POS0722 HISTOPATHOLOGICAL ANALYSIS OF LUPUS NEPHRITIS INCORPORATING BANFF CRITERIA EMPHASIZES THE IMPORTANCE OF TUBULOINTERSTITIAL CHANGES FOR CREATININE AND PROTEINURIA AT 12 MONTHS AFTER RENAL BIOPSY

Background:Lupus nephritis (LN) occurs in about 30-60% of patients with systemic lupus erythematosus (SLE). LN is associated with increased mortality. Currently, the diagnosis relies on histopathologic characteristics according to the ISN/RPS classification (1). This classification relies heavily on glomerular changes and may not accurately reflect all changes occurring in LN. For the description of transplanted kidney, the BANFF classification has been established which, in addition to glomerular changes, also incorporates tubular pathologies (2).Objectives:With the present study, we aim to describe histopathologic changes according to the BANFF classification in a single-center cohort of LN patients.Methods:We retrospectively recorded epidemiological, clinical and laboratory data of 58 patients with LN over a ten-year period. Histopathologic diagnoses according to ISN/RPS classification or the former WHO classification were also documented. We then re-analyzed representative kidney samples according to the BANFF classification and performed Spearman rank correlation for BANFF findings and creatinine at biopsy and 12 months as well as proteinuria at biopsy and at 12 months.Results:We analyzed 58 patients with LN. 9 were male, 49 were female. Median age was 38 (15-78) years. According to ISN/RPS, 3 had class I LN, 6 had class II, 14 had class III, 16 had class IV, 6 had class V, and 0 had class VI. Median eGFR at biopsy was 60 ml/min/1.73m2 (13-137). According to the BANFF classification, tubulointerstitial inflammation (ti) was associated with creatinine at 12 months. Proteinuria at 12 months was associated with interstitial fibrosis (ci) (Figure 1).Conclusion:In LN, the current ISN/RPS classification puts emphasis on glomerular changes. Nevertheless, for the long-term outcome, tubulointerstitial changes (tubulointerstitial inflammation and interstitial fibrosis) may at least be as important as glomerular changes. These findings have to be corroborated in larger cohorts with prespecified renal endpoints.References:[1]Weening et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. JASN 2004.[2]Jeong HY. Diagnosis of renal transplant rejection: Banff classification and beyond. Kidney Res Clin Pract 2020.Disclosure of Interests:Marlene Plüß: None declared, Samy Hakroush: None declared, Noah Niebusch: None declared, Björn Tampe: None declared, PETER KORSTEN Speakers bureau: Abbvie, Pfizer, Chugai, Sanofi, Boehringer-Ingelheim, GSK, Novartis, Consultant of: Abbvie, Pfizer, Chugai, Sanofi, Boehringer-Ingelheim, GSK, Novartis, Lilly, Gilead, Grant/research support from: GSK

MO1001THE OUTCOME OF PLASMA CELL-RICH ACUTE REJECTION IN KIDNEY TRANSPLANTATION, IS IT REALLY POOR?

