University of Wisconsin solution is superior to histidine tryptophan ketoglutarate for preservation of ischemically damaged kidneys.
The current shortage of transplantable organs has renewed interest in kidneys obtained from non-heart-beating donors. Kidneys from these donors have suffered warm ischemia (WI). The effectiveness of two preservation solutions, i.e., the University of Wisconsin (UW) and the histidine tryptophan ketoglutarate (HTK) solutions, for preservation of kidneys that have been subjected to WI was tested in dogs. The left kidney was autotransplanted after 30 min of WI, and subsequent 24-hr cold storage (CS) in either UW (n = 6) or HTK (n = 6), with immediate contralateral nephrectomy. Surgical biopsies from the cortex were taken before WI, after 30 min of WI, after 24 hr of CS, and after 1 hr of reperfusion for electron microscopy and for analysis of energy metabolites. At 2 weeks after transplantation in the UW group, 4 out of 6 and, in the HTK group, 1 out of 6 dogs survived. As from day 2, serum creatinine was lower in the UW group as compared with the HTK group (P < 0.05). After 24 hr of CS, in the HTK group the luminal membranes of proximal tubular cells were partly denuded of microvilli. Moreover, the tubular lumen was filled with blebs and debris. In the UW group, the brush borders remained intact, although microvilli were swollen. Energy metabolites were analyzed with HPLC. Thirty minutes of WI resulted in a +/- 45% reduction of total adenine nucleotide (TAN) content. During CS, TAN levels further decreased in both groups; however, after 24 hr of CS, the levels of adenosine, inosine, hypoxanthine, and xanthine were significantly higher in the UW group as compared with the HTK group (P < 0.05, P < 0.01, P < 0.01, P < 0.01). At 1 hr of reperfusion, TAN levels were higher in the UW group as compared with the HTK group (4.66 +/- 0.16 vs. 4.02 +/- 0.28, P < 0.05). Our results show that UW is a superior solution compared with HTK in the preservation of ischemically damaged kidneys, demonstrating better survival, better recovery of kidney function, better protection against ischemia-induced ultrastructural damage, and better preservation of energy metabolism indicated by (a faster) regeneration of TAN levels after reperfusion.
Booster
M H
MH
Department of Surgery, University Hospital Maastricht, The Netherlands.
van der Vusse
G J
GJ
Wijnen
R M
RM
Yin
M
M
Stubenitsky
B M
BM
Kootstra
G
G
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003080:Cold Temperature; D003404:Creatinine / Q000097:blood; D004285:Dogs; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007511:Ischemia / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D016030:Kidney Transplantation / Q000379:methods*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008353:Mannitol / Q000494:pharmacology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D009929:Organ Size; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D011887:Raffinose / Q000494:pharmacology; D015424:Reperfusion
D000227:Adenine Nucleotides; C039984:Bretschneider cardioplegic solution; D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D008353:Mannitol; D011343:Procaine; D000493:Allopurinol; D011189:Potassium Chloride; D003404:Creatinine; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose