IgG Endopeptidase Has Potential To Reduce Kidney Transplant Rejection

MedicalResearch.com Interview with:

Stanley C. Jordan, M.D Director, Division of Nephrology Medical Director, Kidney Transplant Program Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory Cedars-Sinai, Los Angeles, CA

Dr. Jordan

Stanley C. Jordan, M.D
DirectorDivision of Nephrology
Medical DirectorKidney Transplant Program
Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory
Cedars-Sinai, Los Angeles, CA 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is as follows: Patients who are highly HLA sensitized have antibodies to transplant targets create an immunologic barrier to transplant. Currently, there are no approved therapies for elimination of these antibodies. Desensitization is available but is not always successful and most desensitized patients are still transplanted with a positive crossmatch. Thus, many patients are not able to receive life-saving kidney transplants unless newer therapies to remove antibodies are found.

The findings of our study published in the New England Journal of Medicine revealed that the use of the enzyme from streptococcal pyogenes called IdeS® (IgG endopeptidase) is very effective in eliminating donor specific antibodies and allowing transplantation to occur. Antibodies were eliminated from one week up to two months after one treatment with Ides® allowing a safe environment for the transplant to occur. Rejections episodes did occur in some of the patients but were generally mild and easily treatable. Only one patient of 25 lost his allograft during the study. Thus, the study shows promising results for a new approach for elimination of pathogenic antibodies that did not exist before.

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High Hepatitis C Cure Rate Using Elbasvir plus Grazoprevir In Chronic Kidney Disease

MedicalResearch.com Interview with:

Annette Bruchfeld MD, PhD Senior Consultant Associate Professor Karolinska Institute Dept of Renal Medicine, M99 Karolinska University Hospital Huddinge Stockholm, Sweden

Dr. Bruchfeld

Annette Bruchfeld MD, PhD Senior Consultant
Associate Professor
Karolinska Institute
Dept of Renal Medicine, M99
Karolinska University Hospital Huddinge
Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In patients with stage 4–5 chronic kidney disease(CKD), hepatitis C virus (HCV) infection can accelerate the decline in kidney function, impair health-related quality of life (HRQOL), and decrease survival chances of both patients and grafts in transplantation recipients.

In this study additional data from patients with stage 4–5 chronic kidney disease undergoing treatment for HCV infection in the C-SURFER study, including HRQOL and resistance analyses was presented not previously reported for this patient population with gwnotype 1 infection.

The final virological analysis of this study indicated a high cure rate with sustained virological response at 12 weeks after the end of treatment (SVR12) in more than 98% of all treated patients. Even in patients with resistance-associated substitutions (RASs) the SVR was high in 11 (84·6%) of 13 patients genotype 1a infection.

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Food Costs Can Lead To Less Protein and Phosphorous in Indigent Kidney Transplant Patients

MedicalResearch.com Interview with:

Ms. Shifra Mincer Medical Student in the class of 2019 SUNY Downstate Medical School

Shifra Mincer

Ms. Shifra Mincer
Medical Student in the class of 2019
SUNY Downstate Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hypophosphatemia is commonly encountered in the post-transplant setting. Early post-transplant hypophosphatemia has been ascribed to excess FGF23 and hyperphosphaturia.

Many patients remain hypohosphatemic months or even years after their transplant and the mechanism was assumed to be the same, however, our group recently reported that patients with late post-transplant hypophosphatemia had very little phosphorous in their urine (Wu S, Brar A, Markell, MS. Am J Kidney Dis. 2016,67(5): A18). We hypothesized that they were not eating enough phosphorous to compensate for the acute phosphorous losses they experienced immediately post-transplant.

In this study, using both 3-day diet journals and 24-hour diet recall questionnaires, we found that mean intake of phosphorous and protein was barely at the Recommended Daily Allowance, and that despite 70% of the patients using EBT, 30% of those patients still reported concerns regarding food security. Patients who reported that the cost of food influenced their dietary choices ate 43% less protein (average 48,5 gms vs. 85.8 gms) and 29% less phosphorous (average 887 mg vs 1257 mg). When ability to rise from a chair over a 30 second period was evaluated, only patients who expressed food cost concerns were unable to complete the test.

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Comparison of Posttransplant Dermatologic Diseases by Race

MedicalResearch.com Interview with:
Christina Lee Chung, MD, FAAD
Associate Professor of Dermatology
Director, Center for Transplant Patients
Drexel University College of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It’s long been recognized immunosuppressed organ transplant recipients are at significantly increased risk for skin cancer and other types of skin disease.

