Regression of Peritubular Capillaries Coincides with Angiogenesis and Renal Cyst Growth in Experimental Polycystic Kidney Disease

Abstract

Kristal O’Brien,1,2 Sayanthooran Saravanabavan,1,2 Jennifer QJ Zhang,1,2 Annette TY Wong,1,2 Alexandra Munt,1,2 Jane S Burgess,1,2 Gopala K Rangan1,2 1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia; 2Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, AustraliaCorrespondence: Gopala K RanganCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Level 5, 176 Hawkesbury Road (PO Box 412), Westmead, NSW 2145, AustraliaTel [phone]Fax [phone]Email [email protected]/Aim: The natural history of the renal microvasculature changes in PKD is not known. The aim of this study was to test the hypothesis that angiogenesis is coupled with kidney cyst expansion, and the loss of peritubular capillary networks precedes the onset of interstitial fibrosis.Methods: The renal microvasculature (RECA-1 and CD34) was evaluated in groups of Lewis polycystic kidney (LPK) rats and juvenile cystic kidney (jck) mice during the early, mid and late stage of disease. In addition, LPK rats and jck mice received sirolimus to determine if the reduction in renal cyst growth is in part mediated by the suppression of angiogenesis.Results: In LPK rats, the loss of peritubular capillaries occurred in early-stage disease and paralleled cyst formation whereas in jck mice it was delayed to the mid stage. In both models, vasa recta were displaced by growing cysts and regressed in LPK rats with disease progression but lengthened in jck mice. Cortical and medullary capillary neoangiogenesis occurred during the early stage in both models and persisted with progression. Treatment with sirolimus reduced cyst enlargement but did not alter the progression of renal microvasculature changes in either model.Conclusion: Regression of peritubular capillaries and disruption of vasa recta occur in parallel with angiogenesis and the progressive enlargement of kidney cysts. These data suggest that the regrowth of peritubular capillaries together with inhibition of angiogenesis are potential strategies to be considered in the treatment of PKD.Keywords: juvenile cystic kidney, jck, Lewis polycystic kidney, LPK, peritubular capillary loss, renal vasculature

Keywords

• juvenile cystic kidney (jck)
• lewis polycystic kidney (lpk)
• peritubular capillary loss
• renal vasculature