title: Hyperfiltration-associated biomechanical forces in glomerular injury and response: Potential role for eicosanoids.
abstract: Hyperfiltration is a well-known risk factor in progressive loss of renal function in chronic kidney disease (CKD) secondary to various diseases. A reduced number of functional nephrons due to congenital or acquired cause(s) results in hyperfiltration in the remnant kidney. Hyperfiltration-associated increase in biomechanical forces, namely pressure-induced tensile stress and fluid flow-induced shear stress (FFSS) determine cellular injury and response. We believe the current treatment of CKD yields limited success because it largely attenuates pressure-induced tensile stress changes but not the effect of FFSS on podocytes. Studies on glomerular podocytes, tubular epithelial cells and bone osteocytes provide evidence for a significant role of COX-2 generated PGE2and its receptors in response to tensile stress and FFSS. Preliminary observations show increased urinary PGE2in children born with a solitary kidney. FFSS-induced COX2-PGE2-EP2signaling provides an opportunity to identify targets and, for developing novel agents to complement currently available treatment.
authors.affiliation: MBRF and Research Service, Kansas City VA Medical Center, Kansas City, MO, USA; Kidney Institute, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: Mukut.Sharma@va.gov.
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.affiliation: MBRF and Research Service, Kansas City VA Medical Center, Kansas City, MO, USA. Electronic address: Ram.Sharma2@va.gov.
authors.forename: Ram
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Kidney Institute, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: emccarthy@kumc.edu.
authors.forename: Ellen T
authors.initials: ET
authors.lastname: McCarthy
authors.affiliation: MBRF and Research Service, Kansas City VA Medical Center, Kansas City, MO, USA; Kidney Institute, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: Virginia.Savin@va.gov.
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Savin
authors.affiliation: MBRF and Research Service, Kansas City VA Medical Center, Kansas City, MO, USA; Section of Nephrology, Children's Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO, USA. Electronic address: tsrivastava@cmh.edu.
authors.forename: Tarak
authors.initials: T
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000293:injuries* / Q000378:metabolism / Q000502:physiology*; D055595:Mechanical Phenomena; D050199:Podocytes / Q000378:metabolism
chemical_list: D015777:Eicosanoids; D015232:Dinoprostone
keywords: Fluid flow shear stress; Hyperfiltration; Podocytes; Prostaglandin E(2); Prostanoid receptors; Tensile stress