Di Sessa Anna, Zarrilli Sarah, Forcina Gianmario, Frattolillo Vittoria, Camponesco Ornella, Migliaccio Claudia, Ferrara Serena, Umano Giuseppina Rosaria, Cirillo Grazia, Miraglia Del Giudice Emanuele, Marzuillo Pierluigi
Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
Int J Obes (Lond). 2025 Apr;49(4):605-611. doi: 10.1038/s41366-024-01674-5. Epub 2024 Nov 9.
Evidence linked metabolic associated steatotic liver disease (MASLD) to kidney damage with the potential contribution of the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene. We aimed at investigating the relationship of MASLD and of its genetics with kidney function in children with obesity.
A comprehensive evaluation including genotyping for the I148M PNPLA3 polymorphism was performed in 1037 children with obesity. Fatty liver (FL) was assessed by liver ultrasound. According to MASLD criteria, subjects with obesity but without FL were included in group 1, while patients with obesity and FL (encompassing one MASLD criterion) were clustered into group 2. Group 3 included patients with obesity, FL, and metabolic dysregulation (encompassing >1 MASLD criterion).
Alanine transaminase levels significantly increased while estimated glomerular filtration rate (eGFR) significantly reduced from group 1 to 3. Group 3 showed a higher percentage of carriers of the I148M allele of the PNPLA3 gene compared to other groups (p < 0.0001). Carriers of group 2 and of group 3 showed reduced eGFR levels than noncarriers of group 2 (p = 0.04) and of group 3 (p = 0.02), respectively. A general linear model for eGFR variance in the study population showed an inverse association of eGFR with both MASLD and PNPLA3 genotypes (p = 0.011 and p = 0.02, respectively). An inverse association of eGFR with MASLD was also confirmed only in carriers (p = 0.006).
The coexistence of more than 1 MASLD criterion in children with obesity seems to adversely affect kidney function. The PNPLA3 I148M allele further impacts on this association.
有证据表明代谢相关脂肪性肝病（MASLD）与肾损伤有关，含Patatin样磷脂酶结构域3（PNPLA3）基因的I148M变异可能起了作用。我们旨在研究肥胖儿童中MASLD及其遗传学与肾功能的关系。
对1037名肥胖儿童进行了全面评估，包括对I148M PNPLA3多态性进行基因分型。通过肝脏超声评估脂肪肝（FL）情况。根据MASLD标准，肥胖但无FL的受试者纳入第1组，肥胖且有FL（符合一项MASLD标准）的患者归为第2组。第3组包括肥胖、有FL且存在代谢失调（符合>1项MASLD标准）的患者。
从第1组到第3组，丙氨酸转氨酶水平显著升高，而估计肾小球滤过率（eGFR）显著降低。与其他组相比，第3组中PNPLA3基因I148M等位基因携带者的比例更高（p < 0.0001）。第2组和第3组的携带者的eGFR水平分别低于第2组和第3组的非携带者（p = 0.04和p = 0.02）。研究人群中eGFR方差的一般线性模型显示，eGFR与MASLD和PNPLA3基因型均呈负相关（分别为p = 0.011和p = 0.02）。仅在携带者中也证实了eGFR与MASLD呈负相关（p = 0.006）。
肥胖儿童中存在超过1项MASLD标准似乎会对肾功能产生不利影响。PNPLA3 I148M等位基因进一步影响这种关联。
