Document Type

Article

Publication Date

5-1-2017

Identifier

PMCID: PMC6075083 DOI: 10.1093/ndt/gfw430

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear. We re-examine the phenomenon of hyperfiltration in the context of biomechanical forces with special reference to glomerular podocytes. Capillary stretch exerts tensile stress on podocytes through the glomerular basement membrane. The flow of ultrafiltrate over the cell surface directly causes fluid flow shear stress (FFSS) on podocytes. FFSS on the podocyte surface increases 1.5- to 2-fold in animal models of solitary kidney and its effect on podocytes is a subject of ongoing research. Podocytes (i) are mechanosensitive to tensile and shear forces, (ii) use prostaglandin E2, angiotensin-II or nitric oxide for mechanoperception and (iii) use specific signaling pathways for mechanotransduction. We discuss (i) the nature of and differences in cellular responses to biomechanical forces, (ii) methods to study biomechanical forces and (iii) effects of biomechanical forces on podocytes and glomeruli. Future studies on FFSS will likely identify novel targets for strategies for early intervention to complement and strengthen the current regimen for treating children with CAKUT.

Journal Title

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

Volume

32

Issue

5

First Page

759

Last Page

765

MeSH Keywords

Animals; Biomechanical Phenomena; Glomerular Filtration Rate; Humans; Renal Insufficiency, Chronic; Signal Transduction; Urologic Diseases

Keywords

CAKUT; fluid flow shear stress; hyperfiltration; podocytes; tensile stress

Download

Share

COinS