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Fredrik Palm

Renal physiology and kidney disease

Kidney disease is a major cause for premature mortality. Recently, the focus has shifted from a glomerulocentric to a predominantly tubulocentric view of mechanisms involved in the development of kidney disease caused by diabetes, hypertension or acute kidney injury (Vallon and Thomson 2012). Our research program focuses on better understanding of basic renal physiology and pathological mechanisms leading to kidney disease. Recently, we have directed substantial efforts towards delineating the involvement of deranged kidney oxygen homeostasis for the onset and progression of acute and chronic kidney disease.

Kidney tissue oxygen tension is low already under normal conditions (Aukland and Krog 1960, Leichtweiss et al 1969) and attempts to increase oxygen delivery via increased renal blood flow normally also result in augmented tubular load of electrolytes due to elevated glomerular filtration rate, which in itself increases the metabolic demand. Thus, any increase in kidney metabolism is likely to result in decreased kidney tissue oxygen tension, i.e. hypoxia. Indeed, increased kidney metabolism is associated with diabetic nephropathy (Korner et al 1994) and diabetes is associated with a decreased kidney tissue oxygen tension in both animals and patients (Ries et al 2003, dos Santos et al 2007, Rosenberger et al 2008, Edlund et al 2009, Haidara et al. 2009, Inoue et al. 2011). Fine et al. proposed that an initial glomerular injury decreases blood flow through peritubular capillaries and results in decreased oxygenation of the kidney, promoting tubulointerstitial fibrosis and progression to kidney damage (Fine, Orphanides et al 1998). Importantly, chronic tubulointerstitial hypoxia has been proposed as a common pathway to end stage renal disease irrespective of initial insult (Nangaku 2004, Nangaku 2006, Singh et al 2008, Mimura and Nangaku 2010, Palm and Nordquist 2011).

In 2003, we presented our first report demonstrating intrarenal tissue hypoxia in diabetes (Palm et al. 2003), which after that has been verified by several international laboratories (Ries et al 2003, dos Santos et al 2007, Rosenberger et al 2008, Yin et al 2012). Since then we have continued to investigate the role of kidney tissue hypoxia for the development of diabetic nephropathy, but also during other conditions associated with increased risk of kidney disease, such as hypertension, ischemia-reperfusion injury and surgical 5/6 nephrectomy.

Ongoing Projects...

 


Figure. Unifying hypothesis for the lab’s activities. Most pathways have already been published. A few of the pathways listed in this overall scheme are currently only supported by unpublished data, but are to be published shortly.

For further information about this research group please contact Professor Fredrik Palm

Grants:


  • Swedish Research Council,
  • Swedish Diabetes Association,
  • National Institutes of Health/NIDDK,
  • Fredrik and Ingrid Thurings Foundation,
  • Swedish Heart and Lung Foundation,
  • Family Ernfors Foundation,
  • Magnus Bergvalls foundation,
  • Åke Wibergs foundation,
  • Lars Hierta Foundation

 

Collaborators

within the Department of Medical Cell Biology:

  • Professor Peter Hansell,
  • Professor A. Erik G. Persson.

outside the Department of Medical Cell Biology:

  • Per Liss, Per Ekebom, Jan Weis, Lars-Olov Mangnusson ( Uppsala University),
  • Anders Persson, Petter Quick (Linköping University),
  • John Wahren (Karolinska Institute),
  • Christopher S. Wilcox, William J. Welch, Joseph Verbalis (Georgetown University, USA),
  • Tom Teerlink (VU University Medical Center, The Netherlands),
  • Jerry D. Glickson (University of Pennsylvania, USA),
  • Masaomi Nangaku (Tokyo University, Japan),
  • Kazuhiro Kimura (Hokkaido University, Japan).