Letter to the Editor Open Access
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2021; 27(34): 5793-5795
Published online Sep 14, 2021. doi: 10.3748/wjg.v27.i34.5793
Relationship between nonalcoholic fatty liver disease and chronic kidney disease could start in childhood
Anna Di Sessa, Stefano Guarino, Rosa Melone, Rossella Francesca De Simone, Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
ORCID number: Anna Di Sessa (0000-0002-5877-3757); Stefano Guarino (0000-0002-0551-5236); Rosa Melone (0000-0001-6897-5742); Rossella Francesca De Simone (0000-0001-5807-7121); Pierluigi Marzuillo (0000-0003-4682-0170); Emanuele Miraglia del Giudice (0000-0002-1492-076X).
Author contributions: Di Sessa A wrote the letter; Di Sessa A, Miraglia del Giudice E and Marzuillo P conceived the manuscript; Miraglia del Giudice E supervised the manuscript drafting; Guarino S, Melone R and De Simone RF reviewed the literature data; each author contributed important intellectual content during manuscript drafting or revision.
Conflict-of-interest statement: Nothing to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Pierluigi Marzuillo, MD, PhD, Assistant Professor, Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Via de Crecchio, Naples 80138, Italy. pierluigi.marzuillo@gmail.com
Received: May 4, 2021
Peer-review started: May 4, 2021
First decision: June 12, 2021
Revised: June 21, 2021
Accepted: August 6, 2021
Article in press: August 6, 2021
Published online: September 14, 2021

Abstract

The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has gained considerable scientific interest in adults over the past few years. However, this association has recently emerged in children. Several published studies have suggested a role for NAFLD as a risk factor for CKD from the earliest age, with a potential influence of the major NAFLD risk polymorphisms, resulting in an increased risk of both cardiovascular and metabolic diseases. In view of the progressive course and increased cardiometabolic risk closely related to NAFLD and CKD, we focused on the link between these diseases in childhood.

Key Words: Nonalcoholic fatty liver disease, Chronic kidney disease, Children, Liver

Core Tip: Nonalcoholic fatty liver disease has been linked to chronic kidney disease in childhood. Due to the intrinsic cardiometabolic burden related to both diseases, we highlighted the importance of knowledge of this relationship in pediatric patients.



TO THE EDITOR

We read with interest the review by Mantovani et al[1] on the challenging association of nonalcoholic fatty liver disease (NAFLD) with chronic kidney disease (CKD)[1]. The authors provided a comprehensive overview on this association, linking two chronic diseases with a serious cardiometabolic burden and potentially leading to end-stage organ injury, by discussing both pathophysiological and therapeutic aspects.

In our opinion, it is important to underline that the relationship between NAFLD and CKD already occurs in childhood. Parallel to the increasing prevalence of childhood obesity, NAFLD has become the most common chronic liver disease in pediatric patients[2-4]. As demonstrated in adults, there is convincing evidence in children indicating NAFLD as a risk factor for CKD later in life[5-9]. Owing to the shared metabolic pathogenesis (including ectopic lipid accumulation and insulin resistance)[10], NAFLD has been found to be closely inter-related with renal dysfunction in childhood[9,11-14]. There is compelling evidence of a significant reduction in estimated glomerular filtration rate (eGFR) in obese children with NAFLD[8,12,14], as well as possible modulation of the main NAFLD genes (including the I148M PNPLA3 variant[5,15-17], the E167K allele of TM6SF2, and HSD17B13)[5,15]. Early impairments in renal function (such as reduced eGFR and/or abnormal albuminuria) have been observed in children with obesity and NAFLD and linked to the severity of liver disease[8,12-14].

We wish to draw readers’ attention to the early subclinical renal involvement in children with obesity and NAFLD. In view of the greater cardiometabolic risk (including type 2 diabetes, cardiovascular disease, and metabolic syndrome)[18-21] of these patients and the potential genetic influence of NAFLD polymorphisms, findings from these studies might have important clinical and prognostic implications at an early age. In our opinion, all children with obesity should undergo abdominal ultrasound to detect fatty liver[22], and careful monitoring with intensive lifestyle-dietary intervention programs. In the future, NAFLD management may also include genetic characterization, which could represent a crucial step to counteract the development of cardiovascular and metabolic disorders already occurring in childhood.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: Italy

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Ali H, Du Y S-Editor: Fan JR L-Editor: Kerr C P-Editor: Liu JH

