Abstract

Our studies of protocol biopsy studies have shown that normal allograft histology can not be assumed by crude tests of renal function such as the serum creatinine concentration, and that there is a high prevalence of subclinical rejection in the first 6 months post-transplant (7, 13-17). The apparent ability of urine MR and IR spectra to reliably identify patients with normal allograft histology, if confirmed in a larger database, will preclude the need for a protocol biopsy in approximately 20-50% of patients. Conversely, finding urine MR or IR spectra characteristic of subclinical rejection would provide the opportunity for early treatment. The clear separation between patients with normal histology from those with subclinical rejection can be attributed to the use of the whole urine spectrum to develop the classifiers. Additional advantages of using MR or IR spectra of urine as a diagnostic tool compared to the biopsy include simplicity (i.e. no processing is required), low cost, rapid turnaround (i.e. < 15 minutes/sample), and, particularly, low risk, thus allowing for repetitive sampling. The ability to non-invasively diagnose acute inflammation in the kidney would be of great assistance in the post-transplant monitoring of renal transplant patients. Indeed, by following subclinical inflammation as detected in the MR/IR spectra it will be possible to tailor the intensity of the immunosuppression to the inflammatory status of the graft, thus minimising the risks of both insufficient and excessive immunosuppression. Furthermore, by following subclinical inflammation, as detected in the MR/IR spectra, it will be possible to test the hypothesis that subclinical rejection (i.e. persistence of its MR/IR spectral classifier) is a surrogate marker for the development of chronic rejection.

Keywords: Biological Markers - urine, Chronic Disease, Graft Rejection - diagnosis, Graft Rejection - urine, Kidney Transplantation - pathology, Kidney Transplantation - physiology, Magnetic Resonance Imaging, Spectrophotometry, Infrared, Transplantation, Homologous, Urine - cytology