Evidence for protective roles of polyethylene glycol plus high sodium solution and trimetazidine against consequences of renal medulla ischaemia during cold preservation and reperfusion in a pig kidney model.
BACKGROUND
The renal medulla is particularly sensitive to oxidant stress and to ischaemia-reperfusion injury (IRI). In organ transplantation, delayed graft function is an important problem and cold ischaemia is thought to be the most important factor in short- and long-term complications. Our aim was to study cold-induced damage in proximal tubular segments and renal medulla osmolite excretion during use of various preservation solutions, and to clarify the role of trimetazidine (TMZ) in limiting renal dysfunction.


METHODS
Using an autotransplanted pig kidney model, we assessed renal tubule function, medullary osmolite excretion and renal damage between day 1 and week 2 after 24 or 48 h cold storage in University of Wisconsin solution (UW), Celsior and ECPEG (two new high Na(+) preservation solutions) or the Hopital Edouard Herriot solution (HEH; a high Na(+) version of UW). In additional groups, TMZ was added to these preservation solutions for 24 and 48 h cold storage.


RESULTS
Renal function was reduced under these preservation conditions. Tubular injury was associated with aminoaciduria and with a limited Na(+) reabsorbtion. Medullary damage led to the early appearance of trimethylamine-N-oxide and dimethylamine in urine. However, renal damage was modulated by preservation conditions. In addition, TMZ added to each of the solutions efficiently protected against IRI even after prolonged preservation.


CONCLUSIONS
TMZ efficiently protected kidneys against damage when added to the HEH and particularly ECPEG solutions, even after 24 h cold storage. These findings point to a role for drugs that target mitochondria, and demonstrate that TMZ may provide a valuable therapeutic tool against IRI and could be included in therapeutic protocols.
Faure
Jean Pierre
JP
INSERM ERM Poitiers, Département de Génétique Animale, Hôpital Jean Bernard, Poitiers, France.
Jayle
Christophe
C
Dutheil
Delphine
D
Eugene
Michel
M
Zhang
Keqiang
K
Goujon
Jean Michel
JM
Petit-Paris
Isabelle
I
Tillement
Jean Paul
JP
Touchard
Guy
G
Robert
Rene
R
Wahl
Anne
A
Seguin
Francois
F
Mauco
Gerard
G
Vandewalle
Alain
A
Hauet
Thierry
T
D000818:Animals; D003080:Cold Temperature; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007679:Kidney Medulla / Q000098:blood supply*; D009926:Organ Preservation / Q000009:adverse effects*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000209:etiology* / Q000517:prevention & control*; D012965:Sodium Chloride / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D014292:Trimetazidine / Q000494:pharmacology*
D019188:Organ Preservation Solutions; D011092:Polyethylene Glycols; D012965:Sodium Chloride; D014292:Trimetazidine