Dataset Information

Renal sinus fat and renal hemodynamics: a cross-sectional analysis.

ABSTRACT: OBJECTIVES:Increased renal sinus fat (RSF) is associated with hypertension and chronic kidney disease, but underlying mechanisms are incompletely understood. We evaluated relations between RSF and gold-standard measures of renal hemodynamics in type 2 diabetes (T2D) patients. METHODS:Fifty-one T2D patients [age 63?±?7 years; BMI 31 (28-34) kg/m2; GFR 83?±?16 mL/min/1.73 m2] underwent MRI-scanning to quantify RSF volume, and subcutaneous and visceral adipose tissue compartments (SAT and VAT, respectively). GFR and effective renal plasma flow (ERPF) were determined by inulin and PAH clearances, respectively. Effective renal vascular resistance (ERVR) was calculated. RESULTS:RSF correlated negatively with GFR (r?=?- 0.38; p?=?0.006) and ERPF (r?=?- 0.38; p?=?0.006) and positively with mean arterial pressure (MAP) (r?=?0.29; p?=?0.039) and ERVR (r?=?0.45, p?=?0.001), which persisted after adjustment for VAT, MAP, sex, and BMI. After correction for age, ERVR remained significantly related to RSF. CONCLUSIONS:In T2D patients, higher RSF volume was negatively associated to GFR. In addition, RSF volume was positively associated with increased renal vascular resistance, which may mediate hypertension and CKD development. Further research is needed to investigate how RSF may alter the (afferent) vascular resistance of the renal vasculature.

SUBMITTER: Spit KA

PROVIDER: S-EPMC7021744 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Renal sinus fat and renal hemodynamics: a cross-sectional analysis.

Spit Karlinde A KA Muskiet Marcel H A MHA Tonneijck Lennart L Smits Mark M MM Kramer Mark H H MHH Joles Jaap A JA de Boer Anneloes A van Raalte Daniel H DH

Magma (New York, N.Y.) 20190831 1

<h4>Objectives</h4>Increased renal sinus fat (RSF) is associated with hypertension and chronic kidney disease, but underlying mechanisms are incompletely understood. We evaluated relations between RSF and gold-standard measures of renal hemodynamics in type 2 diabetes (T2D) patients.<h4>Methods</h4>Fifty-one T2D patients [age 63 ± 7 years; BMI 31 (28-34) kg/m<sup>2</sup>; GFR 83 ± 16 mL/min/1.73 m<sup>2</sup>] underwent MRI-scanning to quantify RSF volume, and subcutaneous and visceral adipose t ...[more]

PMID: 31471702

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Project description:Ectopic fat accumulation in the renal sinus is associated with chronic kidney disease and hypertension. The genetic contributions to renal sinus fat accumulation in humans have not been well characterized.The present analysis consists of participants from the Framingham Offspring and Third Generation who underwent computed tomography; renal sinus fat and visceral adipose tissue (VAT) were quantified. Renal sinus fat was natural log transformed and sex- and cohort-specific residuals were created, adjusted for (1) age, (2) age and body mass index (BMI), and (3) age and VAT. Residuals were pooled and used to calculate heritability using variance-components analysis in SOLAR. A genome-wide association study (GWAS) for renal sinus fat was performed using an additive model with approximately 2.5 million imputed single nucleotide polymorphisms (SNPs). Finally, we identified the associations of renal sinus fat in our GWAS results with validated SNPs for renal function (n=16), BMI (n=32), and waist-to-hip ratio (WHR, n=14), and applied a multi-SNP genetic risk score method to determine if the SNPs for each renal and obesity trait were in aggregate associated with renal sinus fat.The heritability of renal sinus fat was 39% (p<0.0001); results were not materially different after adjustment for BMI (39%) or VAT (40%). No SNPs reached genome-wide significance in our GWAS. In our candidate gene analysis, we observed nominal, direction consistent associations with renal sinus fat for one SNP associated with renal function (p=0.01), two associated with BMI (p<0.03), and two associated with WHR (p<0.03); however, none remained significant after accounting for multiple testing. Finally, we observed that in aggregate, the 32 SNPs associated with BMI were nominally associated with renal sinus fat (multi-SNP genetic risk score p=0.03).Renal sinus fat is a heritable trait, even after accounting for generalized and abdominal adiposity. This provides support for further research into the genetic determinants of renal sinus fat. While our study was underpowered to detect genome-wide significant loci, our candidate gene BMI risk score results suggest that variability in renal sinus fat may be associated with SNPs previously known to be associated with generalized adiposity.

