Wij zijn onze website aan het vernieuwen.

Ontdekt u nog een pagina die niet klopt of hebt u een goede suggestie, laat het ons dan weten via webmedia@umcutrecht.nl.

Deze website maakt gebruik van cookies

Deze website toont video’s van o.a. YouTube. Dergelijke partijen plaatsen cookies (third party cookies). Als u deze cookies niet wilt kunt u dat hier aangeven. Lees meer over het cookiebeleid.

Interne geneeskunde, wetenschapsstage nefrologie

Hier vind je het aanbod aan wetenschappelijke keuzestages nefrologie bij de divisie Interne Geneeskunde en Dermatologie. Deze stages zijn bedoeld voor voor geneeskunde studenten van master jaar 1 en 2.

Exosomes matrix remodelling

Exosomes in angiogenesis and extracellular matrix remodelling

Onderwerp: onderzoek of remoelleren van de extracellulaire matrix door exosomen essentieel is voor hun stimulerende activiteit
Specialisme: nefrologie

Inleiding

Exosomes are small (40 – 100 nm) vesicles, which are secreted by cells upon fusion of the multivesicular body (MVB) with the cellular membrane. These vesicles have a membrane that resembles its host cell membrane: a lipid bi-layer with membrane proteins in the correct outward orientation. Furthermore, these vesicles contain cytosolic content, including RNA and proteins, from the host cells. Exosomes play a role in intercellular communication, as well as secretion of non-soluble proteins.

 

Doel van het onderzoek

We are currently studying exosomes secreted by endothelial cells, the cells that line the inside of blood vessels. Our hypothesis is that exosomes secreted by endothelial cells play an important role in both angiogenesis and vascular repair. We have recently discovered that enodothelial exosomes play a role in the secretion of a specific extracellular matrix remodelling protein and endothelial differentiation. We have found several physiological triggers that induce secretion of this protein, and are interested in the effect on angiogenesis of this protein in the context of exosomes.

Methoden

The student will be able to learn cell culture, functional analysis of endothelial cells and exosomes (including sprouting- and scratch wound assays), quantitative PCR, fluorescence microscopy, immunoblotting and potentially more. Website: www.nephrology-utrecht.nl

Combistage mogelijk?

  • in overleg

Beschikbaarheid?

  • 6 - 12 maanden

contact

Coördinator: Prof Dr M.C. Verhaar
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 510 39
m.c.verhaar@umcutrecht.nl
Huispostnummer: F03.223

Aanbieder: Bas van Balkom
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 57570
b.w.m.vanbalkom@umcutrecht.nl
Huispostnummer: G02.402

Markers niertransplantatie

Kidney Transplant prognostic marker discovery

Onderwerp: vinden van markers die de functie van een nier na transplantatie voorspellen

Inleiding

Kidney transplantation is the preferred option for patients with chronic kidney failure. The number of patients requiring kidney replacement therapy rises, and thereby the shortage of donor kidneys. It is therefore important to reduce the risk of allograft dysfunction and rejection, and at the same time increase the number of kidneys suitable for transplantation. Besides efforts to increase the number of people willing to donate their organs after life and stimulation of living-donor transplantations, prior knowledge on the function of available of kidneys after transplantation can contribute to increased availability of donor organs.

Predicting post-transplantation kidney function would have impact on the quality of life of the recipient since predicted non-functioning organs or organs predicted to give major complications can be excluded. Also, prior knowledge on organ quality at the time of transplantation makes a decision on interventions faster. Even greater benefits of this prior (prognostic) knowledge could be that organs that are now rejected for transplantation may be suitable, thereby increasing the availability of donor kidneys.

Allograft quality, function and survival can be monitored after transplantation (blood, urine) or by taking biopsy samples, which can be done at the time of transplantation (zero-hour) or after transplantation. A disadvantage of these approaches is that they can either only take place after transplantation or that the transplanted kidney has to be intentionally damaged. We therefore aim at the identification of prognostic biomarkers before transplantation in samples obtained in a non-invasive manner.

Doel van het onderzoek

During your training period you will be involved in the collection, preparation and analysis of samples. This will involve close interaction with transplantation surgeons in the UMCU and possibly other hospitals as well as basic scientists in the research lab.

