Pulmonary pathology in vasculitis.

Pulmonary involvement is frequent in vasculitis, particularly in ANCA-associated small vessel vasculitis. Laboratory and radiological data alone are often sufficient to confirm the clinical hypothesis, but sometimes the pathologist plays a crucial role in the differential diagnosis and the patient's management. In this review, the pathologic features of pulmonary vasculitis and the pathologist's role in this field are illustrated.

Usefulness and Limitations of Current Diagnostic Strategies for Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: Lessons Learned From a Large Cohort.

CONTEXT.­: The pathologic diagnosis of pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is challenging. OBJECTIVE.­: To evaluate the diagnostic usefulness and limitations of current diagnostic strategies for pulmonary MALT lymphoma. DESIGN.­: A retrospective review of 120 cases of pulmonary MALT lymphoma from 2014 through 2021 was performed. RESULTS.­: Clinicoradiologic presentations overlapped with previous observations in patients with MALT lymphoma, such as a wide age range, female predominance, frequent association with autoimmune disease or immunodeficiency, and broad imaging findings. The histopathologic diagnosis was based on a combination of morphology, immunohistochemistry, and demonstration of B-cell lineage clonality. Two-thirds (76 of 113) of MALT lymphomas had lymphoplasmacytoid cytomorphology. Occasionally, MALT lymphomas were associated with granulomas/giant cells (29%, 35 of 120) or immunoglobulin deposition disease (21%, 25 of 120), including light chain/heavy chain deposition disease, amyloidosis, and/or crystal storing histiocytosis. While CD5, CD10, Bcl-2, and Bcl-6 rarely revealed aberrancies, aberrant CD43 expression either on B-cells or on plasma cells was detected in 42% (27 of 64) of cases, including cases for which proof of clonality could not be obtained. κ/λ in situ hybridization was particularly useful for tumors with lymphoplasmacytoid morphology but performed poorly in lymphomas having no plasmacytic differentiation. κ/λ immunohistochemistry showed no additional usefulness when applied together with κ/λ in situ hybridization. Immunoglobulin gene rearrangement studies by polymerase chain reaction achieved high detection rates of clonality in all cytomorphologic subgroups. CONCLUSIONS.­: Our study offers a practical evaluation of common diagnostic tests in pulmonary MALT lymphoma. We offer recommendations for a diagnostic workup that takes into consideration the usefulness and the specific limitations of the various diagnostic strategies.

Pulmonary Pathology Society Survey on Practice Approaches in the Histologic Diagnosis of Fibrotic Interstitial Lung Disease: Consensus and Opportunities.

CONTEXT.­: The pathologic diagnosis of usual interstitial pneumonia (UIP) remains a challenging area, and application of histologic UIP guidelines has proved difficult. OBJECTIVE.­: To understand current practice approaches by pulmonary pathologists for the histologic diagnosis of UIP and other fibrotic interstitial lung diseases (ILDs). DESIGN.­: The Pulmonary Pathology Society (PPS) ILD Working Group developed and sent a 5-part survey on fibrotic ILD electronically to the PPS membership. RESULTS.­: One hundred sixty-one completed surveys were analyzed. Of the respondents, 89% reported using published histologic features in clinical guidelines for idiopathic pulmonary fibrosis (IPF) in their pathologic diagnosis; however, there was variability in reporting terminology, quantity and quality of histologic features, and the use of guideline categorization. Respondents were very likely to have access to pulmonary pathology colleagues (79%), pulmonologists (98%), and radiologists (94%) to discuss cases. Half of respondents reported they may alter their pathologic diagnosis based on additional clinical and radiologic history if it is pertinent. Airway-centered fibrosis, granulomas, and types of inflammatory infiltrates were considered important, but there was poor agreement on how these features are defined. CONCLUSIONS.­: There is significant consensus among the PPS membership on the importance of histologic guidelines/features of UIP. There are unmet needs for (1) consensus and standardization of diagnostic terminology and incorporation of recommended histopathologic categories from the clinical IPF guidelines into pathology reports, (2) agreement on how to incorporate into the report relevant clinical and radiographic information, and (3) defining the quantity and quality of features needed to suggest alternative diagnoses.

Duration of Dialysis in Acute Kidney Injury Donors and Transplant Outcomes.

