title: Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation.
abstract: Metabolic syndrome (MetS) is associated with glomerular hyperfiltration and is a risk factor for chronic kidney disease, but the underlying mechanisms are poorly defined. This study tested the hypothesis that increased glomerular filtration rate (GFR) in early MetS is associated with renal adiposity and microvascular proliferation. Twelve MetS-prone Ossabaw pigs were randomized to 10 wk of a standard (lean, n = 6) or atherogenic (MetS, n = 6) diet. Kidney hemodynamics and function, perirenal fat volume, and tubular dynamics were assessed in vivo by multidetector computed tomography (CT) and blood oxygen level-dependent (BOLD)-MRI. Microvascular architecture was assessed ex vivo with micro-CT. Candidate injury mechanisms were evaluated in kidney tissue by Western blotting and histology. Basal GFR, renal blood flow, and renal cortical perfusion and volume were elevated in the MetS group. Perirenal and kidney tissue fat, proximal-nephron intratubular fluid concentration, and endothelial nitric oxide synthase expression were increased in MetS. GFR levels correlated with tissue triglyceride levels. Elevated spatial density of 20- to 40-μm cortical microvessels was accompanied by mild oxidative stress, inflammation, and with proximal tubular vacuolization. Medullary size and perfusion were relatively preserved, and BOLD-MRI showed intact medullary tubular response to furosemide. Increased GFR in early MetS is associated with renal adiposity and microvascular proliferation, which involve mainly the renal cortex and precede significant activation of oxidative stress and inflammation. Renal adiposity and proliferative microvessels may represent novel therapeutic targets for preserving renal function in early MetS.
authors.affiliation: Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Zilun
authors.initials: Z
authors.lastname: Li
authors.forename: John R
authors.initials: JR
authors.lastname: Woollard
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Korsmo
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Grande
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002196:Capillaries / Q000502:physiology*; D049109:Cell Proliferation; D004032:Diet; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000502:physiology; D008279:Magnetic Resonance Imaging; D024821:Metabolic Syndrome / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000097:blood; D012079:Renal Circulation / Q000187:drug effects; D013552:Swine; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; D010100:Oxygen