Sun Dan-Qin, Wang Ting-Yao, Zheng Kenneth I, Zhang Hao-Yang, Wang Xiao-Dong, Targher Giovanni, Byrne Christopher D, Chen Yong-Ping, Yuan Wei-Jie, Jin Yan, Zheng Ming-Hua
Affiliated Wuxi Clinical College of Nantong University, Wuxi, China; Department of Nephrology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China; Department of Nephrology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.
Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Nutr Metab Cardiovasc Dis. 2021 Jun 7;31(6):1822-1831. doi: 10.1016/j.numecd.2021.02.018. Epub 2021 Feb 25.
Several susceptibility gene variants predisposing to nonalcoholic fatty liver disease (NAFLD) have been identified in chronic kidney disease (CKD). Evidence supports that 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) rs72613567 plays a role in NAFLD development by affecting lipid homeostasis. Since lipid droplets may accumulate in the kidneys and contribute to renal injury, we investigated the association between the HSD17B13 rs72613567 variant and markers of renal function/injury in NAFLD.
We measured estimated glomerular filtration rate (eGFR), urinary/serum neutrophil gelatinase-associated lipocalin (NGAL), and urinary albumin-to-creatinine ratio (u-ACR) in individuals with biopsy-proven NAFLD. Multivariable regression analyses were undertaken to examine the associations between the HSD17B13 rs72613567 variant and markers of renal function/injury. Individuals were stratified by HSD17B13 rs72613567 genotypes into -/-, A/- and A/A groups. HSD17B13 rs72613567 genotypes were not significantly associated with eGFR and urinary/serum NGAL levels. Conversely, the prevalence of abnormal albuminuria in the A/- + A/A group was lower than in the -/- group (4.92% vs. 19.35%, p = 0.001). Additionally, the mean u-ACR levels were lower among carriers of the A/- or A/A genotypes with coexisting hypertension or diabetes, than among those with the -/- genotype. The risk of abnormal albuminuria (adjusted-odds ratio 0.16, p = 0.001) remained significantly lower in the A/- + A/A group after adjustment for established renal risk factors and histologic severity of NAFLD.
HSD17B13 rs72613567: A allele is associated with a lower risk of having abnormal albuminuria, but not with lower eGFR or urinary/serum NGAL levels, in patients with biopsy-proven NAFLD.
慢性肾脏病（CKD）中已鉴定出几种易患非酒精性脂肪性肝病（NAFLD）的易感基因变异。有证据支持17-β羟类固醇脱氢酶13（HSD17B13）rs72613567通过影响脂质稳态在NAFLD发展中起作用。由于脂滴可能在肾脏中积聚并导致肾损伤，我们研究了HSD17B13 rs72613567变异与NAFLD患者肾功能/损伤标志物之间的关联。
我们测量了经活检证实的NAFLD患者的估计肾小球滤过率（eGFR）、尿/血清中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和尿白蛋白与肌酐比值（u-ACR）。进行多变量回归分析以检查HSD17B13 rs72613567变异与肾功能/损伤标志物之间的关联。个体根据HSD17B13 rs72613567基因型分为-/-、A/-和A/A组。HSD17B13 rs72613567基因型与eGFR以及尿/血清NGAL水平无显著关联。相反，A/- + A/A组中蛋白尿异常的患病率低于-/-组（4.92%对19.35%，p = 0.001）。此外，合并高血压或糖尿病的A/-或A/A基因型携带者的平均u-ACR水平低于-/-基因型携带者。在调整既定的肾脏危险因素和NAFLD的组织学严重程度后，A/- + A/A组中蛋白尿异常的风险（调整后的优势比0.16，p = 0.001）仍然显著较低。
在经活检证实的NAFLD患者中，HSD17B13 rs72613567：A等位基因与蛋白尿异常风险较低相关，但与较低的eGFR或尿/血清NGAL水平无关。
