you have a patient with high blood pressure and CKD that you start them on an ACE inhibitor, and we are often comforted as clinicians that we are doing something to help slow progression of their kidney disease in doing this,” said Dr. Roehm. “But our data suggest that in smokers this may not be the case, and our study underscores the importance of doing all we can as clinicians to encourage our patients to stop smoking.”

The study shows ACE inhibitors alone are not enough to counteract smoking’s affects, said Orth.

“The results are absolutely in line with what we know about the renal effects of smoking in patients with nephrosclerosis and other renal diseases,” he said. “The newest aspect is that ACE inhibition is not able to fully protect from the adverse renal effects of smoking.”

But cessation strategies can make a big difference. “The benefit of quitting smoking was particularly impressive due to the fact that eGFR at the end of the study [for quitters] did not differ from never-smokers,” Orth said.

Studies that show how nephrologists can boost cessation rates would be useful, said Orth.

“Nephrologists should be aware that smoking cessation strategies in smokers with a diseased kidney are part of their therapeutic armamentarium,” he said.

“Cigarette Smoking Partially Negates the Kidney Protective Effect of ACE Inhibition in Stage 2, Non-Diabetic, Hypertension-Associated CKD” (Abstract 2784)