Project description:PURPOSE:We hypothesize that MRI-based renal compartment volumes, particularly renal sinus fat as locally and potentially independently acting perivascular fat tissue, increase with glucose intolerance. We therefore analyze the distribution of renal volumes in individuals with normal glucose levels and prediabetic and diabetic individuals and investigate potential associations with other typical cardiometabolic biomarkers. MATERIAL AND METHODS:The sample comprised N = 366 participants who were either normoglycemic (N = 230), had prediabetes (N = 87) or diabetes (N = 49), as determined by Oral Glucose Tolerance Test. Other covariates were obtained by standardized measurements and interviews. Whole-body MR measurements were performed on a 3 Tesla scanner. For assessment of the kidneys, a coronal T1w dual-echo Dixon and a coronal T2w single shot fast spin echo sequence were employed. Stepwise semi-automated segmentation of the kidneys on the Dixon-sequences was based on thresholding and geometric assumptions generating volumes for the kidneys and sinus fat. Inter- and intra-reader variability were determined on a subset of 40 subjects. Associations between glycemic status and renal volumes were evaluated by linear regression models, adjusted for other potential confounding variables. Furthermore, the association of renal volumes with visceral adipose tissue was assessed by linear regression models and Pearson's correlation coefficient. RESULTS:Renal volume, renal sinus volume and renal sinus fat increased gradually from normoglycemic controls to individuals with prediabetes to individuals with diabetes (renal volume: 280.3±64.7 ml vs 303.7±67.4 ml vs 320.6±77.7ml, respectively, p < 0.001). After adjustment for age and sex, prediabetes and diabetes were significantly associated to increased renal volume, sinus volume (e.g. βPrediabetes = 10.1, 95% CI: [6.5, 13.7]; p<0.01, βDiabetes = 11.86, 95% CI: [7.2, 16.5]; p<0.01) and sinus fat (e.g. βPrediabetes = 7.13, 95% CI: [4.5, 9.8]; p<0.001, βDiabetes = 7.34, 95% CI: [4.0, 10.7]; p<0.001). Associations attenuated after adjustment for additional confounders were only significant for prediabetes and sinus volume (ß = 4.0 95% CI [0.4, 7.6]; p<0.05). Hypertension was significantly associated with increased sinus volume (β = 3.7, 95% CI: [0.4, 7.0; p<0.05]) and absolute sinus fat volume (β = 3.0, 95% CI: [0.7, 5.3]; p<0.05). GFR and all renal volumes were significantly associated as well as urine creatinine levels and renal sinus volume (β = 1.6, 95% CI: [0.1, 2.9]; p<0.05). CONCLUSION:Renal volume and particularly renal sinus fat volume already increases significantly in prediabetic subjects and is significantly associated with VAT. This shows, that renal sinus fat is a perivascular adipose tissue, which early undergoes changes in the development of metabolic disease. Our findings underpin that renal sinus fat is a link between metabolic disease and associated chronic kidney disease, making it a potential imaging biomarker when assessing perivascular adipose tissue.

Dataset Information

Renal sinus fat and renal hemodynamics: a cross-sectional analysis.

Publications

Renal sinus fat and renal hemodynamics: a cross-sectional analysis.

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