But despite advances to improve skin cancer prevention for these patients, little is known about how skin conditions affect African-American, Asian and Hispanic transplant recipients. This is problematic given that, according to the U.S. Department of Health and Human Services, more than half of the 120,000 Americans on the waiting list for organs identify as nonwhite.

We compared medical records of 412 organ transplant recipients — including 154 white patients and 258 nonwhite (black, Asian or Hispanic) — who were referred to the Drexel Dermatology Center for Transplant Patients between 2011 and 2016. As one of the only models of its kind in the country, the center provides post-transplant dermatological care to every patient who is transplanted by and/or followed by the Drexel University and Hahnemann University Hospital Transplant Programs. That means that every patient, regardless of race, is screened annually for skin cancer, which provided a unique dataset for us to analyze.

Two hundred eighty-nine transplant recipients exhibited malignant, infectious or inflammatory conditions during their evaluation, but their primary acute diagnoses differed greatly by race. In 82 white patients, skin cancer was the most common acute problem requiring attention at first visit. Black and Hispanic patients, by contrast, were most often diagnosed with inflammatory or infectious processes, such as fungal infections, warts, eczema, psoriasis, and rashes that required immediate medical attention.

Overall, squamous cell carcinoma in situ was the most common type of skin cancer diagnosed in each racial or ethnic group. But the location of the cancerous lesions again depended on the race of the patient. Most lesions in white and Asian patients occurred in sun-exposed areas of the body, like the scalp, neck, chest and back. For black patients, the lesions were primarily found in the groin.  Moreover, six of the nine lesions found on black patients tested positive for high-risk HPV strains, suggesting an association between the virus and skin cancer for African Americans.

We also provided questionnaires to 66 organ transplant recipients to find out more about the patients’ awareness of skin cancer prevention. Seventy-seven percent of white patients were aware their skin cancer risk was increased, compared to 68 percent of nonwhites. Only 11 percent of nonwhite patients reported having regular dermatologic examinations, compared to 36 percent of whites. Finally, 45 percent of white patients but only 25 percent of nonwhite reported knowing the signs of skin cancer.

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Tocilizumab High Active For Refractory Graft vs Host Disease

MedicalResearch.com Interview with:

Dr. Alex Ganetsky

Dr. Alex Ganetsky

Alex Ganetsky, PharmD, BCOP
Clinical Pharmacy Specialist – Hematology/BMT
Hospital of the University of Pennsylvania

MedicalResearch.com: What is the background for this study? What are the main findings?

• Allogeneic hematopoietic cell transplant (HCT) recipients with steroid-refractory gastrointestinal acute graft-versus-host disease (GI-GVHD) have poor outcomes.
• There is no consensus for optimal treatment of these patients.
• We retrospectively evaluated the efficacy of tocilizumab, an interleukin-6 receptor monoclonal antibody, for the treatment of steroid-refractory GI-GVHD.
• 10/11 (91%) patients achieved a complete response after a median time of 11 days (range, 2 – 18) from tocilizumab initiation.
• The median time to response onset, defined as improvement in GVHD stage by at least 1, was 1 day (range, 1 – 6).
• At a median follow-up of 3 months (range, 1.1 – 12.8) from tocilizumab initiation, 8 of 11 patients are alive and free of the their underlying hematologic malignancy.
• No associations between serum levels of IL-6 and tocilizumab response could be identified.
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A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults

MedicalResearch.com Interview with:
Adam Johnson, MD, PhD, MBA, FACS

Thomas Jefferson University

Dr. Cataldo Doria, senior author and designer of the study, emphasized that the work was a team effort

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The goal was to develop an algorithm to identify which donors would be most suitably transplanted as dual kidneys instead of as single kidneys.

Dual kidney transplantation is a resource intensive procedure, but may make the most out of two kidneys whose function may be too marginal to transplant independently.

Currently allocation decisions are based on individual surgeon and institutional experience and without much available outcome data. This score provide decision support for which donor grafts would have the greatest benefit if transplanted as dual kidneys.

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Three Criteria To Identify Out-of-Hospital Cardiac Arrest Patients With No Chance of Survival

MedicalResearch.com Interview with:

Prof. Xavier Jouven Service de Cardiologie Hôpital Européen Georges Pompidou Paris

Prof. Xavier Jouven

Prof. Xavier Jouven
Service de Cardiologie
Hôpital Européen Georges Pompidou
Paris

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are many cardiac arrests (around 300 000 per year in United States). The possibility to collect organs from a certain proportion of those cardiac arrests represents an important opportunity to fill the gap of the organ shortage.

