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1
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Sumida Y, Toyoda H, Yasuda S, Kimoto S, Sakamoto K, Nakade Y, Ito K, Osonoi T, Yoneda M. Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: the PORTRAIT Study. J Atheroscler Thromb 2024; 31:1620-1633. [PMID: 38777770 PMCID: PMC11537790 DOI: 10.5551/jat.64896] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/15/2024] [Indexed: 05/25/2024] Open
Abstract
AIM No pharmacotherapeutic treatment has been established for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This trial compared the effects of pemafibrate and omega-3-acid ethyl ester on hepatic function in patients with hypertriglyceridemia complicated by MASLD. METHODS Patients with hypertriglyceridemia complicated by MASLD were enrolled, randomly assigned to the pemafibrate or omega-3-acid ethyl ester group, and followed for 24 weeks. The primary endpoint was the change in alanine aminotransferase (ALT) from baseline to week 24. The secondary endpoints included other hepatic enzymes, lipid profiles, and hepatic fibrosis biomarkers. RESULTS A total of 80 patients were enrolled and randomized. The adjusted mean change in ALT from baseline to week 24 was significantly lower in the pemafibrate group (-19.7±5.9 U/L) than in the omega-3-acid ethyl ester group (6.8±5.5 U/L) (intergroup difference, -26.5 U/L; 95% confidence interval, -42.3 to -10.7 U/L; p=0.001). Pemafibrate significantly improved the levels of other hepatic enzymes (aspartate aminotransferase and gamma-glutamyl transpeptidase), lipid profiles (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol), and hepatic fibrosis biomarkers (Mac-2 binding protein glycan isomer and Fibrosis-4 index). No cases of discontinuation due to adverse drug reactions were identified in either group, and there were no safety concerns. CONCLUSIONS Pemafibrate is recommended over omega-3-acid ethyl ester for lipid management and MASLD treatment in patients with hypertriglyceridemia complicated by MASLD. The study results may contribute to the development of future treatment strategies for patients with MASLD/MASH.
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Affiliation(s)
- Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | | | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital
| | - Satoshi Kimoto
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | - Kazumasa Sakamoto
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | - Yukiomi Nakade
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | - Kiyoaki Ito
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | | | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
- Goryokai Clinic
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Degenaar A, Jacobs A, Kruger R, Delles C, Mischak H, Mels C. Cardiovascular risk and kidney function profiling using conventional and novel biomarkers in young adults: the African-PREDICT study. BMC Nephrol 2023; 24:96. [PMID: 37055746 PMCID: PMC10103421 DOI: 10.1186/s12882-023-03100-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 03/02/2023] [Indexed: 04/15/2023] Open
Abstract
BACKGROUND Low- and middle-income countries experience an increasing burden of chronic kidney disease. Cardiovascular risk factors, including advancing age, may contribute to this phenomenon. We (i) profiled cardiovascular risk factors and different biomarkers of subclinical kidney function and (ii) investigated the relationship between these variables. METHODS We cross-sectionally analysed 956 apparently healthy adults between 20 and 30 years of age. Cardiovascular risk factors such as high adiposity, blood pressure, glucose levels, adverse lipid profiles and lifestyle factors were measured. Various biomarkers were used to assess subclinical kidney function, including estimated glomerular filtration rate (eGFR), urinary albumin, uromodulin and the CKD273 urinary proteomics classifier. These biomarkers were used to divide the total population into quartiles to compare extremes (25th percentiles) on the normal kidney function continuum. The lower 25th percentiles of eGFR and uromodulin and the upper 25th percentiles of urinary albumin and the CKD273 classifier represented the more unfavourable kidney function groups. RESULTS In the lower 25th percentiles of eGFR and uromodulin and the upper 25th percentile of the CKD273 classifier, more adverse cardiovascular profiles were observed. In multi-variable adjusted regression analyses performed in the total group, eGFR associated negatively with HDL-C (β= -0.44; p < 0.001) and GGT (β= -0.24; p < 0.001), while the CKD273 classifier associated positively with age and these same risk factors (age: β = 0.10; p = 0.021, HDL-C: β = 0.23; p < 0.001, GGT: β = 0.14; p = 0.002). CONCLUSION Age, lifestyle and health measures impact kidney health even in the third decade.
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Affiliation(s)
- A Degenaar
- Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
| | - A Jacobs
- Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
- MRC Research Unit: Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa
| | - R Kruger
- Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
- MRC Research Unit: Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa
| | - C Delles
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - H Mischak
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
- Mosaiques Diagnostics GmbH, Hannover, Germany
| | - Cmc Mels
- Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.
- MRC Research Unit: Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.
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George C, Hill J, Nqebelele U, Peer N, Kengne AP. Leveraging the South African Diabetes Prevention Programme to screen for chronic kidney disease: an observational study. BMJ Open 2023; 13:e068672. [PMID: 36609330 PMCID: PMC9827250 DOI: 10.1136/bmjopen-2022-068672] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVE To evaluate the viability of leveraging an existing screening programme (the South African Diabetes Prevention Programme (SA-DPP)) to screen for chronic kidney disease (CKD), by assessing the yield of CKD cases among those participating in the programme. DESIGN Observational study conducted between 2017 and 2019. SETTING 16 resource-poor communities in Cape Town, South Africa. PARTICIPANTS 690 participants, aged between 25 and 65 years, identified as at high risk for type 2 diabetes mellitus (T2DM) by the African Diabetes Risk Score. PRIMARY OUTCOME MEASURE The prevalence of CKD among those participating in the SA-DPP. RESULTS Of the 2173 individuals screened in the community, 690 participants underwent further testing. Of these participants, 9.6% (n=66) and 18.1% (n=125) had screen-detected T2DM and CKD (defined as an estimated glomerular filtration rate (eGFR) of<60 mL/min/1.73 m2 and/or albumin-to-creatinine ratio >3 mg/mmol), respectively. Of those with CKD, 73.6% (n=92), 17.6% (n=22) and 8.8% (n=11) presented with stages 1, 2 and 3, respectively. Of the participants with an eGFR <60 mL/min/1.73 m2, 36.4% had no albuminuria and of those with normal kidney function (eGFR ≥90 mL/min/1.73 m2), 10.2% and 3.8% had albuminuria stages 2 and 3, respectively. Of those with T2DM and hypertension, 22.7% and 19.8% had CKD, respectively. CONCLUSION The fact that almost one in five participants identified as high risk for T2DM had CKD underscores the value of including markers of kidney function in an existing screening programme. By using an opportunistic approach to screen high-risk individuals, those with CKD can be identified and appropriately treated to reduce disease progression.
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Affiliation(s)
- Cindy George
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
| | - Jillian Hill
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
| | - Unati Nqebelele
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa
- Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa
| | - Nasheeta Peer
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa
| | - A P Kengne
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa
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Chan YJ, Chang SS, Wu JL, Wang ST, Yu CS. Association between liver stiffness measurement by transient elastography and chronic kidney disease. Medicine (Baltimore) 2022; 101:e28658. [PMID: 35089208 PMCID: PMC8797510 DOI: 10.1097/md.0000000000028658] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 12/23/2021] [Accepted: 01/04/2022] [Indexed: 01/05/2023] Open
Abstract
ABSTRACT Transient elastography or elastometry (TE) is widely used for clinically cirrhosis and liver steatosis examination. Liver fibrosis and fatty liver had been known to share some co-morbidities that may result in chronic impairment in renal function. We conducted a study to analyze the association between scores of 2 TE parameters, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), with chronic kidney disease among health checkup population.This was a retrospective, cross-sectional study. Our study explored the data of the health checkup population between January 2009 and the end of June 2018 in a regional hospital. All patients were aged more than 18 year-old. Data from a total of 1940 persons were examined in the present study. The estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD-simplify-GFR) equation. Chronic kidney disease (CKD) was defined as eGFR < 60 mL/min/1.73 m2.The median of CAP and LSM score was 242, 265.5, and 4.3, 4.95 in non-CKD (eGFR > 60) and CKD (eGFR < 60) group, respectively. In stepwise regression model, we adjust for LSM, CAP, inflammatory markers, serum biochemistry markers of liver function, and metabolic risks factors. The P value of LSM score, ALT, AST, respectively is .005, <.001, and <.001 in this model.The LSM score is an independent factor that could be used to predict renal function impairment according to its correlation with eGFR. This result can further infer that hepatic fibrosis may be a risk factor for CKD.
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Affiliation(s)
- Ya-Ju Chan
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Shy-Shin Chang
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jenny L. Wu
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Sen-Te Wang
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Health Management Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Cheng-Sheng Yu
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Information Management, Fu Jen Catholic University, New Taipei City, Taiwan
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
- Office of Data Science, Taipei Medical University, Taipei, Taiwan
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Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study. Clin Exp Nephrol 2021; 25:822-834. [PMID: 33856608 DOI: 10.1007/s10157-020-02018-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 12/28/2020] [Indexed: 10/21/2022]
Abstract
BACKGROUND A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis assessments of NAFLD such as Fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) have been developed to substitute liver biopsy. Little is known about the association between FIB-4 index or NFS and the components of CKD. METHODS In the present cross-sectional study, we assessed of 3640 Japanese CKD patients. We examined the association between FIB-4index or NFS and the odds of having low estimated glomerular filtration rate (eGFR) defined as eGFR < 60 mL/min/1.73 m2 or albuminuria defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Patients were divided into quartiles according to their baseline FIB-4 index and NFS levels. Linear and logistic regression analysis were conducted, with adjustment for potential confounding factors. RESULTS FIB-4 index and NFS were negatively associated with eGFR, but not UACR, after adjustment for potential confounding factors. Both FIB-4 index and NFS were significantly associated with low eGFR after adjustment for potential confounding factors. Meanwhile, in the multivariable-adjusted model, no associations were found between FIB-4 index or NFS and albuminuria. The addition of FIB-4 index or NFS to the established clinical CKD risk factors improved diagnostic accuracy of prevalence of low eGFR. We also found that there was a significant trend of higher FIB-4 index and NFS with more advanced renal fibrosis using the kidney biopsy data. CONCLUSIONS Higher non-invasive fibrosis assessments of NAFLD were associated with higher odds of decreased eGFR.
