J Friedewald

Publications of J Friedewald

• An update on risk evaluation and mitigation strategies in transplantation.

  Authors: S Gabardi, P F Halloran, J Friedewald

  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 01/2012; 12(1):257-8.

• Managing risk in developing transplant immunosuppressive agents: the new regulatory environment.

  Authors: S Gabardi, P F Halloran, J Friedewald

  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 08/2011; 11(9):1803-9.

  Recent adverse experience with a number of medications after their approval, including rofecoxib, erythropoietin and rosiglitazone, has led to an increased focus on safety in drug development in theRecent adverse experience with a number of medications after their approval, including rofecoxib, erythropoietin and rosiglitazone, has led to an increased focus on safety in drug development in the postmarketing setting. The result was implementation of new measures to address perceived deficits in the system for drug approval and postmarketing safety. The resulting legislation introduced risk evaluation and mitigation strategies (REMS) and postmarketing requirements (PMRs). Although these initiatives have the potential to improve patient outcomes, many healthcare practitioners are not yet familiar with REMS or PMRs or may have misconceptions regarding their goals and limitations. REMS is a program to manage known or potential serious risks associated with pharmaceutical products and is designed to ensure that the benefits of using a particular product outweigh the risks. Although the concepts underlying REMS and PMRs are not novel, the FDA now has legal authority to enforce such measures as part of the drug approval process. This article outlines the objectives and limitations of REMS and PMRs, with a focus on how these regulatory measures may impact the clinical specialty of transplantation. The article also briefly describes efforts to address aspects of drug safety less amenable to management through REMS and PMRs.

• Clinical and plasma proteomic markers correlating with chronic kidney disease after liver transplantation.

  Authors: J Levitsky, D R Salomon, M Abecassis, P Langfelder, S Horvath, J Friedewald, E Wang, S M Kurian, T Mondala, S Gil, R McDade, K Ballard, L Gallon

  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 07/2011; 11(9):1972-8.

  Chronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristicsChronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristics and biomarkers diagnostic of CKD to enable early diagnosis allowing preemptive interventions, as well as mechanistic insights into the progression from kidney injury to irreversible kidney failure. We analyzed 342 patients who had baseline glomerular filteration rate (GFR) >60 at the time of LT and are now >3 years post-LT. Risk factors for post-LT CKD were compared between three different groups defined by current GFR: >90 (n = 40), 60-90 (n = 146) and <60 (n = 156) mL/min. Age, cyclosporine use and pre-LT GFR were independently associated with new onset CKD. A subset (n = 64) without viral/immune disease or graft dysfunction underwent multianalyte plasma proteomic evaluations for correlation with CKD. Plasma proteomic analysis of two independent cohorts, test (n = 22) and validation (n = 42), identified 10 proteins highly associated with new onset CKD. In conclusion, we have identified clinical characteristics and a unique plasma proteomic signature correlating with new onset CKD after LT. These preliminary results are currently being validated in a prospective, multicenter study to determine if this signature precedes the onset of CKD and resolves with early interventions aimed at preserving kidney function.

• Perception Versus Reality?: Virtual Crossmatch-How to Overcome Some of the Technical and Logistic Limitations.

  Authors: A R Tambur, D S Ramon, D B Kaufman, J Friedewald, X Luo, B Ho, A Skaro, J Caicedo, D Ladner, T Baker, J Fryer, L Gallon, J Miller, M M Abecassis, J Leventhal

  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 07/2009;

  The goal of this work was to evaluate concordance between (a) actual flow cytometric crossmatch (FCXM) that is performed by the OPO laboratory servicing our transplant center and (b) virtual XM (vXM)The goal of this work was to evaluate concordance between (a) actual flow cytometric crossmatch (FCXM) that is performed by the OPO laboratory servicing our transplant center and (b) virtual XM (vXM) prediction based on antibody identification by solid-phase methods performed in our laboratory. A total of 1586 FCXM, performed between June 2007 and September 2008, between all potential deceased donors in our region and sera from patients awaiting kidney or kidney-pancreas transplant, listed at Northwestern Memorial Hospital were evaluated. A key finding of this analysis was the understanding that a thorough vXM cannot be performed in some donor/recipient pairs due to the lack of certain antibody profile data specific to the donor in question. Obtaining more in depth and stringent information regarding antibody specificities, we demonstrate an excellent sensitivity and specificity of the vXM assays- 86.1% and 96.8%, respectively, with a positive likelihood ratio and negative likelihood ratios of 26.9 and 0.14, respectively. The vXM can serve as an outstanding tool to predict HLA compatibility between donor and recipient, with the caveat that the presence/absence of all antibodies against the potential donor and their strength have been thoroughly investigated.