Hyperhomocysteinemia and its association with decreased glomerular filtration rate in patients with chronic kidney disease: a comprehensive meta-analysis.

Background: Hyperhomocysteinemia (elevated homocysteine, Hcy) is common in chronic kidney disease (CKD) patients, but its effect on glomerular filtration rate (GFR), a key renal function indicator, is unclear. Objective: This meta-analysis aimed to clarify the association between hyperhomocysteinemia (HHcy, defined as Hcy > 15 µmol/L) and reduced glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients, hypothesizing that HHcy is associated with a more significant GFR reduction. To test this hypothesis, a comprehensive search was conducted in PubMed, Embase, Cochrane databases, and reference lists. The primary outcome of interest was the relationship between HHcy and GFR decline in CKD. Methods For this meta-analysis, we established clear inclusion and exclusion criteria to identify eligible studies. Studies were included if they involved patients with chronic kidney disease (CKD), employed randomized controlled, cross-sectional, or cohort study designs, included participants aged 14 years or older, and reported or permitted the calculation of glomerular filtration rate (GFR) and homocysteine (Hcy) levels. We excluded studies that were not in English, focused on acute kidney injury, end-stage kidney disease, or dialysis patients, lacked clear group definitions, were based on animal models, or used non-standard CKD definitions. A comprehensive search strategy was employed to identify relevant studies. We combined MeSH terms (e.g., "homocysteine [MeSH]" and "renal insufficiency, chronic [MeSH]") with free-text keywords in major databases, including PubMed, Embase, and Web of Science. Additionally, we utilized the "related items" function and applied Boolean operators to refine search results. Data were synthesized through meta-analysis, and the mean ± SD of GFR in CKD patients according to Hcy levels were calculated for comparison. All databases were searched from their inception dates to June 2024. Results: CKD patients with hyperhomocysteinemia had a lower GFR (SMD = 2.26, 95% CI [1.37-3.15]). However, significant inter-study heterogeneity (P < 0.01, I 2 = 99.5%) was found. Five articles (Z 2016, Ye, Z 2017, Zhang, Y 2020, Shen, Z 2022, Wu, and J 2022) contributed to it (P = 0.015 < 0.05). Subgrouping them eliminated heterogeneity (P = 0.52, I 2 = 0.00%). Sensitivity analysis showed individual article exclusion had little effect on the result. But Egger tests showed publication bias (P < 0.05), while scissors graph analysis supported result stability (P < 0.01). Conclusions: In CKD, elevated Hcy is related to kidney function decline.