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Ochiai H, Shirasawa T, Yoshimoto T, Nagahama S, Watanabe A, Sakamoto K, Kokaze A. Elevated alanine aminotransferase and low aspartate aminotransferase/alanine aminotransferase ratio are associated with chronic kidney disease among middle-aged women: a cross-sectional study. BMC Nephrol 2020; 21:471. [PMID: 33172399 PMCID: PMC7653768 DOI: 10.1186/s12882-020-02144-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 10/30/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to ALT ratio (AST/ALT ratio) have been shown to be related to non-alcoholic fatty liver disease or insulin resistance, which was associated with chronic kidney disease (CKD). However, it is unclear whether ALT and AST/ALT ratio are associated with CKD. In this study, we examined the relationship of ALT and AST/ALT ratio to CKD among middle-aged females in Japan. METHODS The present study included 29,133 women aged 40 to 64 years who had an annual health checkup in Japan during April 2013 to March 2014. Venous blood samples were collected to measure ALT, AST, gamma-glutamyltransferase (GGT), and creatinine levels. In accordance with previous studies, ALT > 40 U/L and GGT > 50 U/L were determined as elevated, AST/ALT ratio < 1 was regarded as low, and CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or proteinuria. Logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for CKD. RESULTS "Elevated ALT and elevated GGT" and "elevated ALT and non-elevated GGT" significantly increased the OR for CKD when compared with "non-elevated ALT and non-elevated GGT" (OR: 2.56, 95% CI: 2.10-3.12 and OR: 2.24, 95% CI: 1.81-2.77). Compared with "AST/ALT ratio ≥ 1 and non-elevated GGT", "AST/ALT ratio < 1 and elevated GGT" and "AST/ALT ratio < 1 and non-elevated GGT" significantly increased the OR for CKD (OR: 2.73, 95% CI: 2.36-3.15 and OR: 1.68, 95% CI: 1.52-1.87). These findings still remained after adjustment for confounders. CONCLUSIONS Elevated ALT was associated with CKD regardless of GGT elevation. Moreover, low AST/ALT ratio was also associated with CKD independent of GGT elevation.
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Affiliation(s)
- Hirotaka Ochiai
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
| | - Takako Shirasawa
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
| | - Takahiko Yoshimoto
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
| | - Satsue Nagahama
- All Japan Labor Welfare Foundation, 6-16-11 Hatanodai, Shinagawa-ku, Tokyo, 142-0064, Japan
| | - Akihiro Watanabe
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
| | - Ken Sakamoto
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
| | - Akatsuki Kokaze
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
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7
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Lee DY, Han K, Yu JH, Park S, Heo JI, Seo JA, Kim NH, Yoo HJ, Kim SG, Kim SM, Choi KM, Baik SH, Park YG, Kim NH. Gamma-glutamyl transferase variability can predict the development of end-stage of renal disease: a nationwide population-based study. Sci Rep 2020; 10:11668. [PMID: 32669624 PMCID: PMC7363906 DOI: 10.1038/s41598-020-68603-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 06/24/2020] [Indexed: 12/17/2022] Open
Abstract
The aim of this study is to investigate whether GGT variability is able to predict the risk of end-stage renal disease (ESRD). The study subjects were Koreans who conducted health exams supported by the Korean National Health Insurance Corporation during 2009-2012 (baseline). After excluding individuals aged < 40 years, heavy alcoholics, or those with histories of chronic liver disease or ESRD, we followed 6,058,995 individuals. We calculated the average successive variability (ASV) of GGT values during the 5 years before the baseline as a parameter of variability. Using Cox proportional analyses, we evaluated the risk of ESRD according to GGT ASV quartiles, defined as the initiation of renal replacement therapy or kidney transplantation, or December 31, 2016. During 38,663,279.3 person-years of follow-up, 12,057 cases of ESRD were identified. Compared with GGT ASV quartile 1, the risk of ESRD was higher in ASV quartiles 3-4 and increased serially, even after adjustment for several metabolic parameters, baseline renal function, presence of comorbidities, low income, and baseline GGT and hemoglobin level. The fully adjusted hazard ratios (95% confidence intervals) of GGT ASV quartiles 3 and 4 were 1.06 (1.01-1.12) and 1.12 (1.06-1.18), respectively. In conclusion, GGT variability is a putative risk factor for ESRD in Koreans.
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Affiliation(s)
- Da Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Biostatics, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Ji Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sanghyun Park
- Department of Biostatics, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Jee-In Heo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Seon Mee Kim
- Department of Family Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Yong Gyu Park
- Department of Biostatics, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, 15355, Republic of Korea.
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Kiapidou S, Liava C, Kalogirou M, Akriviadis E, Sinakos E. Chronic kidney disease in patients with non-alcoholic fatty liver disease: What the Hepatologist should know? Ann Hepatol 2020; 19:134-144. [PMID: 31606352 DOI: 10.1016/j.aohep.2019.07.013] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 06/19/2019] [Accepted: 07/08/2019] [Indexed: 02/04/2023]
Abstract
The association of non-alcoholic fatty liver disease (NAFLD) with several other diseases has gained increased interest during the recent years. Among them, the association with chronic kidney disease (CKD) has emerged as an important one regarding both its prevalence and significance. The early recognition of this association is important for the prognosis of patients with NAFLD and CKD. Apart from early diagnosis, the accurate assessment of renal function is also crucial in the clinical practice of hepatologists. Several methods have been used in the literature for the evaluation of kidney function in patients with NAFLD up to now. In this respect, calculators (or formulas) for the estimation of Glomerular Filtration Rate (eGFR) and Albumin to Creatinine Ratio (ACR) are simple, practical and easily available methods for this purpose. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD. The collection of all relevant data regarding this association will provide hepatologists with pertinent knowledge on this topic and allow them to use the most accurate methods for the assessment of kidney function in these patients in their clinical practice.
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Affiliation(s)
- Stefania Kiapidou
- 4th Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Konstantinoupoleos, Thessaloniki, Greece
| | - Christina Liava
- 4th Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Konstantinoupoleos, Thessaloniki, Greece
| | - Maria Kalogirou
- 4th Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Konstantinoupoleos, Thessaloniki, Greece
| | - Evangelos Akriviadis
- 4th Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Konstantinoupoleos, Thessaloniki, Greece
| | - Emmanouil Sinakos
- 4th Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Konstantinoupoleos, Thessaloniki, Greece.
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Abstract
The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites. Mercapturic acids (N-acetyl-l-cysteine S-conjugates) are formed by the sequential action of the glutathione transferases, γ-glutamyltransferases, dipeptidases, and cysteine S-conjugate N-acetyltransferase to yield glutathione S-conjugates, l-cysteinylglycine S-conjugates, l-cysteine S-conjugates, and mercapturic acids; these metabolites constitute a "mercapturomic" profile. Aminoacylases catalyze the hydrolysis of mercapturic acids to form cysteine S-conjugates. Several renal transport systems facilitate the urinary elimination of mercapturic acids; urinary mercapturic acids may serve as biomarkers for exposure to chemicals. Although mercapturic acid formation and elimination is a detoxication reaction, l-cysteine S-conjugates may undergo bioactivation by cysteine S-conjugate β-lyase. Moreover, some l-cysteine S-conjugates, particularly l-cysteinyl-leukotrienes, exert significant pathophysiological effects. Finally, some enzymes of the mercapturic acid pathway are described as the so-called "moonlighting proteins," catalytic proteins that exert multiple biochemical or biophysical functions apart from catalysis.
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Affiliation(s)
- Patrick E Hanna
- Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA
| | - M W Anders
- Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA
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10
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Wilechansky RM, Pedley A, Massaro JM, Hoffmann U, Benjamin EJ, Long MT. Relations of liver fat with prevalent and incident chronic kidney disease in the Framingham Heart Study: A secondary analysis. Liver Int 2019; 39:1535-1544. [PMID: 31033142 PMCID: PMC6675651 DOI: 10.1111/liv.14125] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 04/13/2019] [Accepted: 04/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Prior studies demonstrated an association between non-alcoholic fatty liver disease and chronic kidney disease (CKD), though data are conflicting. We examined the association between liver fat and prevalent and incident CKD in the Framingham Heart Study (FHS). METHODS We included FHS participants who underwent computed tomography (CT) from 2002 to 2005 (n = 1315). After excluding heavy alcohol use (n = 211) and missing covariates (n = 117), the final sample included 987 participants. For the incident CKD analysis, we excluded 73 participants with prevalent CKD. Liver fat was measured by the average liver attenuation on CT. Estimated glomerular filtration rate (eGFR) was obtained using the CKD Epidemiology Collaboration Creatinine-Cystatin C equation, and CKD was defined as eGFR < 60 ml/min/1.73 m2 . Microalbuminuria was defined by sex-specific urinary albumin-creatinine ratio cut-offs. Multivariable-adjusted regression models were performed to determine the association between liver fat and CKD. RESULTS The prevalence of hepatic steatosis and CKD were 19% and 14% respectively (55.9% women, mean age 60 ± 9 years). After adjusting for covariates, we observed no significant associations between liver fat and CKD, microalbuminuria or eGFR in cross-sectional analyses. We observed positive associations between liver fat, incident microalbuminuria and reduced eGFR in age- and sex-adjusted models; these relationships were not significant in multivariable-adjusted models. CONCLUSIONS In this community-based cohort study, we did not observe significant associations between liver fat and prevalent or incident CKD with a median follow-up time of 12.5 years. The association between NAFLD and CKD may be accounted for by shared risk factors; confirmatory studies are needed.
