Transdermal, Continuous, Measurement of Renal Function
非侵袭经皮、连续、肾功能测定
MediBeacon’s系统是用于临床前监测肾小球滤过率(mGFR)的装置。该系统允许研究人员计算和跟踪动物的肾脏功能随时间的推移的连续变化，监测过程中动物仍保持清醒的活动状态。
mGFR的测定和监测对于各种临床前研究至关重要，如肾功能的表征、新的和现有的肾脏治疗方法的评估、肾毒性的评估、新的化学或药物制剂的发现以及对实验动物肾功能的基本机理分析。然而，测量肾功能的研究标准来说，传统的方法抽取血液并利用复杂的实验室设备来分析并测量每个血样中的示踪剂浓度。这种使用血液和/或尿液取样的方法不仅费时费力，并且对实验动物造成了一定的损伤。
使用我们的MediBeacon设备以及荧光示踪技术可以摆脱采血，收集尿液，测试分析等繁琐的步骤，使临床前研究更加简单易操作。
Successful Use in Nephrology Research广泛应用于肾功能研究
全世界有大量的医学院，学术中心，科研院所和医药公司使用MediBeacon设备研究临床前肾脏疾病的治疗效果评估，药物的肾脏毒性评估，以及实验动物肾功能的基本机理分析。大量使用MediBecon临床前产品获得的研究成果均出现在美国肾病学会(ASN)肾脏周会议上展示的许多海报的重要位置。已有超过100多个同行评审的出版物报导并使用了这种透皮mGFR技术(同行评审和会议摘要)。
Key Advantages主要优势：
- 可以对单个实验动物进行长期的GFR监测；
- 设备可用于清醒且自由活动的小鼠、大鼠以及大型实验动物；
- 与内源性标记物相比较可以更早的观察到 GFR的变化；
- 可以使临床前实验简化流程化，简单易操作。
注：该设备使用的技术和临床上使用的一致。
System系统
- 设备和贴片贴在动物身上；
- 使用荧光剂示踪；
- 设备配备的软件用来分析处理数据；
将探测器固定在贴片上，并将贴片置于大鼠脱毛后的背部.
实时采集大鼠体内的FITC荧光强度数据并保存在设备的内存储器中，将数据拷到PC端并用软件分析得到大鼠体内FITC的荧光强度变化图，Y轴表示FITC的荧光强度，X轴表示测量的时间。
肾功能损伤动物模型的体内FITC荧光强度变化图。A.在简单肾功能损伤动物模型中，FITC的消除曲线下的面积增大，且在一定的测量时间后无法达到稳定的基态水平；B.在肾功能严重受损的动物模型中，经皮测试的FITC荧光强度值显示出稳定的状态，表明该模型的肾功能已经衰竭。
相关研究应用领域（已有大量引用文献）：
心血管：
The elevation of circulating fibroblast growth factor 23 without kidney disease does not increase cardiovascular disease risk
Kidney Int. 2018 Jul;94(1):49-59. doi: 10.1016/j.kint.2018.02.017. Epub 2018 May 5.
Altered microRNA regulation of short chain fatty acid receptors in the hypertensive kidney is normalized with hydrogen sulfide supplementation
Received 22 May 2018, Accepted 13 June 2018, Available online 15 June 2018, Pharmacological Research. https://doi.org/10.1016/j.phrs.2018.06.012.
AT1-AA (Angiotensin II Type 1 Receptor Agonistic Autoantibody) Blockade Prevents Preeclamptic Symptoms in Placental Ischemic Rats
Hypertension. 2018 May;71(5):886-893. doi: 10.1161/HYPERTENSIONAHA.117.10681.
Renal Fibrosis and Tubular Transport Adaptation Caused by Cardiac Arrest and Cardiopulmonary Resuscitation (CA/CPR) in Mice
Am. Soc. Nephrol. Kidney Week Abstract Supplement: SA-PO45 2017.
Intrauterine Growth Restriction Programs a Greater Age-related Decline in Renal Function Associated With Increased Susceptibility to Chronic Renal Injury
American Heart Association Journals – Hypertension, Hypertension. 2017;70:AP137.
Combined AT2 Receptor Stimulation AT1 Receptor Blockade Does Not Cause Renal Dysfunction
American Heart Association Journals – Hypertension, Hypertension. 2017;70:A016.