BACKGROUND: Acute kidney injury (AKI) kidneys, including those from donors on dialysis, are often underutilized, although there is increasing data available demonstrating good transplant outcomes. To date, data on the duration of donor dialysis and transplant outcomes are limited. STUDY DESIGN: This was a single-center study of deceased donor kidney transplants from 2010 to 2022. The study cohort consisted of recipients of deceased donor kidney transplants from donors with AKI and on dialysis. Three groups were identified based on the predetermined interquartile range of donor dialysis duration: 1 to 2 dialysis days, 3 to 4 dialysis days, and 5 or more dialysis days. RESULTS: During this period, 765 AKI deceased donor transplants were performed, of which 230 were from donors on dialysis. The median dialysis duration was 2 days with a maximum of 13 days. Across the 3 groups, there were no differences in recipient age (p = 0.23) or dialysis vintage (p = 0.70). Donor age (p = 0.86) and kidney donor profile index (p = 0.57) were comparable between the groups. Recipients of deceased donor kidney transplants from donors on dialysis 5 or more days had lower terminal creatinine levels (p = 0.003) and longer cold ischemia times (p = 0.04). Posttransplant, the median length of hospital stay was 3 days for all groups (p = 0.75). There were no differences in delayed graft function occurrence (94.4% vs 86.8% vs 92.1%, p = 0.19), duration of delayed graft function (p = 0.56), or readmissions (p = 0.99). At 1 year posttransplant, the estimated glomerular filtration rate (p = 0.76), patient survival (p = 0.82), or death-censored graft survival (p = 0.28) were comparable. CONCLUSIONS: Excellent outcomes have been observed in AKI deceased donor kidney transplants, including those coming from donors on dialysis. In this small cohort, the duration of donor dialysis did not adversely affect outcomes. Cautious expansion of the donor pool, including donors on dialysis, should be considered given the ongoing organ shortage.

Case report: JC polyomavirus nephropathy in simultaneous heart-kidney transplantation: the role of viral-specific in situ hybridization staining.

Introduction: JC polyomavirus (JCPyV) is a ubiquitous virus that can be latent in the brain and the kidney. It is the etiologic agent responsible for progressive multifocal leukoencephalopathy, a fatal, demyelinating disease of the central nervous system, and rarely causes polyomavirus nephropathy in immunocompromised kidney transplant recipients. Case description: We present the first case of JCPyV nephropathy in a simultaneous heart-kidney transplant patient, where viral-specific in situ hybridization staining of the kidney tissue was utilized to confirm the diagnosis. The patient was diagnosed 6 years after simultaneous heart-kidney transplantation and was treated with immunosuppression reduction and intravenous immunoglobulin. Discussion: JCPyV nephropathy should be considered in the differential diagnosis of kidney allograft injury, particularly, with suggestive light microscopy histologic features in the absence of BK polyomavirus viremia and/or viruria. In addition to obtaining JCPyV PCR in the blood, in situ hybridization staining may have a utility in confirming the diagnosis. To date, we lack effective JCPyV-specific therapies, and prompt initiation of immunosuppression reduction remains the mainstay of treatment.

Outcomes of asymptomatic histologic pyelonephritis of kidney transplant.

BACKGROUND: Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. METHODS: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. RESULTS: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Tubular and Glomerular Size by Cortex Depth as Predictor of Progressive CKD after Radical Nephrectomy for Tumor.

SIGNIFICANCE STATEMENT: Glomerular size differs by cortex depth. Larger nephrons are prognostic of progressive kidney disease, but it is unknown whether this risk differs by cortex depth or by glomeruli versus proximal or distal tubule size. We studied the average minor axis diameter in oval proximal and distal tubules separately and by cortex depth in patients who had radical nephrectomy to remove a tumor from 2019 to 2020. In adjusted analyses, larger glomerular volume in the middle and deep cortex predicted progressive kidney disease. Wider proximal tubular diameter did not predict progressive kidney disease independent of glomerular volume. Wider distal tubular diameter showed a gradient of strength of prediction of progressive kidney disease in the more superficial cortex than in the deep cortex. BACKGROUND: Larger nephrons are prognostic of progressive kidney disease, but whether this risk differs by nephron segments or by depth in the cortex is unclear. METHODS: We studied patients who underwent radical nephrectomy for a tumor between 2000 and 2019. Large wedge kidney sections were scanned into digital images. We estimated the diameters of proximal and distal tubules by the minor axis of oval tubular profiles and estimated glomerular volume with the Weibel-Gomez stereological model. Analyses were performed separately in the superficial, middle, and deep cortex. Cox proportional hazard models assessed the risk of progressive CKD (dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73 m 2 , or a sustained 40% decline from the postnephrectomy baseline eGFR) with glomerular volume or tubule diameters. At each cortical depth, models were unadjusted, adjusted for glomerular volume or tubular diameter, and further adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, postnephrectomy baseline eGFR, and proteinuria). RESULTS: Among 1367 patients were 62 progressive CKD events during a median follow-up of 4.5 years. Glomerular volume predicted CKD outcomes at all depths, but only in the middle and deep cortex after adjusted analyses. Proximal tubular diameter also predicted progressive CKD at any depth but not after adjusted analyses. Distal tubular diameter showed a gradient of more strongly predicting progressive CKD in the superficial than deep cortex, even in adjusted analysis. CONCLUSIONS: Larger glomeruli are independent predictors of progressive CKD in the deeper cortex, whereas in the superficial cortex, wider distal tubular diameters are an independent predictor of progressive CKD.