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Affiliation(s)
| | - Alison Pedley
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA
| | - Joseph M. Massaro
- Department of Mathematics and Statistics, Boston University, Boston, MA
| | - Udo Hoffmann
- Radiology Department, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Emelia J. Benjamin
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA,Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | - Michelle T. Long
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA,Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
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11
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Fan Y, Jin X, Man C, Gong D. Association of serum gamma-glutamyltransferase with chronic kidney disease risk: a meta-analysis. Free Radic Res 2018; 52:819-825. [PMID: 30208797 DOI: 10.1080/10715762.2018.1492120] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Yu Fan
- Institute of Molecular Biology and Translational Medicine, the Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China
| | - Xin Jin
- Institute of Molecular Biology and Translational Medicine, the Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China
| | - Changfeng Man
- Institute of Molecular Biology and Translational Medicine, the Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China
| | - Dandan Gong
- Institute of Molecular Biology and Translational Medicine, the Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China
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12
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Wong VWS, Chan WK, Chitturi S, Chawla Y, Dan YY, Duseja A, Fan J, Goh KL, Hamaguchi M, Hashimoto E, Kim SU, Lesmana LA, Lin YC, Liu CJ, Ni YH, Sollano J, Wong SKH, Wong GLH, Chan HLY, Farrell G. Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 1: Definition, risk factors and assessment. J Gastroenterol Hepatol 2018; 33:70-85. [PMID: 28670712 DOI: 10.1111/jgh.13857] [Citation(s) in RCA: 354] [Impact Index Per Article: 50.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 05/30/2017] [Accepted: 06/25/2017] [Indexed: 12/12/2022]
Affiliation(s)
- Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease and Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Wah-Kheong Chan
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shiv Chitturi
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Yogesh Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yock Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jiangao Fan
- Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Khean-Lee Goh
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | | | - Etsuko Hashimoto
- Departments of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | | | - Yu-Cheng Lin
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, Hepatitis Research Center and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | - Jose Sollano
- University of Santo Tomas, Manila, The Philippines
| | - Simon Kin-Hung Wong
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease and Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease and Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Geoff Farrell
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
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13
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Zhou X, Wang L, Wang G, Cheng X, Hu S, Ke W, Li M, Zhang Y, Song Z, Zheng Q. A new plasma biomarker enhance the clinical prediction of postoperative acute kidney injury in patients with hepatocellular carcinoma. Clin Chim Acta 2017; 475:128-136. [PMID: 29031454 DOI: 10.1016/j.cca.2017.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Revised: 09/07/2017] [Accepted: 10/10/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND The ratio of serum γ-glutamyl transferase (GGT) to alanine aminotransferase (ALT) (GGT/ALT) is a marker for evaluating effects to antivirotic treatment and a helpful predictive factor for the prognosis of Child-Pugh A hepatocellular carcinoma (HCC) patients after surgery. The relationship between the incidence of postoperative acute kidney injury (AKI) and preoperative GGT/ALT is studied in hepatectomized hepatitis B- or C- associated HCC patients. METHODS A total of 253 hepatitis B or C virus-related HCC patients undergoing hepatectomy between September 2012 and August 2016 at our hospital were included in the retrospective study. Serum ALT and GGT value were recorded, and the GGT/ALT was computed. AKI was defined that based on the "Kidney Disease Improving Global Outcomes (KDIGO) criteria". RESULTS AKI was observed in 22 (8.7%) patients. Mean GGT/ALT of patients with AKI was significantly higher than in those without it (6.0 vs 2.1, P<0.001). Multivariate analysis revealed an increase in GGT/ALT as an independent risk factor for AKI in hepatitis B- or C- associated HCC patients, particularly in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A staged HCC (odds ratio (OR) 1.400, P<0.001). Multivariate analysis showed that ALT (OR 0.966, P=0.044) was somewhat inversely associated with the incidence of AKI in hepatitis B- or C- associated HCC patients. The best cutoff point of GGT/ALT was 2.92. Multivariate analysis showed that preoperative GGT/ALT ≥2.92 predicted poor prognosis of postoperative AKI in patients with HCC after hepatectomy (odds ratio 17.697, P<0.001). After propensity score matching, preoperative GGT/ALT ≥2.92 remained an independent risk factor for AKI in HCC patients (OR 13.947, P=0.003). CONCLUSIONS The GGT/ALT of patients with AKI was significantly higher than those without it. Evaluation of GGT/ALT before surgery can be a helpful predictive tool for postoperative AKI in hepatitis B- or C- associated HCC patients undergoing hepatectomy, particularly in patients with BCLC stage 0 or A staged HCC. Hepatitis B- or C- associated HCC patients with low ALT especially within the normal range may have a high risk of AKI. However, the reason remains to be elucidated.
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Affiliation(s)
- Xing Zhou
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Liyu Wang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Guoliang Wang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xiang Cheng
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shaobo Hu
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Wenbo Ke
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yong Zhang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zifang Song
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Qichang Zheng
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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Kunutsor SK, Laukkanen JA. Gamma-glutamyltransferase and risk of chronic kidney disease: A prospective cohort study. Clin Chim Acta 2017; 473:39-44. [PMID: 28811239 DOI: 10.1016/j.cca.2017.08.014] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 07/03/2017] [Accepted: 08/12/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Elevated serum gamma-glutamyltransferase (GGT) activity has been linked with an increased risk of chronic kidney disease (CKD) in Asian populations. We aimed to assess the prospective association of serum GGT with risk of CKD in a Caucasian population. MATERIALS AND METHODS We related GGT activity to the incidence of CKD in 2338 men aged 42-61years of the Kuopio Ischemic Heart Disease study with normal kidney function at baseline. Repeat measurements of GGT were used to correct for within-person variability. RESULTS During a median follow-up of 25.6years, 221 men developed new-onset CKD. The age-adjusted regression dilution ratio of loge GGT was 0.70 (95% CI: 0.64-0.75). Gamma-glutamyltransferase was log-linearly associated with risk of CKD in age-adjusted analysis. In Cox regression analysis adjusted for age, the hazard ratio (95% CIs) for CKD per standard deviation increase in loge baseline GGT was 1.25 (1.09-1.43) which was attenuated to 1.01 (0.86-1.19) on further adjustment for several confounders. CONCLUSION Contrary to previous evidence of an independent association between elevated GGT and increased risk of CKD in Asian populations, initial evidence of an association between GGT and CKD in Caucasian men was confounded by body mass index, lifestyle factors, and lipids.
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Affiliation(s)
- Setor K Kunutsor
- School of Clinical Sciences, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Southmead Road, Bristol, UK.
| | - Jari A Laukkanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Central Finland Central Hospital, Jyväskylä, Finland
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15
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Afrin MR, Arumugam S, Rahman MA, Karuppagounder V, Harima M, Suzuki H, Miyashita S, Suzuki K, Ueno K, Yoneyama H, Watanabe K. Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling. Int Immunopharmacol 2017; 49:161-167. [DOI: 10.1016/j.intimp.2017.05.035] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 05/16/2017] [Accepted: 05/29/2017] [Indexed: 12/26/2022]
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16
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Zeng J, Sun C, Sun WL, Chen GY, Pan Q, Yan SY, Xu ZJ, Chen YW, Fan JG. Association between non-invasively diagnosed hepatic steatosis and chronic kidney disease in Chinese adults on their health check-up. J Dig Dis 2017; 18:229-236. [PMID: 28296249 DOI: 10.1111/1751-2980.12465] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 02/21/2017] [Accepted: 03/06/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To explore the association between chronic kidney disease (CKD), graded by the estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) using controlled attenuation parameter (CAP) and fatty liver index (FLI) values in Chinese adults undergoing routine health examinations. METHODS A total of 731 adult participants without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included. Their eGFR, CAP, FLI and abdominal ultrasonography results were assessed. RESULTS The prevalence of ultrasound-diagnosed NAFLD and CKD (eGFR <60 mL/min per 1.73 m2 ) was 36.1% and 6.6%, respectively. CKD was more common in NAFLD patients than in those without (10.6% vs 4.3%, P < 0.001). The CAP and FLI values were significantly higher in the NAFLD group than in those without, but the change in the eGFR was negligible between the two groups. eGFR was negatively correlated with CAP (r = -0.189, P = 0.003) and FLI values (r = -0.130, P = 0.045). Moreover, eGFR was significantly lower in participants with CAP >292 dBm or FLI ≥60 than in those with CAP <238 dBm or FLI <30, respectively (both P < 0.05). The CAP value (odds ratio [OR] 1.099, 95% confidence interval [CI] 1.091-1.108, P = 0.021) was an independent risk factor for CKD. CONCLUSIONS A diagnosis of hepatic steatosis is related to an increased risk of CKD among non-alcoholic and non-diabetic Chinese adults regardless of whether the diagnosis was acquired via ultrasound, CAP or FLI. Increased hepatic lipid content may contribute to CKD development.