Methoden

Techniques involve sample collection and fractionation by centrifugation or precipitation, primary cell culture, Luminex analysis of cytokines, ELISA, western blotting, RNA isolation and (quantitative) PCR.
Website: www.nephrology-utrecht.nl

Combistage mogelijk?

  • in overleg

Beschikbaarheid?

  • 6 - 12 maanden

contact

Coördinator: Prof Dr M.C. Verhaar
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 510 39
m.c.verhaar@umcutrecht.nl
Huispostnummer: F03.223

Aanbieder: Bas van Balkom
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 57570
b.w.m.vanbalkom@umcutrecht.nl
Huispostnummer: G02.402

Nephronophthisis NPHP

De rol van cilia deficiënties in nephronophthisis

Onderwerp: De moleculaire mechanismen achter het ontwikkelen van nephronophthisis (NPHP).
Speerpunt: Circulatory Health/Child Health

Inleiding

Cilia zijn antenne-achtige projecties op de cel. Ze kunnen sensorische of motorische functies hebben. Patienten met cilia defecten kunnen een breed scala aan fenotypes ontwikkelen waaronder situs inversus, polidactyli, niercysten, blindheid, etc.
Tijdens deze stage ligt de focus op nephronophthisis (NPHP), dat gekenmerkt wordt door niercysten en fibrose in kinderen.

Doel van het onderzoek

Er is weinig bekend over de mechanismen die samenhangen met cilia defecten en hoe deze NPHP (en verwante fenotypes) veroorzaken. In niercellijnen worden moleculaire technieken toegepast om te onderzoeken wat het effect is van cilia defecten met betrekking tot DNA schade respons en reparatie, cel cyclus en veroudering van de niercellen1,2.

Methoden

Celkweek, RT-QPCR, Western blot, FACS, immunofluorescentie en confocal microscopie, siRNA transfectie

Referenties

  • Chaki M., et al, Exome Capture Reveals ZNF423 and CEP164 Mutations, Linking Renal Ciliopathies to DNA Damage Response Signaling, Cell, 2012 Aug 3;150(3):533-48
  • Zhou W., et al, FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair., Nat Genet. 2012 Jul 8;44(8):910-5. doi: 10.1038/ng.2347

Combistage mogelijk?

  • nee

Beschikbaarheid?

  • Continu

Aanvullende opmerkingen:

Project van minstens 6 maanden

contact

Coördinator/begeleider
Naam: Rachel Giles
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie
Telefoon: 088-7556508
E-mailadres: r.giles@umcutrecht.nl
Huispostnummer: G03.233

Aanbieder
Naam: Gisela Slaats
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie
Telefoon: 088-7551378
E-mailadres: g.g.g.slaats@umcutrecht.nl
Huispostnummer: G02.402

Nrf2 aging aorta

Epigenetic inhibition of the Nrf2-Keap1 pathway in the aging mouse aorta

Onderwerp: Epigenetic regulation of the Nrf2-Keap1 stress-reponse pathway in the aging arterial wall
Speerpunt: Regenerative Medicine

Inleiding

Nrf2 is a transcription factor that controls the endogenous antioxidant defense system of cells. It is induced by oxidative stress and dietary compounds such as sulforaphane. The Nrf2 pathway is activated via modification of the inhibitor Keap1, which leads to Nrf2 accumulation and nuclear translocation. Nrf2 induces expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, catalase and heme oxygenase via antioxidant response promoter elements.

It has recently been shown that Nrf2 expression and activation is inhibited in aging rat aortas [1]. Possibly, this is caused by epigenetic mechanisms that influence the expression of Nrf2 and Keap1 [2-4]. As a result, there is more oxidative stress in the aging vascular wall which eventually leads to vascular disease. Re-activating Nrf2 by lifting the epigenetic inhibition may enhance antioxidant defense in the vascular wall and decrease vascular oxidative stress. This may be a novel mechanism to improve vascular health in elderly patients. In this project we will compare levels of Nrf2 promoter methylation and Nrf2/Keap1-targeting miRNAs in aortas of young and old mice.