Background and Aims The outcome of Plasma cell-rich acute rejection (PCAR) in kidney transplant is reported to be poor. However, PCAR which can be associated with any type of rejection, may not be considered as independent morphological prognostic feature. Different treatment modalities were prescribed with variable responses. We report here four cases of PCAR and describe their presentations, type of rejection, associated conditions and treatment outcome. Method Out of 1920 kidney transplant recipients under follow up in our centre from 1996 till 2019, four patients were reported to have PCAR according to 2007 Banff classification. They were re-evaluated based on 2015 Banff classification. The treatment protocol was tailored according to the type of rejection and associated conditions. Results The four patients, aged 28, 44, 46 and 54 years, had live unrelated renal transplant done somewhere abroad with no data about donor HLA typing. Two of them were females. One had high PRA and she was positive for HBsAg. One patient received induction immunosuppression with basiliximab. They all received prednisolone, mycophenolate and cyclosporine as the maintenance immunosuppression and had immediate graft function. Rejection happened between 23 to 180 months post-transplant. Two patients had acute T-cell mediated Banff 1A rejections with features consistent with early membranous nephropathy. One had acute T-cell mediated rejection Banff 1B and the fourth had borderline T-cell mediated rejection with morphological changes suggestive of chronic active antibody mediated rejection (AMR). Plasma cells constituted 10 to 30% of the interstitial infiltration. All patients received solumedrol pulse. Both patients with features of membranous nephropathy received rituximab and one of them had additionally IVIG. The patient with AMR received plasma exchange and IVIG. However, she did not receive rituximab as she was positive for HBsAg. All patients responded well to treatment and the mean improvement in eGFR was 12.8%, 24.9%, 40.3% and 39.1% at 1-, 3-, 6- and 12-months post treatment. Repeat kidney biopsy at 3 to 12 weeks post treatment showed resolution of plasma cell infiltration in all patients. Conclusion Outcome of PCAR management was favourable among our patients irrespective of the type of rejection and associated conditions.

Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering

BackgroundOver the past decades, an international group of experts iteratively developed a consensus classification of kidney transplant rejection phenotypes, known as the Banff classification. Data-driven clustering of kidney transplant histologic data could simplify the complex and discretionary rules of the Banff classification, while improving the association with graft failure.MethodsThe data consisted of a training set of 3510 kidney-transplant biopsies from an observational cohort of 936 recipients. Independent validation of the results was performed on an external set of 3835 biopsies from 1989 patients. On the basis of acute histologic lesion scores and the presence of donor-specific HLA antibodies, stable clustering was achieved on the basis of a consensus of 400 different clustering partitions. Additional information on kidney-transplant failure was introduced with a weighted Euclidean distance.ResultsBased on the proportion of ambiguous clustering, six clinically meaningful cluster phenotypes were identified. There was significant overlap with the existing Banff classification (adjusted rand index, 0.48). However, the data-driven approach eliminated intermediate and mixed phenotypes and created acute rejection clusters that are each significantly associated with graft failure. Finally, a novel visualization tool presents disease phenotypes and severity in a continuous manner, as a complement to the discrete clusters.ConclusionsA semisupervised clustering approach for the identification of clinically meaningful novel phenotypes of kidney transplant rejection has been developed and validated. The approach has the potential to offer a more quantitative evaluation of rejection subtypes and severity, especially in situations in which the current histologic categorization is ambiguous.

P0127ROUTINE USE OF COMBINATION CD3/PAS STAIN IN EVALUATING RENAL ALLOGRAFT BIOPSIES FOR REJECTION RESULTS IN MORE ACCURATE BANFF SCORES FOR TUBULITIS

