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

Abstract

MAFLD与终末期肾病的相关性：对337783名英国生物银行参与者的前瞻性研究

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.

引言：代谢功能障碍相关脂肪肝（MAFLD）已被发现与慢性肾脏病（CKD）的患病率相关。然而，尚不清楚MAFLD是否与CKD发展和终末期肾病（ESKD）发病率相关。我们的目的是在英国生物银行的前瞻性队列中阐明MAFLD与ESKD事件之间的关联。

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.

方法：我们分析了337783名英国生物银行参与者的数据，并使用Cox回归分析计算ESKD的相对风险。

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.

结果：在337783名参与者中，平均随访12.8年，共诊断出618例ESKD病例。MAFLD患者发生ESKD的可能性是两倍（风险比[HR]2.03，95%置信区间[CI]1.68-2.46，p<0.001）。在非CKD和CKD参与者中，MAFLD与ESKD风险的相关性仍然显著。我们的结果还表明，在MAFLD病例中，肝纤维化评分与ESKD风险之间存在分级关联。与非MAFLD患者相比，NAFLD纤维化评分升高的MAFLD病人ESKD事件的校正HR分别为1.23（95%CI 0.96-1.58）、2.45（1.98-3.03）和7.67（5.48-10.73）。此外，PNPLA3 rs738409、TM6SF2 rs58542926、GCKR rs1260326和MBOAT7 rs641738的风险等位基因扩增了MAFLD对ESKD风险的影响。总之，MAFLD与ESKD事件相关。

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

结论：MAFLD可能有助于识别ESKD发展的高风险受试者，应鼓励MAFLD干预以减缓CKD进展。

Keywords: End-stage kidney disease; Liver fibrosis scores; MAFLD; Polygenic risk score; UK Biobank.