Doel van het onderzoek

We want to test the hypothesis that expression and activation of the Nrf2-ARE pathway is decreased in aortic wall of old mice compared to young controls via DNA methylation and miRNAs that modulate the expression of Nrf2 and Keap1 genes.

Methoden

Aortic DNA, miRNA and protein samples have been collected from 3-20 months old mice. Aortic protein levels of Nrf2, Keap1 and Nrf2 target genes will be measured by Western Blot. The Nrf2 promoter will be screened for CpG methylation using bisulfite sequencing of genomic DNA. In addition, the expression of known Nrf2- and Keap1-modulating miRNAs will be measured by RT-PCR.

Referenties

  • Ungvari Z, Bailey-Downs L, Sosnowska D, Gautam T, Koncz P, Losonczy G, Ballabh P, de Cabo R, Sonntag WE, Csiszar A. Vascular oxidative stress in aging: a homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am J Physiol Heart Circ Physiol. 2011 Aug;301(2):H363-72.
  • Yu S, Khor TO, Cheung KL, Li W, Wu TY, Huang Y, Foster BA, Kan YW, Kong AN. Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS One. 2010 Jan 5;5(1):e8579.
  • Yang M, Yao Y, Eades G, Zhang Y, Zhou Q. MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism. Breast Cancer Res Treat. 2011Oct;129(3):983-91.
  • Eades G, Yang M, Yao Y, Zhang Y, Zhou Q. miR-200a regulates Nrf2 activation by targeting Keap1 mRNA in breast cancer cells. J Biol Chem. 2011 Nov 25;286(47):40725-33.

Combistage mogelijk?

  • nee

Beschikbaarheid?

  • Continu

Aanvullende opmerkingen:

  • Projectduur: 6-9 maanden

 

contact

Coördinator/begeleider
Naam: Prof Dr M.C. Verhaar
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 510 39
m.c.verhaar@umcutrecht.nl
Huispostnummer: F03.223

Aanbieder
Naam: Dr. Joost O. Fledderus
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 598 15
j.o.fledderus@umcutrecht.nl
Huispostnummer: G02.402

Nrf2 chronic kidney disease

Epigenetic inhibition of the Nrf2-Keap1 pathway in chronic kidney disease

Onderwerp: Epigenetic regulation of the Nrf2-Keap1 stress-reponse pathway in the aging arterial wall
Speerpunt: Regenerative Medicine

Inleiding

Nrf2 is a transcription factor that controls the endogenous antioxidant defence system of cells. It is induced by oxidative stress and dietary compounds such as sulforaphane. The Nrf2 pathway is activated via modification of the inhibitor Keap1, which leads to Nrf2 accumulation and nuclear translocation. Nrf2 induces expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, catalase and heme oxygenase via antioxidant response promoter elements.

It has recently been shown that Nrf2 expression and activation is inhibited in the remnant kidney of rats that underwent subtotal (5/6) nephrectomy (SNX) to model chronic kidney disease (CKD) [1]. Possibly, this inhibition is caused by epigenetic mechanisms that influence the expression of Nrf2 and Keap1 [2-4]. It is well-established that kidney function decreases in CKD and that this is associated with increased oxidative stress. In our group, a SNX model for CKD was developed in CD1 nude mice. For this student project, we will compare expression levels of Nrf2, Keap1 and Nrf2 target genes in remnant kidneys from mice that received SNX, uninephrectomy (UNX) or sham operation. In addition, promoter methylation and Nrf2/Keap1-targeting miRNAs will be measured to investigate the epigenetic regulation of the Nrf2-Keap1 pathway.

Doel van het onderzoek

We want to test the hypothesis that expression and activation of the Nrf2-ARE pathway is decreased in the remnant kidney of SNX mice compared to UNX or sham-operated controls by methylation of the Nrf2 promoter and/or miRNAs that target the Nrf2 and Keap1 genes.

