Kidney Tubular Functions in Type 1 Diabetes
1 型糖尿病的肾小管功能
基本信息
- 批准号:10668298
- 负责人:
- 金额:$ 65.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-15 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcidosisAlbuminsAlbuminuriaArginineAtrophicBasement membraneBiological AssayBiopsyBlood capillariesCardiovascular DiseasesCathepsinsCellsCessation of lifeCharacteristicsChronic Kidney FailureCitrullineClinicalClinical TrialsComplicationContinuous Glucose MonitorDataDevelopmentDiabetes MellitusDiabetic NephropathyDiagnosisDiseaseDisease ProgressionDistalEnd stage renal failureEpidermal Growth FactorEpithelial CellsErythropoiesisEvolutionExcretory functionExposure toFibrosisFutureGlomerular Filtration RateGlucoseGlycosylated hemoglobin AGoalsImpairmentInflammatoryInjuryInjury to KidneyInsulin-Dependent Diabetes MellitusInterventionIohexolKidneyKidney DiseasesKidney FailureLaboratoriesLesionMeasurementMeasuresMetabolicMetabolismMethodsMineralsMonitorNatural HistoryNon-Insulin-Dependent Diabetes MellitusParentsPathogenesisPathologicPathologyPathway interactionsPatternPersonsPlasmaPreventionProteomicsRenal functionRenal tubule structureRenin-Angiotensin SystemRisk FactorsSamplingSclerosisSeveritiesSodiumStressStructureTestingThickTimeTranslatingTubular formationUrineWorkabsorptionbiomarker developmentcohortdisorder subtypeglomerular basement membraneglomerular filtrationglomerular functionhigh riskhuman diseaseimprovedinhibitorinterstitialkidney biopsylysosomal proteinsmodifiable risknew therapeutic targetnovelpodocyteprecision medicineprematurepreventprogression riskrat KIM-1 proteinrenal damageresearch clinical testingsolutesymporterurinary
项目摘要
ABSTRACT
Chronic kidney disease is a common and serious complication of type 1 diabetes (T1D). Historically, diabetes
has been viewed as a primary glomerular kidney disorder based on classic pathological features. However,
diabetes also promotes injury to kidney tubular epithelial cells and their microenvironment through increased
work of glucose reabsorption and direct stimulation of pro-inflammatory and pro-fibrotic pathways. Sodium
glucose co-transporter-2 inhibitors, which block glucose entry into proximal tubular cells, are the most
promising new treatment for slowing the progression of kidney disease in type 2 diabetes.
Compelling mechanisms of kidney tubular injury in diabetes have been incompletely translated into human
disease, impeding new strategies for monitoring and treatment. The goal of this proposal is to advance
understanding of the evolution, determinants, and clinical consequences of kidney tubular functions in persons
with type I diabetes (T1D). We will add novel measurements of tubular functions and damage to two landmark
clinical trials of T1D spanning the course of kidney disease. Through these measurements, we will for the first
time characterize the natural history of tubular functions over time in T1D, identify potential risk factors for the
loss of tubular functions, and test whether measures of tubular functions and damage are associated with
metabolic complications, changes in key pathologic features, and a decline in glomerular kidney functions. The
construction of a detailed natural history of kidney tubular functions in T1D will lay needed groundwork for the
future development of new interventions to improve prevention, monitoring, and treatment.
摘要
慢性肾脏病是1型糖尿病(T1D)常见而严重的并发症。从历史上看,糖尿病
根据经典的病理特征,已被视为一种原发性肾小球疾病。然而,
糖尿病还通过增加对肾小管上皮细胞及其微环境的损伤
葡萄糖重吸收和直接刺激促炎和促纤维化途径的工作。钠
阻止葡萄糖进入近端肾小管细胞的葡萄糖共转运蛋白-2抑制剂是最多的
有望找到延缓2型糖尿病肾病进展的新疗法。
糖尿病肾小管损伤的强制机制尚未完全移植到人类身上
疾病,阻碍了监测和治疗的新战略。这项提议的目标是推进
了解人类肾小管功能的演变、决定因素和临床后果
患有I型糖尿病(T1D)。我们将为两个里程碑添加新的肾小管功能和损伤测量
横跨肾脏疾病病程的T1D临床试验。通过这些测量,我们将第一次
时间表征T1D中肾小管功能随时间的自然历史,识别潜在的危险因素
肾小管功能丧失,并测试肾小管功能和损伤的测量是否与
代谢并发症,主要病理特征的改变,以及肾小球功能的下降。这个
构建T1D肾小管功能的详细自然历史将为
未来发展新的干预措施,以改善预防、监测和治疗。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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BRYAN R KESTENBAUM其他文献
BRYAN R KESTENBAUM的其他文献
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{{ truncateString('BRYAN R KESTENBAUM', 18)}}的其他基金
Role of Kidney Proximal Tubular Secretion in Critical Illness
肾近端肾小管分泌在危重疾病中的作用
- 批准号:
10398127 - 财政年份:2020
- 资助金额:
$ 65.64万 - 项目类别:
Role of Kidney Proximal Tubular Secretion in Critical Illness
肾近端肾小管分泌在危重疾病中的作用
- 批准号:
10217335 - 财政年份:2020
- 资助金额:
$ 65.64万 - 项目类别:
Role of Kidney Proximal Tubular Secretion in Critical Illness
肾近端肾小管分泌在危重疾病中的作用
- 批准号:
9916616 - 财政年份:2020
- 资助金额:
$ 65.64万 - 项目类别:
Role of Kidney Proximal Tubular Secretion in Critical Illness
肾近端肾小管分泌在危重疾病中的作用
- 批准号:
10620671 - 财政年份:2020
- 资助金额:
$ 65.64万 - 项目类别:
Midcareer Investigator Award: Metabolic Complications of Chronic Kidney Disease
职业生涯中期研究员奖:慢性肾脏病的代谢并发症
- 批准号:
9901518 - 财政年份:2016
- 资助金额:
$ 65.64万 - 项目类别:
Mineral metabolism disturbances and arteriovenous fistula maturation
矿物质代谢紊乱和动静脉瘘成熟
- 批准号:
8549212 - 财政年份:2012
- 资助金额:
$ 65.64万 - 项目类别:
Mineral metabolism disturbances and arteriovenous fistula maturation
矿物质代谢紊乱和动静脉瘘成熟
- 批准号:
8436693 - 财政年份:2012
- 资助金额:
$ 65.64万 - 项目类别:
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