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      Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus

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          Abstract

          Background

          Chronic kidney disease (CKD) is highly prevalent but identification of patients at high risk for fast CKD progression before reaching end-stage renal disease in the short-term has been challenging. Whether factors associated with fast progression vary by diabetes status is also not well understood. We examined a large community-based cohort of adults with CKD to identify predictors of fast progression during the first 2 years of follow-up in the presence or absence of diabetes mellitus.

          Methods

          Within a large integrated healthcare delivery system in northern California, we identified adults with estimated glomerular filtration rate (eGFR) 30–59 ml/min/1.73 m 2 by CKD-EPI equation between 2008 and 2010 who had no previous dialysis or renal transplant, who had outpatient serum creatinine values spaced 10–14 months apart and who did not initiate renal replacement therapy, die or disenroll during the first 2 years of follow-up. Through 2012, we calculated the annual rate of change in eGFR and classified patients as fast progressors if they lost > 4 ml/min/1.73 m 2 per year. We used multivariable logistic regression to identify patient characteristics that were independently associated with fast CKD progression stratified by diabetes status.

          Results

          We identified 36,195 eligible adults with eGFR 30–59 ml/min/1.73 m 2 and mean age 73 years, 55% women, 11% black, 12% Asian/Pacific Islander and 36% with diabetes mellitus. During 24-month follow-up, fast progression of CKD occurred in 23.0% of patients with diabetes vs. 15.3% of patients without diabetes. Multivariable predictors of fast CKD progression that were similar by diabetes status included proteinuria, age ≥ 80 years, heart failure, anemia and higher systolic blood pressure. Age 70–79 years, prior ischemic stroke, current or former smoking and lower HDL cholesterol level were also predictive in patients without diabetes, while age 18–49 years was additionally predictive in those with diabetes.

          Conclusions

          In a large, contemporary population of adults with eGFR 30–59 ml/min/1.73 m 2, accelerated progression of kidney dysfunction within 2 years affected ~ 1 in 4 patients with diabetes and ~ 1 in 7 without diabetes. Regardless of diabetes status, the strongest independent predictors of fast CKD progression included proteinuria, elevated systolic blood pressure, heart failure and anemia.

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          Most cited references32

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          Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

          The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
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            Blood pressure and end-stage renal disease in men.

            End-stage renal disease in the United States creates a large burden for both individuals and society as a whole. Efforts to prevent the condition require an understanding of modifiable risk factors. We assessed the development of end-stage renal disease through 1990 in 332,544 men, 35 to 57 years of age, who were screened between 1973 and 1975 for entry into the Multiple Risk Factor Intervention Trial (MRFIT). We used data from the national registry for treated end-stage renal disease of the Health Care Financing Administration and from records on death from renal disease from the National Death Index and the Social Security Administration. During an average of 16 years of follow-up, 814 subjects either died of end-stage renal disease or were treated for that condition (15.6 cases per 100,000 person-years of observation). A strong, graded relation between both systolic and diastolic blood pressure and end-stage renal disease was identified, independent of associations between the disease and age, race, income, use of medication for diabetes mellitus, history of myocardial infarction, serum cholesterol concentration, and cigarette smoking. As compared with men with an optimal level of blood pressure (systolic pressure or = 210 mm Hg or diastolic pressure > or = 120 mm Hg) was 22.1 (P < 0.001). These relations were not due to end-stage renal disease that occurred soon after screening and, in the 12,866 screened men who entered the MRFIT study, were not changed by taking into account the base-line serum creatinine concentration and urinary protein excretion. The estimated risk of end-stage renal disease associated with elevations of systolic pressure was greater than that linked with elevations of diastolic pressure when both variables were considered together. Elevations of blood pressure are a strong independent risk factor for end-stage renal disease; interventions to prevent the disease need to emphasize the prevention and control of both high-normal and high blood pressure.
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              Risk factors for end-stage renal disease: 25-year follow-up.

              Few cohort studies have focused on risk factors for end-stage renal disease (ESRD). This investigation evaluated the prognostic value of several potential novel risk factors for ESRD after considering established risk factors. We studied 177 570 individuals from a large integrated health care delivery system in northern California who volunteered for health checkups between June 1, 1964, and August 31, 1973. Initiation of ESRD treatment was ascertained using US Renal Data System registry data through December 31, 2000. A total of 842 cases of ESRD were observed during 5 275 957 person-years of follow-up. This comprehensive evaluation confirmed the importance of established risk factors, including the following: male sex, older age, proteinuria, diabetes mellitus, lower educational attainment, and African American race, as well as higher blood pressure, body mass index, and serum creatinine level. The 2 most potent risk factors were proteinuria and excess weight. For proteinuria, the adjusted hazard ratios (HRs) were 7.90 (95% confidence interval [CI], 5.35-11.67) for 3 to 4+ on urine dipstick, 3.59 (2.82-4.57) for 1 to 2+ on urine dipstick, and 2.37 (1.79-3.14) for trace vs negative on urine dipstick. For excess weight, the HRs were 4.39 (95% CI, 3.38-5.70) for class 2 to class 3 obesity, 3.11 (2.51-3.84) for class 1 obesity, and 1.65 (1.39-1.97) for overweight vs normal weight. Furthermore, several independent novel risk factors for ESRD were identified, including lower hemoglobin level (1.33 [1.08-1.63] for lowest vs highest quartile), higher serum uric acid level (2.14 [1.65-2.77] for highest vs lowest quartile), self-reported history of nocturia (1.36 [1.17-1.58]), and family history of kidney disease (HR, 1.40 [95% CI, 1.02-1.90]). We confirmed the importance of established ESRD risk factors in this large cohort with broad sex and racial/ethnic representation. Lower hemoglobin level, higher serum uric acid level, self-reported history of nocturia, and family history of kidney disease are independent risk factors for ESRD.
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                Author and article information

                Contributors
                510-891-3422 , Alan.S.Go@kp.org
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                22 June 2018
                22 June 2018
                2018
                : 19
                : 146
                Affiliations
                [1 ]ISNI 0000 0000 9957 7758, GRID grid.280062.e, Division of Research, Kaiser Permanente Northern California, ; 2000 Broadway, Oakland, CA USA
                [2 ]ISNI 0000 0001 2297 6811, GRID grid.266102.1, Departments of Epidemiology, Biostatistics and Medicine, , University of California, San Francisco, ; San Francisco, CA USA
                [3 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Health Research and Policy, , Stanford University School of Medicine, ; Palo Alto, CA USA
                [4 ]ISNI 0000 0001 1519 6403, GRID grid.418151.8, Astra-Zeneca, ; Gothenburg, Sweden
                [5 ]ISNI 0000 0004 0445 0201, GRID grid.414886.7, Division of Nephrology, Kaiser Permanente Oakland Medical Center, ; Oakland, CA USA
                Author information
                http://orcid.org/0000-0001-9109-0811
                Article
                942
                10.1186/s12882-018-0942-1
                6014002
                29929484
                6cb4cd8e-2da3-4d70-85ef-6dcc6e9c63d1
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                History
                : 18 September 2017
                : 7 June 2018
                Funding
                Funded by: AstraZeneca (GB)
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Nephrology
                diabetes,chronic kidney disease,progression,risk factors,proteinuria,anemia,blood pressure
                Nephrology
                diabetes, chronic kidney disease, progression, risk factors, proteinuria, anemia, blood pressure

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