Evaluation of a Novel Cold Storage Solution (HBS) in a Rat Kidney Transplant Model

Abstract

We developed an improved solution for hypothermic storage (0-4 degrees C) of kidneys. The cold storage solution (HBS) was composed of macromolecules, high-energy cellular substrates, and a mixture of antiproteolytic amino acids, antioxidants, and anti-inflammatory compounds. The objectives in developing this solution were to achieve superior metabolic support of the kidney during cold storage and to protect against ischemic injury. Inbred Brown Norway rats, weighing 225-250 g, were subjected to orthotopic ultrarapid technique for kidney isotransplantation to minimize warm ischemia and to test the preservation process. The kidney was transplanted after 12 h of preservation. The animals were divided into three groups based upon the preservation solution utilized: HBS solution, HTK solution (Custodiol), and UW solution (UWS)(ViaSpan). Among the recipients, each group had two subsets. The first subset of animals was used to assess survival at 7 days as well as the reperfusion damage index (RDI) based on the macroscopic physical characteristics of the kidney at the time of transplantation. The second subset in each group was utilized to measure serum creatinine and blood urea nitrogen at 4 and 7 days, and histology at death or sacrifice. Mean +/- standard deviation (M +/- SD) was used for all parameters studied. The HBS solution showed significantly better protection at 12 h when compared to HTK and UW solutions. The reperfusion damage index (RDI) showed excellent preservation in the HBS (14 +/- 1), good preservation in UWS (13 +/- 1.5), and moderate preservation in the HTK (11 +/- 2) group. Histology was in concordance with the RDI, showing better histological findings with HBS and UW solutions than with the HTK group. Serum creatinine was significantly better in the HBS group when compared to HTK and UWS. Survival was statistically different, with 80% survival at 7 days in the HBS group, 20% survival in the HTK group, and 50% survival in the UWS group (p < .05). The HBS solution offered a new alternative for kidney cold storage with significantly better results when compared to the current gold standards of HTK and UW solutions in Brown Norway rats. This solution warrants further testing in other mammals.

Preservation Solutions for Kidney Transplantation: History, Advances and Mechanisms

“…Apart from the above mentioned solutions, several other solutions are also utilized for cold storage preservation of kidneys, including phosphate buffered sucrose (PBS) 140 51,52 , HP16 53 , HBS 54 , B2 55 , Lifor 56,57 , Ecosol 58 , Biolasol 59,60 , renal preservation solution 2 (RPS-2) 61 , F-M 62 , AQIXRS-I 63 , WMO-II 64 , CZ-1 65 solutions, etc. Each solution may vary in composition; however, the key strategy with each solution is similar: use colloids, impermeants, electrolytes, antioxidants, and nutrients to minimize ischemic/hypoxic injury and maximize kidney function after reperfusion 66,67 .…”

Perfluorocarbon Improves Post-Transplant Survival and Early Kidney Function following Prolonged Cold Ischemia

“…Other authors using the storage in the UW solution as a standard method usually performed only a unilateral nephrectomy before transplantation which enabled them to investigate the morphology and dynamics of the reparatory process but precluded them from following the onset and early evolution of the graft function [30,31] . In a paper by Schmitz et al [32] , comparable results were reported in a study arm with 24 h cold storage in the UW solution and pretransplant bilateral nephrectomy.…”

Protective effect of zinc-N-acetylcysteine on the rat kidney during cold storage

“…It contains raffinose, lactobionate, and hydroxyethyl starch to prevent edema, adenosine that acts as a precursor of ATP, and allopurinol and glutathione as antioxidants. However, some studies have shown that inhibition of apoptosis by UWS is insufficient (38,43) and yet demonstrated kidney viability only in 50% of cases (21). Hence, further research and improvement of existing cold storage solutions are necessary.…”