Genetical Background of Non-alcoholic Fatty Liver Disease (NAFLD) in Diabetes Mellitus and in Chronic Kidney Disease (NAFLDDMCKD)

The present study investigates relationship between non-alcoholic fatty liver disease and its risk factors, such as genetic background and diseases, such as chronic kidney disease and diabetes mellitus.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus; Non-alcoholic Fatty Liver Disease; Chronic Kidney Disease
• Intervention / Treatment: Other: non-interventional study

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) is a multisystemic disease, also affecting extrahepatic organs (1,2,6). According to former data, not only the prevalence of chronic hepatic disease, chronic cardiovascular diseases, but also the prevalence of chronic kidney disease (CKD) is higher in NAFLD (4,7). A strong association has been shown between diabetes mellitus (DM) and NAFLD as well (3,5,10).

Many genetical factors have been studied in the background of NAFLD. Many studies have proved the effect of patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (8,9). Effect of numerous genetical polymorphisms has been suggested behind oxidative stress responsible for NAFLD (8).

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Study Locations

• Hungary
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • 2nd Department of Medicine and Nephrological Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with CKD without DM, or patients with DM without CKD, or patients with both CKD and DM, aged 18-90

Description

Inclusion Criteria:

• CKD (renal replacement therapy non excluded)
• DM
• CKD+DM

Exclusion Criteria:

• alcohol abuse

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CKD; chronic kidney disease	Other: non-interventional study
DM; diabetes mellitus	Other: non-interventional study
CKD+DM; chronic kidney disease + diabetes mellitus	Other: non-interventional study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of NFS (NAFLD fibrosis score) and HSI (hepatic steatosis index) with underlying conditions	The association of hepatic steatosis with chronic kidney disease, diabetes mellitus and the the persence of these two will be assessed	2 years
Association of genetical factors with NFS and HSI	The association of hepatic steatosis with genetic factors will be assessed. In case of patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) : rs738409, rs2281135, rs2294918 single nuclear polimorfism (SNP) will be examined	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of hepatic steatosis with renal function	The association of serum creatinine, eGFR, blood urea nitrogen, serum sodium, serum potassium, serum calcium with NFS and HSI will be assessed	2 years
Association of glucose metabolism parameters with hepaic steatosis indices	Association of HbA1C, fructosamine, blood glucose, serum insulin, HOMAIR, serum uric acid with NFS and HSI	2 years
Association of liver function and hepatic setatosis indices	Association of serum bilirubine, serum GOT, serum GPT, serum GGT, serum ALP, serum LDH, INR, serum total protein, serum albumin with NFS and HSI	2 years
Association of serum lipid profile and hepatic setatosis indices	Association of serum total cholesterol, serum HDL-cholesterol, serum LDL-cholesterol, serum triglyceride, serum carnitine with NFS and HSI	2 years
Association of iron metabolism parameters with hepatic setatosis indices	association of serum iron, serum transferrine, serum transferrine saturation, serum ferritine with NFS and HSI	2 years
The relationship between blood count, sedimentation and inflammation with hepatic setatosis indices	Association of blood count, erythrocyte sedimentation rate, CRP with NFS and HSI	2 years
Assotion of serum proteins with hepatic setatosis indices	association of urinary total protein, urinary albumin, urinary total protein/creatinine ratio, urinary albumin/creatinine ratio with NFS and HSI	2 years
Association of pathological tyrosine isoforms with hepatic setatosis indices	Association of serum meta-Tyr, serum ortho-Tyr, urinary meta-Tyr, urinary ortho-Tyr, urinary meta-Tyr/creatinine ratio, urinary ortho-Tyr/creatinine ratio with NFS and HSI	2 years

Collaborators and Investigators

• Sponsor: University of Pecs
• Collaborators: Fresenius Medical Care North America; Teaching Hospital Markusovszky, Szombathely

Publications and helpful links

General Publications

• 1. Alp H, Karaarsian S, Selver EB,Atabek ME, Altin H, Baysal T. Association between nonalcoholic fatty liver disease and cardiovascular risk in obese children and adolescents. Can J Cardiol 2013;29:1118-1125. 2. Byrne CD, Targher G: NAFLD: A multisystem disease. Review. Journal of Hepatology, 2015; 62:S47-S64. 3. Kasturiratne A, Weerasinghe S, Dassanayake AS, rajindrajith S, de Silva AP, Kato N, et al. Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus. J Gastroenterol Hepatol 2013;60:384-391. 4. Li G, Shi W, Hug H, Chen Y, Liu L, Yin D. Nonalcoholic fatty liver disease associated with impairment of kidney function in nondiabetes population. Biochem Med 2012;22:92-99. 5. Okamoto M, Takeda Y, Yoda Y, Kobayashi K, Fujino MA, Yamagata Z. The association of fatty liver and diabetes risk. J Epidemiol 2003;13:15-21. 6. Pacifico L, Di MM, De MA, Bezzi M, Osborn JF, Catalano C, et al. Left ventricular dysfunction in obese children and adolescents with nonalcoholic fatty liver disease. Hepatology 2014;59:461-470. 7. Targher G, Choncol MB, Byrne CD. CKD a nonalcoholic fatty liver disease. Am J Kidney Dis 2014;64:638-652. 8. Wood KL, Miller MH, Dillon JF. systematic review of genetic association studies involving histologically confirmed non-alcoholic fatty liver disease BMJ Open Gastro 2015:2:e000019. doi10.1136/bmjgast-2014-000019 9. Zain SM, Mohamed R, Hyogo H, et al. A multi-ethnic study of a PNPLA3 variant and its association with disease severity in non-alcoholic fatty liver disease. Hum genet 2012;131:1145-1152. 10. Zuppini G, Fedeli U, Gennaro N, Saugo M, Targher G, Bonora E. Mortality from chronic liver diseases in diabetes. Am J Gastroenterol 2014;109:1020-1025.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: September 22, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (Estimate): October 28, 2016

Study Record Updates

• Last Update Posted (Actual): February 25, 2019
• Last Update Submitted That Met QC Criteria: February 22, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Chronic Kidney Disease; Cross-sectional; Non-alcoholic Fatty Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Liver Diseases; Diabetes Mellitus; Kidney Diseases; Renal Insufficiency, Chronic; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: Pecs_NAFLD_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO