Non-Alcoholic Steatohepatitis Severity Associates with FGF21 Level and Kidney Glucose Uptake

Souvik Sarkar, Shuai Chen, Benjamin Spencer, Xiaolu Situ, Maryam Afkarian, Karen Matsukuma, Michael T. Corwin, Guobao Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Nonalcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that has been shown to be associated with chronic kidney disease (CKD). Mechanism for the association of NASH with CKD remains unclear. In this study, we examined the association between NASH severity and kidney glucose uptake and the liver-secreted signaling molecule fibroblast growth factor 21 (FGF21). Methods: Kinetic parameters for kidney glucose transport rate (K1) and standardized uptake value (SUV) were determined using dynamic positron emission tomography after injection of 18F-fluorodeoxyglucose. Liver biopsies were scored for NASH activity (inflammation and ballooning), fibrosis, and steatosis FGF21 was measured from fasting serum samples. Patients were categorized by liver biopsy and multivariate analyses were performed to evaluate the associations. Results: Of 41 NASH patients 73% were females, 71% white, 51% with steatosis ≥2, 39% with NASH activity ≥4 and fibrosis ≥3. With severe NASH activity, kidney SUV significantly increased even when adjusted for underlying insulin-resistant (IR) state. Kidney K1 decreased significantly in higher liver activity in unadjusted models but not when adjusted for IR. FGF21 decreased with severe liver activity in adjusted models (P < 0.05) and associated with kidney K1 but not SUV. Conclusion: Our pilot data indicate that kidney glucose metabolism associates with NASH activity and FGF21 levels, suggesting a potential mechanism to NASH-induced CKD. Clinical Trials.gov ID: NCT02754037

Original languageEnglish (US)
Pages (from-to)491-497
Number of pages7
JournalMetabolic Syndrome and Related Disorders
Volume19
Issue number9
DOIs
StatePublished - Nov 1 2021

Keywords

  • fatty liver
  • FDG
  • kidney
  • multiorgan
  • NAFLD
  • PET scan

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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