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Affiliation(s)
- Jing Zeng
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chao Sun
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wan Lu Sun
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Guang Yu Chen
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Qin Pan
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shi Yan Yan
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zheng Jie Xu
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yuan Wen Chen
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jian Gao Fan
- Department of Gastroenterology, Center for Fatty Liver, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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17
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Ko SH, Baeg MK, Han KD, Ko SY, Shin SB, Ko SH, Ahn YB. Association between gamma-glutamyltransferase and albuminuria in nondiabetic adults with normal renal function. Clin Exp Nephrol 2016; 21:835-841. [PMID: 27933415 DOI: 10.1007/s10157-016-1356-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Accepted: 11/01/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND Serum gamma-glutamyltransferase (GGT) has been associated with albuminuria in diabetes patients, but it has not been investigated in the general population. We aimed to investigate the association between serum GGT and albuminuria in the nondiabetic Korean population with normal kidney function. METHODS Study participants (3948; 1549 men and 2399 women) with an estimated glomerular filtration rate ≥60 mL/min/1.73 m2 were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2011). Albuminuria was defined as an albumin-creatinine ratio >30 mg/g. Serum GGT was analyzed by dividing into quartiles. Multiple logistic models were used to analyze the associations between GGT and albuminuria. RESULTS The prevalence of albuminuria was 5.1% and increased linearly according to increasing GGT quartiles (P for trend = 0.005). A linear regression analysis revealed that GGT was positively related with albuminuria (P = 0.008). After adjusting for confounding factors, the odds ratio for albuminuria was 1.80 (95% CI 1.079-3.010, P for trend = 0.029) for the highest quartile group compared with those observed in the lowest quartile of GGT. In addition, this independent relationship did not change when the cut-off value of GGT (30 IU/L) was applied to this analysis. Compared with GGT value ≤30 IU/L, the adjusted odds ratio of albuminuria in participants with GGT >30 IU/L was 1.96 (95% CI 1.319-2.906, P < 0.001). CONCLUSION Higher serum GGT levels within the reference range were significantly associated with albuminuria in nondiabetic Koreans with preserved kidney function, independently of traditional cardio-renal risk factors.
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Affiliation(s)
- Sun-Hye Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 137-701, Seoul, Republic of Korea
| | - Myong Ki Baeg
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyung-Do Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung-Yeon Ko
- Department of General Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sae-Bom Shin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 137-701, Seoul, Republic of Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 137-701, Seoul, Republic of Korea
| | - Yu-Bae Ahn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 137-701, Seoul, Republic of Korea.
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18
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Mikolasevic I, Milic S, Turk Wensveen T, Grgic I, Jakopcic I, Stimac D, Wensveen F, Orlic L. Nonalcoholic fatty liver disease - A multisystem disease? World J Gastroenterol 2016; 22:9488-9505. [PMID: 27920470 PMCID: PMC5116593 DOI: 10.3748/wjg.v22.i43.9488] [Citation(s) in RCA: 135] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/30/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians.
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19
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Yan LH, Mu B, Guan Y, Liu X, Zhao N, Pan D, Wang SZ. Assessment of the relationship between non-alcoholic fatty liver disease and diabetic complications. J Diabetes Investig 2016; 7:889-894. [PMID: 27181828 PMCID: PMC5089952 DOI: 10.1111/jdi.12518] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Revised: 02/20/2016] [Accepted: 03/15/2016] [Indexed: 02/06/2023] Open
Abstract
Aims/Introduction Non‐alcoholic fatty liver disease (NAFLD) is a metabolic disorder of the liver. The relationship between NAFLD and type 2 diabetes remains largely unknown. The aim of the present study was to determine the incidence of complications arising from the interaction between NAFLD and type 2 diabetes. Materials and Methods A total of 212 individuals with type 2 diabetes were included in the study. The presence of NAFLD was determined in individuals using abdominal ultrasonography for the diagnosis of fatty liver disease. Patients were divided into three groups based on the duration of diabetes and NAFLD diagnosis. Type 2 diabetes patients were placed in group A; patients with type 2 diabetes longer than NAFLD were placed in group B; and patients with NAFLD longer than type 2 diabetes were placed in group C. All individuals had undergone electrocardiogram, blood pressure measurements, and thorough medical history and physical examinations (Doppler ultrasound, electrophysiology, fundoscopy, cardiac computed tomography). Laboratory measurements included fasting blood glucose, glycated hemoglobin, oral glucose tolerance test, liver and renal function, lipid profile, and urinary albumin excretion. Results Compared with groups A and B, the patients of group C showed a higher prevalence of significant coronary artery disease and hypertension (P < 0.05). Compared with groups A and B, the patients of group C showed a lower prevalence of diabetic retinopathy and diabetic peripheral neuropathy (P < 0.05). There was no significant difference in the prevalence of diabetic nephropathy among the three groups (P > 0.05). Conclusions NAFLD combined with type 2 diabetes is associated with the presence of significant coronary artery disease and hypertension.
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Affiliation(s)
- Li-Hui Yan
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Biao Mu
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Yue Guan
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Xinyu Liu
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Nan Zhao
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Da Pan
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Shao-Zhen Wang
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
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20
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Zhu YX, Zhang ML, Zhong Y, Wang C, Jia WP. Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver. J Diabetes Res 2016; 2016:8315454. [PMID: 26770990 PMCID: PMC4684860 DOI: 10.1155/2016/8315454] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 06/02/2015] [Accepted: 07/01/2015] [Indexed: 12/14/2022] Open
Abstract
Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγ or PPARα agonist, pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis.
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Affiliation(s)
- Yun-Xia Zhu
- Department of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Ming-Liang Zhang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Yuan Zhong
- Department of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Chen Wang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
- Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai 200233, China
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
- *Chen Wang:
| | - Wei-Ping Jia
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
- Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai 200233, China
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
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21
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Pan LL, Zhang HJ, Huang ZF, Sun Q, Chen Z, Li ZB, Yang SY, Li XY, Li XJ. Intrahepatic triglyceride content is independently associated with chronic kidney disease in obese adults: A cross-sectional study. Metabolism 2015; 64:1077-85. [PMID: 26144271 DOI: 10.1016/j.metabol.2015.06.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Revised: 06/03/2015] [Accepted: 06/04/2015] [Indexed: 01/14/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are associated with some common critical cardio-metabolic risk factors. The aim of this study was to explore the association between intrahepatic triglyceride (IHTG) content and CKD in obese subjects. METHODS A total of 1068 obese participants received anthropometric, biochemical measurements and hepatic ultrasonography. Of those, 485 participants received magnetic resonance spectroscopy ((1)H-MRS) for the determination of IHTG content. CKD was defined as a urinary albumin:creatinine ratio (UACR)≥30 mg/g and/or estimated glomerular filtration rate (eGFR)<60 mL/min per 1.73 m(2). RESULTS The prevalence of CKD was significantly higher in NAFLD subjects compared to subjects without NAFLD, while the prevalence of CKD was gradually increased as the IHTG content increased by quartiles (P for trend<0.001). After adjustment for multivariate metabolic factors, the risk of abnormal albuminuria and CKD was increased by 68% [OR (95% CI): 1.68 (1.21-2.33), P<0.01] and 54% [OR (95% CI): 1.54 (1.14-2.07), P<0.01] respectively per one standard deviation (SD) increase in IHTG content. The association between IHTG content and CKD was not changed by conventional risk factors, including age, BMI and hypertension (all P<0.05). CONCLUSION IHTG content is independently associated with CKD in obese adults.
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Affiliation(s)
- Ling-Ling Pan
- Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
| | - Hui-Jie Zhang
- Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China
| | - Zhu-Feng Huang
- Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China
| | - Qian Sun
- Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China
| | - Zheng Chen
- Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China
| | - Zhi-Bin Li
- Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China
| | - Shu-Yu Yang
- Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China
| | - Xiao-Ying Li
- Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
| | - Xue-Jun Li
- Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
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Sex- and Time-Dependent Patterns in Risk Factors of End-Stage Renal Disease: A Large Austrian Cohort with up to 20 Years of Follow-Up. PLoS One 2015; 10:e0135052. [PMID: 26322515 PMCID: PMC4555650 DOI: 10.1371/journal.pone.0135052] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 07/16/2015] [Indexed: 11/21/2022] Open
Abstract
Objective We investigated the association between metabolic factors and End-Stage Renal Disease (ESRD) and quantified the magnitude of their influence dependent on sex and time of exposure up to 20 years. Material and Methods A prospective cohort study was conducted to determine risk factors for the development of ESRD. From 1988 to 2005 185,341 persons (53.9% women) participated in the “Vorarlberg Health Monitoring and Promotion Programme” (VHM&PP). Data on body mass index (BMI), fasting blood glucose (FBG), systolic (BPsys) and diastolic (BPdia) blood pressure, total cholesterol (TC), triglycerides (TG), gamma-glutamyltransferase (GGT) and smoking status were collected. Data of the population-based VHM&PP were merged with the Austrian Dialysis and Transplant Registry. Cox proportional hazards models were applied to calculate hazard ratios (HRs) for ESRD, stratified by sex and 5-year time intervals. Results During a mean follow-up of 17.5 years 403 patients (39.1% women) developed ESRD. Significant risk factors were: BMI (per 1 kg/m2) HR 1.04 (95% CI 1.01–1.06), FBG (per 1 mmol/L) HR 1.09 (1.05–1.12), BPsys (per 5 mmHg) HR 1.10 (1.07–1.14), BPdia (per 5 mmHg) HR 1.09 (1.03–1.15), TG (per 1 mmol/L) HR 1.07 (1.02–1.13), TC (per 1 mmol/L) HR 1.22 (1.13–1.32). We observed a sex-specific risk pattern with an increased ESRD risk for men for increasing TG and smoking, and for women for increasing BMI and GGT. In time interval analyses BPsys and TC were associated with early ESRD onset, whereas BMI, FBG, BPdia and GGT were associated with later onset. Conclusions Anthropometric and metabolic factors are differentially associated with the long-term risk for ESRD in a sex- and time-dependent manner. Consideration of these patterns in preventive and therapeutic strategies could have an impact on ESRD incidence.
