title: α-Melanocyte stimulating hormone treatment in pigs does not improve early graft function in kidney transplants from brain dead donors.
abstract: Delayed graft function and primary non-function are serious complications following transplantation of kidneys derived from deceased brain dead (DBD) donors. α-melanocyte stimulating hormone (α-MSH) is a pleiotropic neuropeptide and its renoprotective effects have been demonstrated in models of acute kidney injury. We hypothesized that α-MSH treatment of the recipient improves early graft function and reduces inflammation following DBD kidney transplantation. Eight Danish landrace pigs served as DBD donors. After four hours of brain death both kidneys were removed and stored for 18 hours at 4°C in Custodiol preservation solution. Sixteen recipients were randomized in a paired design into two treatment groups, transplanted simultaneously. α-MSH or a vehicle was administered at start of surgery, during reperfusion and two hours post-reperfusion. The recipients were observed for ten hours following reperfusion. Blood, urine and kidney tissue samples were collected during and at the end of follow-up. α-MSH treatment reduced urine flow and impaired recovery of glomerular filtration rate (GFR) compared to controls. After each dose of α-MSH, a trend towards reduced mean arterial blood pressure and increased heart rate was observed. α-MSH did not affect expression of inflammatory markers. Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation possibly due to hemodynamic changes. Thus, in a porcine experimental model α-MSH did not reduce renal inflammation and did not improve short-term graft function following DBD kidney transplantation.
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Willem G
authors.initials: WG
authors.lastname: van Rijt
authors.affiliation: Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Secher
authors.affiliation: Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Keller
authors.affiliation: Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Møldrup
authors.affiliation: Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Yahor
authors.initials: Y
authors.lastname: Chynau
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Ploeg
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; The Water and Salt Research Center, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Birn
authors.affiliation: The Water and Salt Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
authors.affiliation: The Water and Salt Research Center, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
mesh_terms: D058186:Acute Kidney Injury / Q000652:urine; D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D001786:Blood Glucose / Q000187:drug effects; D001926:Brain Death; D006085:Graft Survival / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016030:Kidney Transplantation; D023421:Models, Animal; D013552:Swine; D014019:Tissue Donors; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D020346:Aquaporins; D015415:Biomarkers; D001786:Blood Glucose; D000521:alpha-MSH
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