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      Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases

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          Abstract

          Background

          Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN).

          Methods

          This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m 2, > 25 to ≤30 kg/m 2 and > 30 kg/m 2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model.

          Results

          We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1–66.2) years and BMI 28.2 (IQR 24.9–32.1) kg/m 2. Those with BMI 25-30 kg/m 2 ( n = 210) and with BMI > 30 kg/m 2 ( n = 207) were older ( p = 0.007) with higher systolic and diastolic blood pressures ( p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m 2 ( n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m 2, 7.9% in BMI 25–30 kg/m 2 and 10.7% in BMI > 30 kg/m 2 of biopsies ( p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR ( p = 0.40) and uPCR ( p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97–1.01, p = 0.31) nor blood pressure or GN diagnosis.

          Conclusion

          BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression.

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          Most cited references 21

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          Missing data: our view of the state of the art.

          Statistical procedures for missing data have vastly improved, yet misconception and unsound practice still abound. The authors frame the missing-data problem, review methods, offer advice, and raise issues that remain unresolved. They clear up common misunderstandings regarding the missing at random (MAR) concept. They summarize the evidence against older procedures and, with few exceptions, discourage their use. They present, in both technical and practical language, 2 general approaches that come highly recommended: maximum likelihood (ML) and Bayesian multiple imputation (MI). Newer developments are discussed, including some for dealing with missing data that are not MAR. Although not yet in the mainstream, these procedures may eventually extend the ML and MI methods that currently represent the state of the art.
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            Overweight, obesity, and the development of stage 3 CKD: the Framingham Heart Study.

            Prior research yielded conflicting results about the magnitude of the association between body mass index (BMI) and chronic kidney disease (CKD). Prospective cohort study. Framingham Offspring participants (n = 2,676; 52% women; mean age, 43 years) free of stage 3 CKD at baseline who participated in examination cycles 2 (1978-1981) and 7 (1998-2001). BMI. Stage 3 CKD (estimated glomerular filtration rate < 59 mL/min/1.73 m(2) for women and < 64 mL/min/1.73 m(2) for men). Age-, sex-, and multivariable-adjusted (diabetes, systolic blood pressure, hypertension treatment, current smoking status, and high-density lipoprotein cholesterol level) logistic regression models were used to examine the relationship between BMI at baseline and incident stage 3 CKD and incident dipstick proteinuria (trace or greater). At baseline, 36% of the sample was overweight and 12% was obese; 7.9% (n = 212) developed stage 3 CKD during 18.5 years of follow-up. Relative to participants with normal BMI, there was no association between overweight individuals and stage 3 CKD incidence in age- and sex-adjusted models (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.93 to 1.81; P = 0.1) or multivariable models (OR, 1.06; 95% CI, 0.75 to 1.50; P = 0.8). Obese individuals had a 68% increased odds of developing stage 3 CKD (OR, 1.68; 95% CI, 1.10 to 2.57; P = 0.02), which became nonsignificant in multivariable models (OR, 1.09; 95% CI, 0.69 to 1.73; P = 0.7). Similar findings were observed when BMI was modeled as a continuous variable or quartiles. Incident proteinuria occurred in 14.4%; overweight and obese individuals were at increased odds of proteinuria in multivariable models (OR, 1.43; 95% CI, 1.09 to 1.88; OR, 1.56; 95% CI, 1.08 to 2.26, respectively). BMI is measure of generalized obesity and not abdominal obesity. Participants are predominantly white, and these findings may not apply to different ethnic groups. Obesity is associated with increased risk of developing stage 3 CKD, which was no longer significant after adjustment for known cardiovascular disease risk factors. The relationship between obesity and stage 3 CKD may be mediated through cardiovascular disease risk factors.
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              Body mass index in 1.2 million adolescents and risk for end-stage renal disease.

              The relationship between adolescent body mass index (BMI) and future risk for end-stage renal disease (ESRD) is not fully understood, nor is it known the extent to which this association is limited to diabetic ESRD. We evaluated the association between BMI in adolescence and the risk for all-cause, diabetic, and nondiabetic ESRD. Medical data about 1 194 704 adolescents aged 17 years who had been examined for fitness for military service between January 1, 1967, and December 31, 1997, were linked to the Israeli ESRD registry in this nationwide population-based retrospective cohort study. Incident cases of treated ESRD between January 1, 1980, and May 31, 2010, were included. Cox proportional hazards models were used to estimate the hazard ratio (HR) for treated ESRD among study participants for their BMI at age 17 years, defined in accord with the US Centers for Disease Control and Prevention BMI for age and sex classification. During 30 478 675 follow-up person-years (mean [SD], 25.51 [8.77] person-years), 874 participants (713 male and 161 female) developed treated ESRD, for an overall incidence rate of 2.87 cases per 100 000 person-years. Compared with adolescents of normal weight, overweight adolescents (85th to 95th percentiles of BMI) and obese adolescents (≥95th percentile of BMI) had an increased future risk for treated ESRD, with incidence rates of 6.08 and 13.40 cases per 100 000 person-years, respectively. In a multivariate model adjusted for sex, country of origin, systolic blood pressure, and period of enrollment in the study, overweight was associated with an HR of 3.00 (95% CI, 2.50-3.60) and obesity with an HR of 6.89 (95% CI, 5.52-8.59) for all-cause treated ESRD. Overweight (HR, 5.96; 95% CI, 4.41-8.06) and obesity (HR, 19.37; 95% CI, 14.13-26.55) were strong and independent risk factors for diabetic ESRD. Positive associations of overweight (HR, 2.17; 95% CI, 1.71-2.74) and obesity (HR, 3.41; 95% CI, 2.42-4.79) with nondiabetic ESRD were also documented. Overweight and obesity in adolescents were associated with significantly increased risk for all-cause treated ESRD during a 25-year period. Elevated BMI constitutes a substantial risk factor for diabetic and nondiabetic ESRD.
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                Author and article information

                Contributors
                Benjamin.elyan@nhs.net
                Jennifer.lees2@nhs.net
                keithgillis@nhs.net
                bruce.mackinnon2@ggc.scot.nhs.uk
                jonathan.fox@ggc.scot.nhs.uk
                colin.geddes@ggc.scot.nhs.uk
                Emily.mcquarrie@nhs.net
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                2 July 2019
                2 July 2019
                2019
                : 20
                Affiliations
                [1 ]ISNI 0000 0001 2177 007X, GRID grid.415490.d, Glasgow Renal and Transplant Unit, , Queen Elizabeth University Hospital, ; Glasgow, UK
                [2 ]ISNI 0000 0001 2193 314X, GRID grid.8756.c, Institute of Cardiovascular and Medical Sciences, University of Glasgow, ; Glasgow, UK
                Article
                1434
                10.1186/s12882-019-1434-7
                6604373
                31266462
                © The Author(s). 2019

                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.

                Funding
                Funded by: Kidney Research UK
                Award ID: TF_013_20161125
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000274, British Heart Foundation;
                Award ID: RE/13/5/30177
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Nephrology

                body mass index, obesity, ckd, risk factor, glomerular disease

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