Hyperfiltration-associated biomechanical forces in glomerular injury and response: Potential role for eicosanoids

•Hyperfiltration is responsible for progression of CKD in several diseases.•Tensile stress and fluid flow shear stress (FFSS) mediate the effects of hyperfiltration on podocytes.•Tensile stress and FFSS induce distinct changes in podocytes via separate mechanisms.•FFSS activates COX2-PGE2-EP2 axis i...

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Bibliographic Details
Published in:Prostaglandins & other lipid mediators 2017-09, Vol.132, p.59-68
Main Authors: Sharma, Mukut, Sharma, Ram, McCarthy, Ellen T., Savin, Virginia J., Srivastava, Tarak
Format: Article
Language:English
Subjects:
Fluid flow shear stress
Hyperfiltration
Podocytes
Prostaglandin E2
Prostanoid receptors
Tensile stress
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Summary:•Hyperfiltration is responsible for progression of CKD in several diseases.•Tensile stress and fluid flow shear stress (FFSS) mediate the effects of hyperfiltration on podocytes.•Tensile stress and FFSS induce distinct changes in podocytes via separate mechanisms.•FFSS activates COX2-PGE2-EP2 axis in podocyte, osteocyte and tubular epithelial cell.•Current therapy does not address podocyte injury that stems from FFSS in early hyperfiltration. 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 PGE2 and its receptors in response to tensile stress and FFSS. Preliminary observations show increased urinary PGE2 in children born with a solitary kidney. FFSS-induced COX2-PGE2-EP2 signaling provides an opportunity to identify targets and, for developing novel agents to complement currently available treatment.
ISSN:1098-8823
DOI:10.1016/j.prostaglandins.2017.01.003