Background and Aims The BANFF Classification of renal allograft rejection consists of scores for cellular rejection which rely primarily on the evaluation of lymphocytic infiltration into tubules (t), non-atrophic interstitial inflammation (i), total inflammation (ti), and endotheliatis (v.) CD3/PAS is a combination stain that highlights T lymphocytes (CD3) and basement membrane (PAS). The original BANFF scoring was developed using a hematoxylin and eosin (H&E) stain only. This study compares scores for (t) using H&E versus CD3/PAS. Method 50 consecutive renal allograft biopsies were retrieved and on each case H&E and CD3/PAS combination stains (Ventana/Roche tissue Diagnostics Clone 2GV6 for CD3) were performed. One blinded group of matching CD3/PAS and H&E slides were evaluated and reviewed independently by two renal pathologists (Reviewer 1 and 2). Each case was graded in an identical manner following criteria designated for (t) as previously described in the Banff Classification for Renal Allograft Biopsies. Briefly (t)=0 no lymphocytes in 10 tubule cross section (tcx), (t)=1 between 1-4 lymphocytes per tcx, (t)=2 5-10 lymphocytes per tcx and (t)=3 greater than 10 lymphocytes per tcx. Cases were not graded for (v) as there were too few cases with endotheliatis to allow for statistical evaluation. The difference between CD3/PAS versus H&E scores were tested for significance using the Wilcoxon Signed Rank test. All p values were two-tailed and values of <0.05 were considered statistically significant. Results Mean age was 44 years with a range of 9 -75 years. Standard deviation (SD) for age was 18 years. Gender distribution was 20% female and 80% male. 28 cases were graded as (t) = 0 in H&E versus 18 in the CD3/PAS group (59% versus 36%). 17 cases were graded as (t)=1 in H&E group versus 19 in the CD3/PAS group (36% versus 38% respectively). 2 cases were graded (t)=>2 in H&E versus 12 cases in CD3/PAS groups (4% versus 24% respectively). In all categories of (t) there was a higher (t) score when using a CD3/PAS with 42% showing a one digit score increase and 8% showing a 2 digit increase. The difference in scoring for (t) between the H&E set versus the CD3/PAS set for both Reviewers 1 and 2 were statistically significant (p<0.0001). Conclusion This study showed statistically significant higher tubulitis scores when using a CD3/PAS combination stain to grade allograft biopsies. Since (t) scores directly affect the diagnosis of cellular rejection, we propose routine use of CD3/PAS in addition to H&E when reviewing renal allograft biopsies. Compared with H&E, CD3/PAS makes recognition and quantification of lymphocytes crossing the tubular basement membrane easier to detect and therefore more accurate.

P0093IMPROVED INTEROBSERVER AGREEMENT IN BANFF SCORING OF RENAL ALLOGRAFT BIOPSIES WHEN ROUTINELY USING CD3/PAS STAIN

Background and Aims The BANFF Classification of renal allograft rejection consists of scores for cellular and antibody mediated rejection. The scores for tubulitis (t), interstitial inflammation (i), glomerulitis (g), total inflammation (ti), and endotheliatis (v) have direct prognostic and therapeutic significance as they contribute to a diagnosis of renal allograft rejection. The original BANFF scoring was developed using hematoxylin and eosin (H&E) stain only. This study examines the level of interobserver agreement using H&E and a combination CD3/PAS stain that highlights T lymphocytes and basement membranes. Method 50 consecutive renal allograft biopsies were retrieved and on each case H&E and CD3/PAS stains (Ventana/Roche Tissue Diagnostics clone 2GV6 for CD3) were performed. CD3/PAS and H&E slides were matched and blinded for two reviewers [reviewer (R1) and reviewer 2 (R2)]. Each case was graded in an identical manner following criteria designated for (t),(i),(g) and (ti) as previously described in the Banff Classification for Renal Allograft Biopsies. Cases were not graded for (v) as there were too few cases with endothelialitis to allow for statistical evaluation. The matched scores were analyzed using weighted Kappa statistics for interobserver agreement within each group. Agreement levels were characterized using Landis and Koch descriptions for level of agreement. All p values were two-tailed, values of <0.05 were considered statistically significant. Statistical analyses was performed using SAS Version 9.4, Cary NC. Results Mean age was 44 years with a range of 9 -75 years. Standard deviation (SD) for age was 18 years. Gender distribution was 20% female and 80% male. Agreement between R1 and R2 for (t) scores was moderate (Weighted Kappa 0.5276) as opposed to fair for H&E group (Weighted Kappa 0.4189). Similarly, interobserver agreement was moderate for scores of (i) and (ti) in the CD3/PAS group and fair in the H&E group. For both CD3/PAS and H&E interrater evaluations, agreement was fair to poor for (g) with weighted Kappa of 0.3928 and 0.3559 respectively. Conclusion This study showed increased levels of interobserver agreement when using a CD3/PAS combination stain to score allograft biopsies for (t), (i) and (ti). Since (t), (i) and (ti) scores directly affect a diagnosis of rejection, we propose routine use of CD3/PAS in addition to H&E when reviewing renal allograft biopsies. Glomerulitis (g) shows poor interobserver agreement regardless of the stain used and further studies to refine the criteria for (g) in Banff revisions of the classification may be of value.