Lymphoid Interstitial Pneumonia (LIP) Revisited: A Critical Reappraisal of the Histologic Spectrum of "Radiologic" and "Pathologic" LIP in the Context of Diffuse Benign Lymphoid Proliferations of the Lung.

The use of lymphoid interstitial pneumonia (LIP) as a diagnostic term has changed considerably since its introduction. Utilizing a multi-institutional collection of 201 cases from the last 20 years that demonstrate features associated with the LIP rubric, we compared cases meeting strict histologic criteria of LIP per American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus ("pathologic LIP"; n=62) with cystic cases fulfilling radiologic ATS/ERS criteria ("radiologic LIP"; n=33) and with other diffuse benign lymphoid proliferations. "Pathologic LIP" was associated with immune dysregulation including autoimmune disorders and immune deficiency, whereas "radiologic LIP" was only seen with autoimmune disorders. No case of idiopathic LIP was found. On histology, "pathologic LIP" represented a subgroup of 70% (62/88) of cases with the distinctive pattern of diffuse expansile lymphoid infiltrates. In contrast, "radiologic LIP" demonstrated a broad spectrum of inflammatory patterns, airway-centered inflammation being most common (52%; 17/33). Only 5 cases with radiologic cysts also met consensus ATS/ERS criteria for "pathologic LIP." Overall, broad overlap was observed with the remaining study cases that failed to meet consensus criteria for "radiologic LIP" and/or "pathologic LIP." These data raise concerns about the practical use of the term LIP as currently defined. What radiologists and pathologist encounter as LIP differs remarkably, but neither "radiologic LIP" nor "pathologic LIP" present with sufficiently distinct findings to delineate such cases from other patterns of diffuse benign lymphoid proliferations. As a result of this study, we believe LIP should be abandoned as a pathologic and radiologic diagnosis.

Overcoming the Interobserver Variability in Lung Adenocarcinoma Subtyping: A Clustering Approach to Establish a Ground Truth for Downstream Applications.

CONTEXT.­: The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability. OBJECTIVE.­: To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications. DESIGN.­: Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 17 international expert lung pathologists and 1 pathologist in training. Each image was classified into one or several lung adenocarcinoma subtypes. RESULTS.­: Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes. CONCLUSIONS.­: Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.

Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney Biopsies.

BACKGROUND: Semiquantitative visual inspection for glomerulosclerosis, interstitial fibrosis, and arteriosclerosis is often used to assess chronic changes in native kidney biopsies. Morphometric evaluation of these and other chronic changes may improve the prognostic assessment. METHODS: We studied a historical cohort of patients who underwent a native kidney biopsy between 1993 and 2015 and were followed through 2021 for ESKD and for progressive CKD (defined as experiencing 50% eGFR decline, temporary dialysis, or ESKD). Pathologist scores for the percentages of globally sclerosed glomeruli (GSG), interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis (luminal stenosis) were available. We scanned biopsy sections into high-resolution images to trace microstructures. Morphometry measures were percentage of GSG; percentage of glomerulosclerosis (percentage of GSG, ischemic-appearing glomeruli, or segmentally sclerosed glomeruli); percentage of IFTA; IFTA foci density; percentage of artery luminal stenosis; arteriolar hyalinosis counts; and measures of nephron size. Models assessed risk of ESKD or progressive CKD with biopsy measures adjusted for age, hypertension, diabetes, body mass index, eGFR, and proteinuria. RESULTS: Of 353 patients (followed for a median 7.5 years), 75 developed ESKD and 139 experienced progressive CKD events. Visually estimated scores by pathologists versus morphometry measures for percentages of GSG, IFTA, and luminal stenosis did not substantively differ in predicting outcomes. However, adding percentage of glomerulosclerosis, IFTA foci density, and arteriolar hyalinosis improved outcome prediction. A 10-point score using percentage of glomerulosclerosis, percentage of IFTA, IFTA foci density, and any arteriolar hyalinosis outperformed a 10-point score based on percentages of GSG, IFTA, and luminal stenosis >50% in discriminating risk of ESKD or progressive CKD. CONCLUSION: Morphometric characterization of glomerulosclerosis, IFTA, and arteriolar hyalinosis on kidney biopsy improves prediction of long-term kidney outcomes.