Methoden

Kidney RNA, DNA, protein samples will be collected from SNX, UNX and sham-operated mice. Remnant kidney protein levels of Nrf2, Keap1 and Nrf2 target genes will be measured by RT-PCR, Western Blot and immunohistochemistry. The Nrf2 promoter will be screened for CpG methylation using bisulfite sequencing of genomic DNA. In addition, the expression of known Nrf2- and Keap1-modulating miRNAs will be measured by RT-PCR. Techniques: RNA/DNA/protein isolation, RT-PCR, Western Blotting, immunohistochemistry, bisulfite sequencing.

Referenties

  • Kim HJ, Vaziri ND. Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am J Physiol Renal Physiol. 2010 Mar;298(3):F662-71.
  • Yu S, Khor TO, Cheung KL, Li W, Wu TY, Huang Y, Foster BA, Kan YW, Kong AN. Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS One. 2010 Jan 5;5(1):e8579.
  • Yang M, Yao Y, Eades G, Zhang Y, Zhou Q. MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism. Breast Cancer Res Treat. 2011Oct;129(3):983-91.
  • Eades G, Yang M, Yao Y, Zhang Y, Zhou Q. miR-200a regulates Nrf2 activation by targeting Keap1 mRNA in breast cancer cells. J Biol Chem. 2011 Nov 25;286(47):40725-33.

Combistage mogelijk?

  • nee

Beschikbaarheid?

  • continu

Aanvullende opmerkingen:

  • projectduur: 6-9 maanden

contact

Coördinator/begeleider
Naam: Prof Dr M.C. Verhaar
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 51039
m.c.verhaar@umcutrecht.nl
Huispostnummer: F03.223

Aanbieder
Naam: Dr. Joost O. Fledderus
Divisie: DIGD
Afdeling: Nefrologie en Hypertensie
088 75 59815
j.o.fledderus@umcutrecht.nl
Huispostnummer: G02.402

Nrf2 in CAC-differentiation

Investigating the role of Nrf2 in CAC differentiation and function

Inleiding

Oxidative stress occurs when the balance between production and elimination of reactive oxygen species (ROS) is disturbed. Oxidative stress causes dysfunction of endothelial cells (EC) and endothelial progenitor cells including circulating angiogenic cells (CAC), thereby reducing their angiogenic capacity. CAC have been shown to improve perfusion recovery in a murine hindlimb ischemia model, most likely by their paracrine stimulation of neo-vascularization and angiogenesis [1].

Nrf2 is a transcription factor that controls the endogenous antioxidant defence system of cells. Nrf2 controls the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, catalase and heme oxygenase. While antioxidant function of Nrf2 in endothelial cells has been demonstrated, it is unknown whether Nrf2 plays a role in CAC differentiation and function. Interestingly, it has been shown that paracrine action of mesenchymal stem cells is dependent on heme oxygenase [2]. We have recently demonstrated that Nrf2 and its target genes are induced upon differentiation of CAC from peripheral blood mononuclear cells (PBMNC) [unpublished observation]. Furthermore, CAC have a high capacity to withstand H2O2-induced ROS formation [unpublished observation].

Doel van het onderzoek

In this study we want to test the hypothesis that Nrf2 knockdown inhibits CAC differentiation and function.

 

Methoden

Mononuclear cells will be isolated from adult peripheral blood and cultured for 7 days to obtain CAC. After the first day of culture, PBMNC will be transfected with shNrf2 or shControl and further differentiated to CAC. After 7 days, Nrf2 and target gene expression will be investigated by RT-PCR, immunofluorescence and Western blot. Difference in CAC differentiation between shNrf2- and shControl-transduced CAC will be assessed by CAC counting and measuring surface markers with flow cytometry. Intracellular ROS levels will be measured by an oxidation-sensitive dye. Finally, angiogenic capacity of conditioned medium from shNrf2- and shControl-transduced CAC will be compared in a Matrigel angiogenesis assay and by measuring secreted cytokine levels in the conditioned medium.
Techniques: CAC isolation and culture, flow cytometry, short hairpin lentiviral transduction, RT-PCR, ROS measurement, Matrigel angiogenesis assay, multiplex ELISA.

contact

Coördinator/begeleider
Naam: Prof Dr M.C. Verhaar
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 510 39
m.c.verhaar@umcutrecht.nl
Huispostnummer: F03.223

