Pharmacological limitation of damage to renal medulla after cold storage and transplantation by trimetazidine.
Delayed graft function remains an important complication after renal transplantation. In this study, we investigated the influence of trimetazidine (TMZ), a cytoprotective agent, on renal medullary damage after prolonged preservation and autotransplantation. Pig kidneys were cold-flushed and preserved (48 h at 4 degrees C) with two standard renal preservation solutions Euro-Collins and University of Wisconsin supplemented or not with TMZ (10(-6) M). Analysis of plasma and urine from 48-h-cold-stored and autotransplanted kidneys was performed with biochemical methods and proton NMR spectroscopy. Histological study by light and electron microscopy was performed after reperfusion (30-40 min) and on day 14. The results showed that the preservation in either Euro-Collins or University of Wisconsin solution containing TMZ improved significantly glomerular filtration rate compared with kidneys preserved without TMZ. TMZ significantly reduced renal medullary damage, evidenced by decreased excretion of trimethylamine-N-oxide, dimethylamine, dimethylglycine, and acetate in urine. Proximal tubular injury in TMZ-free groups was assessed by significantly greater Na(+) excretion, amino aciduria, and lactic aciduria than in TMZ-supplemented groups. Urinary concentrating ability was significantly improved in TMZ-preserved groups compared with TMZ-free groups. In TMZ-supplemented groups, there was also a greater excretion of citrate, which is a citric acid cycle metabolite. An extensive reduction in apical brush border of tubular cells, notably those of the proximal tubules, was noted in TMZ-free groups. This study clearly shows that TMZ has a beneficial action on in vivo renal preservation and its major impact is the vulnerable renal medulla.
Hauet
T
T
Unité de Transplantation Expérimentale, Département de Génétique Animale, Institut National de Recherche Agronomique, Domaine du Magneraud, Surgères, and Faculté de Médecine (EA 2624), Poitiers France. hauet@magneraud.inra.fr
Baumert
H
H
Amor
I B
IB
Gibelin
H
H
Tallineau
C
C
Eugene
M
M
Tillement
J P
JP
Carretier
M
M
D000818:Animals; D015415:Biomarkers / Q000652:urine; D019343:Citric Acid / Q000652:urine; D015925:Cryopreservation / Q000379:methods; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008871:Microvilli / Q000187:drug effects* / Q000473:pathology; D010477:Perfusion; D011446:Prospective Studies; D011897:Random Allocation; D013552:Swine; D013997:Time Factors; D014182:Transplantation, Autologous; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015415:Biomarkers; D014665:Vasodilator Agents; D019343:Citric Acid; D014292:Trimetazidine