Recent paper alert!
Genetic susceptibility to diabetic kidney disease is linked to promoter variants of XOR. Wang et al. Nature Metabolism volume 5, pages 607–625 (2023).
In this study we identified a promoter variant in xanthine oxidoreductase associated with diabetic kidney disease through increased podocyte depletion and glomerular injury.
In the Behind the Paper Blog we discuss the journey of how we went about the discovery of the DKD risk variants in our study. Some of the challenges faced during lab closures in the COVID lock down as well a potential future directions for the project.
The glomerular filtration barrier: a structural target for novel kidney therapies
Ilse S. Daehn & Jeremy S. Duffield. Nat Rev Drug Discov. 2021 Oct;20(10):770-788.
Loss of normal kidney function affects more than 10% of the population and contributes to morbidity and mortality. Kidney diseases are currently treated with immunosuppressive agents, anti-hypertensives, and diuretics with partial but limited success. Most kidney disease is characterized by breakdown of the glomerular filtration barrier (GFB). Specialized podocyte cells maintain the GFB, and structure-function experiments, studies of intercellular communication between the podocytes and other GFB cells, combined with advances from genetics and genomics have laid the groundwork for a new generation of therapies that directly intervene at the GFB. These include inhibitors of apolipoprotein L1 (APOL1), short transient receptor potential channels (TRPCs), soluble vascular endothelial growth factor receptor 1 (FLT1), roundabout homolog 2 (ROBO2), endothelin receptor A, soluble urokinase plasminogen activator surface receptor (uPAR), as well as substrate intermediates for coenzyme Q10 (CoQ10). These molecular targets converge on two key components of GFB biology: mitochondrial function and the actin-myosin contractile machinery. This Review discusses therapies and developments focused on maintaining the GFB integrity, and the emerging questions in this evolving field.
Kidney International October 2019
Ebefors K, Wiener RJ, Yu L, Azeloglu EU, Yi Z, Jia F, Zhang W, Baron MH, He JC, Haraldsson B, Daehn I. (2019) Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells. Kidney Int. Oct;96(4):957-970.
https://watch.wibbitz.com/?id=ba64dc0d4c9f74738b390ef70cc8eb410&color=#ffffff&color4=#000000
New answers in search for diabetic kidney disease diagnostics
Mouse Study Discovers Pathway Involved in Diabetic Kidney Disease
Diabetic kidney disease is decoded, offering new avenues for diagnosis and treatment
