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erlenmyer-research
Research group/lab  |  P.I. Ewout J. Hoorn, MD, PhD

Renal tubular disorders

We study the mechanisms of renal tubular transport and the link with human disease including renal tubular disorders, hypertension, and chronic kidney disease.

About our research group/lab

Our research

Renal tubular disorders

We are a tertiary referral center and national center of expertise for inherited kidney disease, including renal tubular disorders and polycystic kidney disease. In our patients with renal tubular disorders we have discovered novel mutations in SCCN1A and KCNJ16 and have complemented this with genotype-phenotype analysis, and functional characterization of the mutations in our lab. We are also involved in clinical trials to identify novel drugs for polycystic kidney disease. Furthermore we study the mechanism of this disease by modeling it using kidney organoids developed from patient materials.

Regulation of the sodium-chloride cotransporter

The sodium-chloride cotransporter (NCC, encoded by SLC12A3) is one of the major sodium transporters in the kidney. Both decreased and increased activity of NCC is linked to human disease, including Gitelman syndrome and hypertension. Our group studies the regulation of NCC and recent contributions include its regulation by angiotensin II, WNK-SPAK kinases, calcineurin inhibitors and – more recently – potassium. The clinical implications of these findings are addressed in investigator-initiated trials.

Urinary extracellular vesicles

Urinary extracellular vesicles (uEVs) are nanosized vesicles excreted by the kidney and urinary tract. To analyze renal tubular transport non-invasively, our group has developed novel methods to isolate, quantify, and characterize uEVs. Analysis of human uEVs is used to identify disease-associated proteins for renal tubular disorders, hypertension, polycystic kidney disease, and renal fibrosis.

Salt sensitivity of chronic kidney disease

Chronic kidney disease is characterized by salt-sensitive hypertension.
We are analyzing the mechanisms by which chronic kidney disease increases the sensitivity to salt. In vivo, we model chronic kidney disease and study the blood pressure response to dietary and pharmacological interventions. In the kidney we analyze how chronic kidney disease changes the activity of the various sodium transporters. We are also analyzing the anti-hypertensive and renoprotective effect of dietary potassium in chronic kidney disease. These laboratory studies are complemented with investigator-initiated clinical trials to address these mechanisms clinically.

Our projects

  • K+onsortium (2017–2022): national research consortium to study the renoprotective effects of dietary potassium in chronic kidney disease experimentally and clinically. 
  • Targeting prostaglandins in chronic kidney disease (2019–2023): experimental and clinical studies to address the untapped potential of modulating renal prostaglandin effects as a novel intervention for chronic kidney disease (in collaboration with the University of Aarhus). 
  • Targeting Accelerated Senescence in Kidney Fibrosis (2019–2023): Opportunities for Regeneration and CurE (TASKFORCE): national research consortium on the role of senescence in kidney fibrosis. 
  • Human salt taste (2018–2022): project to investigate the role of the salivary proteome in human salt taste and to model human salt taste in C. elegans (in collaboration with cell biology). 

Key Publications

Key publications

Collaborations

Collaboration within Erasmus MC

  • Nephrology and transplanation (dr. M. Hoogduijn, prof.dr. R. Kramann)
  • Vascular medicine (prof.dr. A.H.J. Danser, dr. J. Versmissen)
  • Epidemiology (prof.dr. M.A. Ikram, prof.dr. B.H.C. Stricker)
  • Cell biology (dr. G. Jansen)
  • Developmental biology (prof.dr. J. Gribnau)
  • Clinical genetics (dr. A.S. Brooks)
  • Pediatric nephrology (drs. E. Dorresteijn)
  • Clinical chemistry (dr. C.R.B. Ramakers)
  • Pathology (dr. M.C. Clahsen – van Groningen)

Collaboration outside of Erasmus MC

  • Dr. Robert Fenton (University of Aarhus)
  • Dr. Stephen Walsh and Dr. Detlef Bockenhauer  (University College London, UK)
  • Dr. David Ellison (Oregon Health & Science University, USA)
  • Dr. Mark Knepper (National Institutes of Health, USA)
  • Dr. Tom Nijenhuis and prof. Jack Wetzels (Radboudumc, Nijmegen)
  • Prof. René Bindels, prof. Joost Hoenderop, and dr. Jeroen de Baaij (Radboudumc, Nijmegen)
  • Dr. Liffert Vogt (Amsterdam UMC)
  • Dr. Joris Rotmans (LUMC, Leiden)
  • Dr. Martin de Borst and Prof. Ron Gansevoort (UMCG, Groningen) 
  • Prof.dr. R. Goldschmeding and dr. T.Q. Nguyen (UMCU, Utrecht)

Funding & Grants

  • Dutch Kidney Foundation (2 Consortium grants, Senior Postdoc grant, 2 Innovation grants, PhD student grant)
  • Tandem Grant, Novo Nordisk Foundation
  • Erasmus MC grant

Career opportunities

For current career opportunities, please contact us by clicking the 'Contact form' button.

Our team

Principal Investigator

 

  • 10 PhD students
  • Robert Zietse, MD, PhD
  • David Severs, MD
  • Cathy Cuevas Gallardo, PhD
  • Usha Musterd-Bhaggoe

Any questions or comments?

Please contact our office.

Contact form