Surgical Pathology of Diffuse Parenchymal Lung Disease in Patients With Psoriasis or Psoriatic Arthritis.

CONTEXT.­: Diffuse parenchymal lung disease (DPLD) is a well-recognized complication of systemic connective tissue disease (CTD) but rarely arises in patients with psoriasis or psoriatic arthritis, a poorly understood phenomenon. OBJECTIVE.­: To characterize DPLD associated with psoriasis or psoriatic arthritis, with or without prior immunomodulation. DESIGN.­: Pathology consultation files were searched for patients having psoriasis or psoriatic arthritis and DPLD. After excluding cases with active infection or smoking-related DPLD only, 44 patients (22 women; median age, 60 years; range, 23-81 years) were enrolled. Clinical history and pathology slides were reviewed. RESULTS.­: Twenty-seven of 44 patients (61%) had psoriatic arthritis; the remainder had psoriasis alone. Most presented many years later with nonspecific respiratory symptoms. Nearly one-third had no prior immunosuppression, and most had no concomitant CTD. Radiographically, ground-glass opacities, consolidation, and/or reticulation were typical. Histologically, nonspecific interstitial pneumonia and unclassifiable fibrosis were seen in 24 patients (55%) and 8 patients (18%), respectively; usual interstitial pneumonia and airway-centered fibrosis were rare. Superimposed acute lung injury was common, usually manifesting as organizing pneumonia. Lymphoplasmacytic infiltrates, lymphoid aggregates, and chronic pleuritis were frequent. Interstitial granulomas were seen in 17 patients (39%) but were usually rare, poorly formed, and nonnecrotizing. No histologic differences were apparent among patients with or without concomitant CTDs or prior therapy. CONCLUSIONS.­: Some patients with psoriasis or psoriatic arthritis develop clinically significant DPLD, even without prior therapy. Histopathologic findings mirror changes seen with other CTDs. Additional studies are warranted to clarify the association between psoriasis or psoriatic arthritis and DPLD.

Late Complications of COVID-19.

CONTEXT.­: Studies of lungs in patients with COVID-19 have focused on early findings. OBJECTIVE.­: To systematically study histopathologic and imaging features and presence of SARS-CoV-2 RNA in lung tissue from patients in later stages of COVID-19. DESIGN.­: Autopsies, explants, surgical lung biopsies, transbronchial biopsies, cryobiopsies, and needle biopsies from patients with COVID-19 whose onset of symptoms/confirmed diagnosis was more than 28 days before the procedure were studied. Available images were reviewed. Reverse transcription droplet digital polymerase chain reaction for SARS-CoV-2 RNA was performed on lung tissue. RESULTS.­: Of 44 specimens (43 patients; median age, 59.3 years; 26 [60.5%] male) features of acute lung injury (ALI) were seen in 39 (88.6%), predominantly organizing pneumonia and diffuse alveolar damage, up to 298 days after onset of COVID-19. Fibrotic changes were found in 33 specimens (75%), most commonly fibrotic diffuse alveolar damage (n = 22) and cicatricial organizing pneumonia (n = 12). Time between acquiring COVID-19 and specimen was shorter in patients with diffuse ALI (median, 61.5 days) compared with patients with focal (140 days) or no ALI (130 days) (P = .009). Sixteen (of 20; 80%) SARS-CoV-2 reverse transcription droplet digital polymerase chain reaction tests were positive, up to 174 days after COVID-19 onset. Time between COVID-19 onset and most recent computed tomography in patients with consolidation on imaging was shorter (median, 43.0 days) versus in patients without consolidation (87.5 days; P = .02). Reticulations were associated with longer time to computed tomography after COVID-19 onset (median, 82 versus 23.5 days; P = .006). CONCLUSIONS.­: ALI and SARS-CoV-2 RNA can be detected in patients with COVID-19 for many months. ALI may evolve into fibrotic interstitial lung disease.

