Improved renal transplant preservation using a modified intracellular flush solution (PB-2). Characterization of mechanisms by renal clearance, high performance liquid chromatography, phosphorus-31 magnetic resonance spectroscopy, and electron microscopy studies.
A number of new intracellular renal flush solutions have been found to be more efficacious than Collins-2 (C-2) solution in extending organ viability during simple cold storage. However, the mechanism of action of these solutions remains poorly understood. To delineate better underlying intracellular mechanisms, we studied a modified, simple, hypothermic, intracellular (340 mOsm/kg) flush solution (PB-2). The development of PB-2 solution is based on the ability of some of its individual components to minimize ischemic adenine nucleotide (AN) catabolism and endothelial post "reperfusion injury." Preliminary results in 10 canine autorenal transplants show a significant (P less than 0.02) improvement in renal recovery and viability (recipient posttransplant inulin clearance and survival) after 50 h of cold storage compared with 10 canine kidneys similarly preserved using conventional C-2 flush solution. High performance liquid chromotography (HPLC) studies show a significant (P less than 0.01) loss of AN using C-2, while PB-2 was associated with regeneration of AN within 45 min of reperfusion. Magnetic resonance spectroscopy using phosphorus 31 (31P-MRS) showed more high energy phosphorus metabolites (phosphomonoester and nicotinamide-adenine-dinucleotide phosphate: P less than 0.001) at 50 h cold storage using PB-2 compared with C-2. Electron micrographs (EM) revealed normal microcapillary morphology for the PB-2 group; however, moderate vascular red and white blood cell clumping was observed in the C-2 group. Characterization of the basic preservation mechanisms by HPLC, 31P-MRS, and EM studies indicates that PB-2 solution enhances renal preservation by diminution of both reperfusion injury and the loss of intracellular high energy metabolites that are necessary for viability.
Bretan
P N
PN
Department of Urology, Case Western Reserve University, Cleveland, Ohio.
Baldwin
N
N
Martinez
A
A
Stowe
N
N
Scarpa
A
A
Easley
K
K
Erturk
E
E
Jackson
C
C
Pestana
J
J
Novick
A C
AC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D006982:Hypertonic Solutions; D007668:Kidney / Q000648:ultrastructure; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D009926:Organ Preservation / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control
C024102:Collins' solution; D006982:Hypertonic Solutions