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      Adverse outcomes associated with rapid linear and non-linear patterns of chronic kidney disease progression

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          Abstract

          Background

          Patients with rapidly declining renal function face the dual threat of end-stage renal disease (ESRD) and mortality prior to ESRD. What is less well characterised is whether the pattern of the renal trajectory, linear or non-linear, unmasks subgroups of rapidly progressing patients that face adverse outcomes in a differential manner.

          Methods

          An individual eGFR slope was applied to all outpatient estimated glomerular filtration rate (eGFR) values for each patient in the Salford Kidney Study from 2002 to 2018 who had at least 2 years follow-up, ≥4 eGFR values and baseline eGFR 15 to < 60 ml/min/1.73m 2. Rapid progression was defined as an annual eGFR slope of ≤ − 3 ml/min/1.73m 2/yr and patients were categorised as linear or non-linear progressors based on the nature of their eGFR-time graphs. A Fine-Gray competing risk hazard model was used to determine factors associated with progression to ESRD and with mortality prior to ESRD. Cumulative incidence function curves highlighted differences in outcomes between linear and non-linear patients.

          Results

          There were 211 rapidly deteriorating patients with linear eGFR trajectories and 61 rapid non-linear patients in the study cohort. Factors associated with ESRD included younger age, male gender, lower baseline eGFR and higher serum phosphate, whilst older age, history of myocardial infarction and anaemia predicted mortality prior to ESRD. Over a median follow-up of 3.7 years, linear progressors reached ESRD sooner whilst those with non-linear progression faced significantly higher rates of mortality prior to ESRD.

          Conclusions

          Patients with rapid eGFR decline have high rates of adverse outcomes that are differentially expressed in those progressing linearly and non-linearly as a result of differing phenotypic profiles. Consequently, addressing individual risk factor profiles is important to deliver optimal personalised patient care.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12882-021-02282-5.

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          Most cited references24

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          A Proportional Hazards Model for the Subdistribution of a Competing Risk

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            A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk

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              The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report.

              The definition and classification for chronic kidney disease was proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) in 2002 and endorsed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2004. This framework promoted increased attention to chronic kidney disease in clinical practice, research and public health, but has also generated debate. It was the position of KDIGO and KDOQI that the definition and classification should reflect patient prognosis and that an analysis of outcomes would answer key questions underlying the debate. KDIGO initiated a collaborative meta-analysis and sponsored a Controversies Conference in October 2009 to examine the relationship of estimated glomerular filtration rate (GFR) and albuminuria to mortality and kidney outcomes. On the basis of analyses in 45 cohorts that included 1,555,332 participants from general, high-risk, and kidney disease populations, conference attendees agreed to retain the current definition for chronic kidney disease of a GFR 30 mg/g, and to modify the classification by adding albuminuria stage, subdivision of stage 3, and emphasizing clinical diagnosis. Prognosis could then be assigned based on the clinical diagnosis, stage, and other key factors relevant to specific outcomes. KDIGO has now convened a workgroup to develop a global clinical practice guideline for the definition, classification, and prognosis of chronic kidney disease.
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                Author and article information

                Contributors
                ibrahim.ali@srft.nhs.uk
                rajkumar.chinnadurai@srft.nhs.uk
                sarataha_86@yahoo.com
                philip.kalra@srft.nhs.uk
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                6 March 2021
                6 March 2021
                2021
                : 22
                : 82
                Affiliations
                [1 ]GRID grid.412346.6, ISNI 0000 0001 0237 2025, Department of Renal Medicine, , Salford Royal NHS Foundation Trust, ; Stott Lane, Salford, M6 8HD UK
                [2 ]GRID grid.5379.8, ISNI 0000000121662407, Division of Cardiovascular Sciences, , University of Manchester, ; Manchester, M13 9PL UK
                [3 ]GRID grid.7155.6, ISNI 0000 0001 2260 6941, Department of Internal Medicine and Nephrology, Faculty of Medicine, , Alexandria University, ; Alexandria, Egypt
                Article
                2282
                10.1186/s12882-021-02282-5
                7937251
                33676423
                d9e0c4ba-9da1-4a89-8844-074e3fd15962
                © The Author(s) 2021

                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
                : 25 October 2020
                : 25 February 2021
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Nephrology
                chronic kidney disease,ckd,linear,non-linear,progression,end-stage renal disease,esrd
                Nephrology
                chronic kidney disease, ckd, linear, non-linear, progression, end-stage renal disease, esrd

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