Exposure to placental ischemia impairs postpartum maternal renal and cardiac function in rats
American Journal of Physiology – Regulatory, Integrative and Comparative Physiology Published 15 February 2017 Vol. no. , DOI: 10.1152/ajpregu.00510.2016.
Intrarenal ACE as a Catalyst for Hypertension
J. Am. Soc. Nephrol. Kidney Week 2016.
Chronic recurrent dehydration associated with periodic water intake exacerbates hypertension and promotes renal damage in male spontaneously hypertensive rats
Sci Rep. 2016 Sep 22;6:33855. doi: 10.1038/srep33855.
Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension
Hypertension. 2016 Apr;67(4):740-7. doi: 10.1161/HYPERTENSIONAHA.115.06783. Epub 2016 Feb 1.
Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice
Am J Physiol Renal Physiol; Epub ahead of print Jan 13th 2016.
Salt Sensitivity in Response to Renal Injury Requires Renal Angiotensin-Convertin Enzyme
G 2015 Jul 6. Epub ahead of print.
Physiol Rep. March 2015 Vol. 3 no. e12316.
Hypertension 2015 Mar;65(3):561-8.
Renal generation of angiotensin II and the pathogenesis of hypertension
J. Am. Soc. Nephrol., 2014 Dec;25(12):2752-63.
Hypertension 62(1): 85–90, 2013.
Nat. Med. 19(12): 1655–60, 2013.
Diabetes
Losartan improves renal function and pathology in obese ZSF-1 rats
Journal of Basic and Clinical Physiology and Pharmacology, Published Online: 2018-02-05 | DOI: https://doi.org/10.1515/jbcpp-2017-0157.
Renal Tubular ACE-Mediated Tubular Injury is The Major Contributor to Microalbuminuria in Early Diabetic Nephropathy
American Journal of Physiology – Renal Physiology Published 29 November 2017 Vol. no. , DOI: 10.1152/ajprenal.00523.2017.
Transcutaneous Measurement of Glomerular Filtration Rate in a Mouse Model of Diabetic Kidney Disease
Am. Soc. Nephrol. Kidney Week Abstract Supplement: PUB451 2017.
Scientific Reports 2017, 7: 15190, DOI:10.1038/s41598-017-15589-x.
Pharmacology Research & Perspectives 2017, Vol. 5, Iss. 5, e00354.
Renal Olfactory Receptor 1393 May Contribute to the Progression of Diabetic Nephropathy
The FASEB Journal April 2017, vol. 31 no. 1 Supplement 716.4.
Renal Discovery, AbbVie, North Chicago, Ill., USA, Am J Nephrol 2016;44:339-353 / DOI:10.1159/000449324 Full PDF is available at: http://www.karger.com/Article/Abstract/449324
Vascular Actions of AT1 Angiotensin Receptors Do Not Contribute to Albuminuria or Hyperfiltration in Diabetic Kidney Disease
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: FR-PO275 2016.
A Potent Pan-AMPK Activator Improves Renal Structure and Function in the ZSF-1 Rat Model of Diabetic Nephropathy
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: FR-OR055 2016.
Renal Tubular ACE Affects Microalbuminuria in Early Diabetic Nephropathy
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: FR-OR054 2016.
Renal Olfactory Receptor 1393 Contributes to Glucose Reabsorption
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-OR128 2016.
Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring
Diabetes Metab Res Rev. 2016 Nov;32(8):816-826.
PBI-4425, A novel anti-inflamantory/fibrotic compound, improves kidney function and glomerular integrity in the diabetic DB/DB mouse mode
ERA-EDTA 2016 conference abstract SO022.
Sci Rep.2016 May 26;6:26428. doi: 10.1038/srep26428.
Diabetes Metab Res Rev. 2016 Apr 2. doi: 10.1002/dmrr.2805. [Epub ahead of print].
A Longitudinal Study on Kidney Function, Pathology, and Multiple Urinary Biomarkers in ZSF1 Rat Model of Type II Diabetic Nephropathy
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 709A, 2015.
Losartan improves renal function and pathology in a rat model of type II diabetic nephropathy
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (25): 1073A, 2014.
