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      Predictive factors of rapid linear renal progression and mortality in patients with chronic kidney disease

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          Abstract

          Background

          Risk factors predictive of rapid linear chronic kidney disease (CKD) progression and its associations with end-stage renal disease (ESRD) and mortality requires further exploration, particularly as patients with linear estimated glomerular filtration rate (eGFR) trajectory represent a clear paradigm for understanding true CKD progression.

          Methods

          A linear regression slope was applied to all outpatient eGFR values for patients in the Salford Kidney Study who had ≥2 years follow-up, ≥4 eGFR values and baseline CKD stages 3a-4. An eGFR slope (ΔeGFR) of ≤ − 4 ml/min/1.73m 2/yr defined rapid progressors, whereas − 0.5 to + 0.5 ml/min/1.73m 2/yr defined stable patients. Binary logistic regression was utilised to explore variables associated with rapid progression and Cox proportional hazards model to determine predictors for mortality prior to ESRD.

          Results

          There were 157 rapid progressors (median ΔeGFR − 5.93 ml/min/1.73m 2/yr) and 179 stable patients (median ΔeGFR − 0.03 ml/min/1.73m 2/yr). Over 5 years, rapid progressors had an annual rate of mortality or ESRD of 47 per 100 patients compared with 6 per 100 stable patients. Factors associated with rapid progression included younger age, female gender, higher diastolic pressure, higher total cholesterol:high density lipoprotein ratio, lower albumin, lower haemoglobin and a urine protein:creatinine ratio of > 50 g/mol. The latter three factors were also predictive of mortality prior to ESRD, along with older age, smoking, peripheral vascular disease and heart failure.

          Conclusions

          There is a heterogenous interplay of risk factors associated with rapid linear CKD progression and mortality in patients with CKD. Furthermore, rapid progressors have high rates of adverse outcomes and require close specialist monitoring.

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          Most cited references26

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          Left Ventricular Remodeling After Myocardial Infarction: Pathophysiology and Therapy

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            Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study.

            The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.
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              Slower decline of glomerular filtration rate in the Japanese general population: a longitudinal 10-year follow-up study.

              The prevalence of stage 3 to 5 chronic kidney disease (CKD) in Japan (18.7%) is considerably higher than that in the United States (4.5%). This study investigated in the Japanese general population whether this higher prevalence of CKD might reflect to a progressive decline of renal function, and in turn to the increased risk of end-stage renal disease. A decline in renal function over 10 years was examined in 120,727 individuals aged 40 years or older who participated in the annual health examination program of the two periods over 10 years, 1988-1993 and 1998-2003. Renal function was assessed with estimated glomerular filtration rate (GFR) using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation modified by a Japanese coefficient. The rate of GFR decline in the participants was 0.36 mL/min/1.73 m2/year on average. In the male population aged 50-79, the mean rate of GFR decline was significantly higher in the presence of hypertension than in its absence. The rate of GFR decline was more than two times higher in participants with proteinuria than in those without proteinuria in both sexes. The rate was significantly higher in participants with an initial GFR<50 mL/min/1.73 m2 among the groups younger than age 70 and in participants with an initial GFR<40 mL/min/1.73 m2 in the group with age 70-79. Based on the slow rate of GFR decline, we concluded that the decline in renal function progresses slowly in the Japanese general population. Hypertension, proteinuria and lower GFR were found to be significant risk factors for a faster decline of GFR.
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                Author and article information

                Contributors
                ibrahim.ali@srft.nhs.uk
                rajkumar.chinnadurai@srft.nhs.uk
                sarataha_86@yahoo.com
                darren.green@srft.nhs.uk
                philip.kalra@srft.nhs.uk
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                14 August 2020
                14 August 2020
                2020
                : 21
                : 345
                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.7155.6, ISNI 0000 0001 2260 6941, Department of Internal Medicine and Nephrology, Faculty of Medicine, , Alexandria University, ; Alexandria, Egypt
                Author information
                http://orcid.org/0000-0001-7328-2529
                Article
                1982
                10.1186/s12882-020-01982-8
                7427893
                32795261
                94d6a4e9-38ee-4b30-9d1e-0c3223e0ad0a
                © 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
                : 22 April 2020
                : 24 July 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Nephrology
                chronic kidney disease,ckd,progression,prediction,mortality,end-stage renal disease
                Nephrology
                chronic kidney disease, ckd, progression, prediction, mortality, end-stage renal disease

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