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Association of MAFLD with end-stage kidney disease: a prospective study of 337,783 UK Biobank participants

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Abstract

Introduction

Metabolic dysfunction-associated fatty liver (MAFLD) has been found to be associated with the prevalence of chronic kidney disease (CKD). However, it is unknown whether MAFLD is associated with CKD development and the incidence of end-stage kidney disease (ESKD). We aimed to clarify the association between MAFLD and incident ESKD in the prospective UK Biobank cohort.

Methods

We analyzed the data of 337,783 UK Biobank participants and relative risks for the ESKD were calculated by using the Cox regression analysis.

Results

Among 337,783 participants over a median duration of 12.8 years follow-up, a total of 618 ESKD cases were diagnosed. Participants with MAFLD were twice likely to develop ESKD (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.68–2.46, p < 0.001). The association of MAFLD with ESKD risk remained significant in both non-CKD and CKD participants. Our results also showed that there were graded associations between liver fibrosis scores and the risk of ESKD in MAFLD cases. Compared to non-MAFLD individuals, the adjusted HRs for incident ESKD in MAFLD patients with increasing levels of NAFLD fibrosis score were 1.23 (95% CI 0.96–1.58), 2.45 (1.98–3.03) and 7.67 (5.48–10.73), respectively. Furthermore, the risking alleles of PNPLA3 rs738409, TM6SF2 rs58542926, GCKR rs1260326 and MBOAT7 rs641738 amplified the MAFLD effect on ESKD risk. In conclusion, MAFLD is associated with incident ESKD.

Conclusion

MAFLD may help identify the subjects at high risk of ESKD development and MAFLD interventions should be encouraged to slow down CKD progression.

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Data availability

Data may be obtained from a third party and are not publicly available. The UK Biobank will make the source data available to all bonafide researchers for all types of health-related research that is in the public interest, without preferential or exclusive access for any persons. All researchers will be subject to the same application process and approval criteria as specified by UK Biobank. For more details on the access procedure, see the UK Biobank website: http://www.ukbiobank.ac.uk/register-apply.

Abbreviations

AKI:

Acute kidney injury

ALP:

Alkaline phosphatase

ALT:

Alanine transaminase

AST:

Aspartate transaminase

CI:

Confidence interval

CKD:

Chronic kidney disease

CRP:

C-reactive protein

eGFR:

Estimated glomerular filtration rate

ESKD:

End-stage kidney disease

FIB-4:

Fibrosis 4 score

GBD:

Global burden of disease

GGT:

Gamma-glutamyl transferase

HDL-c:

High-density lipoprotein (HDL) cholesterol

ICD-10:

International classification of disease version 10

HR:

Hazard ratio

LDL-c:

Low-density lipoprotein- cholesterol

MAFLD:

Metabolic dysfunction-associated fatty liver disease

NAFLD:

Non-alcoholic fatty liver disease

PRS:

Polygenic risk score

RRT:

Renal replacement therapy

SD:

Standard deviation

T2D:

Type 2 diabetes

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Funding

This study was supported and funded by the National Natural Science Foundation of China (Grant number 82103823).

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Author notes

  1. Shen Chen and Juan Pang contributed equally to this article.

Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

    Shen Chen

  2. Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), No.74, 2nd Zhongshan Road, Guangzhou, 510080, People’s Republic of China

    Juan Pang & Xu Chen

  3. Medical Science and Technology Innovation Center, Jinan Central Hospital, Shandong First Medical University, Taian, Jinan, China

    Rong Huang

  4. Department of Nutrition, School of Public Health, Guangzhou Medical University, 195 Dongfeng W Rd., Guangzhou, 510080, People’s Republic of China

    Hongliang Xue

  5. Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, USA

    Xu Chen

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  1. Shen Chen
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Contributions

SC: was responsible for formal analysis and writing—original draft. JP: was responsible for data curation, formal analysis, and validation. RH: was responsible for writing- original draft. HX: was responsible for conceptualization and supervision, and writing. XC: was responsible for conceptualization, design, supervision, funding acquisition, and writing- review and editing.

Corresponding authors

Correspondence to Hongliang Xue or Xu Chen.

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Conflict of interest

Shen Chen, Juan Pang, Rong Huang, Hongliang Xue and Xu Chen: Nothing to report.

Ethical approval

The UK Biobank research was approved by the North West Multi-Centre Research Ethics Committee (Ref: 11/NW/0382) and all participants provided written informed consent.

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Chen, S., Pang, J., Huang, R. et al. Association of MAFLD with end-stage kidney disease: a prospective study of 337,783 UK Biobank participants. Hepatol Int 17, 595–605 (2023). https://doi.org/10.1007/s12072-023-10486-0

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