Pediatric non-alcoholic fatty liver disease and kidney function: Effect ofHSD17B13variant

BACKGROUND Growing evidence supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Interesting data demonstrated that both the major NAFLD risk polymorphisms such as the I148M polymorphism in thepatatin like phospholipase containing domain 3(PNPLA3) and the E167K allele in thetransmembrane 6 superfamily member 2gene (TM6SF2) affect renal function. Recently thehydroxysteroid 17-beta dehydrogenase 13(HSD17B13) gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology. In particular, it has been showed the protective effect of thers72613567:TAvariant of this gene against liver damage both in adults and children. AIM To investigate the impact of thers72613567:TAvariant of theHSD17B13gene on estimated glomerular filtration rate (eGFR) in obese children. METHODS We enrolled 684 obese children (mean age 10.56 +/- 2.94 years; mean BMI-SDS 2.98 +/- 0.78) consecutively attending our Obesity Clinic. All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation. To detect hepatic steatosis, a liver ultrasound was performed. NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase (ALT) levels > 40 IU/L. The study population was divided on the basis of the NAFLD presence. Genotyping for thers72613567:TAvariant of theHSD17B13gene in all the enrolled subjects was also made. RESULTS Patients carrying theHSD17B13rare A allele showed higher eGFR levels compared with homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values withHSD17B13genotype independently ofPNPLA3andTM6SF2polymorphisms both in patients with and without NAFLD. A comparison of regression line confirmed the influence ofHSD17B13genotype on the relationship between eGFR and age both among patients with and without NAFLD.Homozygous patients forHSD17B13genotype with NAFLD showed a significantly higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying theHSD17B13rare A allele (Pvalue for intercepts = 0.005;Pvalue for slopes = 0.94). The same effect was observed among patients without NAFLD (Pvalue for intercepts = 0.0012;Pvalue for slopes = 0.87). CONCLUSION Carriers of theHSD17B13rare A allele showed higher eGFR levels than homozygous subjects both among subjects with and without NAFLD and independently ofPNPLA3 I148MandTM6SF6E167K polymorphisms.