It is absolutely mandatory to identify patients with no chance of survival. This study showed 3 criteria which allow this early identification. Several thousands of patients die every year waiting for organ transplantation.

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After CPR, Some Donor Hearts Still Suitable For Heart Transplantation

MedicalResearch.com Interview with:

Jaimin Trivedi, MD, MPH Instructor Department of Cardiovascular and Thoracic Surgery University of Louisville Louisville, KY 40202

Dr. Jaimin Trivedi

Jaimin Trivedi, MD, MPH
Instructor
Department of Cardiovascular and Thoracic Surgery
University of Louisville
Louisville, KY 40202

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Trivedi: There is a donor heart shortage in United States and certain donor hearts are likely to be turned down because the donors required cardiopulmonary resuscitation (CPR) prior to procurement. The rationale behind conducting the study was to identify impact of donor CPR and its duration on recipient survival after transplantation.

Our findings show that presence of CPR and duration of CPR does not adversely impact the post heart transplant survival. The study also shows that ejection fraction and peak cardiac troponins between the CPR and non-CPR donors were comparable at time of transplant suggesting recovery of cardiac function.

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Females Tolerate Ischemia After Kidney Transplantion Better Than Males

MedicalResearch.com Interview with:

Matthew Levine, MD, PhD Associate professor of Transplant Surgery Perelman School of Medicine University of Pennsylvania

Dr. Mathew Levine

Matthew Levine, MD, PhD
Assistant Professor of Transplant Surgery
Perelman School of Medicine
University of Pennsylvania

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Levine: This work stemmed from a known finding that female mice tolerate kidney injury better than males and this is true of mice that share exactly the same genes.  Therefore, the gender difference was the driving factor.  My basic science laboratory works at the intersection between scientific discovery and clinical application and this led us to question whether the same phenomenon was true in humans and whether we could identify a way in which this could be used to improve injury tolerance above what is seen in untreated subjects.  What we found was that the hormonal environment seems to impact ischemia tolerance, with female environment being protective and the male environment worsening injury tolerance in ischemia models where blood flow is interrupted and then restored.  The kidneys seemed to adapt to take on the injury response of the host after transplantation, indicating that the differences were not forged into the kidney itself and therefore could be altered.  We then found that estrogen therapy improved kidney injury tolerance when given to female mice in advance of injury, but no effect was seen in male mice.  And most importantly, we found that in a large cohort of transplant recipients that female recipients had better injury tolerance after transplant than male recipients, as shown by ability to avoid dialysis in the first week after transplant, otherwise known as delayed graft function (DGF). This is a fairly major finding since it has not been observed in the literature despite several decades of transplant data being carefully studied.

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Kidney Transplant Patients May Not Be Protected From HPV Strains in Vaccines

MedicalResearch.com Interview with:

Dr. Delphine Robotham MD Division of Pediatric Nephrology Johns Hopkins University School of Medicine Baltimore, Maryland

Dr. Robotham

Dr. Delphine Robotham MD
Division of Pediatric Nephrology
Johns Hopkins University School of Medicine
Baltimore, Maryland

Medical Research: What is the background for this study? What are the main findings?

Response: Cervical cancer is the second most common cancer in women worldwide and is almost entirely caused by high risk HPV genotypes.  Vaccines to high risk HPV genotypes have shown great success in protecting healthy women from the sequelae of infection, including cervical cancer and genital warts. Young women with a kidney transplant as well as those with chronic kidney disease have abnormal immune systems and as a result have a significantly increased burden of HPV-related disease making the potential health benefits of the HPV vaccine substantial in this particularly vulnerable population.  This study examined the immune response to the HPV vaccine among girls and young women with kidney disease.

The goal of this research was to determine if girls and young women with chronic kidney disease (abnormal kidney function, on dialysis, or post kidney transplant) showed evidence of immune response to the quadrivalent HPV vaccine.  Immune response was determined by measuring the amount of antibody made by the patients against each of the 4 HPV genotypes included in the vaccine.  There are established thresholds of antibody above which patients are believed to have protection from infection.  We found that study participants with chronic kidney disease and those on dialysis had antibody levels above the threshold, indicating the vaccine should be effective in protecting them from HPV related disease.  A significant proportion of patients with kidney transplants showed evidence of inadequate antibody response.  This is important information as it means patients with a kidney transplant, whom we know are at increased risk of developing cervical cancer from HPV infection, may not be protected from HPV infections from the HPV genotypes included in the vaccine.
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