The Effect of Gastric Bypass Surgery on Renal Function and Metabolism

胃绕道手术对肾功能和代谢的影响

基本信息

  • 批准号:
    8536270
  • 负责人:
  • 金额:
    $ 14.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-09-23 至 2015-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Obese patients are at increased risk for kidney disease due to circulation of pro-inflammatory mediators and underlying renal metabolic and hemodynamic disturbances, including glomerular hyperfiltration. These patients also have unfavorable lithogenic urinary metabolic profiles, such as low urinary pH, hypocitrituria, hyperuricosuria, that predispose them to kidney stone disease. Gastric operations, in particular Roux-en-Y-gastric bypass (RYGB), are increasing as an interventional strategy to facilitate weight loss in this population. Despite the theoretical renal advantages gained during weight loss for glycemic and hypertension control, up to 75% of RYGB patients will develop sustained hyperoxaluria post-operatively, and a subset will develop kidney stones, nephrocalcinosis, impaired renal function, or even renal failure due to oxalate nephropathy. Currently, the mechanisms behind these adverse renal events are unknown. Preliminary data from an obese rat model of RYGB surgery indicates that gastric bypass causes more glomerular injury, interstitial macrophage migration, increased osteopontin production than sham surgery or pair-fed obese controls. Therefore, we hypothesize that obesity is a low-grade inflammatory process that amplifies renal host responses to RYGB-associated hyperoxaluria. In this setting, glomerular, interstitial, and papillary cells are chronically exposed to high amounts of oxalate and/or calcium oxalate crystals, leading to the production of reactive oxygen species, oxidative stress, renal injury, and inflammation. The objective of this application is to provide a training environment for the principal investigator to examine the role of RYGB-associated hyperoxaluria in the development of renal injury and nephrolithiasis, with special focus on renal histology, transport physiology, tissue proteomics, and genomics. Our specific aims are: 1) To further characterize renal effects of RYGB surgery in a diet-induced obese rodent model versus controls by comparing metabolic profiles, pro-inflammatory mediators, histology, protein expression, and pathway-focused gene expression profiles; 2) To further our understanding of RYGB induced hyperoxaluria by investigating segmental differences in intestinal oxalate handling and the effect of Oxalobacter colonization on urinary oxalate levels; 3) To compare protein and gene expression profiles from renal papillary tips of human RYGB stone formers with and without Randall's plaque deposition. Understanding the mechanisms of hyperoxaluria following RYGB will provide insights into the pathogenesis of oxalate nephrolithiasis associated with obesity. My K08 program is structured to allow me to further explore relevant rodent models of obesity, to validate preliminary hypothesis generated by a recent minority supplement award, to enhance my understanding of oxalate transport within the gut and kidney, and then, most importantly, translate these efforts into mechanisms of disease within human renal tissue.
描述(由申请人提供):由于促炎介质的循环和潜在的肾脏代谢和血流动力学紊乱,包括肾小球高滤过,肥胖患者患肾脏疾病的风险增加。这些患者也有不利的尿代谢特征,如尿pH值低、低尿量、高尿量,使他们易患肾结石。胃手术,特别是roux -en- y胃旁路手术(RYGB),越来越多地作为一种介入性策略来促进这类人群的减肥。尽管理论上在减肥过程中获得了控制血糖和高血压的肾脏优势,但高达75%的RYGB患者术后会出现持续的高草酸尿症,一部分患者会出现肾结石、肾钙化症、肾功能受损,甚至由于草酸肾病而导致肾功能衰竭。目前,这些不良肾脏事件背后的机制尚不清楚。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Benjamin K Canales其他文献

