Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium

Chang, Alex R.; Grams, Morgan E.; Ballew, Shoshana H.; Bilo, Henk J. G.; Correa, Adolfo; Evans, Marie; Gutiérrez, Orlando M.; Hosseinpanah, Farhad; Iseki, Kunitoshi; Kenealy, Timothy; Klein, Barbara E.K.; Kronenberg, Florian; Lee, Brian J.; Li, Yuanying; Miura, Katsuyuki; Navaneethan, Sankar D.; Roderick, Paul; Valdivielso, José M.; Visseren, Frank L.J.; Zhang, Luxia; Gansevoort, Ron T.; Hallan, Stein; Levey, Andrew S.; Matsushita, Kunihiro; Shalev, Varda; Woodward, Mark

doi:10.1136/bmj.k5301

Cited by 169 publications

(138 citation statements)

References 35 publications

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“…Despite the absence of a clear inflammatory phenotype, at both systemic and renal levels, the existence of oxidative stress and renal lipidosis might explain the renal damage, as previously suggested by others [59,60]. These possibilities are in line with the association between obesity/adiposity and increased risk of GFR decline and mortality in individuals with and without CKD [27]. Renal damage induced by lipotoxicity is a complex process that has been progressively disclosed [60,61].…”

Section: Discussionmentioning

confidence: 66%

Crescent-Like Lesions as an Early Signature of Nephropathy in a Rat Model of Prediabetes Induced by a Hypercaloric Diet

et al. 2020

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Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.

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Section: Discussionmentioning

confidence: 66%

Crescent-Like Lesions as an Early Signature of Nephropathy in a Rat Model of Prediabetes Induced by a Hypercaloric Diet

et al. 2020

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“…Our study demonstrated that waist circumference had a stronger association with CMM than BMI because waist circumference but not BMI was statistically significant in the fully adjusted model (model 3 in table 3) Earlier studies have shown a clear incremental association of abdominal obesity over BMI for non-fatal myocardial infarction, stroke, diabetes and CKD 33–36. Also, a strong association of renal function decline with central obesity and BMI has been reported in a recent meta-analysis of 39 general population cohorts from 40 countries 37. Taken together, our findings suggest that central obesity should probably be included in multimorbidity indices in Asians, and especially underscore the same for adults with hypertension 38…”

Section: Discussionmentioning

confidence: 86%

Prevalence and correlates of cardiometabolic multimorbidity among hypertensive individuals: a cross-sectional study in rural South Asia—Bangladesh, Pakistan and Sri Lanka

et al. 2019

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ObjectiveTo determinate the prevalence and correlates of cardiometabolic multimorbidity (CMM), and their cross-country variation among individuals with hypertension residing in rural communities in South Asia.DesignA cross-sectional study.SettingRural communities in Bangladesh, Pakistan and Sri Lanka.ParticipantsA total of 2288 individuals with hypertension aged ≥40 years from the ongoing Control of Blood Pressure and Risk Attenuation- Bangladesh, Pakistan and Sri Lanka clinical trial.Main outcome measuresCMM was defined as the presence of ≥2 of the conditions: diabetes, chronic kidney disease, heart disease and stroke. Logistic regression was done to evaluate the correlates of CMM.ResultsAbout 25.4% (95% CI 23.6% to 27.2%) of the hypertensive individuals had CMM. Factors positively associated with CMM included residing in Bangladesh (OR 3.42, 95% CI 2.52 to 4.65) or Sri Lankan (3.73, 95% CI 2.48 to 5.61) versus in Pakistan, advancing age (2.33, 95% CI 1.59 to 3.40 for 70 years and over vs 40–49 years), higher waist circumference (2.15, 95% CI 1.42 to 3.25) for Q2–Q3 and 2.14, 95% CI 1.50 to 3.06 for Q3 and above), statin use (2.43, 95% CI 1.84 to 3.22), and higher levels of triglyceride (1.01, 95% CI 1.01 to 1.02 per 5 mg/dL increase). A lower odds of CMM was associated with being physically active (0.75, 95% CI 0.57 to 0.97). A weak inverted J-shaped association between International Wealth Index and CMM was found (p for non-linear=0.058), suggesting higher risk in the middle than higher or lower socioeconomic strata.ConclusionsCMM is highly prevalent in rural South Asians affecting one in four individuals with hypertension. There is an urgent need for strategies to concomitantly manage hypertension, cardiometabolic comorbid conditions and associated determinants in South Asia.

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“…Increased general adiposity, estimated from body mass index (BMI), is associated with higher risk of advanced CKD (i.e. stage 4 or 5) [ 2 – 5 ]. Compared with the apparent optimum BMI (20 to <25 kg/m 2 ), advanced CKD risk is increased by about one-third in those who are overweight (BMI 25 to <30 kg/m 2 ), is approximately doubled in early obesity (BMI 30 to <35 kg/m 2 ); and is tripled at a BMI ≥ 35 kg/m 2 [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank

et al. 2020

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Background Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain. Methods Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators. Results Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53–57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30–34%). Each 5 kg/m2 higher BMI was associated with a 47% (46–49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33–37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure. Conclusions Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity–albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.

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Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium

Cited by 169 publications

References 35 publications

Crescent-Like Lesions as an Early Signature of Nephropathy in a Rat Model of Prediabetes Induced by a Hypercaloric Diet

Crescent-Like Lesions as an Early Signature of Nephropathy in a Rat Model of Prediabetes Induced by a Hypercaloric Diet

Prevalence and correlates of cardiometabolic multimorbidity among hypertensive individuals: a cross-sectional study in rural South Asia—Bangladesh, Pakistan and Sri Lanka

Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank

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