title: Glomerular hypertrophy precedes albuminuria and segmental loss of podoplanin in podocytes in Munich-Wistar-Frömter rats.
abstract: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease. Albuminuria is a risk factor for FSGS and is influenced by environmental, genetic, and sex-specific factors. Podocytes play a central role in the development of albuminuria, but the precise relationship between early glomerular and podocyte-associated damage and albuminuria is unclear. Furthermore, experimental findings demonstrate a sex difference in development of albuminuria and FSGS. We investigated the early glomerular changes in male Munich-Wistar-Frömter (MWF) rats, which spontaneously develop albuminuria, and male albuminuria-resistant spontaneously hypertensive rats (SHR). In addition, since female MWF rats are protected from overt proteinuria and progressive renal disease, we compared the phenotypic changes in podocytes during early development of albuminuria in male and female MWF rats. In male MWF rats, glomerular hypertrophy preceded the onset of albuminuria and was greater than in male SHR. Albuminuria developed starting at 6 wk of age and coincided with focal and segmental loss of podoplanin, increased expression of desmin, entrapment of albumin in affected podocytes, and focal and segmental foot process effacement at the ultrastructural level. Other podocyte-associated molecules, such as nephrin and zonula occludens 1, were unaffected. Early glomerular hypertrophy and podocyte damage did not differ between male and female MWF rats. Our data show for the first time that albuminuria in male and female MWF rats is preceded by glomerular hypertrophy and accompanied by focal and segmental loss of podoplanin when FSGS was not yet present.
authors.affiliation: Leiden Univ. Medical Center, Dept. of Pathology Bldg. 1, L1Q, P.O. Box 9600, 2300 RC Leiden, The Netherlands. d.ijpelaar@lumc.nl
authors.forename: D H T
authors.initials: DH
authors.lastname: Ijpelaar
authors.forename: A
authors.initials: A
authors.lastname: Schulz
authors.forename: K
authors.initials: K
authors.lastname: Koop
authors.forename: M
authors.initials: M
authors.lastname: Schlesener
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: D
authors.initials: D
authors.lastname: Kerjaschki
authors.forename: R
authors.initials: R
authors.lastname: Kreutz
authors.forename: E
authors.initials: E
authors.lastname: de Heer
mesh_terms: D000419:Albuminuria / Q000175:diagnosis*; D000818:Animals; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D006984:Hypertrophy; D007672:Kidney Cortex / Q000473:pathology / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D050199:Podocytes / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012727:Sex Characteristics; D000098853:Podoplanin
chemical_list: D008562:Membrane Glycoproteins; C092025:Pdpn protein, rat; D000098853:Podoplanin