*Purpose: Molecular diagnostic methods are now included in the Banff classification of kidney transplant pathology. Traditional histopathology may be limited by intra/inter pathologist variation. The Molecular Microscope (MMDx™) uses microarrays to detect gene transcripts in pathology samples from transplanted organs. We report the first UK experience of using MMDx™ in the kidney transplant clinic.

*Methods: Patients were consented for renal transplant biopsy and molecular and genetic testing. Samples were sent simultaneously for MMDx™ to the Kashi Laboratory (Portland, OR) and to the local histopathlogy department for 22 consecutive renal transplant biopsies performed in 20 patients (13M:7F; Age 53±15 years, Median ABDR MM 3 (0-5), 13 DD/5 LD/1 SPK/1 ABOi). Time since transplant was 78.8±73 months. Indication for biopsy ‘for cause’ (20/22 including 2 repeated post treatment), 1 non-adherence and 1 pre-conception). Histopathology was reported by the on call renal pathologist. As MMDx^TM only requires approximately 4mm of renal cortex no additional biopsy cores were required. To assess inter-pathologist variations biopsies were later re-assessed by a single, blinded, histopathologist.

*Results: MMDx™ results were available 50 hours after the biopsy c.f. 24 hours for light microscopy and 48 hours for immunohistochemistry. The initial histopathological diagnoses were of rejection in 6/22 samples. Additionally MMDx™ identified moderate mixed rejection in the non-adherent patient whereas light microscopy was non specific / showed patchy scarring only. MMDx^TM was particularly useful in a number of clinical scenarios, including showing resolution of molecular signal of T cell mediated rejection in one patient whose graft function had not improved after treatment.

*Conclusions: MMDx™ provides a powerful new diagnostic tool in assessing kidney transplant dysfunction. Results are available in a similar timeframe to conventional methods, although faster if electron microscopy turnaround time is considered. There is excellent correlation between pathologists and between pathologist and MMDx™. MMDx™ detects gene expression (upstream of damage) rather than downstream histopathological consequences. MMDx™ is limited by not being able to detect glomerulonephritis. The role of MMDx™ in everyday practice is to be established but its usefulness in reproducibly categorising rejection in clinical trials will be clear.

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