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      Derivation and Validation of a Renal Risk Score for People With Type 2 Diabetes

      research-article
      , MBCHB, PHD 1 , , MBCHB, MPH 1 , , MSC 1 , , MBCHB, PHD 1 , , MBCHB 2 , , MSC 1 , , MBCHB 3 , , MA, MB, BCHIR 4
      Diabetes Care
      American Diabetes Association

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          Abstract

          OBJECTIVE

          Diabetes has become the leading cause of end-stage renal disease (ESRD). Renal risk stratification could assist in earlier identification and targeted prevention. This study aimed to derive risk models to predict ESRD events in type 2 diabetes in primary care.

          RESEARCH DESIGN AND METHODS

          The nationwide derivation cohort included adults with type 2 diabetes from the New Zealand Diabetes Cohort Study initially assessed during 2000–2006 and followed until December 2010, excluding those with pre-existing ESRD. The outcome was fatal or nonfatal ESRD event (peritoneal dialysis or hemodialysis for ESRD, renal transplantation, or death from ESRD). Risk models were developed using Cox proportional hazards models, and their performance was assessed in a separate validation cohort.

          RESULTS

          The derivation cohort included 25,736 individuals followed for up to 11 years (180,497 person-years; 86% followed for ≥5 years). At baseline, mean age was 62 years, median diabetes duration 5 years, and median HbA 1c 7.2% (55 mmol/mol); 37% had albuminuria; and median estimated glomerular filtration rate (eGFR) was 77 mL/min/1.73 m 2. There were 637 ESRD events (2.5%) during follow-up. Models that included sex, ethnicity, age, diabetes duration, albuminuria, serum creatinine, systolic blood pressure, HbA 1c, smoking status, and previous cardiovascular disease status performed well with good discrimination and calibration in the derivation cohort and the validation cohort ( n = 5,877) (C-statistics 0.89–0.92), improving predictive performance compared with previous models.

          CONCLUSIONS

          These 5-year renal risk models performed very well in two large primary care populations with type 2 diabetes. More accurate risk stratification could facilitate earlier intervention than using eGFR and/or albuminuria alone.

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          Most cited references23

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          Modeling Survival Data: Extending the Cox Model

          This is a book for statistical practitioners, particularly those who design and analyze studies for survival and event history data. Its goal is to extend the toolkit beyond the basic triad provided by most statistical packages: the Kaplan-Meier estimator, log-rank test, and Cox regression model. Building on recent developments motivated by counting process and martingale theory, it shows the reader how to extend the Cox model to analyse multiple/correlated event data using marginal and random effects (frailty) models. It covers the use of residuals and diagnostic plots to identify influential or outlying observations, assess proportional hazards and examine other aspects of goodness of fit. Other topics include time-dependent covariates and strata, discontinuous intervals of risk, multiple time scales, smoothing and regression splines, and the computation of expected survival curves. A knowledge of counting processes and martingales is not assumed as the early chapters provide an introduction to this area. The focus of the book is on actual data examples, the analysis and interpretation of the results, and computation. The methods are now readily available in SAS and S-Plus and this book gives a hands-on introduction, showing how to implement them in both packages, with worked examples for many data sets. The authors call on their extensive experience and give practical advice, including pitfalls to be avoided. Terry Therneau is Head of the Section of Biostatistics, Mayo Clinic, Rochester, Minnesota. He is actively involved in medical consulting, with emphasis in the areas of chronic liver disease, physical medicine, hematology, and laboratory medicine, and is an author on numerous papers in medical and statistical journals. He wrote two of the original SAS procedures for survival analysis (coxregr and survtest), as well as the majority of the S-Plus survival functions. Patricia Grambsch is Associate Professor in the Division of Biostatistics, School of Public Health, University of Minnesota. She has collaborated extensively with physicians and public health researchers in chronic liver disease, cancer prevention, hypertension clinical trials and psychiatric research. She is a fellow the American Statistical Association and the author of many papers in medical and statistical journals.
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            Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

            Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.
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              Maintenance dialysis population dynamics: current trends and long-term implications.

              Despite a general recognition that treatment of end-stage renal disease (ESRD) has become a large-scale undertaking, the size of the treated population and the associated costs are not well quantified. This report combines data available from a variety of sources and places the current (midyear 2001) estimated global maintenance dialysis population at just over 1.1 million patients. The size of this population has been expanding at a rate of 7% per year. Total therapy cost per patient per year in the United States is approximately 66,000 dollars. Assuming that this figure is a reasonable global average, the annual worldwide cost of maintenance ESRD therapy in the year 2001, excluding renal transplantation, will be between 70 and 75 billion US dollars. If current trends in ESRD prevalence continue, as seems probable, the ESRD population will exceed 2 million patients by the year 2010. The care of this group represents a major societal commitment: the aggregate cost of treating ESRD during the coming decade will exceed 1 trillion dollars, a thought-provoking sum by any economic metric.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                October 2013
                14 September 2013
                : 36
                : 10
                : 3113-3120
                Affiliations
                [1] 1School of Population Health, University of Auckland, Auckland, New Zealand
                [2] 2Department of Renal Medicine, Auckland District Health Board, Auckland, New Zealand
                [3] 3Department of Endocrinology, Counties Manukau District Health Board, Auckland, New Zealand
                [4] 4Auckland Diabetes Centre, Auckland District Health Board, Auckland, New Zealand.
                Author notes
                Corresponding author: C. Raina Elley, c.elley@ 123456auckland.ac.nz .
                Article
                0190
                10.2337/dc13-0190
                3781509
                23801726
                3c0039d4-6e2d-4812-912c-6c18df4a08eb
                © 2013 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 22 January 2013
                : 16 April 2013
                Page count
                Pages: 8
                Categories
                Original Research
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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