Urine Cotinine Improves Assessment of CKD Risk

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Compared with patient-reported smoking history, a urine cotinine measurement may provide a more reliable indicator of the risk for developing chronic kidney disease (CKD), according to a study in Nephrology Dialysis Transplantation.

The analysis included data on 4333 individuals from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) trial, a population cohort study examining the progression of urinary albumin excretion (UAE) and its impact on kidney diseases and cardiometabolic conditions. The participants (mean age, 52 years) had no history of CKD at baseline. Self-reported smoking status was 31% in participants who never smoked; 41.5%, former smokers; 10%, light and current smokers; and 17%, heavy and current smokers. Smoking status was also assessed by measurement of urine cotinine.

Self-reported smoking status was strongly correlated with urine cotinine level. However, the two measures showed only weak agreement in classification of smoking status. Of 3140 self-reported never or former smokers, 1.8% were classified as active smokers on cotinine measurement, with an overall misclassification rate of 4.6%.

At 7 years’ follow-up, CKD developed in 593 participants. After adjustment for established risk factors, the likelihood of CKD was elevated for light and heavy current smokers: hazard ratio (HR), 1.48 for each compared with never smokers. On further adjustment for UAE, the HRs associated with self-reported smoking were no longer significant. In contrast, HRs associated with cotinine-assessed light and heavy smoking were 1.23 and 1.32, respectively, with “minimal” effect of adjustment for UAE.

Previous reports of the association between smoking and CKD risk have been based mainly on patient–patient-reported smoking status. The new study examines CKD risks associated with urine cotinine, an objective measure of nicotine exposure.

The results suggest that urine cotinine measurement provides a more reliable indicator of CKD risk compared with self-reported smoking. Associations between patient-reported current smoking and CKD appear to be dependent on UAE.

The findings indicate a “considerable rate of misclassification” of smoking status based on patient report, whether associated with underreporting or lack of awareness of exposure to tobacco smoke. Citing the effects of adjustment for UAE, smoking-related kidney damage may be “partly mediated through its effects on or biological mechanisms related to increasing albumin excretion,” the researchers write [Kunutsor SK, et al. Urine cotinine versus self-reported smoking and the risk of chronic kidney disease. Nephrol Dial Transpl, published online February 24, 2024. doi: 10.1093/ndt/gfae054].