α-melanocyte stimulating hormone treatment does not improve early graft function in porcine brain dead kidney transplantation
W.G. van Rijt, N. Secher, A.K. Keller, U. Møldrup, Y. Chynau, R.J. Ploeg, H. van Goor, R. Nørregaard, H. Birn, J. Frøkiaer, S. Nielsen, H.G.D. Leuvenink, B. Jespersen
Location(s): Rondgang 1e verdieping
Category:
Introduction 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 has been demonstrated to have renoprotective effects 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. Material & Methods 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 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. Glomerular filtration rate (GFR) was defined as 51Cr-EDTA renal clearance. Results 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 gene expression of inflammatory markers. Thirty minutes post-reperfusion α-MSH increased plasma aldosterone levels.
Discussion Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation. This is explained by activation of the renin-angiotensin-aldosterone system due to hemodynamic instability. 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.
- View W.G. van Rijt
- View N. Secher
- View A.K. Keller
- View U. Møldrup
- View Y. Chynau
- View R.J. Ploeg
- View H. van Goor
- View R. Nørregaard
- View H. Birn
- View J. Frøkiaer
- View S. Nielsen
- View H.G.D. Leuvenink
- View B. Jespersen