395 COMPARISON OF RENAL PRECONDITIONING TECHNIQUES IN A RAT MODEL

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011395 COMPARISON OF RENAL PRECONDITIONING TECHNIQUES IN A RAT MODEL Kapil Sethi, Oneel Patel, Michael Chang, Graham Baldwin, Arthur Schulkes, and Damien Bolton Kapil SethiKapil Sethi Melbourne, Australia More articles by this author , Oneel PatelOneel Patel Melbourne, Australia More articles by this author , Michael ChangMichael Chang Melbourne, Australia More articles by this author , Graham BaldwinGraham Baldwin Melbourne, Australia More articles by this author , Arthur SchulkesArthur Schulkes Melbourne, Australia More articles by this author , and Damien BoltonDamien Bolton Melbourne, Australia More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.483AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renal preconditioning is a technique that exposes tissue susceptible to ischaemia into triggering a family of intracellular transcription factors, the Hypoxia Inducible Factors (HIFs), to upregulate renoprotective genes and protect against injury. Proven methods of preconditioning are cobalt stimulation and transient hypoxia (ischaemic preconditioning), which may offer protection to renal cells against irreversible nephron loss and tolerate ischaemia beyond the accepted critical ischaemia time. Whilst explored in other organs, no study has compared the effects of these two techniques against each other in the kidney. There is emerging evidence that transient ischaemia and cobalt stimulation may act through different mechanisms in conferring renoprotection, with the concept of combination preconditioning offering better protection yet to be explored. METHODS 24 solitary kidney-model Sprague Dawley rats were divided into groups of 6 undergoing either a) control treatment, b) 30mg/kg subcutaneous cobalt chloride (CoCl2) treatment for 24 and 6 hours pre-ischemia c) intermittent clamping (IC) consisting of 5 minutes renal artery clamping followed by 10 minutes reperfusion over 4 cycles, or d) a combination of both CoCl2 and IC. Following preconditioning, all rats underwent 40 minutes of renal artery clamping and were followed up with serum renal function tests and animal health assessment scores as a measure of renal impairment for 7 days. RESULTS All rats demonstrated the greatest rise in serum urea and creatinine peaking at 24 hours, with levels return to basal levels by day 7. All preconditioning methods offered biochemical improvement up to 72 hours (mean +/− SEM creatinine in mol/l: control group, 328.3 +/− 46; CoCl2, 76.3 +/− 10.7 p<0.005; IC, 76.3 +/− 36.2 p<0.01; combination, 271.1 +/− 76). Rats treated with CoCl2 had the lowest rise in serum creatinine at 24 hours (Control 406.8 +/− 62.1; CoCl2, 144.7 +/− 31.5 p<0.0001). Whilst the control group had a 50% mortality rate, no rats in the preconditioning groups died (p<0.005). CONCLUSIONS Individual Cobalt treatment offers greater protection against renal damage than IC or a combination of techniques in the kidney. Development of similar hypoxia-mimetic agents that specifically target the prolyl hydroxylation pathway of HIF activation would offer the greatest benefit in renal preconditioning for clinical application. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e159-e160 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kapil Sethi Melbourne, Australia More articles by this author Oneel Patel Melbourne, Australia More articles by this author Michael Chang Melbourne, Australia More articles by this author Graham Baldwin Melbourne, Australia More articles by this author Arthur Schulkes Melbourne, Australia More articles by this author Damien Bolton Melbourne, Australia More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...