title: Protective role of NHE-3 inhibition in rat renal transplantation undergoing acute rejection.
abstract: Acute rejection in renal transplantation disturbs solute and volume maintenance in humans accompanied by delayed graft function and poor prognosis. We recently reported that decreased expression and function of Na+/H+ exchanger type 3 (NHE-3) in proximal tubules and epithelial Na+ channels and aquaporin 2 in collecting ducts are major mechanisms involved in Na+ and water imbalances shortly after transplantation in rat undergoing acute rejection. We performed kidney transplantations in rats with bilaterally nephrectomized recipients with acute rejection and, in addition, systemically administered a specific inhibitor of NHE-3 (NHE-I). NHE inhibition in acute renal failure was shown to improve tubular function and recovery. The aim of this therapy was to reduce energy consumption of the graft and preserve NHE-3 function. Imbalances in electrolyte excretion declined in NHE-I-treated animals and NHE-3 activity was preserved. Observed NHE-I-dependent changes in electrolyte excretion, polyuria, and reduced protein reabsorption in the acute postoperative phase are predictors of favorable graft outcome in humans.
authors.affiliation: Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
authors.forename: Ana
authors.initials: A
authors.lastname: Velic
authors.forename: Bayram
authors.initials: B
authors.lastname: Edemir
authors.forename: Rita
authors.initials: R
authors.lastname: Schröter
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.forename: Gert
authors.initials: G
authors.lastname: Gabriëls
authors.forename: Markus
authors.initials: M
authors.lastname: Bleich
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schlatter
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation / Q000187:drug effects; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
chemical_list: C000613385:SLC9A3 protein, human; C000613387:Slc9a3 protein, rat; D015222:Sodium Channels; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000255:Adenosine Triphosphate; D012964:Sodium