Research group Kidney physiology

Aims

• Identification of hereditary electrolyte disorders

  The development of next-generation diagnostics and innovative functional methods to measure magnesium transport are essential to diagnose and to understand magnesium-wasting tubulopathies. We envision that patient-specific models are the future of pathophysiological research. Personalized drug screening to identify therapeutics that fit the needs of individual patients will become the new standard for treatment of rare diseases

• Prevention of vascular calcification

  Cardiovascular complications are the main cause of death for patients with chronic kidney disease (CKD). Our research on magnesium in vascular calcification demonstrates that novel interventions can contribute to prevent cardiovascular disease in CKD. In our vision, better understanding of mechanisms of vascular calcification is essential to develop dietary and pharmacological approaches to reduce cardiovascular mortality and morbidity in CKD.

• Understanding the role of metabolism in ion transport

  Our recent findings demonstrate that disturbed metabolic process result in urinary electrolyte wasting. We aim understand how metabolism and ion transport are related in the distal convoluted tubule of the kidney.

• Decipher the pathophysiological mechanisms of magnesium disorders

  Our mission is to decipher the pathophysiological mechanisms of magnesium disorders. By identification of genes involved in hereditary hypomagnesemia, we aim to increase our understanding of the molecular mechanisms of magnesium reabsorption in the kidney.

• Patient-specific models for genetic tubulopathies

  We develop patient-specific models for genetic tubulopathies and perform drug screening to identify therapeutics that fit the needs of individual patients

• State-of-the-art technology to measure ion transport

  We introduce state-of-the-art technology to measure ion transport in vitro and in vivo, using multiphoton microscopy and radio-labeled and stable isotopes

Achievements

• Provided insights into mechanisms of magnesium reabsorption in kidney

  We have identified of novel magnesium-wasting and salt-losing tubulopathies caused by mutations in CNNM2, PCBD1, KCNJ16, RRAGD and TRPM7. By linking genetic screening to functional studies, we have provided insights into the mechanisms of magnesium reabsorption in the kidney and improved diagnostics of patients with genetic kidney diseases.

• Magnesium prevents vascular calcification in vitro and in vivo

  We have shown that magnesium prevents vascular calcification in vitro and in vivo. In vascular smooth muscle cells (VSMC), magnesium effectively prevented high phosphate-induced mineralization, as well as in mouse models of CKD. Currently, clinical trials are in progress to determine the clinical relevance of magnesium supplements in CKD.

• Demonstrated that a percentage of people with diabetes suffer from hypomagnesemia

  We have demonstrated that 10-30% of all people with diabetes suffers from hypomagnesemia. Our work shows that magnesium affects insulin sensitivity and lipid metabolism. In clinical trials, we have evaluated benefits of magnesium for insulin sensitivity and immune function.

Publications

See the publication list of the research group leader on Web of Science.

• A selection of our publications

  • Magnesium Disorders - Touyz RM, de Baaij JHF, Hoenderop JGJ - 2024
  • Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA - Viering D, Schlingmann KP, Hureaux M, Nijenhuis T, Mallett A, Chan MMY, van Beek A, van Eerde AM, Coulibaly JM, Vallet M, Decramer S, Pelletier S, Klaus G, Kömhoff M, Beetz R, Patel C, Shenoy M, Steenbergen EJ, Anderson G, Bongers EMHF, Bergmann C, Panneman D, Rodenburg RJ, Kleta R, Houillier P, Konrad M, Vargas-Poussou R, Knoers NVAM, Bockenhauer D, de Baaij JHF; Genomics England Research Consortium - 2022
  • mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy - Schlingmann KP, Jouret F, Shen K, Nigam A, Arjona FJ, Dafinger C, Houillier P, Jones DP, Kleinerüschkamp F, Oh J, Godefroid N, Eltan M, Güran T, Burtey S, Parotte MC, König J, Braun A, Bos C, Rehmann H, Zwartkruis FJT, Renkema KY, Klingel K, Schulze-Bahr E, Schermer B, Bergmann C, Altmüller J, Thiele H, Beck BB, Dahan K, Sabatini D, Liebau MC, Vargas-Poussou R, Knoers NVAM, Konrad M, de Baaij JHF - 2021
  • Electrolyte Disorders in Mitochondrial Cytopathies: A Systematic Review - Viering DHHM, Vermeltfoort L, Bindels RJM, Deinum J, de Baaij JHF - 2023
  • Long-Read Sequencing Identifies Novel Pathogenic Intronic Variants in Gitelman Syndrome - Viering DHHM, Hureaux M, Neveling K, Latta F, Kwint M, Blanchard A, Konrad M, Bindels RJM, Schlingmann KP, Vargas-Poussou R, de Baaij JHF. - 2023 
  • Liver and spleen predominantly mediate calciprotein particle clearance in a rat model of chronic kidney disease - Zeper LW, Bos C, Leermakers PA, Franssen GM, Raavé R, Hoenderop JGJ, de Baaij JHF - 2024
  • Magnesium prevents vascular calcification in Klotho deficiency - Ter Braake AD, Smit AE, Bos C, van Herwaarden AE, Alkema W, van Essen HW, Bravenboer N, Vervloet MG, Hoenderop JGJ, de Baaij JHF - 2020
  • Serum Magnesium Is Inversely Associated With Heart Failure, Atrial Fibrillation, and Microvascular Complications in Type 2 Diabetes - Oost LJ, van der Heijden AAWA, Vermeulen EA, Bos C, Elders PJM, Slieker RC, Kurstjens S, van Berkel M, Hoenderop JGJ, Tack CJ, Beulens JWJ, de Baaij JHF - 2021
  • Magnesium increases insulin-dependent glucose uptake in adipocytes - Oost LJ, Kurstjens S, Ma C, Hoenderop JGJ, Tack CJ, de Baaij JHF - 2022
  • Magnesium reabsorption in the kidney - de Baaij JHF - 2023