Aanbieder
Naam: Dr. Joost O. Fledderus
Divisie: Interne Geneeskunde en Dermatologie 
Afdeling: Nefrologie en Hypertensie
088 7559815
j.o.fledderus@umcutrecht.nl
Huispostnummer: G02.402

Referenties

  • Hur J, Yoon CH, Kim HS, Choi JH, Kang HJ, Hwang KK, Oh BH, Lee MM, Park YB. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):288-93.
  • Zarjou A, Kim J, Traylor AM, Sanders PW, Balla J, Agarwal A, Curtis LM. Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1. Am J Physiol Renal Physiol. 2011 Jan;300(1):F254-62.

Combistage mogelijk?

  • nee

Beschikbaarheid?

  • continu

Aanvullende opmerkingen:

  • projectduur: 6-9 maanden

Nrf2 in therapy-resistance of renal cell carcinoma

The role of Nrf2 in therapy-resistance of renal cell carcinoma

Specialisme: Vasculaire Geneeskunde en Nefrologie

Inleiding

Renal cell carcinomas do not respond well to chemotherapy or irradiation. A possible mechanism is hyperactivation of the Nrf2-ARE pathway, which increases expression of drug efflux transporters and augments intracellular defenses against oxidative stress and radiation.

Doel van het onderzoek

We hypothesize that increased Nrf2-ARE pathway activation is responsible for therapy-resistance of renal cell carcinoma.

Methoden

Levels of Nrf2 and several target genes including antioxidant enzymes and efflux transporters will be determined in human renal cell carcinoma biopsies using immunohistochemistry. Next, expression and activity of the Nrf2-ARE pathway will be measured in renal cell carcinoma cell lines. Nrf2 activity will be modulated in these cell lines using short hairpin lentiviruses. After this, the transduced cells will be treated with chemotherapeutic agents to measure their sensitivity. Techniques: immunohistochemistry, cell culture, lentiviral transduction, short hairpin-mediated knockdown, RNA isolation, RT-PCR, Western blot, cell viability assay, X-Celligence.

Combistage mogelijk?

  • nee

Beschikbaarheid?

  • In overleg

contact

Coördinator/begeleider
Naam: Joost Fledderus
Divisie: DIGD
Afdeling: Vasculaire Geneeskunde & Nefrologie
088 7559815
j.o.fledderus@umcutrecht.nl

Nrf2 kidney

Epigenetic regulation of the Nrf2-Keap1 stress-reponse pathway in the aging arterial wall

Inleiding

Nrf2 is a transcription factor that controls the endogenous antioxidant defence system of cells. It is induced by oxidative stress and dietary compounds such as sulforaphane. The Nrf2 pathway is activated via modification of the inhibitor Keap1, which leads to Nrf2 accumulation and nuclear translocation. Nrf2 induces expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, catalase and heme oxygenase via antioxidant response promoter elements.

It has recently been shown that Nrf2 expression and activation is inhibited in aging rat aortas [1]. Possibly, this is caused by epigenetic mechanisms that influence the expression of Nrf2 and Keap1 [2-4]. It is well-established that kidney function decreases with age and that this is associated with increased oxidative stress. In this project we will compare expression levels of Nrf2, Keap1 and Nrf2 target genes in kidneys from young versus old mice. In addition, promoter methylation and Nrf2/Keap1-targeting miRNAs will be measured to investigate the epigenetic regulation of the Nrf2-Keap1 pathway.

contact

Coördinator/begeleider
Naam: Prof Dr M.C. Verhaar
Divisie: DIGD
Afdeling: Nefrologie en Hypertensie
088 75 510 39
m.c.verhaar@umcutrecht.nl
Huispostnummer: F03.223

Aanbieder
Naam: Dr. Joost O. Fledderus
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
088 75 59815
j.o.fledderus@umcutrecht.nl
Huispostnummer: G02.402

Doel van het onderzoek

We want to test the hypothesis that expression and activation of the Nrf2-ARE pathway is decreased in the kidney of old mice compared to young controls by methylation of the Nrf2 promoter and miRNAs that target the Nrf2 and Keap1 genes.