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Shen Z, Munker S, Luo F, Ma H, Yu C, Li Y. Effect of Non-Alcoholic Fatty Liver Disease on Estimated Glomerular Filtration Rate Could Be Dependent on Age. PLoS One 2015; 10:e0130614. [PMID: 26087253 PMCID: PMC4472701 DOI: 10.1371/journal.pone.0130614] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/21/2015] [Indexed: 01/14/2023] Open
Abstract
There is a gap between the association of non-alcoholic fatty liver disease (NAFLD) and renal function in an apparently healthy population. This study aims to assess whether NAFLD is associated with estimated glomerular filtration rate (eGFR) levels and to understand early changes of eGFR in NAFLD. A cross-sectional study was performed among apparently healthy persons who underwent general health screening including laboratory assessments and hepatic ultrasonography from January 2013 to December 2013 at the First Affiliated Hospital of Zhejiang University, College of Medicine, China. This study included 1,193 subjects with a mean age of 48 years. Prevalence of NAFLD was 31.3%. Mean eGFR was significantly lower in NAFLD than in controls (107 ± 19 mL/min/1.73 m(2) vs. 113 ± 23 mL/min/1.73 m(2), P<0.001). Correlation analysis between eGFR and NAFLD related risk factors revealed an inverse correlation between eGFR levels and some NAFLD risk factors (all P<0.01). All subjects were classified into five phases according to age. Average eGFR levels of NAFLD were lower than controls in three phases for subjects with ≤ 50 years of age (all P<0.05), while there were no significant differences on average eGFR levels between NAFLD and controls in two phases for subjects with >50 years of age (Both P>0.05). The eGFR level is significantly associated with NAFLD and its risk factors in an apparently healthy population. Effects of NAFLD on eGFR could be dependent on age.
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Affiliation(s)
- Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China
| | - Stefan Munker
- Molecular Hepatology-Alcohol Associated Diseases, II. Medical Clinic Faculty of Medicine at Mannheim, University of Heidelberg, 68167, Mannheim, Germany
| | - Fugang Luo
- College of Medicine, Zhejiang University, 310058, Hangzhou, China
| | - Han Ma
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China
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Athyros VG, Tziomalos K, Katsiki N, Doumas M, Karagiannis A, Mikhailidis DP. Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update. World J Gastroenterol 2015; 21:6820-6834. [PMID: 26078558 PMCID: PMC4462722 DOI: 10.3748/wjg.v21.i22.6820] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 03/31/2015] [Accepted: 05/07/2015] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.
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Abstract
Proteomic biomarkers offer the hope of improving the management of patients with kidney diseases by enabling more accurate and earlier detection of renal pathology than is possible with currently available biomarkers, serum creatinine and urinary albumin. In addition, proteomic biomarkers could also be useful to define the most suitable therapeutic targets in a given patient or disease setting. This Review describes the current status of proteomic and protein biomarkers in the context of kidney diseases. The valuable lessons learned from early clinical studies of potential proteomic biomarkers in kidney disease are presented to give context to the newly identified biomarkers, which have potential for actual clinical implementation. This article also includes an overview of protein-based biomarker candidates that are undergoing development for use in nephrology, focusing on those with the greatest potential for clinical implementation. Relevant issues and problems associated with the discovery, validation and clinical application of proteomic biomarkers are discussed, along with suggestions for solutions that might help to guide the design of future proteomic studies. These improvements might remove some of the current obstacles to the utilization of proteomic biomarkers, with potentially beneficial results.
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Fargion S, Porzio M, Fracanzani AL. Nonalcoholic fatty liver disease and vascular disease: State-of-the-art. World J Gastroenterol 2014; 20:13306-13324. [PMID: 25309067 PMCID: PMC4188888 DOI: 10.3748/wjg.v20.i37.13306] [Citation(s) in RCA: 165] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 05/02/2014] [Accepted: 07/30/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.
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Pallayova M, Taheri S. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies. Clin Obes 2014; 4:243-53. [PMID: 25825857 DOI: 10.1111/cob.12068] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 05/15/2014] [Accepted: 05/28/2014] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery.
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Affiliation(s)
- M Pallayova
- Faculty of Medicine, PJ Safarik University, Kosice, Slovak Republic
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Noborisaka Y, Ishizaki M, Yamazaki M, Honda R, Yamada Y. Elevated Blood Pressure and Serum γ -Glutamyltransferase as Significant Characteristics of Smokers With Chronic Kidney Disease. Nephrourol Mon 2014; 6:e20746. [PMID: 25695028 PMCID: PMC4317723 DOI: 10.5812/numonthly.20746] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 06/05/2014] [Accepted: 06/14/2014] [Indexed: 02/07/2023] Open
Abstract
Background: Smoking is a risk factor for chronic kidney disease (CKD). However, it is speculated that only a small subset of sensitive smokers develop CKD. Objectives: We aimed to reveal the characteristics of such smokers sensitive to the renal effects of smoking with respect to cardiovascular (CV) risk factors associated with smoking and/or CKD. Patients and Methods: Renal functions and CVD risk factors were assessed in middle-aged male workers. The patients were comprised of 336 nonsmokers, 332 smokers currently smoking up to one pack per day, and 38 who smoked more than one pack per day. CKD was determined by estimated glomerular filtration rate (eGFR) from serum creatinine and urinary albumin to creatinine ratio (ACR). The independent and interactive effects of smoking and CKD on the CVD risk factors adjusted for age, body mass index, alcohol consumption, and physical activity were statistically analyzed. Results: In comparison to nonsmokers, smokers had significantly higher waist circumference, white blood cells (WBC), serum triglycerides, γ-glutamyltransferase (GGT), and C-reactive protein (CRP) and lower serum high-density lipoprotein cholesterol and uric acid. On the other hand, blood pressure (BP) and WBC tended to be higher in those showing CKD than others. Serum GGT and fasting plasma glucose were significantly higher, and insulin resistance index of homeostatic model assessment (HOMA-IR) tended to be higher in those with CKD. Serum CRP was especially high in those with moderate to severe CKD. A significant interactive effect of smoking and CKD on BP and serum GGT levels was detected, i.e. BP and GGT were not different in the subjects among nonsmokers with and without CKD, but were conspicuously high among smokers with CKD. No significant interactive effect was found on either HOMA-IR or serum CRP. Conclusions: Smokers with a higher BP and/or serum GGT may be at a higher risk of developing CKD. The associations of BP and serum GGT with CKD in smokers are not entirely mediated by increased insulin resistance or chronic inflammation caused by smoking.
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Affiliation(s)
- Yuka Noborisaka
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Uchinada, Japan
- Corresponding author: Yuka Noborisaka, Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, 920-0293 Japan. Tel: +81-762188101, Fax: +81-762869723, E-mail:
| | - Masao Ishizaki
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Uchinada, Japan
| | - Michiko Yamazaki
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Uchinada, Japan
| | - Ryumon Honda
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Uchinada, Japan
| | - Yuichi Yamada
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Uchinada, Japan
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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. [PMID: 25050550 PMCID: PMC4106719 DOI: 10.1371/journal.pmed.1001680] [Citation(s) in RCA: 518] [Impact Index Per Article: 47.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Accepted: 06/12/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies. CONCLUSION The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.
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Affiliation(s)
| | - Roberto Gambino
- Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy
| | - James H. Tabibian
- Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America
| | - Mattias Ekstedt
- Division of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden
| | - Stergios Kechagias
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Masahide Hamaguchi
- Department of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
| | - Rolf Hultcrantz
- Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Hannes Hagström
- Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Seung Kew Yoon
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kangnam St. Mary Hospital, Catholic University Medical College, Seoul, Korea
| | | | - Jacob George
- Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Francisco Barrera
- Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Svanhildur Hafliðadóttir
- Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland
| | - Einar Stefan Björnsson
- Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland
| | - Matthew J. Armstrong
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom
| | - Laurence J. Hopkins
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
| | - An Verrijken
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
| | - Yusuf Yilmaz
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey
| | - Keith D. Lindor
- Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America
| | - Michael Charlton
- Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America
| | - Robin Haring
- Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany
| | - Markus M. Lerch
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Rainer Rettig
- Institute of Physiology, Ernst-Moritz-Arndt-University Medicine Greifswald, Karlsburg, Germany
| | - Henry Völzke
- Institute for Community Medicine, Ernst-Moritz-Arndt University Medicine Greifswald, Greifswald, Germany
| | - Seungho Ryu
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea
| | - Guolin Li
- College of Life Sciences, Hunan Normal University, Changsha, China
| | - Linda L. Wong
- John A. Burns School of Medicine at University of Hawaii, Transplant Institute, Hawaii Medical Center, Honolulu, Hawaii, United States of America
| | - Mariana Machado
- Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal
| | - Helena Cortez-Pinto
- Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal
| | - Kohichiroh Yasui
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Japan
| | - Maurizio Cassader
- Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy
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Orlić L, Mikolasevic I, Bagic Z, Racki S, Stimac D, Milic S. Chronic kidney disease and nonalcoholic Fatty liver disease-is there a link? Gastroenterol Res Pract 2014; 2014:847539. [PMID: 24729784 PMCID: PMC3963366 DOI: 10.1155/2014/847539] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Accepted: 02/04/2014] [Indexed: 01/12/2023] Open
Abstract
Research in recent years has led to the recognition of the importance of nonalcoholic fatty liver disease (NAFLD) and its relationship to the metabolic syndrome (MS). This has led to a growing interest in the potential prognostic value of NAFLD for adverse cardiovascular disease (CVD) outcome. On the other hand, searching for new risk factors for chronic kidney disease (CKD) development and progression is very important. Growing evidence suggests that the MS is an important factor in the pathogenesis of CKD. The best confirmation of this pathogenic link is hypertensive and diabetic nephropathy as the main causes of CKD. Furthermore, the possible link between NAFLD and CKD has also attracted research interest and recent data suggest an association between these two conditions. These findings have fuelled concerns that NAFLD may be a new and added risk factor for the development and progression of CKD. NAFLD and CKD share some important cardiometabolic risk factors and possible common pathophysiological mechanisms, and both are linked to an increased risk of incident CVD events. Therefore, common factors underlying the pathogenesis of NAFLD and CKD may be insulin resistance, oxidative stress, activation of rennin-angiotensin system, and inappropriate secretion of inflammatory cytokines by steatotic and inflamed liver.
