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      Prediction of ESRD and Death Among People With CKD: The Chronic Renal Impairment in Birmingham (CRIB) Prospective Cohort Study

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          Abstract

          Background

          Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD).

          Study Design

          Prospective cohort study with validation in a separate cohort.

          Setting & Participants

          Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort).

          Factors

          44 baseline characteristics (including 30 blood and urine assays).

          Outcomes

          ESRD and all-cause mortality.

          Results

          In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly ( P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death.

          Limitations

          Other important factors may have been missed because of limited study power.

          Conclusions

          Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

          Related collections

          Most cited references 34

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          Chronic kidney disease and mortality risk: a systematic review.

          Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.
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            Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999.

            Knowledge of the excess risk posed by specific cardiovascular syndromes could help in the development of strategies to reduce premature mortality among patients with chronic kidney disease (CKD). The rates of atherosclerotic vascular disease, congestive heart failure, renal replacement therapy, and death were compared in a 5% sample of the United States Medicare population in 1998 and 1999 (n = 1,091,201). Patients were divided into the following groups: 1, no diabetes, no CKD (79.7%); 2, diabetes, no CKD (16.5%); 3, CKD, no diabetes (2.2%); and 4, both CKD and diabetes (1.6%). During the 2 yr of follow-up, the rates (per 100 patient-years) in the four groups were as follows: atherosclerotic vascular disease, 14.1, 25.3, 35.7, and 49.1; congestive heart failure, 8.6, 18.5, 30.7, and 52.3; renal replacement therapy, 0.04, 0.2, 1.6, and 3.4; and death, 5.5, 8.1, 17.7, and 19.9, respectively (P < 0.0001). With use of Cox regression, the corresponding adjusted hazards ratios were as follows: atherosclerotic vascular disease, 1, 1.30, 1.16, and 1.41 (P < 0.0001); congestive heart failure, 1, 1.44, 1.28, and 1.79 (P < 0.0001); renal replacement therapy, 1, 2.52, 23.1, and 38.9 (P < 0.0001); and death, 1, 1.21, 1.38, and 1.56 (P < 0.0001). On a relative basis, patients with CKD were at a much greater risk for the least frequent study outcome, renal replacement therapy. On an absolute basis, however, the high death rates of patients with CKD may reflect accelerated rates of atherosclerotic vascular disease and congestive heart failure.
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              Use of multiple biomarkers to improve the prediction of death from cardiovascular causes.

              The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly. We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index). During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit. Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors. Copyright 2008 Massachusetts Medical Society.
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                Author and article information

                Journal
                Am J Kidney Dis
                Am. J. Kidney Dis
                American Journal of Kidney Diseases
                W.B. Saunders
                0272-6386
                1523-6838
                December 2010
                December 2010
                : 56
                : 6-2
                : 1082-1094
                Affiliations
                [1 ]Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK
                [2 ]Queen Elizabeth Hospital, University Hospitals (Birmingham) NHS Foundation Trust, Edgbaston, Birmingham, UK
                [3 ]School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
                [4 ]Department of Clinical Biochemistry, East Kent Hospitals University NHS Trust, Kent and Canterbury Hospital, Canterbury, UK
                [5 ]Department of Chemical Pathology, Barnet and Chase Farm Hospitals NHS Trust, Barnet General Hospital, Barnet, UK
                [6 ]Department of Biochemistry, Royal Free Hospital, London, UK
                [7 ]WellChild Laboratory, King's College London, Evelina Children's Hospital, London, UK
                [8 ]Centre for Nephrology, University College London Medical School, Royal Free Campus, London, UK
                Author notes
                [* ]Address correspondence to Martin J. Landray, PhD, FRCP, Clinical Trial Service Unit and Epidemiological Studies Unit, Richard Doll Bldg, University of Oxford, Old Road Campus, Roosevelt Dr, Oxford, OX3 7LF, United Kingdom martin.landray@ 123456ctsu.ox.ac.uk
                Article
                YAJKD53508
                10.1053/j.ajkd.2010.07.016
                2991589
                21035932
                © 2010 Elsevier Inc.

                This document may be redistributed and reused, subject to certain conditions.

                Categories
                Original Investigation
                Pathogenesis and Treatment of Kidney Disease

                Nephrology

                death, end-stage renal disease, risk prediction, chronic kidney disease, outcomes

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