Determination of warm ischemia time at donor nephrectomy.

Abstract

To assess the warm ischemia time of kidneys with obscure donor histories we attempted to develop an index for the duration of ischemia by analysis of adenine nucleotides and their degradation products in cortical biopsies of canine kidneys. Two biopsy harvesting techniques were compared. The use of a laboratory technique (dentist's drill) resulted in higher concentrations of adenosine triphosphate (ATP) in normoxic tissue specimens as compared with a clinical method of harvesting biopsies (wedge biopsy). However the sum of adenine nucleotides (AN) (ATP, adenosine diphosphate [ADP], and adenosine monophosphate [AMP]) was not significantly different in both groups (P less than 0.05). Therefore, wedge biopsies were used to study the degradation of AN following 0, 30, 60, 90, and 120 min of ischemia. Adenine nucleotides and their degradation products were assayed by high-performance liquid chromatography. Concentrations of individual adenine nucleotides did not show a consistent correlation with warm ischemia time. However, as the sum of the AN and the sum of their degradation products (DP) decreased and increased, respectively, the balance between these metabolites offered a good correlation with duration of warm ischemia. The ratio of DP to AN was significantly different at each interval (P less than 0.05). To study the influence of temperature on the degradation process, ischemia was induced at 37 degrees C and 32 degrees C. Lowering of the temperature reduced the catabolic rate of the AN. The ratio of DP to AN was significantly different from corresponding values at 37 degrees C. In biopsies of nonischemic human donor kidneys, concentrations of adenine nucleotides and their degradation products were measured. Biopsies weighing less than 0.01% of total renal mass were large enough to meet analytical demands. The ratio of DP to AN in human kidney biopsies was in the same range as in the corresponding dog kidney biopsies. These findings demonstrate that the ratio of DP to AN, as determined from concentrations of purine metabolites in canine cortical wedge biopsies, is a sensitive and potentially useful index of warm ischemia time.