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The serum uric acid/creatinine ratio is associated with nonalcoholic fatty liver disease in the general population

Journal of Physiology and Biochemistry (2022)Cite this article

Abstract

Serum uric acid-to-creatinine ratio (sUA/CrR) may be associated with metabolic syndrome components, but limited evidence exists on a relationship between sUA/Cr and NAFLD. Here, we investigated the association between sUA/CrR and NAFLD.

We performed a cross-sectional analysis in 3359 subjects who participated in the NHANES 2017–2018 survey and consumed less than 30 and 20 g alcohol (men and women, respectively), with no positive tests of viral hepatitis. Liver steatosis was defined by controlled attenuation parameter and fibrosis by stiffness measurements obtained via transient elastography. We modeled the relationship between NAFLD and relevant demographic, anthropometric, and biochemical variables.

sUA/CrR was significantly higher in participants with NAFLD than those without NAFLD. LASSO logit regression showed that only logarithmized age (p = 1.2e-3), waist circumference (WC) (p = 1.8e-5), triglycerides (p = 5e-6), and sUA/CrR (p = 3e-5) were retained in the model. Multivariate logistic analysis demonstrated a significant association between sUA/CrR and NAFLD; the OR for NAFLD of one log(sUA/CrR) increase was 2.61 (95% CI: 1.86–3.68, p < 3e-8) after adjusting for relevant covariables, including aminotransaminase levels and the effect of sUA/CrR remained significant for highest WC quintiles. The model’s predictive power with vs. without sUA/CrR was slightly but significantly better (Auroc: 0.859 ± 0.006 vs. 0.855 ± 0.007, p < 1.1e-2). Mediation analysis showed that SUA/CrR modestly mediates the effect of WC and insulin resistance but not glycohemoglobin on NAFLD.

In conclusion, elevated sUA/CrR was significantly associated with NAFLD in the general population. Therefore, kidney function should be closely monitored in NAFLD patients.

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Funding

This study was partially supported by grants PICT 2018–889 and PICT 2019–0528 (SS), PICT 2016–0135 and PICT2018-0620 (CJP) (Agencia Nacional de Promoción Científica y Tecnológica, FONCyT), CONICET Proyectos Unidades Ejecutoras 2017, PUE 0055 (SS, CJP).

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Authors and Affiliations

  1. Facultad de Medicina, Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina

    Silvia Sookoian & Carlos J. Pirola

  2. Instituto de Investigaciones Médicas (IDIM), Unidad de Biología de Sistemas de Enfermedades Complejas, Departamento de Hepatología Clínica Y Molecular, Consejo Nacional de Investigaciones Científicas Y Técnicas-Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina

    Silvia Sookoian

  3. Instituto de Investigaciones Médicas (IDIM), Unidad de Biología de Sistemas de Enfermedades Complejas, Departamento de Genética Y Biología Molecular de Enfermedades Complejas, Consejo Nacional de Investigaciones Científicas Y Técnicas-Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina

    Carlos J. Pirola

Authors
  1. Silvia Sookoian
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Contributions

SS and CJP designed research (project conception, development of overall research plan, and study oversight); CJP conducted data collection; CJP and SS analyzed data or performed statistical analysis; SS and CJP wrote the paper and had primary responsibility for the final content. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Silvia Sookoian or Carlos J. Pirola.

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Key Points

• Increased serum uric acid (UA) is a hallmark of the MetSyn, but its association with NAFLD has been less explored. The normalization of serum UA by serum creatinine (sUA/CrR) may help to correct for renal dysfunction.

• sUA/CrR was independently associated with NAFLD in a large representative sample of the US general population surveyed by NHANES 2017–2018.

• sUA/CrR seems not to influence liver fibrosis.

• Adding sUA/CrR to traditional risk factors increases the model's predictive power of having NAFLD.

• Only a minor portion of the impact on liver fat infiltration and disease progression of central adiposity and insulin resistance is mediated by sUA/CrR.

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Sookoian, S., Pirola, C.J. The serum uric acid/creatinine ratio is associated with nonalcoholic fatty liver disease in the general population. J Physiol Biochem (2022). https://doi.org/10.1007/s13105-022-00893-6

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  • DOI: https://doi.org/10.1007/s13105-022-00893-6

Keywords

  • Biomarkers
  • Renal function
  • Metabolic syndrome
  • Diabetes
  • Central obesity
  • Insulin resistance
  • NHANES