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Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study.

ABSTRACT: Ectopic fat depots may mediate local and systemic disease. Animal models of diet-induced obesity demonstrate increased fat accumulation in the renal sinus. The association of renal sinus fat with hypertension, chronic kidney disease, and other metabolic disorders has not been studied in a large, community-based sample. Participants from the Framingham Heart Study (n=2923; mean age: 54 years; 51% women) underwent quantification of renal sinus fat area using computed tomography. High renal sinus fat ("fatty kidney") was defined using sex-specific 90th percentiles in a healthy referent subsample. Multivariable linear and logistic regression was used to model metabolic risk factors as a function of fatty kidney and log-transformed renal sinus fat. Multivariable models were adjusted for age, sex, and outcome-specific covariates and then additionally adjusted for body mass index or abdominal visceral adipose tissue. The prevalence of fatty kidney was 30.1% (n=879). Individuals with fatty kidney had a higher odds ratio (OR) of hypertension (OR: 2.12; P<0.0001), which persisted after adjustment for body mass index (OR: 1.49; P<0.0001) or visceral adipose tissue (OR: 1.24; P=0.049). Fatty kidney was also associated with an increased OR for chronic kidney disease (OR: 2.30; P=0.005), even after additionally adjusting for body mass index (OR: 1.86; P=0.04) or visceral adipose tissue (OR: 1.86; P=0.05). We observed no association between fatty kidney and diabetes mellitus after adjusting for visceral adipose tissue. In conclusion, fatty kidney is a common condition that is associated with an increased risk of hypertension and chronic kidney disease. Renal sinus fat may play a role in blood pressure regulation and chronic kidney disease.

SUBMITTER: Foster MC

PROVIDER: S-EPMC3204377 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study.

Foster Meredith C MC Hwang Shih-Jen SJ Porter Stacy A SA Massaro Joseph M JM Hoffmann Udo U Fox Caroline S CS

Hypertension (Dallas, Tex. : 1979) 20110919 5

Ectopic fat depots may mediate local and systemic disease. Animal models of diet-induced obesity demonstrate increased fat accumulation in the renal sinus. The association of renal sinus fat with hypertension, chronic kidney disease, and other metabolic disorders has not been studied in a large, community-based sample. Participants from the Framingham Heart Study (n=2923; mean age: 54 years; 51% women) underwent quantification of renal sinus fat area using computed tomography. High renal sinus f ...[more]

PMID: 21931075

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Project description:Background Data are limited on the association of mildly reduced estimated glomerular filtration rate (eGFR 60-89 mL/min per 1.73 m2) with cardiovascular disease (CVD) in the community. Methods and Results We evaluated 3066 Framingham Offspring Study participants (55% women, mean age 58 years), without clinical CVD. Using multivariable regression, we related categories of mildly reduced eGFR (80-89, 70-79, or 60-69 versus ≥90 mL/min per 1.73 m2 [referent]) to prevalent coronary artery calcium, carotid intima media thickness, and left ventricular hypertrophy, and to circulating concentrations of cardiac stress biomarkers. We related eGFR categories to CVD incidence and to progression to ≥Stage 3 chronic kidney disease (eGFR <60 mL/min per 1.73 m2) using Cox regression. Individuals with eGFR 60-69 mL/min per 1.73 m2 (n=320) had higher coronary artery calcium score (odds ratio 1.69; 95% CI 1.02-2.80) compared with the referent group. Individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 had higher blood growth differentiating factor-15 concentrations (β=0.131 and 0.058 per unit-increase in log-biomarker, respectively). Participants with eGFR 60-69 and 80-89 mL/min per 1.73 m2 had higher blood B-type natriuretic peptide concentrations (β=0.119 and 0.116, respectively). On follow-up (median 16 years; 691 incident CVD and 252 chronic kidney disease events), individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 experienced higher CVD incidence (hazard ratio [HR], 1.40; 95% CI, 1.02-1.93 and 1.45, 95% CI, 1.05-2.00, respectively, versus referent). Participants with eGFR 60-69 mL/min per 1.73 m2 experienced higher chronic kidney disease incidence (HR, 2.94; 95% CI, 1.80-4.78 versus referent). Conclusions Individuals with mildly reduced eGFR 60-69 mL/min per 1.73 m2 have a higher burden of subclinical atherosclerosis cross-sectionally, and a greater risk of CVD and chronic kidney disease progression prospectively. Additional studies are warranted to confirm our findings.

Project description:BackgroundBiomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases.MethodsWe evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants with cross-sectional continuous eGFR and with longitudinal change in eGFR from baseline to follow-up (ΔeGFR). We also evaluated the associations of the 71 CVD proteins with the following dichotomous secondary outcomes: prevalent CKD stage ≥3 (cross-sectional), new-onset CKD stage ≥3 (longitudinal), and rapid decline in eGFR (longitudinal). Proteins significantly associated with eGFR and ΔeGFR were subsequently validated in 3,951 FHS Third Generation cohort participants and were tested using Mendelian randomization (MR) analysis to infer putatively causal relations between plasma protein biomarkers and kidney function.ResultsIn cross-sectional analysis, 37 protein biomarkers were significantly associated with eGFR at FDR<0.05 in the FHS Offspring cohort and 20 of these validated in the FHS Third Generation cohort at p<0.05/37. In longitudinal analysis, 27 protein biomarkers were significantly associated with ΔeGFR at FDR<0.05 and 12 of these were validated in the FHS Third Generation cohort at p<0.05/27. Additionally, 35 protein biomarkers were significantly associated with prevalent CKD, five were significantly associated with new-onset CKD, and 17 were significantly associated with rapid decline in eGFR. MR suggested putatively causal relations of melanoma cell adhesion molecule (MCAM; -0.011±0.003 mL/min/1.73m2, p = 5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m2, p = 0.0001) concentration with eGFR.Discussion/conclusionsEight protein biomarkers were consistently associated with eGFR in cross-sectional and longitudinal analysis in both cohorts and may capture early kidney impairment; others were implicated in association and causal inference analyses. A subset of CVD protein biomarkers may contribute causally to the pathogenesis of kidney impairment and should be studied as targets for CKD treatment and early prevention.

Dataset Information

Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study.

Publications

Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study.

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