Banff consensus recommendations for steatosis assessment in donor livers.

BACKGROUND AND AIMS: No consensus criteria or approaches exist regarding assessment of steatosis in the setting of human donor liver suitability for transplantation. The Banff Working Group on Liver Allograft Pathology undertook a study to determine the consistency with which steatosis is assessed and reported in frozen sections of potential donor livers. APPROACH AND RESULTS: A panel of 59 pathologists from 16 countries completed a questionnaire covering criteria used to assess steatosis in donor liver biopsies, including droplet size and magnification used; subsequently, steatosis severity was assessed in 18 whole slide images of donor liver frozen sections (n = 59). Survey results (from 56/59) indicated a wide variation in definitions and approaches used to assess and report steatosis. Whole slide image assessment led to a broad range in the scores. Findings were discussed at a workshop held at the 15th Banff Conference on Allograft Pathology, September 2019. The aims of discussions were to (i) establish consensus criteria for defining "large droplet fat" (LDF) that predisposes to increased risk of initial poor graft function and (ii) develop an algorithmic approach to determine fat droplet size and the percentage of hepatocytes involved. LDF was defined as typically a single fat droplet that expands the involved hepatocyte and is larger than adjacent nonsteatotic hepatocytes. Estimating severity of steatosis involves (i) low magnification estimate of the approximate surface area of the biopsy occupied by fat, (ii) higher magnification determination of the percentage of hepatocytes within the fatty area with LDF, and (iii) final score calculation. CONCLUSIONS: The proposed guidelines herein are intended to improve standardization in steatosis assessment of donor liver biopsies. The calculated percent LDF should be provided to the surgeon.

The histologic diagnosis of usual interstitial pneumonia of idiopathic pulmonary fibrosis. Where we are and where we need to go.

In the 50 years since its inception by Dr. Liebow, the diagnosis of usual interstitial pneumonia (UIP) by pathologists has changed significantly. This manuscript reviews the progressive history of the histologic diagnosis of UIP and summarizes the current state of histologic UIP and its relationship to the clinical syndrome idiopathic pulmonary fibrosis (IPF). Fibrotic lung disease mimics of UIP/IPF are reviewed and pearls for distinguishing these diseases from UIP/IPF are provided. Strategies for increasing the value of histologic assessment of biopsies in the setting of pulmonary fibrosis are also discussed.

Correlation of Chronic Histologic Changes on Preimplantation Frozen Section Biopsy With Transplant Outcomes After Deceased Donor Kidney Transplantation.

CONTEXT.­: It is unclear if preimplantation frozen section biopsy correlates with outcomes after deceased donor kidney transplantation. OBJECTIVE.­: To assess if chronic histologic changes on the preimplant frozen section correlates with graft loss and estimated glomerular filtration rate independently of kidney donor profile index (KDPI). DESIGN.­: Seven hundred three preimplantation biopsies were reviewed and a Banff sum score was calculated using glomerular sclerosis, interstitial fibrosis, vascular intimal thickening, and arteriolar hyalinosis. The posttransplant outcomes were compared for preimplantation biopsy Banff sum 0-1, 2-3, and 4-9. The cohort was also stratified by KDPI 85 or less versus more than 85. RESULTS.­: For the entire biopsy cohort, graft survival, estimated glomerular filtration rate at 1 year, and chronic changes on a 1-year posttransplant biopsy were superior in the group with preimplantation Banff sum 0-1. After stratifying by KDPI, the Banff sum no longer correlated with graft survival. In a univariate mode, using the Banff sum score as a continuous variable, a higher Banff sum score was significantly associated with graft failure (P = .03); however, after adjusting the KDPI, the Banff sum score no longer correlated with graft failure (P = .45). The 1-year estimated glomerular filtration rate and 1-year biopsy changes were superior in the group with Banff sum 0-1 only in the cohort with KDPI 85 or less. CONCLUSIONS.­: In donor kidneys used for transplant, preimplantation biopsy chronic changes correlate with estimated glomerular filtration rate and biopsy findings at 1 year, but biopsies with mostly mild chronicity and Banff sum scores less than or equal to 5 did not impact graft survival beyond KDPI.

Progressive decline of function in renal allografts with normal 1-year biopsies: Gene expression studies fail to identify a classifier.

Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c-statistic = .59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and .58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1-year biopsy and eGFR > 40) remains difficult.