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Basic & Clinical Research

We use an integrative physiological approach to learn more about the central role that the kidneys play in the homeostatic regulation of body fluid composition. The research of Kidney.CH is organized in 3 work packages, each of which focuses on a kidney centred homeostatic theme.

Basic & Clinical Research
  • Oxygen

    Oxygen

    • Oxygen

      Work Package 1

      Oxygen

      WP Leader: Roland Wenger

      WP Co-Leader: Sophie de Seigneux

    • O<sub>2</sub> Computing & visualization

      Project 1

      O2 Computing & visualization

      Project Leader: Vartan Kurtcuoglu

      Additional Contributors: Ian Frew, Roland Wenger, Sophie de Seigneux

    • Mitochondria & oxygen gradients

      Project 2

      Mitochondria & oxygen gradients

      Project Leader: Andrew Hall

      Additional Contributors: Carsten Lundby, Sophie de Seigneux, Ian Frew, Wolf-Georg Forssmann, Murielle Bochud, Olivier Devuyst

    • Epo regulation in renal disease and development

      Project 3

      Epo regulation in renal disease and development

      Project Leader: Roland Wenger

    • Nephron loss & hypoxia

      Project 4

      Nephron loss & hypoxia

      Project Leader: Sophie de Seigneux

      Additional Contributors: Andrew Hall, Ian Frew, Vartan Kurtcuoglu, Carsten Lundby, Roland Wenger, Eric Féraille

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    Oxygen biology in kidney disease

    The kidney is a major O2 consumer and a main O2 sensor. Both of these functions profoundly change during development and during kidney disease, leading to a progressive decline of the excretory and erythropoietin (Epo)-producing capacity of the kidney. The main objective of this WP is to elucidate the intricate interplay between tissue O2 (re)-distribution, and tubular as well as renal Epo-producing cell function in chronic kidney disease (CKD) progression.

    O2 Computing & visualization

    Vartan Kurtcuoglu

    This project focuses on investigations of renal oxygenation in CKD, relying on progressive renal failure as reference pathology. Computational modeling is employed to quantify kidney tissue oxygenation at successive stages of the disease. As the anatomic basis of the model, renal vascular and tubular anatomies are acquired using synchrotron radiation based high-resolution phase-contrast micro computed tomography. The image datasets additionally serve to characterize morphologic and structural changes to the vascular tree and tubular structures. One of the primary goals of the project is to determine whether a reduction in spatial gradients of O2 partial pressure or an increase in renal oxygenation leads to a reduction of EPO production in CKD.

    • Olgac U, Kurtcuoglu V. The Bohr effect is not a likely promoter of renal preglomerular oxygen shunting. Frontiers in Physiology 7: 1-14 (2017)
    • Kuo W, Kurtcuoglu V. Renal arteriovenous oxygen shunting. Current Opinion in Nephrology and Hypertension 26: 290-95 (2017)

    Mitochondria & oxygen gradients

    Andrew Hall

    This project shall provide novel insights into the role of tubular mitochondria in shaping intra-renal O2 gradients. This is investigated by intravital microscopy and other complementary techniques. Specific aims are (i) to investigate segment-specific differences in baseline mitochondrial function along the renal tubule, (ii) to characterize in real-time the impact of acute kidney injury (AKI) and CKD causing insults on mitochondria and the downstream consequences on tubular transport function, and (iii) to understand how changes in mitochondrial function in damaged tubules affect the behavior of Epo producing cells in the kidney interstitium.

    • Schuh C, Polesel M, Platonova E, Haenni D, Gassama A, Tokonami N, Ghazi S, Bugarski M, Devuyst O, Ziegler U and Hall AM. Combined structural and functional imaging of the kidney reveals major axial differences in proximal tubule endocytosis. The Journal of The American Society of Nephrology 11: 2696-712 (2018)
    • Bugarski M, Martins J, Haenni D and Hall AM. Multiphoton imaging reveals axial differences in metabolic auto-fluorescence signals along the kidney proximal tubule. Am J Physiol Renal Physiol. 6: F1613-25 (2018)

    Epo regulation in renal disease and development

    Roland Wenger

    Taking advantage of newly developed mouse and cell culture models, this project aims for the elucidation of how: (i) Epo is regulated on the molecular level in renal erythropoietin-producing (REP) cells, (ii) Epo expression switches from liver to kidney during embryonic development, (iii) Epo-production is re-established in CKD by pharmacologic hydroxylase inhibition.

    • Imeri F, Nolan KA, Bapst AM, Santambrogio S, Abreu Rodríguez I, Spielmann P, Pfundstein S, Libertini S, Crowther L, Orlando IMC, Dahl SL, Keodara A, Kuo W, Kurtcuoglu V, Scholz CC, Qi W, Hummler E, Hoogewijs D, Wenger RH. Generation of renal Epo-producing cell lines by conditional gene tagging reveals rapid HIF-2 driven Epo kinetics, cell autonomous feedback regulation and a telocyte phenotype. Kidney Int. 95: 375-87 (2019)
    • Nolan KA, Wenger RH. Source and microenvironmental regulation of erythropoietin in the kidney. Curr. Opin. Nephrol. Hypertens. 27: 277-82 (2018)

    Nephron loss & hypoxia

    Sophie de Seigneux

    The aim of the project is to determine the role of hypoxia and the HIF and FIH pathway in CKD progression. The pathway and impact of HIF/FIH pathway regulation on fibrosis, the microvascular evolution in progressive CKD and its impact on anemia and role of tubular HIF-1alpha in compensatory nephron growth after nephron loss is investigated.

  • Dietary Ions

    Dietary Ions

  • Mineralisation

    Mineralisation

  • SKSC Research

    SKSC Research

  • Clinical Study Group

    Clinical Study Group