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Affiliation(s)
- L. Orlić
- Division of Internal Medicine, Department of Nephrology and Dialysis, University Hospital Center Rijeka, 51000 Rijeka, Croatia
| | - I. Mikolasevic
- Division of Internal Medicine, Department of Nephrology and Dialysis, University Hospital Center Rijeka, 51000 Rijeka, Croatia
| | - Z. Bagic
- Division of Internal Medicine, Department of Gastroenterology, University Hospital Center Rijeka, 51000 Rijeka, Croatia
| | - S. Racki
- Division of Internal Medicine, Department of Nephrology and Dialysis, University Hospital Center Rijeka, 51000 Rijeka, Croatia
| | - D. Stimac
- Division of Internal Medicine, Department of Gastroenterology, University Hospital Center Rijeka, 51000 Rijeka, Croatia
| | - S. Milic
- Division of Internal Medicine, Department of Gastroenterology, University Hospital Center Rijeka, 51000 Rijeka, Croatia
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Armstrong MJ, Adams LA, Canbay A, Syn WK. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 2014; 59:1174-97. [PMID: 24002776 DOI: 10.1002/hep.26717] [Citation(s) in RCA: 433] [Impact Index Per Article: 39.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Accepted: 08/26/2013] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease, and is strongly associated with the metabolic syndrome. In the last decade, it has become apparent that the clinical burden of NAFLD is not restricted to liver-related morbidity or mortality, and the majority of deaths in NAFLD patients are related to cardiovascular disease (CVD) and cancer. These findings have fuelled concerns that NAFLD may be a new, and added risk factor for extrahepatic diseases such as CVD, chronic kidney disease (CKD), colorectal cancer, endocrinopathies (including type 2 diabetes mellitus [T2DM] and thyroid dysfunction), and osteoporosis. In this review we critically appraise key studies on NAFLD-associated extrahepatic disease. There was marked heterogeneity between studies in study design (cross-sectional versus prospective; sample size; presence/absence of well-defined controls), population (ethnic diversity; community-based versus hospital-based cohorts), and method of NAFLD diagnosis (liver enzymes versus imaging versus biopsy). Taking this into account, the cumulative evidence to date suggests that individuals with NAFLD (specifically, nonalcoholic steatohepatitis) harbor an increased and independent risk of developing CVD, T2DM, CKD, and colorectal neoplasms. We propose future studies are necessary to better understand these risks, and suggest an example of a screening strategy.
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Affiliation(s)
- Matthew J Armstrong
- NIHR Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
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Fruci B, Giuliano S, Mazza A, Malaguarnera R, Belfiore A. Nonalcoholic Fatty liver: a possible new target for type 2 diabetes prevention and treatment. Int J Mol Sci 2013; 14:22933-66. [PMID: 24264040 PMCID: PMC3856099 DOI: 10.3390/ijms141122933] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 10/30/2013] [Accepted: 11/08/2013] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.
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Affiliation(s)
- Barbara Fruci
- Endocrinology, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro 88100, Italy.
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Noborisaka Y, Ishizaki M, Yamazaki M, Honda R, Yamada Y. Elevated Serum Gamma-Glutamyltransferase (GGT) Activity and the Development of Chronic Kidney Disease (CKD) in Cigarette Smokers. Nephrourol Mon 2013; 5:967-73. [PMID: 24693503 PMCID: PMC3955288 DOI: 10.5812/numonthly.13652] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Revised: 07/24/2013] [Accepted: 08/03/2013] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Elevated serum gamma-glutamyltransferase (GGT) is predictive of various cardiovascular (CV) risk factors including chronic kidney disease (CKD). Elevated serum GGT has been recognized in smokers who are likely to develop CKD, but no study has focused on serum GGT and CKD in smokers. OBJECTIVES The aim of this study was to clarify the associations between cigarette consumption, elevation of serum GGT and the development of proteinuria and CKD. PATIENTS AND METHODS A retrospective 6-year observational study was conducted on 2,603 male workers aged between 40 and 64 years. Incidences of proteinuria detected by dipstick and CKD defined by proteinuria and/or reduced estimated glomerular filtration rate (eGFR) measured in health check-ups were determined 6 years later for those who had been free of them at baseline. RESULTS Higher means of serum GGT in smokers than in nonsmokers at baseline, and a higher incidence of elevated serum GGT in smokers than in nonsmokers during the 6-year period were recognized only for alcohol consumers. Incidences of proteinuria and moderate or severe CKD which has a high risk of future renal failure or CV disease were higher in the subjects with greater cigarette consumption or a higher serum GGT level. Multiple logistic regression analyses adjusting for major CV risk factors showed a significant interactive effect between smoking and elevated serum GGT on the development of proteinuria and an additive effect of smoking and serum GGT on the development of high-risk CKD. CONCLUSIONS Elevation of serum GGT in smokers, to a large extent, depends on the associated alcohol consumption. Elevated GGT in smokers plays at least a partial role in the development of CKD, mainly proteinuria, and the underlying mechanisms remain to be elucidated.
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Affiliation(s)
- Yuka Noborisaka
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Ishikawa, Japan
- Corresponding author: Yuka Noborisaka, Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, 1-1 Uchinada, Ishikawa 920-0293 Japan. Tel: +81-762188101, Fax: +81-762869723, E-mail:
| | - Masao Ishizaki
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Ishikawa, Japan
| | - Michiko Yamazaki
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Ishikawa, Japan
| | - Ryumon Honda
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Ishikawa, Japan
| | - Yuichi Yamada
- Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine, Ishikawa, Japan
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Mikolasevic I, Racki S, Bubic I, Jelic I, Stimac D, Orlic L. Chronic kidney disease and nonalcoholic Fatty liver disease proven by transient elastography. Kidney Blood Press Res 2013; 37:305-310. [PMID: 24029696 DOI: 10.1159/000350158] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2013] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND/AIM Preliminary data suggest an association between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to further investigate the association between NAFLD and decreased kidney function. METHODS A total of 62 patients with CKD were enrolled in the study. Liver stiffness was used to detect liver fibrosis and CAP (controlled attenuation parameter) was used to detect and quantify liver steatosis (Fibroscan®). NAFLD was defined by CAP values ≥238 dB.m(-1). RESULTS CKD stage III was present in 29 patients (46.8%) and CKD stage IV in 33 patients (53.2%). Out of 62 CKD patients 53 (85.5%) had NAFLD and of these 14/53 patients (26.4%) had also liver stiffness >7 kPa. The severity of liver steatosis was positively correlated with serum creatinine (r=0.399;p<0.01) and CRP (r=0.261; p<0.05) and negatively correlated with eGFR (r=-0.413; p<0.01) and serum iron concentration (r=-0.365; p<0.01). CONCLUSION The results suggest a high prevalence of NAFLD in CKD patients. The severity of liver steatosis is negatively correlated with kidney function. The study documents the value of ultrasonographic elastography as an effective non-invasive screening method for the diagnosis of NAFLD.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Nephrology and Dialysis, Division of Internal medicine, University Hospital Center Rijeka, Rijeka, Croatia
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Nagel G, Zitt E, Peter R, Pompella A, Concin H, Lhotta K. Body mass index and metabolic factors predict glomerular filtration rate and albuminuria over 20 years in a high-risk population. BMC Nephrol 2013; 14:177. [PMID: 23962027 PMCID: PMC3765663 DOI: 10.1186/1471-2369-14-177] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Accepted: 08/01/2013] [Indexed: 01/09/2023] Open
Abstract
Background The number of individuals suffering from chronic kidney disease (CKD) is increasing. Therefore, early identification of modifiable predictors of CKD is highly desirable. Previous studies suggest an association between body mass index (BMI), metabolic factors and CKD. Methods Data of 241 high risk patients with information on renal function and albuminuria from the Renal Disease in Vorarlberg (RENVOR) study (2010–2011) were linked with long-term measurements of metabolic factors in the same patients from the population-based Vorarlberg Health Monitoring & Prevention Program (VHM&PP) cohort study (1988–2005). Actual estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (ACR) were determined. BMI, blood pressure, fasting glucose, total cholesterol, triglycerides and Gamma-glutamyltransferase (GGT) were available from previous health examinations performed up to 25 years ago. Linear regression models were applied to identify predictors of current renal function. Results At all-time points BMI was significantly inversely associated with actual eGFR and positively with actual albuminuria in men, but not in women. Serum GGT and triglycerides were significantly positively associated with albuminuria in men at all-time points. Fasting glucose levels more than 20 years earlier were associated with increased albuminuria in women and reduced eGFR in men, whereas at later time points it was associated with albuminuria in men. Conclusions BMI, serum GGT, and triglycerides are long-term predictors of renal function in men. In women however, anthropometric and metabolic parameters seem to be less predictive of eGFR and albuminuria.
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Ahn AL, Choi JK, Kim MN, Kim SA, Oh EJ, Kweon HJ, Cho DY. Non-alcoholic Fatty Liver Disease and Chronic Kidney Disease in Koreans Aged 50 Years or Older. Korean J Fam Med 2013; 34:199-205. [PMID: 23730487 PMCID: PMC3667227 DOI: 10.4082/kjfm.2013.34.3.199] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2011] [Accepted: 05/07/2013] [Indexed: 12/16/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and many risk factors, and both are linked to an increased risk of cardiovascular diseases. The aim of this study was to assess the association between NAFLD and CKD according to the presence of hypertension and diabetes mellitus in Koreans aged 50 years or older. Methods A cross-sectional study of 1,706 subjects who received their routine health examination was conducted between May 2008 and April 2010 at Konkuk University medical center. Biochemical tests for liver and abdominal ultrasonography were performed. CKD was defined as either proteinuria or glomerular filtration rate ≤60 mL/min per 1.73 m2. Results Among the 1,706 subjects, There were 545 (31.9%) with non-alcoholic fatty liver disease and 424 (24.9%) with chronic kidney disease. In univariate logistic regression analysis, NAFLD was significantly associated with CKD (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.34 to 2.12). In multivariate logistic regression analysis adjusted for age, sex, current smoking, abdominal obesity, aspartate aminotransferases, alanine aminotransferases, γ-glutamyltransferase, hypertension, diabetes mellitus, hypertriglyceridemia, and low high-density lipoprotein cholesterol, NAFLD was associated with CKD (adjusted OR, 1.68; 95% CI, 1.27 to 2.24). This relationship remained significant after classification according to the presence of hypertension or diabetes mellitus. Conclusion NAFLD diagnosed by ultrasonography was significantly associated with CKD in Koreans aged 50 years or older.
