Effect of uric acid and estimated glomerular filtration rate on the Fibrosis-4 index: A cross-sectional and cohort analysis.
4 affiliations
- 1Department of General Medicine, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu City, Zhejiang Province, China.
- 2Department of Geriatric Medicine, Center for Regeneration and Aging Medicine, International Institutes of Medicine, Zhejiang University, Yiwu City, Zhejiang Province, China.
- 3Faculty of Information, University of Toronto, Toronto, ON, Canada.
- 4Department of Information Technology, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu City, Zhejiang Province, China.
Abstract
Hepatic steatosis and fibrosis present a significant public health burden, especially in China. Emerging evidence suggests an association between liver fibrosis and kidney function, indicating a potential relationship among uric acid (UA) levels, estimated glomerular filtration rate (eGFR), and the Fibrosis-4 (FIB-4) index. This retrospective cohort study investigates the correlation between UA, estimated GFR, and FIB-4 index in Chinese adults with metabolic dysfunction-associated steatotic liver disease (MASLD) using cross-sectional and longitudinal analyses. A total of 5051 adults with MASLD were included from 8857 individuals initially screened at the International Healthcare Center, Fourth Affiliated Hospital, Zhejiang University School of Medicine. The main outcome measure was the FIB-4 index. Among the 5051 participants (75.4% male; mean age, 42.3 years), the mean baseline eGFR was 98.7 mL/min/1.73 m2. Participants with lower eGFR had significantly older age and higher body mass index, systolic blood pressure, triglycerides, UA levels, and FIB-4 index than those with higher eGFR (P < .001 for all). In multivariable Cox regression analyses, each 1-standard deviation decrease in eGFR was associated with a 21% higher risk of an increased FIB-4 index (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.14-1.29; P < .001). Hyperuricemia (UA ≥ 420 μmol/L) was independently associated with a 38% higher risk of elevated FIB-4 (HR, 1.38; 95% CI: 1.23-1.55; P < .001). In the unadjusted model, a significant nonlinear dose-response relationship was observed between eGFR and FIB-4 (P for nonlinear trend < .001). However, after progressive adjustment for demographic variables, family history, and metabolic covariates, the nonlinear signal was markedly attenuated. Mediation analysis demonstrated that UA partially mediated the association between eGFR and FIB-4, accounting for 6.88% of the total effect. Reduced eGFR and hyperuricemia were independently associated with an elevated FIB-4 index in adults with MASLD, with a nonlinear relationship indicating a greater liver fibrosis risk in individuals with moderate to severe renal impairment (eGFR < 60 mL/min/1.73 m2). Partial mediation by UA suggests that metabolic dysregulation contributes to the kidney-liver interaction. Routine assessment of eGFR and UA may improve liver fibrosis risk stratification in patients with MASLD.
Related
- Anemia and Red-Cell Size Across Estimated Glomerular Filtration Rate in a Hospital Laboratory Cohort
- Kidney Health Biomarkers and Estimated Glomerular Filtration Rate Among Indonesian Tofu Production Workers: A Pilot Cross-Sectional Study.
- Longitudinal Changes in Albuminuria and Estimated Glomerular Filtration Rate in Patients with Type 2 Diabetes Treated with Empagliflozin or Canagliflozin: A Real-World Cohort Study
- Non-invasive assessment of estimated glomerular filtration rate using lens autofluorescence in a population without chronic kidney disease
- Meeting a Proposed Estimated Glomerular Filtration Rate Slope-Based Criterion for Clinical Remission of Chronic Kidney Disease During Sequential Kidney-Protective Therapy in Type 2 Diabetes Mellitus: A Case Report
BibTeX
@article{xu2026effect,
title = {{Effect of uric acid and estimated glomerular filtration rate on the Fibrosis-4 index: A cross-sectional and cohort analysis.}},
author = {Weina Xu and Danxiang Chen and Saiyun Lou and Jiannan Wu and Yinshan Liu and Ruiqi Liu and Hanjie Chen},
journal = {Medicine},
year = {2026},
month = oct,
doi = {10.1097/md.0000000000051217},
url = {https://europepmc.org/article/MED/42888618},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effect of uric acid and estimated glomerular filtration rate on the Fibrosis-4 index: A cross-sectional and cohort analysis.
AU - Weina Xu
AU - Danxiang Chen
AU - Saiyun Lou
AU - Jiannan Wu
AU - Yinshan Liu
AU - Ruiqi Liu
AU - Hanjie Chen
PY - 2026
DA - 2026/10/01
JO - Medicine
DO - 10.1097/md.0000000000051217
UR - https://europepmc.org/article/MED/42888618
AB - Hepatic steatosis and fibrosis present a significant public health burden, especially in China. Emerging evidence suggests an association between liver fibrosis and kidney function, indicating a potential relationship among uric acid (UA) levels, estimated glomerular filtration rate (eGFR), and the Fibrosis-4 (FIB-4) index. This retrospective cohort study investigates the correlation between UA, estimated GFR, and FIB-4 index in Chinese adults with metabolic dysfunction-associated steatotic liver disease (MASLD) using cross-sectional and longitudinal analyses. A total of 5051 adults with MASLD were included from 8857 individuals initially screened at the International Healthcare Center, Fourth Affiliated Hospital, Zhejiang University School of Medicine. The main outcome measure was the FIB-4 index. Among the 5051 participants (75.4% male; mean age, 42.3 years), the mean baseline eGFR was 98.7 mL/min/1.73 m2. Participants with lower eGFR had significantly older age and higher body mass index, systolic blood pressure, triglycerides, UA levels, and FIB-4 index than those with higher eGFR (P < .001 for all). In multivariable Cox regression analyses, each 1-standard deviation decrease in eGFR was associated with a 21% higher risk of an increased FIB-4 index (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.14-1.29; P < .001). Hyperuricemia (UA ≥ 420 μmol/L) was independently associated with a 38% higher risk of elevated FIB-4 (HR, 1.38; 95% CI: 1.23-1.55; P < .001). In the unadjusted model, a significant nonlinear dose-response relationship was observed between eGFR and FIB-4 (P for nonlinear trend < .001). However, after progressive adjustment for demographic variables, family history, and metabolic covariates, the nonlinear signal was markedly attenuated. Mediation analysis demonstrated that UA partially mediated the association between eGFR and FIB-4, accounting for 6.88% of the total effect. Reduced eGFR and hyperuricemia were independently associated with an elevated FIB-4 index in adults with MASLD, with a nonlinear relationship indicating a greater liver fibrosis risk in individuals with moderate to severe renal impairment (eGFR < 60 mL/min/1.73 m2). Partial mediation by UA suggests that metabolic dysregulation contributes to the kidney-liver interaction. Routine assessment of eGFR and UA may improve liver fibrosis risk stratification in patients with MASLD.
SN - 0304-5412
SN - 1536-5964
ER -