title: Fluid flow shear stress over podocytes is increased in the solitary kidney.
abstract: BACKGROUND
  Glomerular hyperfiltration is emerging as the key risk factor for progression of chronic kidney disease (CKD). Podocytes are exposed to fluid flow shear stress (FFSS) caused by the flow of ultrafiltrate within Bowman's space. The mechanism of hyperfiltration-induced podocyte injury is not clear. We postulated that glomerular hyperfiltration in solitary kidney increases FFSS over podocytes.
  
  
  METHODS
  Infant Sprague-Dawley rats at 5 days of age and C57BL/6J 14-week-old adult mice underwent unilateral nephrectomy. Micropuncture and morphological studies were then performed on 20- and 60-day-old rats. FFSS over podocytes in uninephrectomized rats and mice was calculated using the recently published equation by Friedrich et al. which includes the variables-single nephron glomerular filtration rate (SNGFR), filtration fraction (f), glomerular tuft diameter (2RT) and width of Bowman's space (s).
  
  
  RESULTS
  Glomerular hypertrophy was observed in uninephrectomized rats and mice. Uninephrectomized rats on Day 20 showed a 2.0-fold increase in SNGFR, 1.0-fold increase in 2RT and 2.1-fold increase in FFSS, and on Day 60 showed a 1.9-fold increase in SNGFR, 1.3-fold increase in 2RT and 1.5-fold increase in FFSS, at all values of modeled 's'. Similarly, uninephrectomized mice showed a 2- to 3-fold increase in FFSS at all values of modeled SNGFR.
  
  
  CONCLUSIONS
  FFSS over podocytes is increased in solitary kidneys in both infant rats and adult mice. This increase is a consequence of increased SNGFR. We speculate that increased FFSS caused by reduced nephron number contributes to podocyte injury and promotes the progression of CKD.
authors.affiliation: Section of Nephrology, Children's Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO, USA.
authors.forename: Tarak
authors.initials: T
authors.lastname: Srivastava
authors.forename: Gianni E
authors.initials: GE
authors.lastname: Celsi
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.forename: Hongying
authors.initials: H
authors.lastname: Dai
authors.forename: Ellen T
authors.initials: ET
authors.lastname: McCarthy
authors.forename: Melanie
authors.initials: M
authors.lastname: Ruiz
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cudmore
authors.forename: Uri S
authors.initials: US
authors.lastname: Alon
authors.forename: Ram
authors.initials: R
authors.lastname: Sharma
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Savin
mesh_terms: D000818:Animals; D005374:Filtration; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009399:Nephrons / Q000502:physiology; D050199:Podocytes / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014564:Urogenital Abnormalities
keywords: fluid flow shear stress; glomerular hyperfiltration; podocyte; solitary kidney