Plasma Homocysteine Is a Predictive Factor for Accelerated Renal Function Decline and Chronic Kidney Disease in a Community-Dwelling Population

Abstract

<b><i>Background:</i></b> Whether elevated plasma total homocysteine (tHcy) is a risk factor for the progression of kidney disease in general population has not been well established. The purpose of this study was to investigate the prognostic properties of plasma tHcy for renal function decrement and early chronic kidney disease (CKD) in community-dwelling populations with normal renal function at baseline. <b><i>Methods:</i></b> A total of 1,426 participants were enrolled and followed for a median of 4.8 years (interquartile range, 4.5–5.2), and estimated glomerular filtration rate (eGFR) was evaluated. One main outcome was the rapid eGFR decline defined as a decline in eGFR of >3 mL/min per 1.73 m<sup>2</sup> per year; the other was the new incidence of CKD. <b><i>Results:</i></b> At the end of follow-up, the incidence of rapid eGFR decline and new-onset CKD was 20.7 and 5.6%, respectively. In multivariate linear regression analysis, age, central pulse pressure, fasting blood glucose, and concentration of tHcy were independent determinants of the change in eGFR. There was a graded association between tHcy quartiles and eGFR decline. Compared with participants with the lowest quartile of tHcy levels, those with the highest quartile had significantly increased risk for rapid eGFR decline (adjusted odds ratio [aOR] = 1.81; 95% confidence interval [CI]: 1.25–2.94) and new onset of CKD (adjusted hazard ratio = 4.29; 95% CI: 1.42–12.99) after adjusting for various confounders. Similarly, significant associations were also found when baseline tHcy was classified as hyperhomocysteinemia (>15 μmol/L) versus normal tHcy level (≤15 μmol/L). However, there was only association between the change in tHcy levels and new occurrence of CKD but not with rapid eGFR decline (aOR = 0.99, <i>p</i> = 0.613). <b><i>Conclusions:</i></b> In this prospective cohort of individuals from community-based population, elevated plasma tHcy emerged as an independent predictor of renal function decline and incident CKD, which might support selection of at-risk individuals.

Association of hyperhomocysteinemia and chronic kidney disease in the general population: a systematic review and meta-analysis

“…The characteristics of the 11 studies are shown in Table 1 [ 6 , 15 – 24 ]. A total of 79,416 participants were included, with sample sizes ranging from 999 to 19,372.…”

“…In a cohort study, tHcy concentration was found to be an independent determinant of eGFR changes. There was a graded association between tHcy quartiles and eGFR decline [ 6 ]. However, these results remain inconclusive due to the complex bidirectional interaction between changes in Hcy levels and renal function, while the coexistence of risk factors such as diabetes and hypertension [ 7 , 8 ] complicates the definition of the role of Hcy.…”

Relationship between plasma homocysteine and chronic kidney disease in US patients with type 2 diabetes mellitus:a cross-sectional study

“…[17][18][19] Increasing evidence indicates that the potential causes of Hcy excretion are reduced in CKD patients. 20 Fig. 2 indicates that renal function gradually deteriorated with increasing Hcy levels.…”

Relationship between plasma homocysteine and chronic kidney disease in US patients with type 2 diabetes mellitus: a cross-sectional study

“…Increasing evidence indicated that there was a graded association between Hcy quartiles and eGFR decline. Compared with participants with the lowest quartile of Hcy levels, those with the highest quartile had significantly increased risk for rapid eGFR decline [ 21 ]. Figure.…”