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Renal impairment is prevalent in pediatric NAFLD/MASLD and associated with disease severity
Marialena Mouzaki1, Katherine P Yates2, Ana Catalina Arce-Clachar1
1Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Insights
Renal impairment and hyperfiltration are common in children with metabolic dysfunction associated steatotic liver disease (MASLD). Almost 1/5 children showed worsening kidney function over two years, highlighting the need for further research.
Area of Science:
- Pediatric Nephrology
- Hepatology
- Metabolic Disorders
Background:
- Renal impairment is common in adults with nonalcoholic fatty liver disease (NAFLD/metabolic dysfunction associated steatotic liver disease [MASLD]) and linked to mortality.
- Limited pediatric data exist on renal function in children with NAFLD/MASLD.
Purpose of the Study:
- To determine the prevalence of hyperfiltration and chronic kidney disease (CKD) in children with NAFLD/MASLD.
- To investigate the association between renal dysfunction and liver disease severity in pediatric NAFLD/MASLD patients.
Main Methods:
- Analysis of data from 1164 children in prospective, multicenter pediatric studies (NASH-CRN).
- Renal function assessed via calculated glomerular filtration rate (cGFR); hyperfiltration defined as cGFR > 135 mL/min/1.73m², CKD stage ≥2 as cGFR < 90 mL/min/1.73m².
- Multinomial logistic regression used to identify associations between CKD and liver disease severity.
Main Results:
- 12% of children had CKD stage 2-5, and 27% had hyperfiltration.
- Hyperfiltration was independently associated with significant liver fibrosis (OR: 1.45).
- 19% of children experienced worsening renal dysfunction over 2 years, independent of other risk factors.
Conclusions:
- Renal impairment and hyperfiltration are prevalent in pediatric NAFLD/MASLD.
- Hyperfiltration is linked to significant liver fibrosis in this population.
- Progression of renal dysfunction occurs in a significant minority of children, warranting further investigation with additional biomarkers.
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.
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