NMR spectroscopy as a novel approach to the monitoring of renal transplant function

Abstract

High field 1H NMR spectroscopy was used for the rapid multicomponent analysis of low molecular wt compounds in urine in order to investigate the patterns of metabolic changes associated with early renal allograft dysfunction. Urine samples were collected daily for 14 days from 33 patients who underwent primary renal allograft transplantation, and analyzed by 500 and/or 600 MHz 1H NMR spectroscopy. All patients received 20 mg prednisolone and 5 mg/kg b.d. oral cyclosporin A (CsA) solution. In this study no patient showed clinical or histopathological evidence of CsA nephrotoxicity. For each patient the NMR-generated metabolite data were correlated with the clinical observations, graft biopsy pathology, and data from conventional laboratory techniques for assessing renal function. The NMR spectra of urine from patients with immediate functioning grafts were similar with respect to their patterns of amino acids, organic acids and organic amines, whereas the patients with delayed or non-functioning grafts showed significantly different metabolite excretion patterns. In longitudinal studies on individual patients there were increased urinary levels of trimethylamine-N-oxide (TMAO), dimethylamine (DMA), lactate, acetate, succinate, glycine and alanine during episodes of graft dysfunction. However, only the urinary concentration of TMAO was statistically significantly higher (P < 0.025) in the urine collected from patients during episodes of graft dysfunction (410 +/- 102 microM TMAO/mM creatinine) than in patients with good graft function (91 +/- 18 microM TMAO/mM creatinine) or healthy control subjects (100 +/- 50 microM TMAO/mM creatinine). These findings suggest that graft dysfunction is associated with damage to the renal medulla which causes the release of TMAO into the urine from the damaged renal medullary cells. This provides a possible novel urinary marker for post-transplant graft dysfunction. This study shows that NMR spectroscopy of biofluids, when used in combination with conventional laboratory techniques, is a valuable aid to renal transplant monitoring.

Trimetazidine Reverses Deleterious Effects of Ischemia-Reperfusion in the Isolated Perfused Pig Kidney Model

“…Markers deteted by proton NMR spectroscopy were also greater in urine from kidneys preserved with EC solution than from kidneys preserved with EC+TMZ. TMAO is a metabolite which is exclusively present in the intracellular compartment, and this metabolite is not usually found in normal urine [25, 26, 27]. Its excretion in urine is related to leakage from renal medulla cells [28].…”

Gender‐related and age‐related urinalysis of healthy subjects by NMR‐based metabonomics

“…Urinalysis by NMR spectroscopy has led to detailed investigation of human excretion patterns in various pathological conditions such as inborn errors of metabolism (12), organ transplantation (13), kidney dysfunction (14,15), diabetes mellitus (16), and renal damage caused by exposure to xenobiotics (17)(18)(19)(20)(21)(22)(23). NMR-based metabonomics in human urine has contributed to the investigation of excretion profiles in patients with multiple sclerosis (24), neurological disorders (25), and interstitial and bacterial cystitis (26).…”

Metabolomics of Human Intestinal Transplant Rejection

“…Metabolomics has only recently been applied to organ transplantation (14,15) and few groups have published the results of metabolomics for the evaluation of acute rejection (16), graft dysfunction (17), ischemia-reperfusion injury (18) and for drug monitoring (19). In kidney transplantation a number of urinary and serum biomarkes have been identified to correlate with a rejection episode including trimethylamine-N-oxide (TMAO) (20) and others (21,22). In liver transplantation a change in the bile acids profile between pre-and postreperfusion bile samples has been recently reported by Legido-Quigley et al (23).…”