Recent Publications: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College

I. Published in Transplantation on August 27, 2008

Type of Submission: Original Article

Title: Epidemiology of BK Virus in Renal Allograft Recipients: Identification of Steroid Maintenance Therapy and Rabbit Anti-Human Thymocyte Globulin Induction as Independent Risk Factors for BKV replication

Authors: Darshana Dadhania, Catherine Snopkowski, Ruchuang Ding, Thangamani Muthukumar, Christina Chang, Meredith Aull, Jun Lee, Vijay K. Sharma, Sandip Kapur, and Manikkam Suthanthiran

ABSTRACT

Background: Identification of risk factors for BKV replication may improve transplant outcome. We investigated the impact of immunosuppressive drugs on the prevalence of BKV replication in recipients of human renal allografts.

Methods: One hundred twenty renal allograft recipients were studied prospectively at one, three, and six months post-transplantation to identify risk factors for BKV replication. BKV replication was quantified by measurement of urinary cell BKV VP1 mRNA levels using BKV specific primers and TaqMan® probe in a real-time quantitative PCR assay. Levels of urinary cell mRNA for granzyme B, CD103 and TGF-β1 were measured to ascertain whether BKV replication is associated with an inflammatory signature.

Results: The prevalence of BKV replication increased over time and was highest at six-months compared to 1 or 3 months post-transplantation (P<0.001 ). A logistic regression model analysis demonstrated that steroid maintenance therapy (odds ratio: 8.3, P= 0.003) and induction with rabbit anti-human thymocyte globulin (ATG) (odds ratio: 5.8, P= 0.008) were independent risk factors for BKV replication. Neither mycophenolate mofetil dose nor tacrolimus dose or trough levels were different between those with or without BKV replication. The development of acute rejection or anti-rejection treatment with methylprednisolone did not increase the risk of BKV replication. BKV replication was associated with heightened levels of urinary cell mRNA for granzyme B (P<0.002), CD103 (P<0.005) but not for TGF-β1 (P>0.05).

Conclusions: Steroid maintenance therapy and induction with ATG are independent risk factors for BKV replication in renal allograft recipients treated with tacrolimus and mycophenolate mofetil.


II. Published in Transplantation on July 27, 2008

Type of Submission: Overview

Title: Noninvasive Prediction of Organ Graft Rejection and Outcome Using Gene Expression Patterns

Authors: Dany Anglicheau and Manikkam Suthanthiran

ABSTRACT

Development of predictive, diagnostic and prognostic biomarkers of allograft status and outcome is important and challenging, and may be rewarded with individualized therapy of the organ graft recipient. Herein, we summarize noninvasive mRNA profiling studies for ascertaining allograft status and outcome. Nucleic acid based biomarkers of allograft status have been developed by a number of laboratories but the studies have primarily been single center investigations. Ongoing multi-center trials including the Clinical Trials in Organ Transplantation (https://www.ctotstudies.org) should help further define the clinical utility of noninvasively developed mRNA profiles as biomarkers of allograft status and outcome.


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