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      The SURF (Italian observational study for renal insufficiency evaluation in liver transplant recipients): a post-hoc between-sex analysis

      research-article
      1 , 2 , 2 , 1 , , on behalf of the SURF Study Group
      BMC Nephrology
      BioMed Central
      Sex differences, Gender, Renal insufficiency, Liver transplant, Calcineurin inhibitors, Meta-analysis

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          Abstract

          Background

          Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage.

          Methods

          All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m 2 at inclusion and follow-up visit.

          Results

          Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR < 60 mL/min/1.73 m 2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O’Riordan eGFR levels were observed at time of transplant and study initial visit ( p = 0.0005 and 0.0299 respectively), but not at follow-up.

          Conclusions

          Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth.

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          Most cited references39

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          Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010.

          Knowledge of the number of persons with chronic hepatitis C virus (HCV) infection in the United States is critical for public health and policy planning. To estimate the prevalence of chronic HCV infection between 2003 and 2010 and to identify factors associated with this condition. Nationally representative household survey. U.S. noninstitutionalized civilian population. 30,074 NHANES (National Health and Nutrition Examination Survey) participants between 2003 and 2010. Interviews to ascertain demographic characteristics and possible risks and exposures for HCV infection. Serum samples from participants aged 6 years or older were tested for antibody to HCV; if results were positive or indeterminate, the samples were tested for HCV RNA, which indicates current chronic infection. Based on 273 participants who tested positive for HCV RNA, the estimated prevalence of HCV infection was 1.0% (95% CI, 0.8% to 1.2%), corresponding to 2.7 million chronically infected persons (CI, 2.2 to 3.2 million persons) in the U.S. noninstitutionalized civilian population. Infected persons were more likely to be aged 40 to 59 years, male, and non-Hispanic black and to have less education and lower family income. Factors significantly associated with chronic HCV infection were illicit drug use (including injection drugs) and receipt of a blood transfusion before 1992; 49% of persons with HCV infection did not report either risk factor. Incarcerated and homeless persons were not surveyed. This analysis estimated that approximately 2.7 million U.S. residents in the population sampled by NHANES have chronic HCV infection, about 500,000 fewer than estimated in a similar analysis between 1999 and 2002. These data underscore the urgency of identifying the millions of persons who remain infected and linking them to appropriate care and treatment. None.
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            Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups.

            Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression. We recruited 2235 patients from the Observatoire de l'Hépatite C (OBSVIRC) population, the Cohorte Hépatite C Pitié-Salpétrière (DOSVIRC) population, and the original METAVIR population. All the patients had a biopsy sample compatible with chronic hepatitis C as assessed by the METAVIR scoring system (grades the stage of fibrosis on a five-point scale, F0 = no fibrosis, F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity, A3 = severe activity). No patient had received interferon treatment before the liver biopsy sample was obtained. We assessed the effect of nine factors on fibrosis progression: age at biopsy; estimated duration of infection; sex; age at infection; alcohol consumption; hepatitis C virus C (HCV) genotype; HCV viraemia; cause of infection; and histological activity grade. We defined fibrosis progression per year as the ratio between fibrosis stage in METAVIR units and the duration of infection (1 unit = one stage, 4 units = cirrhosis). The median rate of fibrosis progression per year was 0.133 fibrosis unit (95% CI 0.125-0.143), which was similar to the estimates from previous studies (0.146 to 0.154). Three independent factors were associated with an increased rate of fibrosis progression: age at infection older than 40 years, daily alcohol consumption of 50 g or more, and male sex. There was no association between fibrosis progression and HCV genotype. The median estimated duration of infection for progression to cirrhosis was 30 years (28-32), ranging from 13 years in men infected after the age of 40 to 42 years in women who did not drink alcohol and were infected before the age of 40. Without treatment, 377 (33%) patients had an expected median time to cirrhosis of less than 20 years, and 356 (31%) will never progress to cirrhosis or will not progress for at least 50 years. The host factors of ageing, alcohol consumption, and male sex have a stronger association with fibrosis progression than virological factors in HCV infection.
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              Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation.

              The objective of this study was to determine the impact of pretransplant renal function on graft and patient survival rates after orthotopic liver transplantation (OLT) using the United Network for Organ Sharing (UNOS) database for adults who underwent OLT between 1988 and 1996. Based on calculated creatinine clearance (CCr) at the time of OLT, patients were classified arbitrarily into those with normal renal function (>70 mL/min) and mild (40-69.9 mL/min), moderate (20-39.9 mL/min), and severe (<20 mL/min) renal insufficiency. Of the 20,281 patients who underwent transplantation, complete data were available for 19,261 patients. Of these, 12,778 (67%) had normal CCr (mean, 118 +/- 50 mL/min) and 4,419 (22%) had mild (56 +/- 8.5 mL/min), 1,560 (8%) had moderate (30 +/- 5.7 mL/min), and 504 (3%) had severe (14 +/- 3.6 mL/min) renal failure. UNOS status 1 was more common in patients with moderate and severe renal failure. Primary graft nonfunction and 30-day mortality rates were higher and 1-, 2-, and 5-year graft and patient survival rates were lower in patients with moderate or severe renal failure. Multiple regression analysis showed that renal failure was an independent predictor of 30-day and 2-year mortality after adjusting for the recipient's age, sex, etiology of liver disease, diabetes status, body mass index, cold ischemic time, and UNOS status. CCr less than 40 mL/min was associated with significantly lower short-term and long-term graft and patient survival rates. In conclusion, our findings suggest that when Mayo End-Stage Liver Disease (MELD) score is used to prioritize organ allocation, lower-than-expected graft and patient survival rates may be seen.
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                Author and article information

                Contributors
                delia.colombo@novartis.com
                a.zullo@medineos.com
                l.simoni@medineos.com
                emanuela.zagni@novartis.com , medidata@medineos.com
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                23 December 2019
                23 December 2019
                2019
                : 20
                : 475
                Affiliations
                [1 ]GRID grid.15585.3c, Novartis Farma S.p.A, ; Largo Umberto Boccioni, 21040 Origgio, VA Italy
                [2 ]MediNeos Observational Research, Modena, Italy
                Author information
                http://orcid.org/0000-0003-2772-9769
                Article
                1656
                10.1186/s12882-019-1656-8
                6929500
                31870321
                15dbed8b-13d9-4aa9-a48b-c8d344298bae
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 March 2019
                : 3 December 2019
                Funding
                Funded by: Novartis Farma Spa
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Nephrology
                sex differences,gender,renal insufficiency,liver transplant,calcineurin inhibitors,meta-analysis

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