Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

Peritubular ischemia has more impact on tubular damage than proteinuria in immune-mediated glomerulonephritis

  • Dr Muh Geot Wong, Royal North Shore Hospital, Australia
  • Dr Yusuke Suzuki, Juntendo University School of Medicine, Tokyo, Japan
  • Dr Ko Okumura, Juntendo University School of Medicine, Tokyo, Japan
  • Dr Takeshi Sugaya, Juntendo University School of Medicine, Tokyo, Japan
  • Dr Tokunori Sugaya, Nagoya School of Medicine, Nagoya, Japan
  • Dr Satoshi Horikoshi, Juntendo University School of Medicine, Tokyo, Japan
  • Dr Si Yen Tan, University Malaya Medical Center, Kuala Lumpur, Malaysia
  • Dr Yasuhiko Tomino, Juntendo University School of Medicine, Tokyo, Japan

    • Background: In glomerulonephritis (GN), the severity of tubulointerstitial (TI) damage is associated with renal prognosis. It is accepted that proteinuria has a critical role in the initiation of TI inflammation and fibrosis. More recently, tubular ischemia, due to peritubular capillary loss or hypoperfusion is considered a major factor for progression of TI damage. However, the relative impact of each of these insults is unclear.
    Aim: The aim of the study was to determine the relative effects of proteinuria and ischaemia on TI damage.
    Methods: Kidney injury molecule-1 (Kim-1) mRNA expression, as a marker of TI injury, was examined in murine proximal tubular epithelial cells subjected to various cellular stresses including hypoxia, starvation and exposure to excessive protein. Anti-glomerular basement membrane antibody-induced GN (anti-GBM GN) was induced in both wild type (WT) and Fc receptor-deficient mice (FcR KO). Immunohistochemical analysis of Kim-1 was performed and the degree of proteinuria assessed. Pimonidazole was used to evaluate tissue hypoxia. Peritubular blood flow was determined by intravital videoscopy.
    Results: In vitro studies demonstrate an increase in Kim-1 expression under all experimental conditions. Despite WT and FcR KO mice exhibiting similar degrees of proteinuria, a significant increase in Kim-1 expression was observed in WT mice compared to FcR KO mice, associated with a parallel decrease in peritubular blood flow. Consistent with more marked tissue hypoxia ocuring in the WT mice, an increased level of pimonidazole was observed
    Conclusion: The data suggest that hypoxic insults are more likely to induce TI pathology than is persistent proteinuria.

    Conference Organiser - ICMS Pty Ltd