Analysis of RNA Transcripts by the Molecular Microscope^® Diagnostic System (MMDx^®) Can Direct Management after Indication Kidney Transplant Biopsy

Key Takeaways

• Both “Borderline” and “Banff 1a” TCMR may be incorrectly attributed.
• MMDx can provide diagnostic certainty where histopathology is uncertain.
• MMDx pre- and post-treatment can demonstrate efficacy (or lack of efficacy) of treatment.

Summary Statement

These two cases describe how MMDx was used to aid the management of two patients with Banff diagnoses of “borderline” and “Banff 1a TCMR.”

Summary

Our medical affairs director is a transplant nephrologist and, before joining One Lambda, used the Molecular Microscope® Diagnostic System in clinical practice in his kidney transplant clinic.

Echoing the Madill-Thomsen 2019 AJT paper on discrepancy analysis, Lawrence et al report on cases of two kidney transplant recipients who were biopsied for a rise in the serum creatinine.

In the first case, a patient who, for medical reasons, had had minimization of immunosuppression presented with an asymptomatic rise in the serum creatinine. The histology was reported as “borderline” for T cell-mediated rejection (TCMR); however, the MMDx® results reported severe TCMR. Therefore, the patient was treated for TCMR with pulsed intravenous corticosteroids, followed by a tapering dose of oral corticosteroids. Despite this, the kidney function did not improve. A repeat biopsy was performed, and this time both histology and MMDx showed no rejection. The authors observe that it is possible to see the resolution of the molecular changes associated with rejection after successful treatment for rejection.

When the second patient was biopsied for creeping creatinine, histology showed an interstitial infiltrate associated with tubulitis in 25% of the cortex. The Banff “I” score was 2, and the “t” score was 2. The MMDx report, however, did not show any rejection. Due to an abundance of caution, the patient was treated with high dose oral corticosteroids. There was no improvement in the serum creatinine, and so the patient underwent a repeat biopsy.

The repeat biopsy was interpreted as no rejection by histology and remained quiescent in the MMDx results. On reviewing the histology of the first biopsy by a blinded second histopathologist, it was determined that the patient’s first biopsy did not meet the Banff criteria for TCMR.

These two cases highlight the difficulties in diagnosing TCMR and the “discrepancy” between histopathologists and between MMDx and histology. The clinicians are convinced that the original biopsy of the first patient-reported by histology as “borderline” was clinically relevant TCMR. The first biopsy in the second patient reported as TCMR was, in fact, not rejection. In both of these cases, MMDx outperformed histology with clinically relevant consequences.

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