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      Baseline liver function tests and full blood count indices and their association with progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people: the eGFR follow- up study

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          Abstract

          Background

          Determination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities.

          Methods

          Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR < 60 mL/min/1.73 m 2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs.

          Results

          Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8–3.6) years. Annual decline in eGFR was associated with low serum albumin ( p < 0.001) and haemoglobin ( p = 0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin ( p < 0.001), haemoglobin ( p = 0.012) and bilirubin ( p = 0.011) were associated with annual decline in eGFR.

          Renal outcomes were inversely associated with serum albumin (p < 0.001), bilirubin (p = 0.012) and haemoglobin (p < 0.001) and directly with GGT (p = 0.007) and ALP (p < 0.001). Other FBC indices and LFTs were not associated with annual decline in eGFR or renal outcomes.

          Conclusions

          GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12882-020-02185-x.

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          Most cited references46

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          Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC.

          Increased risk of mortality in patients with CKD has been attributed to inflammation. However, the association between kidney function, albuminuria, and biomarkers of inflammation has not been examined in a large cohort of CKD patients. This study measured the plasma levels of IL-1β, IL-1 receptor antagonist (IL-1RA), IL-6, TNF-α, TGF-β, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin in 3939 participants enrolled in the Chronic Renal Insufficiency Cohort study between June 2003 and September 2008. An inflammation score was established based on plasma levels of IL-1β, IL-6, TNF-α, hs-CRP, and fibrinogen. Estimated GFR (eGFR) and serum cystatin C were used as measures of kidney function. Albuminuria was quantitated by urine albumin to creatinine ratio (UACR). Plasma levels of IL-1β, IL-1RA, IL-6, TNF-α, hs-CRP, and fibrinogen were higher among participants with lower levels of eGFR. Inflammation score was higher among those with lower eGFR and higher UACR. In regression analysis adjusted for multiple covariates, eGFR, cystatin C, and UACR were strongly associated with fibrinogen, serum albumin, IL-6, and TNF-α. Each unit increase in eGFR, cystatin C, and UACR was associated with a -1.2% (95% confidence interval, -1.4, -1), 64.9% (56.8, 73.3) and 0.6% (0.4, 0.8) change in IL-6, respectively (P<0.001). Biomarkers of inflammation were inversely associated with measures of kidney function and positively with albuminuria.
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            Inflammation and Progression of CKD: The CRIC Study

            CKD is a global public health problem with significant mortality and morbidity.
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              The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease

              Background The correlation of low serum albumin with mortality in patients with chronic kidney disease (CKD) is partly linked to its association with systemic inflammation. However, it is not clear to what extent albumin's correlation with mortality depends on concomitant systemic inflammation. Here we addressed this question in patients with CKD stage 5. Methods Serum albumin (S-Alb), systemic inflammation (high-sensitive C-reactive protein, hsCRP), cardiovascular disease (CVD) and nutritional status (subjective global assessment, SGA) were assessed at baseline in 822 patients: 523 incident dialysis patients, 212 prevalent hemodialysis (HD) and 87 prevalent peritoneal dialysis (PD) patients. Patients were divided into four groups according to hsCRP and S-Alb in each cohort: Group 1 –normal S-Alb and normal hsCRP (reference); Group 2 –low S-Alb and normal hsCRP; Group 3—normal S-Alb and high hsCRP; Group 4—low S-Alb and high hsCRP. Survival over 60 months was analyzed. Results In Cox analysis, Group 4 had an increased mortality risk (adjusted Hazard ratio (95% confidence interval): 1.62 (1.06–2.47); p = 0.02) whereas the augmented mortality risks for Groups 2 and 3 in univariate analyses were not significant after adjustments for age, gender, blood pressure, diabetes mellitus, smoking, SGA, renal function and renal replacement technique. Conclusions Whereas mortality risk was increased in CKD stage 5 patients with low S-Alb and high CRP, it was not increased in patients with low S-Alb and normal CRP. Our observation suggests that inflammatory status should be taken into account when using S-albumin for risk assessment in CKD stage 5 patients.
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                Author and article information

                Contributors
                sandawanaw@aol.com
                Federica.barzi@menzies.edu.au
                w.hoy@uq.edu.au
                r.macisaac@unimelb.edu.au
                Alan.Cass@menzies.edu.au
                Maple-Brown@menzies.edu.au
                jaqui.hughes@menzies.edu.au
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                1 December 2020
                1 December 2020
                2020
                : 21
                : 523
                Affiliations
                [1 ]GRID grid.240634.7, ISNI 0000 0000 8966 2764, Department of Nephrology, Division of Medicine, , Royal Darwin Hospital, ; P.O. Box 41326, Casuarina, Darwin, Northern Territory Australia
                [2 ]Flinders University and Northern Territory Medical Program, Royal Darwin Hospital Campus, Darwin, Australia
                [3 ]GRID grid.1043.6, ISNI 0000 0001 2157 559X, Wellbeing and Preventable Chronic Diseases, Menzies School of Health Research, , Charles Darwin University, ; Darwin, Australia
                [4 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Centre for Chronic Disease, , The University of Queensland, ; Brisbane, St Lucia Australia
                [5 ]GRID grid.1051.5, ISNI 0000 0000 9760 5620, Baker Heart and Diabetes Institute, ; Melbourne, Australia
                [6 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Department of Medicine, , University of Melbourne, ; Melbourne, Australia
                [7 ]GRID grid.413105.2, ISNI 0000 0000 8606 2560, St. Vincent’s Hospital Melbourne, ; Melbourne, Australia
                [8 ]GRID grid.413105.2, ISNI 0000 0000 8606 2560, Department of Endocrinology & Diabetes, , St Vincent’s Hospital Melbourne and The University of Melbourne, ; Fitzroy, Victoria Australia
                Author information
                http://orcid.org/0000-0003-0039-1913
                Article
                2185
                10.1186/s12882-020-02185-x
                7709437
                33261565
                cf698e6a-20ac-4361-b587-ca6897be511e
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 3 August 2020
                : 24 November 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Nephrology
                aboriginal and torres strait islander australians,estimated glomerular filtration rate,liver function tests,full blood count indices,renal outcomes

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