Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation

Zilun Li, John R. Woollard, Shenming Wang, Michael J. Korsmo, Behzad Ebrahimi, Joseph Peter Grande, Stephen C Textor, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 2011

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Adiposity
Glomerular Filtration Rate
Kidney
Microvessels
Oxidative Stress
Perfusion
Fats
Oxygen
Inflammation
Multidetector Computed Tomography
Nitric Oxide Synthase Type III
Renal Circulation
Nephrons
Furosemide
Chronic Renal Insufficiency
Histology
Triglycerides
Swine
Hemodynamics
Western Blotting

Keywords

  • Obesity
  • Renal function

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation. / Li, Zilun; Woollard, John R.; Wang, Shenming; Korsmo, Michael J.; Ebrahimi, Behzad; Grande, Joseph Peter; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O.

In: American Journal of Physiology - Renal Physiology, Vol. 301, No. 5, 11.2011.

Research output: Contribution to journalArticle

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