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Variation in Assessing Renal Allograft Rejection: A National Assessment of Nephrology Practice.

ABSTRACT: Background:The clinical utility of early detection and treatment of allograft rejection is well-established. Despite frequent testing called for by standard of care protocols, the five-year kidney allograft survival rate is estimated to be as low as 71%. Herein, we report on posttransplant care provided to kidney allograft recipients by board-certified nephrologists in the United States. Methods:We measured clinical practice in a representative sample of 175 practicing nephrologists. All providers cared for simulated patients' status after renal transplant ranging from 30-75 years in age and 3-24 months after transplant. Our sample of nephrologists cared for a total of 525 allograft cases. Provider responses to the cases were reviewed by trained clinicians, and care was compared to evidence-based care standards and accepted standard of care protocols. Results:Among nephrologists, practicing in settings ranging from transplant centers to community practice, we found that the clinical workup of kidney injury in posttransplant patients is highly variable and frequently deviates from evidence-based care. In cases with pathologic evidence of rejection, only 29.1% (102/350) received an appropriate, evidence-based biopsy, whereas, in cases with no pathological evidence of rejection, 41.3% (45/109) received low-value, unnecessary biopsies. Conclusion:Clinical care in the posttransplant setting is highly variable. Biopsies are often ordered in cases where their results do not alter treatment. Additionally, we found that misdiagnosis was common as were opportunities for earlier biopsy and detection of rejection. This evidence suggests that better diagnostic tools may be helpful to determine which transplant patients should be biopsied and which should not. This study suggests that nephrologists and transplant patients need better tests than creatinine and proteinuria and less invasive approaches than routine biopsies to determine when transplant patients should be investigated for rejection and additional treatment.

SUBMITTER: Peabody J

PROVIDER: S-EPMC6535838 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Variation in Assessing Renal Allograft Rejection: A National Assessment of Nephrology Practice.

Peabody John J Billings Paul P Valdenor Czarlota C Demko Zach Z Moshkevich Solomon S Paculdo David D Tran Mary M

International journal of nephrology 20190513

<h4>Background</h4>The clinical utility of early detection and treatment of allograft rejection is well-established. Despite frequent testing called for by standard of care protocols, the five-year kidney allograft survival rate is estimated to be as low as 71%. Herein, we report on posttransplant care provided to kidney allograft recipients by board-certified nephrologists in the United States.<h4>Methods</h4>We measured clinical practice in a representative sample of 175 practicing nephrologis ...[more]

PMID: 31214362

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Project description:The data set contains 67 array (lymphochip cDNA array), published in N Engl J Med 2003 Jul 10;349(2):125-38. PMID: 12853585. TITLE: Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. BACKGROUND: The causes and clinical course of acute rejection vary, and it is not possible to predict graft outcome reliably on the basis of available clinical, pathological, and genetic markers. We hypothesized that previously unrecognized molecular heterogeneity might underlie some of the variability in the clinical course of acute renal allograft rejection and in its response to treatment. METHODS: We used DNA microarrays in a systematic study of gene-expression patterns in biopsy samples from normal and dysfunctional renal allografts. A combination of exploratory and supervised bioinformatic methods was used to analyze these profiles. : We found consistent differences among the gene-expression patterns associated with acute rejection, nephrotoxic effects of drugs, chronic allograft nephropathy, and normal kidneys. The gene-expression patterns associated with acute rejection suggested at least three possible distinct subtypes of acute rejection that, although indistinguishable by light microscopy, were marked by differences in immune activation and cellular proliferation. Since the gene-expression patterns pointed to substantial variation in the composition of immune infiltrates, we used immunohistochemical staining to define these subtypes further. This analysis revealed a striking association between dense CD20+ B-cell infiltrates and both clinical glucocorticoid resistance (P=0.01) and graft loss (P<0.001). CONCLUSIONS: Systematic analysis of gene-expression patterns provides a window on the biology and pathogenesis of renal allograft rejection. Biopsy samples from patients with acute rejection that are indistinguishable on conventional histologic analysis reveal extensive differences in gene expression, which are associated with differences in immunologic and cellular features and clinical course. The presence of dense clusters of B cells in a biopsy sample was strongly associated with severe graft rejection, suggesting a pivotal role of infiltrating B cells in acute rejection. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: normal vs disease Keywords: disease_state_design

Project description:Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change >or=1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and beta(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring.

Dataset Information

Variation in Assessing Renal Allograft Rejection: A National Assessment of Nephrology Practice.

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Variation in Assessing Renal Allograft Rejection: A National Assessment of Nephrology Practice.

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