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      Nonalcoholic Fatty Liver Disease (NAFLD) And Cardiovascular Risk In Renal Transplant Recipients


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          Background/Aims: Renal transplant recipients (RTRs) are at high risk for cardiovascular (CVD) mortality. Recently, nonalcoholic fatty liver disease (NAFLD) has been recognized as a new risk factor for adverse CVD events in the general population. We examined whether transient elastography (TE) defined NAFLD was associated with atherosclerosis in RTRs, as measured by ultrasound in the carotid arteries. Methods: Carotid atherosclerosis was assesses in 71 RTRs with a TE proven NAFLD. With the help of TE liver stiffness was used to assess liver fibrosis and Controlled Attenuation Parameter (CAP) was used to detect and quantify liver steatosis. NAFLD was defined by the presence of steatosis with CAP values ≥238 dB.m<sup>-1</sup>. Results: RTRs with NAFLD showed more carotid atherosclerosis than RTRs without NAFLD. RTRs-NAFLD patients had the mean intima-media measurements (ITM) of 1.1±0.1 mm and that was statistically significant higher than the mean ITM founded in RTRs without NAFLD (1.1±0.1 vs. 0.9±0.1 mm; p<0.0001). Furthermore, RTRs-NAFLD patients had statistically significant higher prevalence of plaques in comparison with RTRs without NAFLD (p=0.021). Conclusion: We showed for the first time that carotid atherosclerosis is advanced in RTRs with NAFLD. Detection of NAFLD by TE should alert to the existence of an increased cardiovascular risk in RTRs.

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          Most cited references19

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          Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease.

          Nonalcoholic fatty liver disease (NAFLD) is consistently associated with features of the metabolic syndrome, a condition carrying a high risk of cardiovascular events. We measured the vasodilatory response of the brachial artery in response to ischemia (a test of endothelial function) (FMV) as well as cardiovascular risk profile in 52 NAFLD cases and 28 age- and sex-matched controls. The 10-year risk of coronary events was calculated according to the Framingham equation and the scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33% +/- 5.93% in NAFLD versus 12.22% +/- 5.05% in controls (P < .0001), and higher in pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%) (P = .010). No differences were observed in flow-independent vasodilation (response to sublingual nitroglycerin). Percent FMV was negatively associated with insulin resistance (homeostasis model assessment) in the whole population (r = -0.243; P = .030). In logistic regression analysis, NAFLD was associated with a percent FMV in the lower tertile (OR, 6.7; 95% CI, 1.26-36.1), after adjustment for age, sex, body mass index, and insulin resistance. Among NAFLD patients, low FMV was associated with nonalcoholic steatohepatitis (adjusted OR, 6.8; 95% CI, 1.2-40.2). The 10-year probability of cardiovascular events was moderately increased in NAFLD, and particularly in nonalcoholic steatohepatitis. In conclusion, our study provides evidence of endothelial dysfunction and increased risk of cardiovascular events in NAFLD. The risk of advanced liver disease is well recognized in NAFLD patients, but the large majority of cases might experience cardiovascular disease in the long term, indirectly limiting the burden of liver failure.
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            Non-alcoholic fatty liver disease and increased risk of cardiovascular disease.

            Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the general population and in the majority of patients with cardio-metabolic risk factors such as abdominal obesity, type 2 diabetes and other components of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship to the MetS is increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of cardiovascular disease (CVD). Indeed, the impact of NAFLD on CVD risk deserves particular attention in view of the implications for screening/surveillance strategies in this growing number of patients. Recent evidence suggests that the severity of liver histology in NAFLD patients is closely associated with markers of early atherosclerosis such as greater carotid artery wall thickness and lower endothelial flow-mediated vasodilation independently of classical risk factors and components of the MetS. Moreover, NAFLD is associated with greater overall mortality and independently predicts the risk of future CVD events. Overall, the current body of evidence strongly suggests that NAFLD is likely to be associated with increased CVD risk, and raises the possibility that NAFLD may be not only a marker but also an early mediator of atherosclerosis.
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              Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease.

              Nonalcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome features. We assessed whether NAFLD is associated with carotid artery intima-media thickness (IMT) as a marker of subclinical atherosclerosis and whether such an association is independent of classical risk factors, insulin resistance, and metabolic syndrome features. We compared carotid IMT, as assessed by ultrasonography, in 85 consecutive patients with biopsy-proven NAFLD and 160 age-, sex-, and BMI-matched healthy control subjects. NAFLD patients had a markedly greater carotid IMT (1.14 +/- 0.20 vs. 0.82 +/- 0.12 mm; P < 0.001) than control subjects. The metabolic syndrome (according to Adult Treatment Panel III criteria) and its individual components were more frequent in those with NAFLD (P < 0.001). The marked differences in carotid IMT observed between the groups were only slightly weakened after adjustment for age, sex, BMI, smoking history, LDL cholesterol, insulin resistance (by homeostasis model assessment), and metabolic syndrome components. Notably, carotid IMT was strongly associated with degree of hepatic steatosis, necroinflammation, and fibrosis among NAFLD patients (P < 0.001 for all). Similarly, by logistic regression analysis, the severity of histological features of NAFLD independently predicted carotid IMT (P < 0.001) after adjustment for all potential confounders. These results suggest that the severity of liver histopathology among NAFLD patients is strongly associated with early carotid atherosclerosis, independent of classical risk factors, insulin resistance, and the presence of metabolic syndrome.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                November 2014
                19 September 2014
                : 39
                : 4
                : 308-314
                aDepartment of Nephrology, Dialysis and Transplantation; bDepartment of Cardiology, University Hospital Rijeka, Rijeka; cDepartment of Internal Medicine, General Hospital “Dr. Josip Bencevic”, Slavonski Brod, Croatia
                Author notes
                *Ivana Mikolasevic, MD, Department of Nephrology, Dialysis and Transplantation, University Hospital Rijeka,, Tome Strižića 3, Rijeka (Croatia), Tel. +38551407156, Fax +38551407-156, E-Mail ivana.mikolasevic@gmail.com
                355808 Kidney Blood Press Res 2014;39:308-314
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                : 26 June 2014
                Page count
                Pages: 7
                Original Paper

                Cardiovascular Medicine,Nephrology
                Transient elastography,Renal transplant recipients,Cardiovascular disease,Nonalcoholic fatty liver disease (NAFLD)


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