免疫与炎症：
Rolipram Improves Outcome in a Rat Model of Infant Sepsis-Induced Cardiorenal Syndrome
Frontiers in Pharmacology. 2017 Vol 8 Article 237, doi:10.3389/fphar.2017.00237.
Role of Adenosine 1a Receptor Signaling on GFR Early after the Induction of Sepsis
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-PO106 2016.
Role of Interleukin 17 Receptor A in Enhanced Atherosclerotic Inflammation in Renal Impairment
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-OR TH-PO354 2016.
Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation
J Am Soc Nephrol 2016 May 5. pii: ASN.2015111285. [Epub ahead of print].
Sepsis Reduces Kidney Function in Mice Before Hemodynamic Alterations or Clinical Symptoms Become Apparent
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 94A, 2015.
GFR in Conscious Mice After Sepsis: Role of Tubuloglomerular Feedback
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 686A, 2015.
Human recombinant alkaline phosphatase protects against lipopolysaccharide-induced renal inflammation
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (25): 147A, 2014.
代谢与调节：
Long-Term Endothelin-A Receptor Antagonism Provides Robust Renal Protection in Humanized Sickle Cell Disease Mice
J. Am. Soc. Nephrol. 2017 Mar 27 [Epub ahead of print].
Hydroxyproline metabolism in a mouse model of Primary Hyperoxaluria Type 3
Biochim Biophys Acta 2015 Sep 29. Epub ahead of print.
A western diet leading to maternal glucose intolerance and obesity elevates offspring nephron endowment without adverse effects on adult renal function
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (25): 534A, 2014.
肾脏：
Divergent effects of AKI to CKD models on inflammation and fibrosis
American Journal of Physiology, Renal Physiology, https://doi.org/10.1152/ajprenal.00179.2018.
Tubular cell hypertrophy via endocycle and proliferation of tubular progenitors are central mechanisms of response after AKI
University of Florence, Department of Biomedical Experimental and Clinical Sciences, Florence, Italy, ERA-EDTA meeting Copenhagen 2018 FP312.
Papillary renal cell carcinoma originates from a population of renal progenitor cells and is promoted by Acute Kidney Injury
University of Florence, Department of Experimental, Clinical and Biomedical Sciences “Mario Serio”, Florence, Italy, University Hospital Careggi, Histopathology and Molecular Diagnostics, Florence, Italy, Meyer Children’s University Hospital, Nephrology Unit, Florence, Italuy, ERA-EDTA meeting Copenhagen 2018 SaO032.
Endogenous pentraxin 3 inhibits nephrocalcinosis and protects from hyperoxalluria-induced Chronic Kidney Disease
Klinikum der Universität München, Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum, Munich, Germany, Istituto Clinico Humanitas (ICH) IRCCS, Laboratory of Immunopharmacology, Rozzano, Italy, ERA-EDTA meeting Copenhagen 2018 SuO027.
Macrophage polarization and granuloma formation in hyperuricemia-associated chronic kidney disease
Klinikum der Universität München, Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum, München, GERMANY, Klinikum der Universität München, Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum, Munich, GERMANY, Klinikum der Universtität München, Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum, Munich, Germany, ERA-EDTA meeting Copenhagen 2018 FP312.
Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury
Kidney Int. 2018 May;93(5):1131-1141. doi: 10.1016/j.kint.2017.11.018.
Kidney dysfunction in the low birth weight murine adult: implications of oxidative stress
Am J Physiol Renal Physiol. 2018 May 30. doi: 10.1152/ajprenal.00164.2018.
Short-term oral gavage administration of adenine induces a model of fibrotic kidney disease in rats
Journal of Pharmacological and Toxicological Methods, https://doi.org/10.1016/j.vascn.2018.04.003.
Anti-Transforming Growth Factor β IgG Elicits a Dual Effect on Calcium Oxalate Crystallizationand Progressive Nephrocalcinosis-Related Chronic Kidney Disease
Frontiers in Immunology March 2018, doi: 10.3389/fimmu.2018.00619.
Nature Communications (2018)9:1344, DOU: 10.1038/s41467-018-03753-4.
Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response
American Journal of Physiology 28 MAR 2018, https://doi.org/10.1152/ajprenal.00030.2018.
Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney
Kidney International (2018) 93, 110-127.