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Affiliation(s)
- Ah-Leum Ahn
- Department of Family Medicine, Konkuk University School of Medicine, Seoul, Korea
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Suh YJ, Park SK, Choi JM, Ryoo JH. The clinical importance of serum γ-glutamyltransferase level as an early predictor of obesity development in Korean men. Atherosclerosis 2013; 227:437-41. [PMID: 23395520 DOI: 10.1016/j.atherosclerosis.2013.01.029] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2012] [Revised: 01/11/2013] [Accepted: 01/20/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVE Serum γ-glutamyl transferase (GGT) levels are known to be positively associated with obesity. We aimed at verifying an association between baseline GGT levels and the development of obesity in Korean men. PATIENTS AND METHODS This prospective cohort study was performed on 18,510 initially non-obese Korean men. The total follow-up period was 66,993.3 person years and the average follow-up period was 3.62 years (standard deviation [SD], 1.44). Cox proportional hazards model was used to determine hazard ratios for the risk of obesity development. RESULTS We found a strong positive association between serum GGT levels at baseline and obesity development, after adjusting for multiple covariates. The risk of obesity development was found to be significantly and dose-dependently associated with serum GGT level. Moreover, estimated hazard ratios for severe obesity (BMI (body mass index) ≥30 kg/m(2)) attributable to serum GGT levels were much higher than those for obesity (BMI ≥ 25 kg/m(2)). The significant association was also found for WC (waist circumference)-defined obesity (WC > 90 cm). CONCLUSIONS Our findings, which were obtained from a large cohort, indicate that serum GGT is an early predictor of obesity development. Furthermore, this association was remained significant after adjusting for multiple baseline covariates.
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Affiliation(s)
- Young Ju Suh
- Institute of Clinical Research, School of Medicine, Inha University, Incheon, Republic of Korea
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Abstract
NAFLD is very common in the general population and its prevalence is increasing worldwide in parallel with the increasing incidences of obesity and metabolic diseases, mainly type 2 diabetes. In some cases, however, the diagnosis of NAFLD remains uncertain because other causes of liver disease are not easy to exclude in patients who are diagnosed with NAFLD after a biochemical or ultrasonographic analysis. Several studies have documented a strong association between NAFLD and traditional and nontraditional risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Accordingly, patients with NAFLD have an increased prevalence and incidence of both CVD and CKD. It is reasonable to believe that NAFLD, CVD and CKD share common risk factors (such as visceral obesity, insulin resistance, dysglycaemia, dyslipidaemia and hypertension) and therefore that NAFLD might simply be a marker rather than a causal risk factor of CVD and CKD. In this context, the identification of NAFLD might be an additional clinical feature to improve the stratification of patients for their risk of CVD and CKD. Growing evidence suggests that in patients with NAFLD, especially if NASH is present, several molecules released from the steatotic and inflamed liver might have pathogenic roles in the development of atherosclerosis and kidney damage. If these findings are confirmed by further studies, NAFLD could become a target for the prevention and treatment of CVD and CKD. NAFLD, whatever its role (marker or causal risk factor), is therefore a clinical condition that deserves greater attention from gastroenterologists, endocrinologists, cardiologists and nephrologists, as well as internists and general practitioners.
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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 (Zagreb) 2012; 22:92-9. [PMID: 22384523 PMCID: PMC4062319 DOI: 10.11613/bm.2012.010] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with the increased burden of kidney. However, there is still no large population study to explore the potential relationship between NAFLD and mild kidney function damage (MKFD) after adjusted for confounding factors. This study is to test the hypothesis that NAFLD is associated with MKFD under controlling the effects of confounding factors. MATERIALS AND METHODS Levels of serum fasting glucose, creatinine, cholesterol, triglyceride, alanine aminotransferase and aspartate aminotransferase were analyzed from 1412 Chinese Han adults. Questionnaire and physical examination were performed to explore the potential association of NAFLD with kidney function. RESULTS NAFLD was associated with impairment of kidney function. Multivariate-adjusted odds ratio illustrated that, compared to subjects with normal liver, NAFLD subjects had a significantly higher risk of MKFD with or without adjusted for blood glucose and other covariates (P = 0.041). Further results from multi-interaction analysis demonstrated that the underlying mechanisms linked NAFLD with impaired kidney function may be that they share common risk factors and similar pathological processes. CONCLUSIONS The most striking finding of this study is that NAFLD is negatively associated with kidney function, in nondiabetic population. NAFLD and MKFD may share similar risk factors and/or pathological processes.
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Affiliation(s)
- Guolin Li
- The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, PR China.
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Targher G, Pichiri I, Zoppini G, Trombetta M, Bonora E. Increased prevalence of chronic kidney disease in patients with Type 1 diabetes and non-alcoholic fatty liver. Diabet Med 2012; 29:220-6. [PMID: 21883436 DOI: 10.1111/j.1464-5491.2011.03427.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIMS We determined whether non-alcoholic fatty liver is associated with an increased prevalence of chronic kidney disease in Type 1 diabetes. METHODS We studied 343 patients with Type 1 diabetes, who had no history of excessive alcohol consumption or other secondary causes of chronic liver disease. Non-alcoholic fatty liver was diagnosed by ultrasonography. Chronic kidney disease was defined as presence of either abnormal albuminuria (i.e., urinary albumin/creatinine ratio ≥ 30 mg/g) or estimated glomerular filtration rate of less than 60 ml min(-1) 1.73 m(-2) . RESULTS Compared with those without steatosis, patients with non-alcoholic fatty liver (n = 182) had significantly lower estimated GFR (83.0 ± 27 vs. 93.3 ± 29 ml min(-1) 1.73 m(-2) , P < 0.001) and a greater prevalence of abnormal albuminuria (50.0 vs. 20.5%, P < 0.0001) and chronic kidney disease (54.4 vs. 24.2%, P < 0.0001). Multivariable logistic regression analysis revealed that non-alcoholic fatty liver was associated with an increased risk of either abnormal albuminuria (adjusted odds ratio 2.21, 95% CI 1.2-4.1, P = 0.01) or chronic kidney disease (adjusted odds ratio 1.93, 95% CI 1.1-3.6, P = 0.02), independently of age, gender, smoking status, physical activity, diabetes duration, HbA(1c) , BMI, systolic blood pressure, plasma lipids and use of anti-hypertensive and lipid-lowering medications. CONCLUSIONS Our findings demonstrate that ultrasound-diagnosed non-alcoholic fatty liver is associated with a higher prevalence of chronic kidney disease in patients with Type 1 diabetes, independently of several risk factors, including the components of the metabolic syndrome.
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Affiliation(s)
- G Targher
- Section of Endocrinology and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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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; 32:241-8. [PMID: 22098270 DOI: 10.1111/j.1478-3231.2011.02623.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2011] [Accepted: 07/17/2011] [Indexed: 02/13/2023]
Abstract
INTRODUCTION AND AIMS Obesity is a common risk factor for nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). NAFLD and CKD have been associated in many epidemiological studies. We hypothesize that more severe liver disease, namely nonalcoholic steatohepatitis (NASH), is related with further renal impairment. We aimed to evaluate if changes in renal function were present in morbid obese patients with NAFLD. METHODS Prospective and consecutive recruitment of morbid obese patients with biopsy proven NAFLD obtained during bariatric surgery. Renal function was evaluated with CKD-Epidemiology Collaboration estimated glomerular filtration rate (eGFR). Plasmatic adiponectin, leptin and active ghrelin concentrations were determined. RESULTS One hundred and forty-eight patients were included of whom 25% had NASH and 75% simple steatosis. NASH patients were older, with higher body mass index and had more frequently metabolic syndrome and lower eGFR (97 ± 22 vs 106 ± 16 ml/min/1.73(2), P = 0.035). NASH conferred an odds ratio (OR) 3.0 (1.3-7.0) for eGFR < 90 and OR 9.7 (1.0-96.4) for eGFR < 60 ml/min/1.73(2). eGFR < 90 ml/min/1.73(2) associated with aspartate aminotransferase [OR 2.9 (1.1-7.6)] and γ-glutamyl transpeptidase elevation [OR 3.0 (1.3-7.2)], NASH [OR 3.0 (1.3-7.0)], any lobular inflammatory activity [OR 3.0 (1.3-7.0)] and severe fibrosis [OR 3.4 (1.1-10.8)]. Neither eGFR nor liver histology was associated with adipokines levels. CONCLUSIONS In morbid obese patients, NASH, particularly lobular inflammation and advanced fibrosis, associates with mild decreases in eGFR, suggesting a common inflammatory link between liver and renal lesion.