Methoden

Kidney DNA, miRNA and protein samples have been collected from 3-20 months old mice. Renal protein levels of Nrf2, Keap1 and Nrf2 target genes will be measure by Western Blot. The Nrf2 promoter will be screened for CpG methylation using bisulfite sequencing of genomic DNA. In addition, the expression of known Nrf2- and Keap1-modulating miRNAs will be measured by RT-PCR. Techniques: Western Blotting, bisulfite sequencing, RT-PCR.

Referenties

  • Ungvari Z, Bailey-Downs L, Sosnowska D, Gautam T, Koncz P, Losonczy G, Ballabh P, de Cabo R, Sonntag WE, Csiszar A. Vascular oxidative stress in aging: a homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am J Physiol Heart Circ Physiol. 2011 Aug;301(2):H363-72.
  • Yu S, Khor TO, Cheung KL, Li W, Wu TY, Huang Y, Foster BA, Kan YW, Kong AN. Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS One. 2010 Jan 5;5(1):e8579.
  • Yang M, Yao Y, Eades G, Zhang Y, Zhou Q. MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism. Breast Cancer Res Treat. 2011Oct;129(3):983-91.
  • Eades G, Yang M, Yao Y, Zhang Y, Zhou Q. miR-200a regulates Nrf2 activation by targeting Keap1 mRNA in breast cancer cells. J Biol Chem. 2011 Nov 25;286(47):40725-33.

Combistage mogelijk?

  • nee

Beschikbaarheid?

  • continu

Aanvullende opmerkingen:

  • Projectduur: 6-9 maanden

Ontwikkelingsbiologie Hypertensie en Nierschade

Ontwikkelingsbiologie van Hypertensie en Nierschade

Speerpunt: Circulatory Health
Specialisme: Nefrologie en Hypertensie

Inleiding

In experimentele en bevolkingsstudies is gebleken dat perinatale omstandigheden de cardiovasculaire risico’s op latere leeftijd nadelig kunnen beïnvloeden (Barker hypothese). In ons laboratorium hebben wij laten zien dat verlaging van de oxidatieve stress of het verhogen van stikstofoxide in zwangere en lacterende hypertensive ratten de bloeddruk bij de nakomelingen langdurig verlaagde en de ontwikkeling van proteïnurie en nierschade vertraagde. Deze omgekeerde bevinding (perinatale manipulatie, langdurige protectie) schept vanzelfsprekend allerlei vragen.
Indien wij met een kortdurende neonatale interventie hoge bloeddruk en targetorgaan schade gedeeltelijk kunnen voorkomen zou dit verstrekkende gevolgen voor de gezondheidszorg hebben.

Doel van het onderzoek

Inmiddels is het waarschijnlijk dat een gestoorde regulatie van transcriptie factoren zoals NFkB en PGC1a bijdraagt aan een ontwikkeling die hoge bloeddruk stimuleert. Wij willen dit nu verder onderzoeken, door te analyseren of epigenetische veranderingen van deze transcriptie factoren geïnduceerd worden tijdens de vroege ontwikkeling.

Methoden

Dit onderzoek is dierexperimenteel, waarbij verschillende perinatale interventies worden getest, de consequenties voor bloeddruk en nierschade op latere leeftijd worden geëvalueerd, en DNA uit verschillende organen wordt geïsoleerd om epigenetische veranderingen vast te stellen.

Referenties

  • Racasan S, Braam B, van der Giezen DM, Goldschmeding R, Boer P, Koomans HA, Joles JA. Perinatal L-arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats. Hypertension. 2004;44:83-8.
  • Koeners MP, van Faassen EE, Wesseling S, de Sain-van der Velden M, Koomans HA, Braam B, Joles JA. Maternal supplementation with citrulline increases renal nitric oxide in young spontaneously hypertensive rats and has long-term antihypertensive effects. Hypertension. 2007;50:1077-84.
  • Koeners MP, Braam B, van der Giezen DM, Goldschmeding R, Joles JA. A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1847-55.
  • Wesseling S, Koeners MP, Kantouh F, Joles JA, Braam B. Consequences of perinatal treatment with L-arginine and antioxidants for the renal transcriptome in spontaneously hypertensive rats. Pflugers Arch. 2009;458:513-24.
  • Koeners MP, Braam B, Joles JA. Perinatal inhibition of NF-kappaB has long-term antihypertensive effects in spontaneously hypertensive rats. J Hypertens. 2011;29:1160-6.
  • Wesseling S, Essers PB, Koeners MP, Pereboom TC, Braam B, van Faassen EE,Macinnes AW, Joles JA. Perinatal exogenous nitric oxide in fawn-hooded hypertensive rats reduces renal ribosomal biogenesis in early life. Front Genet. 2011;2:52.