Murine Nephrotoxic Nephritis as a Model of Chronic Kidney Disease
Novel Differences in Renal Gene Expression in a Diet Induced Obesity Model
American Journal of Physiology – Renal Physiology Published 15 November 2017 Vol. no. , DOI: 10.1152/ajprenal.00345.2017.
Gli1+ Pericytes Are Required for AKI Recovery and Regulate Renal Function
Am. Soc. Nephrol. Kidney Week Abstract Supplement: SA-OR087 2017.
The Impact of Uninephrectomy on Subsequent AKI Outcomes
Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-PO316 2017.
Endocycle-Mediated Hypertrophy and Progenitor Proliferation as Central Mechanisms of Response to AKI
Am. Soc. Nephrol. Kidney Week Abstract Supplement: SA-OR085 2017.
Liraglutide Treatment Improves Renal Vascular Function in Zucker Rats as Visualized by Microangiography
Am. Soc. Nephrol. Kidney Week Abstract Supplement: SA-OR098 2017.
Tubule Specific Deletion of Cullin 3 Causes Cell Cycle Dysregulation and Kidney Fibrosis
Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-PO353 2017.
Transcutaneous Glomerular Filtration Rate Measurement in a Canine Animal Model of Chronic Kidney Disease
Journal of Pharmacological and Toxicological Methods
(2017) https://doi.org/10.1016/j.vascn.2017.10.009.
Low birth weight is associated with impaired murine kidney development and function
Pediatric Research (2017) doi:10.1038/pr.2017.53.
Anti-Histone IGG attenuates CKD upon AKI related to postischemic tubular necrosis in mice
Nephrology Dialysis Transplatation (2017) 32 (suppl_3):iii512., DOI:https://doi.org/10.1093/ndt/gfx166.
Combining new tools to assess renal function and morphology: a holistic approach to study the effects of aging and a congenital nephron deficit
American Journal of Physiology – Renal Physiology May 10, 2017, DOI:10.1152/ajprenal.00329.2015.
Intrauterine Growth Restriction Programs Greater Susceptibility to Chronic Kidney Injury in Male and Female Aged Rats
The FASEB Journal April 2017, vol. 31 no. 1 Supplement 852.4.
The Effect Of Dietary Amino Acids On Chronic Kidney Disease Progression in Rats
The FASEB Journal April 2017, vol. 31 no. 1 Supplement 1030.22.
Human Kidney-Derived Cells Ameliorate Acute Kidney Injury Without Engrafting into Renal Tissue
Stem Cells Translational Medicine. 2017;00:00-00.
Physiological Reports Published 31 March 2017 Vol. 5 no. e13228 DOI: 10.14814/phy2.13228.
Assessment of acute kidney injury in rhabdomyolytic mice by transcutaneous measurement of sinistrin excretion
Nephrol Dial Transplant. 2017 Feb 27. doi: 10.1093/ndt/gfw438. Epub ahead of print.
Scientific Reports: 7:43538, DOI:10.1038/srep43538.
Murine Double Minute-2 Prevents Tubular Atrophy by Inhibiting p53 Overactivation-Dependent Cell Death (Podoptosis) in Tubular Cells
Am. Soc. Nephrol. Kidney Week Abstract Supplement: SA-PO360 2016.
MDM2 Prevents Spontaneous Tubular Epithelial Cell Death and Acute Kidney Injury
D Cell Death and Disease (2016) 7, e2482; doi:10.1038/cddis.2016.390.
Dietary Salt Impacts Active Sodium Transport and Metabolic Sensing along the Kidney Tubule
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: SA-PO119 2016.
Tubular Cell Endocycle-Related Hypertrophy and Renal Progenitor Mitosis Drive Kidney Function Recovery after AKI but Cannot Avoid Persistent Tubular Cell Loss
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: FR-PO317 2016.
The Role of IL-6 Signaling on the Transition of Acute Kidney Injury to Chronic Kidney Disease
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: FR-PO275 2016.
Long-Term Selective ETA Receptor Antagonism Prevents Renal Injury in Humanized Sickle Cell Mice
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: FR-PO182 2016.
Longitudinal Characterization of Glomerular Filtration Rate of the Naïve ZSF1 Rat
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-PO464 2016.
Adenine Overload Causes Severe AKI Progressing to CKD by Activation of Innate Immunity in Rats and Mice
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-PO092 2016.
