Intragraft gene expression in native kidney BK virus nephropathy versus T cell–mediated rejection: Prospects for molecular diagnosis and risk prediction

Abstract

Funding information Canadian Donation and Transplantation Research Program Novel tools are needed to improve diagnostic accuracy and risk prediction in BK virus nephropathy (BKVN). We assessed the utility of intragraft gene expression testing for these purposes. Eight hundred genes were measured in 110 archival samples, including a discovery cohort of native kidney BKVN (n = 5) vs pure T cell-mediated rejection (TCMR; n = 10). Five polyomavirus genes and seven immune-related genes (five associated with BKVN and two associated with TCMR) were significantly differentially expressed between these entities (FDR < 0.05). These three sets of genes were further evaluated in samples representing a spectrum of BK infection (n = 25), followed by a multicenter validation cohort of allograft BKVN (n = 60) vs TCMR (n = 10). Polyomavirus 5-gene set expression reliably distinguished BKVN from TCMR (validation cohort AUC = 0.992), but the immune gene sets demonstrated suboptimal diagnostic performance (AUC ≤ 0.720). Within the validation cohort, no significant | 3487 ADAM et Al.

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts

“…The NanoString ® nCounter ® gene expression system has been recently shown to evaluate archival formalin‐fixed paraffin‐embedded tissues ( 27 , 28 ). This technology allows gene expression analysis to be performed on the same tissue assessed with histology, permitting direct molecular–histologic correlations ( 29 ). Although this technology enables measuring up to 800 selected probes, its classification accuracy for kidney graft rejection based on formalin-fixed samples has not been validated in larger cohorts yet.…”

The 2018 Banff Working Group classification of definitive polyomavirus nephropathy: A multicenter validation study in the modern era

“…Patients with evidence of acute or chronic transplant endarteritis, C4d positivity, transplant glomerulitis/glomerulopathy, acute pyelonephritis, thrombotic microangiopathy, an immune complex mediated glomerulonephritis, focal‐segmental glomerulosclerosis (FSGS), diabetic nephropathy, or sepsis at time of index biopsy were excluded from the study cohort because of significant concurrent diagnoses skewing functional and outcome analyses. Note: no attempts were made to diagnose or exclude C4d negative tubulointerstial T cell–mediated Banff type 1 rejection 14‐16 . Data on renal function (serum creatinine [S‐Cr]) were collected before index biopsy (baseline: lowest value within 4 months before index biopsy), at time of initial diagnosis (highest available value within ± 4 days of index biopsy) and at preset intervals up to 24 months post diagnosis (1, 3, 6, 12, 24 months).…”

<p>BK Virus Nephropathy: Prevalence, Impact and Management Strategies</p>

“…8,9 Intragraft polyomavirus gene expression on renal biopsy has recently been reported as a useful adjunct to the diagnosis of PVN with the potential to differentiate from T-cell-mediated rejection. 13 Biopsy proven "definite" PVN has an incidence of 5-6%, with a higher incidence in ABO-incompatible donors and following desensitization in highly sensitized recipients. [14][15][16] The Banff Working Group on Polyomavirus Nephropathy recently published a morphologic classification of definite PVN into three groups, Class I, II, and III, based on polyomavirus load and Banff ci score (interstitial fibrosis) for ease of diagnostic communication and comparative data analysis.…”