Liver Disease Diagnosis and Treatment · Journal article

Metabolic Burden and Hyperuricemia Are Associated With CKD‐Related Outcomes in Individuals With and Without Steatotic Liver Disease

Hepatology Research · August 14, 2026

Strong Evidence Why this matters to you Expert discussion

Well-designed and adequately powered for the question it asks.

AI Summary

In a large Japanese health screening cohort, cardiometabolic abnormalities—particularly type 2 diabetes, obesity, and hyperuricemia—were independently associated with CKD outcomes (proteinuria and reduced eGFR), whereas hepatic steatosis itself showed an inverse association after adjustment. Hyperuricemia provided significant incremental value for renal risk stratification beyond other cardiometabolic factors, in both steatotic liver disease and non-steatotic liver disease populations.

What was studied

Cross-sectional cohort study. Japanese health screening cohort stratified by presence or absence of steatotic liver disease; participants assessed for cardiometabolic abnormalities including type 2 diabetes, obesity, and hyperuricemia.. Compared with: Non-SLD participants versus SLD participants. Japan.

Key findings

Type 2 diabetes mellitus, obesity, and hyperuricemia were independently associated with proteinuria Advanced age (≥65 years), low alcohol intake, and hyperuricemia were strongly associated with reduced eGFR After multivariable adjustment, SLD showed an inverse association with CKD-related outcomes

Safety

Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.

Who this may help

Clinicians should prioritise assessment of cardiometabolic risk factors (diabetes, obesity, hyperuricemia) over hepatic steatosis status alone when stratifying renal disease risk. Hyperuricemia warrants specific clinical attention as an independent predictor of both proteinuria and reduced eGFR.

Plain-language summary

Large cohort study with multivariable analysis demonstrating that cardiometabolic burden, not hepatic steatosis, drives CKD outcomes; finding is consistent across strata and hyperuricemia shows incremental predictive value.

Study design

As stated by the source record.

MethodsMultivariable logistic regression and trend analyses performed to identify factors associated with CKD-related outcomes (proteinuria and reduced eGFR). Analyses conducted stratified by steatotic liver disease status to assess consistency of cardiometabolic associations across SLD and non-SLD populations.

DesignCross-sectional cohort study

PopulationJapanese health screening cohort stratified by presence or absence of steatotic liver disease; participants assessed for cardiometabolic abnormalities including type 2 diabetes, obesity, and hyperuricemia.

ComparatorNon-SLD participants versus SLD participants

SettingJapan

Reported figures

Quoted from the source exactly as published.

Model fit improvement for reduced eGFR with hyperuricemiaΔ-2 log likelihood = 119.4

p-value for reduced eGFR model improvementp < 0.001

p-value for proteinuria model improvementp = 0.002

Age threshold for advanced age association≥65 years

Clinical bottom line

Caveats

Cross-sectional design prevents causal inference; temporal relationships between risk factors and CKD outcomes not established
Total sample size and per-stratum group sizes not reported
Inverse association of SLD with CKD outcomes after adjustment is unexplained and may reflect unmeasured confounding or selection bias
Generalizability to non-Japanese populations or non-screening populations unclear

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

strong

Large Japanese health screening cohort with multivariable logistic regression and trend analyses.

Directness

strong

Directly addresses CKD outcomes (proteinuria, reduced eGFR) as primary endpoints in relevant population.

Consistency

strong

Findings consistent across SLD and non-SLD populations; stepwise associations observed with cardiometabolic risk burden.

Risk of bias

moderate

Cross-sectional design limits causal inference; inverse association of SLD post-adjustment unexplained, raises potential confounding.

Sample adequacy

insufficient

Source does not state total sample size or per-group numbers analysed.

Source abstract

AIM: Although steatotic liver disease (SLD) has been associated with chronic kidney disease (CKD), it remains unclear whether CKD-related outcomes are driven by hepatic steatosis itself or by accompanying cardiometabolic abnormalities. We investigated the relative contribution of hepatic steatosis and cardiometabolic risk factors to CKD-related outcomes using a large Japanese health screening cohort. METHODS: ) and proteinuria. Multivariable logistic regression and trend analyses were performed to identify factors associated with these outcomes. RESULTS: Compared with non-SLD participants, those with SLD exhibited a higher burden of cardiometabolic abnormalities. Type 2 diabetes mellitus, obesity, and hyperuricemia were independently associated with proteinuria, whereas advanced age (≥ 65 years), low alcohol intake, and hyperuricemia were strongly associated with reduced eGFR. After multivariable adjustment, SLD showed an inverse association with CKD-related outcomes. In both SLD and non-SLD populations, the prevalence of CKD-related outcomes increased stepwise with a higher number of cardiometabolic risk factors. Incorporation of hyperuricemia significantly improved model fit for reduced eGFR (Δ-2 log likelihood = 119.4, p < 0.001) and modestly improved model fit for proteinuria (p = 0.002). CONCLUSIONS: CKD-related outcomes were more strongly associated with the burden of cardiometabolic abnormalities than with hepatic steatosis itself, and these associations were consistent in individuals with and without SLD. Hyperuricemia provided incremental value for renal risk stratification within this cardiometabolic framework, underscoring the importance of comprehensive metabolic risk assessment beyond liver fat status.

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Michihiro IwakiKoji SawadaYoshihiro KamadaHideki FujiiLiver Disease Diagnosis and TreatmentJapan Study Group of Nonalcoholic Fatty Liver Disease (JSG‐NAFLD)Yuichiro Suzuki