References
1.  Mantovani A, Petracca G, Beatrice G, Tilg H, Byrne CD, Targher G. Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals. Gut. 2021;70:962-969.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 174]  [Cited by in F6Publishing: 205]  [Article Influence: 68.3]  [Reference Citation Analysis (0)]
2.  Sahota AK, Shapiro WL, Newton KP, Kim ST, Chung J, Schwimmer JB. Incidence of Nonalcoholic Fatty Liver Disease in Children: 2009-2018. Pediatrics. 2020;146.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 64]  [Article Influence: 16.0]  [Reference Citation Analysis (0)]
3.  Shaunak M, Byrne CD, Davis N, Afolabi P, Faust SN, Davies JH. Non-alcoholic fatty liver disease and childhood obesity. Arch Dis Child. 2021;106:3-8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 37]  [Article Influence: 12.3]  [Reference Citation Analysis (0)]
4.  Dunn W, Schwimmer JB. The obesity epidemic and nonalcoholic fatty liver disease in children. Curr Gastroenterol Rep. 2008;10:67-72.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 74]  [Cited by in F6Publishing: 71]  [Article Influence: 4.4]  [Reference Citation Analysis (0)]
5.  Di Sessa A, Guarino S, Passaro AP, Liguori L, Umano GR, Cirillo G, Miraglia Del Giudice E, Marzuillo P. NAFLD and renal function in children: is there a genetic link? Expert Rev Gastroenterol Hepatol. 2021;1-10.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
6.  Musso G, Gambino R, Tabibian JH, Ekstedt M, Kechagias S, Hamaguchi M, Hultcrantz R, Hagström H, Yoon SK, Charatcharoenwitthaya P, George J, Barrera F, Hafliðadóttir S, Björnsson ES, Armstrong MJ, Hopkins LJ, Gao X, Francque S, Verrijken A, Yilmaz Y, Lindor KD, Charlton M, Haring R, Lerch MM, Rettig R, Völzke H, Ryu S, Li G, Wong LL, Machado M, Cortez-Pinto H, Yasui K, Cassader M. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014;11:e1001680.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 408]  [Cited by in F6Publishing: 442]  [Article Influence: 44.2]  [Reference Citation Analysis (0)]
7.  Targher G, Chonchol M, Zoppini G, Abaterusso C, Bonora E. Risk of chronic kidney disease in patients with non-alcoholic fatty liver disease: is there a link? J Hepatol. 2011;54:1020-1029.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 122]  [Cited by in F6Publishing: 124]  [Article Influence: 9.5]  [Reference Citation Analysis (0)]
8.  Yodoshi T, Arce-Clachar AC, Sun Q, Fei L, Bramlage K, Xanthakos SA, Flores F, Mouzaki M. Glomerular Hyperfiltration Is Associated with Liver Disease Severity in Children with Nonalcoholic Fatty Liver Disease. J Pediatr. 2020;222:127-133.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 14]  [Article Influence: 3.5]  [Reference Citation Analysis (0)]
9.  Pacifico L, Perla FM, Roggini M, Andreoli G, D'Avanzo M, Chiesa C. A Systematic Review of NAFLD-Associated Extrahepatic Disorders in Youths. J Clin Med. 2019;8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 18]  [Article Influence: 3.6]  [Reference Citation Analysis (0)]
10.  Byrne CD, Targher G. NAFLD as a driver of chronic kidney disease. J Hepatol. 2020;72:785-801.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 162]  [Cited by in F6Publishing: 213]  [Article Influence: 53.3]  [Reference Citation Analysis (0)]
11.  Manco M, Ciampalini P, DeVito R, Vania A, Cappa M, Nobili V. Albuminuria and insulin resistance in children with biopsy proven non-alcoholic fatty liver disease. Pediatr Nephrol. 2009;24:1211-1217.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 25]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
12.  Lin H, Fu J, Chen X, Huang K, Wu W, Liang L. [Early identification of impaired renal function in obese children with non-alcoholic fatty liver disease]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2013;42:381-387.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Machado MV, Gonçalves S, Carepa F, Coutinho J, Costa A, Cortez-Pinto H. Impaired renal function in morbid obese patients with nonalcoholic fatty liver disease. Liver Int. 2012;32:241-248.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 55]  [Cited by in F6Publishing: 54]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
14.  Pacifico L, Bonci E, Andreoli GM, Di Martino M, Gallozzi A, De Luca E, Chiesa C. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity. Int J Mol Sci. 2016;17.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 39]  [Article Influence: 4.9]  [Reference Citation Analysis (0)]
15.  Targher G, Mantovani A, Alisi A, Mosca A, Panera N, Byrne CD, Nobili V. Relationship Between PNPLA3 rs738409 Polymorphism and Decreased Kidney Function in Children With NAFLD. Hepatology. 2019;70:142-153.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 35]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
16.  Mantovani A, Zusi C, Sani E, Colecchia A, Lippi G, Zaza GL, Valenti L, Byrne CD, Maffeis C, Bonora E, Targher G. Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease. Diabetes Metab. 2019;45:480-487.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 33]  [Article Influence: 6.6]  [Reference Citation Analysis (0)]
17.  Musso G, Cassader M, Gambino R. PNPLA3 rs738409 and TM6SF2 rs58542926 gene variants affect renal disease and function in nonalcoholic fatty liver disease. Hepatology. 2015;62:658-659.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 42]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
18.  Goldner D, Lavine JE. Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges. Gastroenterology. 2020;158:1967-1983.e1.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 55]  [Cited by in F6Publishing: 63]  [Article Influence: 15.8]  [Reference Citation Analysis (0)]
19.  Bendor CD, Bardugo A, Pinhas-Hamiel O, Afek A, Twig G. Cardiovascular morbidity, diabetes and cancer risk among children and adolescents with severe obesity. Cardiovasc Diabetol. 2020;19:79.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 93]  [Cited by in F6Publishing: 112]  [Article Influence: 28.0]  [Reference Citation Analysis (1)]
20.  Peng L, Wu S, Zhou N, Zhu S, Liu Q, Li X. Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity. BMC Pediatr. 2021;21:122.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 20]  [Article Influence: 6.7]  [Reference Citation Analysis (0)]
21.  Scapaticci S, D'Adamo E, Mohn A, Chiarelli F, Giannini C. Non-Alcoholic Fatty Liver Disease in Obese Youth With Insulin Resistance and Type 2 Diabetes. Front Endocrinol (Lausanne). 2021;12:639548.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 31]  [Article Influence: 10.3]  [Reference Citation Analysis (0)]
22.  Marzuillo P, Grandone A, Perrone L, Miraglia Del Giudice E. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease. World J Gastroenterol. 2015;21:6444-6450.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 21]  [Cited by in F6Publishing: 23]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]