Transcutaneous Measurement of Glomerular Filtration Rate to Assess the Progression from Acute to Chronic Kidney Disease following Bilateral Ischemic Injury in Mice
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement: TH-PO085 2016.
Improved kinetic model for transcutaneous measurement of glomerular filtration rate in experimental animals
Kidney int. In press, accepted for publication 14-Jul-2016 DOI: http://dx.doi.org/10.1016/j.kint.2016.07.024.
Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice
PLoS One. 2016 Aug 22;11(8):e0161578. doi: 10.1371/journal.pone.0161578. eCollection 2016.
Beta-Hydroxybutyrate inhibits NLRP3-Mediated inflammation and delays progressive renal failure during primary hyperoxaluria related kidney stone Disease
ERA-EDTA 2016 conference abstract TO027.
Effect of Aging on Kidney Function in Male Intrauterine Growth Restricted Rats
April 2016 The FASEB Journal vol. 30 no. 1 Supplement 1214.6
Transcutaneous Assessment of Renal Function in Conscious Rodents
J. Vis. Exp. (109), e53767, doi:10.3791/53767 (2016).
An Aristolochic Acid-Induced Nephropathy (AAN) Model for Stable CKD in Mice
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 148A, 2015.
Analysis of Exogenous Near Infrared Fluorescent Markers fort he Transcutaneous Measurement of Glomerular Filtration Rate
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 259A, 2015.
Studying the Effect of Induced Expandable Human Kidney Progenitor Cells on Renal Function Using Transcutaneous Assessment
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 410A, 2015.
Longitudinal Transcutaneous Glomerular Filtration Rate (GFR) After Uninephrectomy (UNx) in Mice
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 728A, 2015.
SLIT2 Is Upregulated in Proximal Tubules and Urine following Folic Acid Induced Kidney Injury
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (26): 978A, 2015.
A Novel Analysis Technique for Transcutaneous Measurement of Glomerular Filtration Rate With Ultralow Dose Marker Concentrations
IEEE Trans Biomed Eng. 2016 Aug;63(8):1742-50.
Autophagy Induces Prosenescent Changes in Proximal Tubular S3 Segments
J Am Soc Nephrol.2015 Oct 20. pii: ASN.2014111059. [Epub ahead of print]
Sci Rep. 2015 Sep 2;5:13601. doi: 10.1038/srep13601.
LoS ONE 2014 Nov 25;9(11):e111734.
Transcutaneous Assessment of Renal Function in Conscious Rodents
J. Vis. Exp. (109), e53767, doi:10.3791/53767 (2016).
Nephrology (Carlton), 2015 Mar;20(3):117-23.
Non–Invasive GFR assessment in conscious rats with puromycin induced nephropathy
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (25): 392A, 2014.
Ablation of Proximal Tubular Autophagy Prevents Senescence and Fibrosis after Acute Kidney Injury
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (25): 527A, 2014.
Endotoxemia-induced decrease in GFR is mediated in part by COX-1 derived prostanoids in mice
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (25): 149A, 2014
A Renal olfactory receptor aids in glucose handling in the proximal tubule
J. Am. Soc. Nephrol. Kidney Week Abstract Supplement (25): 102A, 2014.
Automatic artifact removal from GFR measurements
Biomed Signal Process Control., November 2014, Pages 30–4.
Transcutaneous assessment of glomerular filtration rate
Stud Health Technol Inform 2014;200:105-10.
Reliability of transcutaneous measurement of renal function in various strains of conscious mice
Online feedback-controlled renal constant infusion clearances in rats
Kidney Int. 82(3): 314–20, 2012.
Transcutaneous measurement of renal function in conscious mice
Am. J. Physiol. Renal Physiol. 303(5): F783-8, 2012.
Two non-invasive GFR-estimation methods in rat models of polycystic kidney disease: 3.0 Tesla dynamic contrast enhanced MRI and optical imaging
Nephrol. Dial. Transplant. 26(10): 3101–8, 2011
Kidney Int. 79(11): 1254–8, 2011.
毒性：
Renal studies in safety pharmacology and toxicology: A survey conducted in the top 15 pharmaceutical companies
J. Pharmacol Toxicol Methods, 2015 Sept-Oct; 7: 101-10.
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