Study Finds Discrepancies in Relationship Between CKD and Smoking

According to results from a recent study published in Health Data Science, there is a positive correlation between smoking and chronic kidney disease (CKD). The authors noted that although the relationship is not considered a casual effect, covariates in which smoking is a risk factor (eg, hypertension, diabetes) can be factors leading to the onset of CKD. ^1,2

Image credit: ehabeljean | stock.adobe.com

Prior research showed that smoking behavior or smoking status was associated with an elevated risk of CKD, though whether the association was “casual” was unknown. For this study, the investigators enrolled approximately 500,000 participants aged 40 to 69 years of age from the UK Biobank cohort. A traditional observational study was performed to assess the statistical association between smoking and CKD based on the data, and a subsequent 1-sample mendelian randomization (MR) was conducted to evaluate the potential casual association between smoking and CKD.¹

Lifetime smoking information was gathered from all participants and included smoking intensity, duration, and smoking initiation and cessation. The study’s main outcome was the development of stages 3 to 5 CKD.¹

In the observational study, 15,135 patients (3.1%) were diagnosed with CKD over a median of 12.8 years of follow-up. Additionally, 220,752 (45.1%) had reported never smoking. Compared with nonsmokers, smokers were more likely to develop CKD, be unemployed, have a lower income, and have a body mass index (BMI) of at least 30 kg/m². Further, in the 1-sample MR, 13,573 (3.9%) participants were diagnosed with incident CKD.¹

Both smoking status (HR: 1.26, 95% CI: 1.22-1.30) and lifetime smoking index (HR: 1.22, 95% CI: 1.20-1.24) were positively associated with a higher risk of CKD in the traditional observational study. Despite these associations, the MR analyses demonstrated no casual association between lifetime smoking index and CKD (P > .05). Further, lifetime smoking index was shown to be near-linearly associated with incident CKD. The authors note that these associations may be a result of unmeasured confounding during evaluation.¹

Limitations of this research include the lack of generalizability because of the UK-based population and enrolled age range (40-69 years) and the potential biases when measuring lifetime smoking indexes. Recall bias may also be a factor because patients were asked to record smoking intensity, duration, as well as smoking initiation and cessation through self-reported questionnaires.¹

“Our results emphasize the need for more detailed mediation analyses on large-scale, multi-ethnic datasets to fully understand the interplay between smoking and CKD,” Luxia Zhang, professor, National Institute of Health Data Science at Peking University, said in a news release. “While smoking remains a significant health risk factor, its direct role in CKD development requires further investigation.”²

The authors determined that although there are discrepancies in the observational study and MR analysis results, an implication that smoking can contribute to CKD onset is present; however, this association may be a result of covariates related to smoking, rather than between smoking and CKD. Further research and analyses are needed to better understand associations between smoking or smoking-related covariates and CKD. Insights may contribute to treatment or mitigating CKD risk factors, therefore, improving overall kidney health.^1,2

REFERENCES

1. Zhang Z, Zhang F, Zhang X, Lu L, Zhang L. Association of Smoking with Chronic Kidney Disease Stages 3 to 5: A Mendelian Randomization Study. Health Data Sci. 2024;4:0199. doi:10.34133/hds.0199

2. Study finds smoking linked to increased risk of chronic kidney disease in later stages. News release. January 1, 2025. Accessed January 3, 2025. https://www.eurekalert.org/news-releases/1069201