High homocysteine levels increases TyG index-CKD imbalance in hypertensive patients: Study
A recent study published in the journal of BMC Nephrology revealed that elevated homocysteine levels can significantly intensify the risk of chronic kidney disease (CKD) associated with metabolic imbalance, measured by the triglyceride-glucose (TyG) index, in people with hypertension.
Chronic kidney disease is a growing public health concern worldwide, particularly among people with high blood pressure. While traditional risk factors such as diabetes and age are well known, homocysteine has gained recognition as a contributor to kidney damage. At the same time, the TyG index is increasingly used as a surrogate marker of insulin resistance.
This study analyzed data from 26,679 hypertensive adults recruited from multiple centers across China. CKD was defined as an estimated glomerular filtration rate below 60 ml/min/1.73 m², which indicates a reduced kidney function. Overall, 7% of participants met the criteria for CKD.
The participants were grouped according to their homocysteine (Hcy) levels and further categorized into quartiles based on their TyG index values. This research examined not only whether TyG was associated with CKD, but also whether this association differed depending on homocysteine levels.
The analyses showed that among individuals with elevated homocysteine, every one-unit increase in the TyG index was associated with a 37 percent higher odds of having CKD. In contrast, the relationship was weaker and statistically uncertain among those with lower homocysteine levels. When looking across TyG quartiles, people with both high TyG and high homocysteine consistently showed progressively higher odds of CKD as their TyG levels rose.
After accounting for age, sex, lifestyle habits, blood pressure, and other potential confounding factors, participants who had both a high TyG index and elevated homocysteine faced more than an 11-fold increase in the odds of CKD when compared to the ones who had lower levels of both markers. This suggests a strong synergistic effect, meaning the combined impact of these 2 factors is much greater than either alone.
Overall, the results indicate that hypertensive patients with high homocysteine may be particularly vulnerable to kidney damage if they also show signs of metabolic imbalance reflected by a high TyG index. Since both triglycerides, glucose, and homocysteine can be measured through routine blood tests, this combined assessment could offer clinicians a simple and cost-effective way to improve early risk stratification for CKD.
Reference:
Zhou, W., Yu, C., Bao, H., & Cheng, X. (2025). Homocysteine levels alter the TyG index-CKD link in Chinese hypertensive patients. BMC Nephrology. https://doi.org/10.1186/s12882-025-04714-y