DIFFERNTIAL RENAL TISSUE PROTEIN PROFILING IN A MOUSE MODEL OF HYPERCALCIURIA: EFFECT OF HIGH OXALATE DIET
  • DOI:
    10.1016/s0022-5347(09)62022-x
  • 发表时间:
    2009-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Benjamin K Canales;Leticia Reyes;Patricia A Glenton;Marjorie Chow;Sixue Chen;Saeed R Khan
  • 通讯作者:
    Saeed R Khan
SYMPTOMS AND RISK FACTORS ASSOCIATED WITH FIRST UTI IN COLLEGE-AGED WOMEN: A PROSPECTIVE COHORT STUDY
  • DOI:
    10.1016/s0022-5347(09)60410-9
  • 发表时间:
    2009-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Charles R Vincent;Mary Brown;Leticia Reyes;Benjamin K Canales;Keith Muller;Veronique Vincent;Qin Li;Tami Thomas
  • 通讯作者:
    Tami Thomas
RENAL HISTOLOGICAL CHANGES AFTER RYGB IN A DIET INDUCED OBESE RAT MODEL
  • DOI:
    10.1016/s0022-5347(09)62013-9
  • 发表时间:
    2009-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Benjamin K Canales;Saeed R Khan;Patricia A Glenton;Leticia Reyes;Mary K Reinhard;Carolina G Goncalves;Michael M Meguid
  • 通讯作者:
    Michael M Meguid
IS BIOFILM AND MATRIX RELATED? COMPREHENSIVE PROTEOMIC PROFILE OF EARLY URETERAL STENT BIOFILM.
  • DOI:
    10.1016/s0022-5347(08)61663-8
  • 发表时间:
    2008-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Benjamin K Canales;Lorraine Anderson;LeeAnn Higgins;Manoj Monga
  • 通讯作者:
    Manoj Monga
VIDEO DEMONSTRATION OF ROBOTIC TESTICULAR SPERM EXTRACTION: CRITICAL EVALUATION COMPARED TO OPEN TESE AND PERCUTANEOUS NEEDLE LAVAGE TECHNIQUES IN CANINE MODEL AND THE FIRST HUMAN CASES
  • DOI:
    10.1016/s0022-5347(08)61064-2
  • 发表时间:
    2008-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Scott A Polackwich;Patrick Villicana;Carl Bischoff;Bayo Tojuola;Benjamin K Canales;Marc S Cohen;Philipp Dahm;Johannes Vieweg;Sijo J Parekattil
  • 通讯作者:
    Sijo J Parekattil

Benjamin K Canales的其他文献

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{{ truncateString('Benjamin K Canales', 18)}}的其他基金

Phentermine/tOpiramate to eND Obesity and Uric acid stones Trial (POuND OUT)
芬特明/托吡酯消除肥胖和尿酸结石试验(英镑)
  • 批准号:
    10203955
  • 财政年份:
    2020
  • 资助金额:
    $ 14.35万
  • 项目类别:
Phentermine/tOpiramate to eND Obesity and Uric acid stones Trial (POuND OUT)
芬特明/托吡酯消除肥胖和尿酸结石试验(英镑)
  • 批准号:
    9979362
  • 财政年份:
    2020
  • 资助金额:
    $ 14.35万
  • 项目类别:
Non-vitamin D related mechanisms of bone loss after gastric bypass
胃绕道术后骨丢失的非维生素 D 相关机制
  • 批准号:
    8624117
  • 财政年份:
    2014
  • 资助金额:
    $ 14.35万
  • 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
  • 批准号:
    7957498
  • 财政年份:
    2010
  • 资助金额:
    $ 14.35万
  • 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
  • 批准号:
    8631157
  • 财政年份:
    2010
  • 资助金额:
    $ 14.35万
  • 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
  • 批准号:
    8319558
  • 财政年份:
    2010
  • 资助金额:
    $ 14.35万
  • 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
  • 批准号:
    8146899
  • 财政年份:
    2010
  • 资助金额:
    $ 14.35万
  • 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
  • 批准号:
    8721941
  • 财政年份:
    2010
  • 资助金额:
    $ 14.35万
  • 项目类别:

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