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Affiliation(s)
- Mariana V Machado
- Departamento de Gastrenterologia, Unidade de Nutrição e Metabolismo, Hospital Santa Maria, Faculdade de Medicina de Lisboa, IMM, Lisboa, Portugal
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Sesti G, Succurro E, Arturi F, Andreozzi F, Laino I, Perticone M, Sciacqua A, Hribal ML, Perticone F. IGF-1 levels link estimated glomerular filtration rate to insulin resistance in obesity: a study in obese, but metabolically healthy, subjects and obese, insulin-resistant subjects. Nutr Metab Cardiovasc Dis 2011; 21:933-940. [PMID: 20685093 DOI: 10.1016/j.numecd.2010.02.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2009] [Revised: 02/09/2010] [Accepted: 02/10/2010] [Indexed: 11/24/2022]
Abstract
BACKGROUND AND AIMS Metabolically healthy but obese (MHO) subjects have a favourable cardio-metabolic risk profile, but whether they are also at lower risk for kidney dysfunction is still questionable. METHODS AND RESULTS A total of 106 MHO, 122 normal-weight and 212 insulin-resistant obese (IRO) subjects were stratified on the basis of their insulin sensitivity and body mass index (BMI). The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR) and ISI index was used to estimate insulin sensitivity. eGFR was significantly lower in IRO as compared to MHO subjects after adjusting for age, gender and BMI (P = 0.008). In a logistic regression model adjusted for age, gender and BMI, IRO subjects showed an increased risk of having eGFR in the lowest quartile (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.01-3.58; P = 0.04) as compared with MHO subjects. This association was maintained when waist, lean body mass, blood pressure, HDL cholesterol, triglyceride, fasting glucose and insulin levels were additionally included into the model (OR 2.49, 95%CI 1.17-5.27; P = 0.01), but its independence was not retained with further inclusion of insulin-like growth factor-1 (IGF-1) levels (OR 2.16, 95%CI 0.93-5.04; P = 0.07) No differences in eGFR were observed between non-obese and MHO individuals. CONCLUSIONS These results indicate that heterogeneity in obese phenotypes may account for conflicting evidence regarding the significance of obesity as a risk factor for chronic kidney disease. Our findings suggest that obesity is associated with lower kidney function only when insulin sensitivity is reduced, and that plasma IGF-1 is likely to be an important mechanism linking the IRO phenotype with reduced eGFR.
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Affiliation(s)
- G Sesti
- Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Catanzaro, Italy.
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Targher G, Chonchol M, Pichiri I, Zoppini G. Risk of cardiovascular disease and chronic kidney disease in diabetic patients with non-alcoholic fatty liver disease: just a coincidence? J Endocrinol Invest 2011; 34:544-51. [PMID: 21427524 DOI: 10.3275/7614] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is estimated to afflict ~20-30% of the general population, and over 70% of the patients with Type 2 diabetes. Given the expected rise in the prevalence of obesity and diabetes, NAFLD will be, if not already there, an epidemic. The consequences of NAFLD are numerous, and range from progression to chronic liver disease with its associated morbidity and mortality, to worsening insulin resistance and Type 2 diabetes, to being a contributor to both cardiovascular disease (CVD) and chronic kidney disease (CKD). NAFLD is, therefore, a complex problem with implications far beyond the liver. This review focuses on the rapidly expanding body of clinical evidence suggesting that NAFLD is associated with an increased prevalence and incidence of both CVD and CKD in patients with diabetes. This association appears to be independent of obesity, hypertension, and other potential confounding factors. However, given the heterogeneity and small number of observational studies, further research is urgently required to corroborate the prognostic role of NAFLD in the development and progression of CVD and CKD among patients with diabetes, and to further elucidate the complex and intertwined mechanisms that link NAFLD with these adverse outcomes.
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Affiliation(s)
- G Targher
- Section of Endocrinology and Metabolism, Department of Medicine, University Hospital, 37126 Verona, Italy.
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Abstract
Chronic kidney disease (CKD) is a major public health problem. The classification of CKD by KDOQI and KDIGO and the routine eGFR reporting have resulted in increased identification of CKD. It is important to be able to identify those at high risk of CKD progression and its associated cardiovascular disease (CVD). Proteinuria is the most sensitive marker of CKD progression in clinical practice, especially when combined with eGFR, but these have limitations. Hence, early, more sensitive, biomarkers are required. Recently, promising biomarkers have been identified for CKD progression and its associated CVD morbidity and mortality. These may be more sensitive biomarkers of kidney function, the underlying pathophysiological processes, and/or cardiovascular risk. Although there are some common pathways to CKD progression, there are many primary causes, each with its own specific pathophysiological mechanism. Hence, a panel measuring multiple biomarkers including disease-specific biomarkers may be required. Large, longitudinal observational studies are needed to validate candidate biomarkers in a broad range of populations prior to implementation into routine CKD management. Recent renal biomarkers discovered include neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and liver-type fatty acid-binding protein. Although none are ready for use in clinical practice, it is timely to review the role of such biomarkers in predicting CKD progression and/or CVD risk in CKD.
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Risk of chronic kidney disease in patients with non-alcoholic fatty liver disease: is there a link? J Hepatol 2011; 54:1020-9. [PMID: 21145850 DOI: 10.1016/j.jhep.2010.11.007] [Citation(s) in RCA: 132] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2010] [Revised: 11/05/2010] [Accepted: 11/09/2010] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as a growing public health problem worldwide. Increasing recognition of the importance of NAFLD and its association with the features of the metabolic syndrome has stimulated an interest in its putative role in the development and progression of chronic kidney disease (CKD). Accumulating evidence suggests that NAFLD and CKD share many important cardio-metabolic risk factors and common pathogenetic mechanisms and that NAFLD is associated with an increased prevalence and incidence of CKD. This association appears to be independent of obesity, hypertension, and other potentially confounding factors, and it occurs both in patients without diabetes and in those with diabetes. Although further research is needed to establish a definitive conclusion, these observations raise the possibility that NAFLD is not only a marker of CKD but also might play a part in the pathogenesis of CKD, possibly through the systemic release of several pro-inflammatory/pro-coagulant mediators from the steatotic/inflamed liver or through the contribution of NAFLD itself to insulin resistance and atherogenic dyslipidemia. However, given the heterogeneity and small number of observational longitudinal studies, further research is urgently required to corroborate the prognostic significance of NAFLD for the incidence of CKD, and to further elucidate the complex and intertwined mechanisms that link NAFLD and CKD. If confirmed in future large-scale prospective studies, the potential adverse impact of NAFLD on kidney disease progression will deserve particular attention, especially with respect to the implications for screening and surveillance strategies in the growing number of patients with NAFLD.
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Targher G, Bertolini L, Rodella S, Lippi G, Zoppini G, Chonchol M. Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol 2010; 5:2166-71. [PMID: 20724519 DOI: 10.2215/cjn.05050610] [Citation(s) in RCA: 180] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND OBJECTIVES We assessed whether nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy is associated with decreased kidney function and whether such association is independent of insulin resistance and features of the metabolic syndrome. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS We enrolled 80 consecutive overweight patients with biopsy-proven NASH and 80 nonsteatotic control subjects who were matched for age, gender, and body mass index. Chronic kidney disease (CKD) was defined as the presence of estimated GFR (eGFR) of ≤60 ml/min per 1.73 m(2) and/or abnormal albuminuria (i.e., urinary albumin/creatinine ratio ≥30 mg/g). RESULTS NASH patients had significantly (P < 0.001) lower eGFR (75.3 ± 12 versus 87.5 ± 6 ml/min per 1.73 m(2)) and a greater frequency of abnormal albuminuria (14 versus 2.5%) and CKD (25 versus 3.7%) than control subjects. The significant differences in eGFR, albuminuria, and CKD that were observed between the two groups were only slightly weakened after adjustment for age, gender, body mass index, smoking status, insulin resistance (by homeostasis model assessment), and components of the metabolic syndrome. Notably, histologic severity of NASH (i.e., fibrosis stage) was strongly associated with either decreasing eGFR or increasing albuminuria (P < 0.01 or less), independently of potential confounding factors. CONCLUSIONS Our findings suggest that patients with biopsy-proven NASH have moderately decreased eGFR and a higher frequency of abnormal albuminuria and CKD than matched control subjects and that the severity of NASH histology is associated with decreased kidney function, independently of traditional risk factors, insulin resistance, and components of the metabolic syndrome.
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Affiliation(s)
- Giovanni Targher
- Division of Endocrinology and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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Targher G, Bertolini L, Chonchol M, Rodella S, Zoppini G, Lippi G, Zenari L, Bonora E. Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and retinopathy in type 1 diabetic patients. Diabetologia 2010; 53:1341-8. [PMID: 20369224 DOI: 10.1007/s00125-010-1720-1] [Citation(s) in RCA: 117] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2010] [Accepted: 02/22/2010] [Indexed: 02/07/2023]
Abstract
AIMS/HYPOTHESIS Non-alcoholic fatty liver disease (NAFLD) is associated with an increased prevalence of chronic kidney disease (CKD) and retinopathy in patients with type 2 diabetes. Information on this issue is lacking for type 1 diabetes. We evaluated whether NAFLD is associated with increased prevalence of retinopathy and CKD in type 1 diabetic patients. METHODS All type 1 diabetic patients (n = 202) who regularly attended our diabetes clinic and did not have any clinical evidence of cirrhosis or other secondary causes of chronic liver disease were studied. Main study measures were detection of NAFLD (by patient history and liver ultrasound), diabetic retinopathy (diagnosed by ophthalmoscopy) and CKD (defined as abnormal albuminuria or estimated GFR of < or =60 ml min(-1) 1.73 m(-2)). RESULTS The age- and sex-adjusted prevalence of diabetic retinopathy (53.2 vs 19.8%) and CKD (37.8 vs 9.9%) was markedly higher in patients with NAFLD than in those without (p < 0.0001). In multivariate logistic regression analysis, NAFLD was associated with prevalent retinopathy (adjusted OR 3.31, 95% CI 1.4-7.6, p = 0.005) or CKD (adjusted OR 3.90, 95% CI 1.5-10.1, p = 0.005). These associations were independent of age, sex, diabetes duration, HbA(1c), medication use and presence of the metabolic syndrome. CONCLUSIONS/INTERPRETATION Our findings suggest that ultrasound-diagnosed NAFLD is associated, independently of several confounding factors, with a higher prevalence of CKD and retinopathy in type 1 diabetic individuals.
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Affiliation(s)
- G Targher
- Section of Endocrinology and Metabolism, Department of Biomedical and Surgical Sciences, University of Verona, Ospedale Civile Maggiore, Piazzale Stefani 1, 37126, Verona, Italy.
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