Beyond Histology

Mannon, Roslyn B.; Kirk, Allan D.

doi:10.2215/cjn.01681105

Cited by 29 publications

(18 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These methods include gene and protein expression profiles in the peripheral blood, the urine, and the graft itself, all compartments relevant to the alloimmune response (reviewed in reference [16]). The recent sequencing of the human genome also provides a unique opportunity to develop genomic (17) and proteomic approaches (18) to increase our understanding of events that lead to TA/IF.…”

Section: Role Of the Allograft Biopsymentioning

confidence: 99%

Late Kidney Allograft Loss

Jevnikar

Mannon

2008

Clinical Journal of the American Society of Nephrology

Self Cite

103

View full text Add to dashboard Cite

Despite dramatic improvements in immunosuppression, late graft loss after kidney transplantation remains a common and difficult problem. Histologic evaluation may reveal changes related to BK polyomavirus infection, hypertension, or calcineurin inhibitor toxicity, which can help to guide therapy. The designation chronic allograft nephropathy should thus be reserved for biopsies with tubular atrophy and interstitial fibrosis without an apparent cause. Although the cause clearly includes both antigen-dependent and antigen-independent events, the approach remains largely to exclude immune mechanisms. Although this review discusses the potential contribution of antibody to chronic injury, it focuses on the basic elements of kidney injury, the role of parenchymal cells in promoting injury, and the proliferative and inflammatory responses that accompanying injury. Strategies to manage these recipients include close attention to accompanying hypertension, diabetes, and hyperlipidemia, as well as consideration for altering immunosuppression; however, therapies that limit epithelial-to-mesenchymal transition or directly block fibrosis pathways may reduce chronic allograft fibrosis and may prove to be useful. Understanding the basic pathogenesis sufficiently to allow early intervention may finally benefit patients who are at high risk for tubular atrophy and interstitial fibrosis and promote their long-term graft function.

show abstract

Section: Role Of the Allograft Biopsymentioning

confidence: 99%

Late Kidney Allograft Loss

Jevnikar

Mannon

2008

Clinical Journal of the American Society of Nephrology

Self Cite

103

View full text Add to dashboard Cite

show abstract

“…Histological examination of native kidney biopsy remains the gold standard to determine pathology and predict long-term native kidney function [5]. In line with this, IB of the donor kidney was initially suggested by Gaber et al [6] for the prediction of future allograft function, and thereafter by many researchers.…”

Section: Evolution Of the Concept Of Implantation Biopsy Conceptmentioning

confidence: 99%

Can Donor Implantation Renal Biopsy Predict Long-Term Renal Allograft Outcome?

El-Husseini¹,

Sabry²,

Zahran³

et al. 2007

Am J Nephrol

View full text Add to dashboard Cite

Background: Donor kidney implantation biopsy (IB) is performed on a regular basis, particularly as part of clinical studies. Objective: To determine the utility of donor implantation renal biopsy to predict the long-term renal allograft outcome. Methods: A Medline search for studies in English was performed with the following key words: implantation biopsy, renal transplantation and long-term outcome. Results: Sixteen trials involving 8,122 kidney transplants were identified, of which 6 were prospective studies. The histological abnormalities were scored mainly by the Banff schema and the graft outcome was defined either by delineating the delta changes in the pathology score or glomerular filtration rate. Normal histology with a well-functioning renal allograft had a favorable outcome. The extent to which the baseline tubular atrophy, interstitial fibrosis, glomerulosclerosis and vascular changes had on the long-term outcome varied from one study to another. Conclusion: Abnormal IB has a better chance of predicting early graft outcome. The review questions the current wisdom for routine IB on all donors. In some donor kidneys, a biopsy provides significant prognostic information, such as older donor kidney, those with history of hypertension, diabetes, cardiovascular disease, and kidneys with abnormal creatinine. Future research on IB is necessary to find a more useful method to predict the long-term transplant outcome.

show abstract

“…PCR based assays, such as used herein, offer the potential of cost effectiveness, repeatability, and rapidity. 45 Additionally, given the relatively long-term survival of renal allografts, prospective application of such models to transplant biopsies may allow for early diagnosis, therapy alterations, and guidance in clinical trials. 2,46 Admittedly, this study is limited by the current dataset size and disease process.…”

Section: Discussionmentioning

confidence: 99%

Probabilistic (Bayesian) Modeling of Gene Expression in Transplant Glomerulopathy

Elster

Hawksworth

Cheng

et al. 2010

The Journal of Molecular Diagnostics

Self Cite

View full text Add to dashboard Cite

Transplant glomerulopathy (TG) is associated with rapid decline in glomerular filtration rate and poor outcome. We used low-density arrays with a novel probabilistic analysis to characterize relationships between gene transcripts and the development of TG in allograft recipients. Retrospective review identified TG in 10.8% of 963 core biopsies from 166 patients; patients with stable function were studied for comparison. The biopsies were analyzed for expression of 87 genes related to immune function and fibrosis by using real-time PCR , and a Bayesian model was generated and validated to predict histopathology based on gene expression. A total of 57 individual genes were increased in TG compared with stable function biopsies (P < 0. Long-term kidney allograft function continues to improve only modestly, despite dramatic improvements in acute rejection rates and short term patient and graft survivals. Despite its limitations, measurement of serum creatinine remains the primary monitoring modality following kidney transplantation. Significant changes in serum creatinine, and/or the development of proteinuria, result in a series of maneuvers to define the many potential etiologies of acute and chronic allograft dysfunction. Allograft biopsy is the "gold-standard" of these maneuvers, although morphological analysis may not easily distinguish these etiologies. Furthermore, the analysis may be limited in regards to prognostic importance and functional outcome. Thus, identification of biomarkers of allograft failure and the development of tools for their interpretation is of critical interest, both in providing disease detection in a more sensitive and specific fashion, and in allowing sufficient lead time for intervention. Additionally, such markers may allow for risk assessment and medical-regimen tailoring that is personalized to provide optimum outcomes.Transplant glomerulopathy (TG) is a disease of the kidney allograft initiated by endothelial injury. Morphologically, there is widening of the subendothelial space with accumulation of debris, mesangial interpositioning, and matrix deposition in the glomerular capillary wall, as well as capillary wall double-contouring in the absence of immune complex Supported in part by the US Navy Bureau of Medicine and Surgery and by the intramural research program of the National Institute of Diabetes Digestive and Kidney Diseases Z01-DK062008 (R.B.M.).The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government. This work was prepared as part of our official duties. Title 17 U.S.C. §105 provides that "Copyright protection under this title is not available for any work of the United States Government." Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties.The author contributions are as follows: conception and design: E.A.E., ...

show abstract

Beyond Histology

Cited by 29 publications

References 74 publications

Late Kidney Allograft Loss

Late Kidney Allograft Loss

Can Donor Implantation Renal Biopsy Predict Long-Term Renal Allograft Outcome?

Probabilistic (Bayesian) Modeling of Gene Expression in Transplant Glomerulopathy

Contact Info

Product

Resources

About