PMCID: PMC5513797 DOI: 10.1016/j.prostaglandins.2017.01.003
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.
Prostaglandins & other lipid mediators
Animals; Biomechanical Phenomena; Dinoprostone; Eicosanoids; Humans; Kidney Glomerulus; Mechanical Phenomena; Podocytes
Fluid flow shear stress; Hyperfiltration; Podocytes; Prostaglandin E(2); Prostanoid receptors; Tensile stress
Sharma M, Sharma R, McCarthy ET, Savin VJ, Srivastava T. Hyperfiltration-associated biomechanical forces in glomerular injury and response: Potential role for eicosanoids. Prostaglandins Other Lipid Mediat. 2017;132:59-68. doi:10.1016/j.prostaglandins.2017.01.003