Noninvasive monitoring of citrate, acetate, lactate, and renal medullary osmolyte excretion in urine as biomarkers of exposure to ischemic reperfusion injury

Injury during the transplant process affects the alloantigen-dependent fact ors and the alloantigen-independent processes of "chronic" rejection. Conse quently, the determination of reliable parameters for the assessment of isc hemic damage is essential for the prediction of renal changes after ischemi a/reperfusion injury. The aim of this study was to assess the ability of H- 1 NMR spectroscopy to predict the early graft dysfunction in an ischemia/re perfusion model after preservation in two standard preservation solutions. Euro-Collins (EC) and University of Wisconsin (UW). The second aim was to s pecify the role of the UW solution in preventing renal medullary injury. Ur ine and plasma samples From three experimental groups were examined during 2 weeks: control group (n = 5), EC group (cold flushed and 48-h cold storag e of kidney in EC and autotransplantation.,I = 12), and UW group (cold flus hed and 48-h cold storage of kidney in UW and autotransplantation; n = 12). We also examined these kidneys 30-40 min after implantation and on the sac rifice day. Creatinine clearance was significantly reduced in the EC group during the second week. Fractional excretion of sodium and urine N-acetyl-b eta -D-glucosaminidase activity were improved but not significantly differe nt in the preserved groups. Urinary concentrations of the alpha-class gluta thione S-transferase were significantly greater in the EC group during the first week after transplantation. The most relevant resonances for evaluati ng renal function after transplantation determined by H-1 NMR spectroscopy were those arising from citrate. dimethylamine (DMA), lactate, and acetate in urine and trimethylamine N-oxide (TMAO) in urine and plasma. These findi ngs suggest that graft dysfunction is associated with damage to the renal m edulla determined by TMAO release in urine and plasma associated with DMA a nd acetate excretion. Citrate is al so a urinary marker that can discrimina te kidneys with a favorable evolution. Our results suggest that H-1 NMR spe ctroscopy is an efficient technique for detecting ischemic damage when accu rate and precise data on graft injury is required. In addition, this study outlines the specific impact of the UW solution against injury to the renal medulla. (C) 2000 Academic Press.