Dataset Information

Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): reproducibility of polyomavirus immunohistochemistry in kidney allografts.

ABSTRACT: Immunohistochemistry (IHC) is the gold standard for diagnosing (positive vs. negative) polyomavirus BK (BKV) nephropathy and has the potential for disease staging based on staining intensity and quantification of infected cells. This multicenter trial evaluated the reproducibility of BKV IHC among 81 pathologists at 60 institutions. Participants stained tissue microarray slides and scored them for staining intensity and percentage of positive nuclei. Staining protocol details and evaluation scores were collected online. Slides were returned for centralized panel re-evaluation and kappa statistics were calculated. Individual assessment of staining intensity and percentage was more reproducible than combined scoring. Inter-institutional reproducibility was moderate for staining intensity (??=?0.49) and percentage (??=?0.42), fair for combined (??=?0.25) and best for simple positive/negative scoring (??=?0.78). Inter-observer reproducibility was substantial for intensity (??=?0.74), percentage (??=?0.66), positive/negative (??=?0.78) and moderate for combined scoring (??=?0.43). Inter-laboratory reproducibility was fair for intensity (??=?0.37), percentage (??=?0.40) and combined (??=?0.24), but substantial for positive/negative scoring (??=?0.67). BKV RNA copies/cell correlated with staining intensity (r?=?0.56) and percentage (r?=?0.62). These results indicate that BKV IHC is reproducible between observers but scoring should be simplified to a single-feature schema. Standardization of tissue processing and staining protocols would further improve inter-laboratory reproducibility.

SUBMITTER: Adam B

PROVIDER: S-EPMC4194133 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): reproducibility of polyomavirus immunohistochemistry in kidney allografts.

Adam B B Randhawa P P Chan S S Zeng G G Regele H H Kushner Y B YB Colvin R B RB Reeve J J Mengel M M

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20140804 9

Immunohistochemistry (IHC) is the gold standard for diagnosing (positive vs. negative) polyomavirus BK (BKV) nephropathy and has the potential for disease staging based on staining intensity and quantification of infected cells. This multicenter trial evaluated the reproducibility of BKV IHC among 81 pathologists at 60 institutions. Participants stained tissue microarray slides and scored them for staining intensity and percentage of positive nuclei. Staining protocol details and evaluation scor ...[more]

PMID: 25091177

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Project description:BACKGROUND:BK Polyomavirus (BKPyV) causes premature graft failure in 1 to 15% of kidney transplant (KT) recipients. High-level BKPyV-viruria and BKPyV-DNAemia precede polyomavirus-associated nephropathy (PyVAN), and guide clinical management decisions. In most cases, BKPyV appears to come from the donor kidney, but data from biopsy-proven PyVAN cases are lacking. Here, we report the early fulminant course of biopsy-proven PyVAN in two male KT recipients in their sixties, receiving kidneys from the same deceased male donor. CASE PRESENTATIONS:Both recipients received intravenous basiliximab induction, and maintenance therapy consisting of tacrolimus (trough levels 3-7?ng/mL from time of engraftment), mycophenolate mofetil 750?mg bid, and prednisolone. At 4?weeks post-transplant, renal function was satisfactory with serum creatinine concentrations of 106 and 72??mol/L in recipient #1 and recipient #2, respectively. Plasma BKPyV-DNAemia was first investigated at 5 and 8?weeks post-transplant being 8.58?×?104 and 1.12?×?106 copies/mL in recipient #1 and recipient #2, respectively. Renal function declined and biopsy-proven PyVAN was diagnosed in both recipients at 12?weeks post-transplant. Mycophenolate mofetil levels were reduced from 750?mg to 250?mg bid while tacrolimus levels were kept below 5?ng/mL. Recipient #2 cleared BKPyV-DNAemia at 5.5?months post-transplant, while recipient #1 had persistent BKPyV-DNAemia of 1.07?×?105 copies/mL at the last follow-up 52?weeks post-transplant. DNA sequencing of viral DNA from early plasma samples revealed apparently identical viruses in both recipients, belonging to genotype Ib-2 with archetype non-coding control region. Retrospective serological work-up, demonstrated that the donor had high BKPyV-IgG-virus-like particle ELISA activity and a high BKPyV-genotype I neutralizing antibody titer, whereas both KT recipients only had low neutralizing antibody titers pre-transplantation. By 20?weeks post-transplant, the neutralizing antibody titer had increased by >?1000-fold in both recipients, but only recipient #2 cleared BKPyV-DNAemia. CONCLUSIONS:Low titers of genotype-specific neutralizing antibodies in recipients pre-transplant, may identify patients at high risk for early fulminant donor-derived BKPyV-DNAemia and PyVAN, but development of high neutralizing antibody titers may not be sufficient for clearance.

Dataset Information

Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): reproducibility of polyomavirus immunohistochemistry in kidney allografts.

Publications

Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): reproducibility of polyomavirus immunohistochemistry in kidney allografts.

Similar Datasets

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