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Multicenter Study
. 2024 Aug;79(2):238-249.
doi: 10.1002/jpn3.12272. Epub 2024 Jun 3.

Renal impairment is prevalent in pediatric NAFLD/MASLD and associated with disease severity

Marialena Mouzaki  1 , Katherine P Yates  2 , Ana Catalina Arce-Clachar  1 , Cindy Behling  3 , Niviann M Blondet  4 , Mark H Fishbein  5 , Francisco Flores  1 , Kathryn Harlow Adams  6 , Paula Hertel  7 , Ajay K Jain  8 , Jean P Molleston  6 , Jeffrey B Schwimmer  3   9 , Miriam B Vos  10 , Stavra A Xanthakos  1 ; NASH Clinical Research Network
Affiliations
Multicenter Study

Renal impairment is prevalent in pediatric NAFLD/MASLD and associated with disease severity

Marialena Mouzaki et al. J Pediatr Gastroenterol Nutr. 2024 Aug.

Abstract

Objectives: Renal impairment is prevalent in adults with nonalcoholic fatty liver disease (NAFLD/metabolic dysfunction associated steatotic liver disease [MASLD]) and is associated with increased mortality. Pediatric data are limited. Our objective was to determine the prevalence of hyperfiltration or chronic kidney disease (CKD) in children with NAFLD/MASLD and determine links with liver disease severity.

Methods: Data from children who had previously participated in prospective, multicenter, pediatric studies by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH-CRN) were collected. Renal function was determined using the calculated glomerular filtration rate (cGFR). Hyperfiltration was defined as cGFR > 135 mL/min/1.73m2, while CKD stage 2 or higher as cGFR < 90 mL/min/1.73 m2. Renal dysfunction progression was defined as transition from normal to hyperfiltration or to CKD stage ≥ 2, or change in CKD by ≥1 stage. Multinomial logistic regression models were used to determine the prevalence of CKD and independent associations between CKD and liver disease severity.

Results: The study included 1164 children (age 13 ± 3 years, 72% male, 71% Hispanic). The median cGFR was 121 mL/min/1.73 m2; 12% had CKD stage 2-5, while 27% had hyperfiltration. Hyperfiltration was independently associated with significant liver fibrosis (odds ratio: 1.45). Baseline renal function was not associated with progression in liver disease over a 2-year period (n = 145). Renal dysfunction worsened in 19% independently of other clinical risk factors. Progression of renal impairment was not associated with change in liver disease severity.

Conclusions: Renal impairment is prevalent in children with NAFLD/MASLD and hyperfiltration is independently associated with significant liver fibrosis. Almost 1/5 children have evidence of progression in renal dysfunction over 2 years, not associated with change in liver disease severity. Future assessments including additional renal impairment biomarkers are needed.

Keywords: MASLD; children; fatty liver; kidney function.

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Conflict of interest statement

Dr. Jain is a Consultant and Advisor for Mirum Pharma, Camp 4 Pharma. Dr. Molleston receives grant funding from CF Foundation, Mirium, Albireo, Abbvie, Gillead. Dr. Mouzaki receives grant funding the Soy Nutrition Institute. Dr. Vos consults and/or does research with Novo Nordisk, Boehringer Ingelheim, Intercept, Ei Lilly, Intercept, Albireo, Thiogenesis, Takeda, Quest and Target Real World Evidence. Dr. Xanthakos does research wtih Research with Target Real World Evidence. The remaining authors declare no conflicts to interest.

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