A recent study has highlighted the protective role of soluble Klotho (sKlotho) in individuals with diabetes and hypertension, suggesting that higher levels of this protein are associated with a lower prevalence of chronic kidney disease (CKD). However, the research also indicates that hypertension may modify the effect of sKlotho on kidney function.
Soluble Klotho, a protein known to support kidney health, has been the subject of considerable debate regarding its role in diabetes and hypertension. Previous research has indicated connections between Klotho and hypertension, but treatments have predominantly focused on blood pressure management rather than addressing underlying causes of hypertension, due to the incomplete understanding of its mechanisms.
The study analyzed data from 3,302 adults aged 40 and older with diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Researchers used multivariate logistic regression models to examine the relationship between sKlotho levels and CKD prevalence, stratified by hypertension status. They found that in individuals with both diabetes and hypertension, those with higher sKlotho levels (≥ 806 pg/mL) had a significantly lower prevalence of CKD compared to those with lower levels (< 806 pg/mL), with an odds ratio of 0.54 (95% CI, 0.41-0.72; P < .001).
Importantly, no such association between sKlotho and CKD was found in participants with diabetes but without hypertension. The study also revealed a synergistic effect between low sKlotho levels and hypertension, where the combined presence of these factors increased CKD risk more than either factor alone.
In individuals with diabetes but no hypertension, a trend emerged indicating that very high sKlotho levels (> 1400 pg/mL) were associated with a higher prevalence of CKD. This group also exhibited higher blood glucose levels and kidney function markers, which may be influenced by more aggressive anti-diabetic treatments that could elevate Klotho levels. However, the researchers noted that the reasons for this trend remain unclear and require further exploration.
While the study provides valuable insights, its cross-sectional design limits the ability to draw causal conclusions. The researchers acknowledged the potential for reverse causality and unmeasured confounding factors. Moreover, since the study was conducted among U.S. adults, its findings may not be generalizable to other populations.
Overall, the study suggests that hypertension may act as a key modifier in the relationship between sKlotho levels and CKD, potentially clarifying inconsistencies found in earlier research on the subject. Further investigation is needed to understand the complex interactions and to explore whether interventions targeting sKlotho levels could benefit patients with both diabetes and hypertension.
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