Combistage mogelijk?

  • ja

contact

Coördinator/begeleider
Naam: Joost O. Fledderus
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
Telefoon: 088-755 98 15
E-mailadres: j.o.fledderus@umcutrecht.nl
Huispostnummer: F03.223

Aanbieder
Naam: Jaap A. Joles
Divisie: Interne Geneeskunde en Dermatologie
Afdeling: Nefrologie en Hypertensie
Telefoon: 030-2535269
E-mailadres: j.a.joles@umcutrecht.nl
Huispostnummer: F03.223

Chloride en nierfalen

Etiologisch onderzoek naar de relatie tussen chloride en achteruitgang van nierfunctie

Overmatige zoutconsumptie kan leiden tot hoge bloeddruk, nierschade en hart- en vaatziekten. Wanneer men spreekt over zout, wordt vaak natrium bedoeld. Terwijl het meeste zout in voeding bestaat uit natriumchloride. Uit eerder ‘zout’ studies is onzeker of natrium, chloride of de combinatie de ongunstige effecten op vaten en nieren veroorzaakt. Voedingsrichtlijnen noemen alleen een natriumbeperking en adviseren zoutvervangers waar wel chloride in zit (zoals LoSalt, bestaande uit kaliumchloride). Maar wat als chloride nu juist de boosdoener is?

Doel van het onderzoek

Het doel van het onderzoek is om het effect van natrium, chloride en de combinatie van beide op achteruitgang van nierfunctie te onderzoeken in een groot prospectief cohort patiënten met een normale nierfunctie.

Methoden

De afdeling nefrologie is een stimulerende afdeling waar zowel basaal als klinisch onderzoek wordt verricht. We zijn op zoek naar een student in de laatste fase van de opleiding met interesse in nefrologie en klinisch onderzoek. De data om deze vraag te beantwoorden is reeds beschikbaar. Je kunt direct beginnen met analyseren van de data. Het doel is een periode van 3 tot 6 maanden de resultaten te verwerken in een paper. Kortere stages in overleg.

Referenties

  • Forman JP, Scheven L, De Jong PE, Bakker SJL, Curhan GC, Gansevoort RT. Association between sodium intake and change in uric acid, urine albumin excretion, and the risk of developing hypertension. Circulation 2012; 125: 3108–16.
  • Cook NR, Cutler JA, Obarzanek E, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: Observational follow-up of the trials of hypertension prevention (TOHP). Br Med J 2007; 334: 885–8.
  • Kotchen TA. Contributions of sodium and chloride to NaCl-induced hypertension. Hypertension 2005; 45: 849–50.

Combistage mogelijk?

  • Nee

Beschikbaarheid?

  • 2019-2020

Tijdens de stage:

  • Krijg je individuele begeleiding door AIOS nefrologie, post-doc onderzoeker en staflid
  • Doe je ervaring op in epidemiologisch onderzoek (vraagstelling, onderzoeksopzet, analyse en verwerken van resultaten, schrijven paper)
  • Werk je samen met AIOS en arts-onderzoekers binnen de nefrologie

Contact

Begeleider

Dr. J. van der Leeuw
Divisie Interne Geneeskunde en Dermatologie
Afdeling nefrologie
088 75 511 56
j.vanderleeuw-4@umcutrecht.nl
Huispostnummer: F02.126

Aanbieder

Dr. M. Rookmaaker
Divisie Interne Geneeskunde en Dermatologie
Afdeling nefrologie
m.rookmaaker@umcutrecht.nl
Huispostnummer: F03.223

Naar boven