Author Interviews, Brigham & Women's - Harvard, Kidney Disease, Transplantation / 12.03.2021 Interview with: Jamil R. Azzi MD Associate Professor of Medicine, Harvard Medical School Medical Director, Vascularized Composite Allotransplantation Associate Director, Kidney and Pancreas Transplantation Director, Kidney Transplant Fellowship Engineering in Medicine, Brigham and Women’s Hospital Renal Division, Brigham and Women's Hospital What is the background for this study? Would you explain what is meant by an exosome?  Response: Kidney transplant recipients are always at risk of developing rejection where the immune system recognizes the transplanted kidney as “foreign body” and attacks it. The risk is up to 20% the first year after transplant and many more develop chronic rejection which ultimately leads to kidney failure. Currently, most clinicians monitor for kidney rejection by measuring serum creatinine and urine protein. However, creatinine is neither sensitive nor specific for rejection. On the other hand, performing kidney biopsies to make accurate diagnosis of rejection is invasive and has many complications. In our study, when clinicians decided on performing biopsies based on the clinical informations they have including changes in serum creatinine, the biopsies did not show rejection in almost 70% of the cases. Furthermore, serum creatinine can remain stable while the patient may be undergoing a rejection (subclinical rejection). In fact, some centers currently perform routine biopsies at different time points for all their patients regardless of creatinine despite the high risks, costs and inconveniences of doing biopsies. Out of this frustration with the current tools, we have been working on novel technologies to diagnose rejection through the urine. The idea started from the bench as we were studying exosomes, those are tiny vesicles (less than 100 nm in size) released by all cells. We were interested on how immune cells communicate via those vesicles so we developed assays to identify them. We then showed that if immune cells are invading the kidney during rejection, vesicles derived from those immune cells are found in the urine. This gave us the idea of developing a urine test based on these findings. (more…)
Author Interviews, Kidney Disease / 16.10.2020 Interview with: Mallika Mendu, MD, MBA MedicalDirector of Clinical Operations Brigham and Women’s Hospital What is the background for this study? What are the main findings? Response: African-Americans with chronic kidney disease have poorer outcomes with respect to hypertension control, timely nephrology referral, progression to end stage renal disease, placement of vascular access and transplantation compared to other racial groups. For the past two decades a race multiplier has been applied in equations that estimate glomerular filtration rate (a proxy for kidney function) for African-Americans. We sought to determine whether what the impact of the race multiplier term was on care delivered to African-Americans, by using our health system-wide CKD registry. We were particularly focused on advanced CKD patient outcomes, knowing that there are health disparities that could be potentially exacerbated.

The original CKD-EPI and MDRD studies showed an association between African-American race with higher measured GFR at the same blood creatinine concentration. However, there have been concerns raised about the application of the race multiplier to all African-American patients. First, there is no clear biological explanation for the association, the identification of Black race was unclear in some of the cohorts used in these studies, and there is vast genetic and ancestral heterogeneity among those who self-identify as black. The use of the race multiplier also ignores the fact that race is a social, not biological construct.

We found that with the removal of the race multiplier, up to one in every three African-American patients would be reclassified as having a more severe stage of CKD, with one-quarter of African-American patients going from stage 3 to stage 4. We also found that with the removal of the race multiplier, 64 patients would have had an eGFR <20, the threshold for referral for kidney transplant, and none of these patients were referred, evaluated or waitlisted for transplant. This is in contrast, to those African-American patients with an eGFR <20 with the race multiplier applied, who had a higher odds of being referred, evaluated or waitlisted for transplant compared to other racial groups (Odds ratio of 2.28, compared to White cohort).

Author Interviews, Kidney Disease, Transplantation / 09.10.2020 Interview with: Jim Gleason, National President of Transplant Recipients International Organization (TRIO), discusses what organ transplant patients are experiencing during the pandemic, and some tips they ought to consider to help ease some of the burden. Mr. Gleason also discusses his role in the development of the recently released AlloCare app is in the AppStore -- – to help post-transplant recipients navigate their day-to-day health. Would you describe your journey with organ transplantation? Mr. Gleason: I was diagnosed with heart failure at the age of 49, 2 years later listed with Penn Medicine in Philadelphia in September of 1994, and received my donor heart on October 19, 1994. After I received my transplant, I was home from the hospital 7 days later and able to return to work in 3 months as a computer manager with Unisys Corp in Blue Bell, PA, where I worked for the next dozen years before my retirement. Once retired, I dedicated my time to raising awareness of the need for organ donation and the success of transplants ever since. Today, 26 active and fulfilled years with my new heart and gift of life, I am able to live life to its fullest at age 77. I am now also coincidentally married to an organ donor of 15 years, who donated her 13-year-old son’s organs when he was hit by a car on his bike back in 1997.  (more…)
Author Interviews, Gout, Kidney Disease, Rheumatology, Transplantation / 10.11.2019 Interview with: Megan Francis-Sedlak, PhD Director of Medical Affairs Horizon Therapeutics Lake Forest, Illinois What is the background for this study? Response: The prevalence of gout is more than ten-fold greater among patients who have undergone a kidney transplant than the general population as post-transplant medications to prevent organ rejection can contribute to increased uric acid levels. Overall studies have shown this can lead to higher rates of uncontrolled gout among this vulnerable population with organ transplants. While we have seen higher mortality rates for patients who have received a kidney transplant with uncontrolled gout compared to kidney transplant patients without uncontrolled gout, we wanted to evaluate the impact of gout on transplant-related complications to better inform patient care and treatment approaches.  (more…)
Author Interviews, Emory, Health Care Systems, JAMA, Kidney Disease, Transplantation / 11.09.2019

 A retraction and replacement have been issued due to a major coding error that resulted in the reporting of incorrect data in this study surrounding the difference in transplant rates between for-profit and non-profit dialysis centers. Please see link below:

Bauchner H, Flanagin A, Fontanarosa PB. Correcting the Scientific Record—Retraction and Replacement of a Report on Dialysis Ownership and Access to Kidney Transplantation. JAMA. 2020;323(15):1455. doi:10.1001/jama.2020.4368 Interview with: Rachel Patzer, PhD, MPH Associate Professor Director, Health Services Research Center Department of Medicine Department of Surgery Emory University School of Medicine What is the background for this study? Response: We know that historically, for-profit dialysis facilities have been shown to have lower rates of kidney transplantation than patients who receive treatment in non-profit dialysis facilities. However, these studies are outdated, and did not examine access to living donor transplantation or include the entirety of the end-stage kidney disease population  (more…)
Author Interviews, JAMA, Kidney Disease, Transplantation / 26.08.2019 Interview with: Alexandre Loupy, MD PhD Nephrologist, Department of Nephrology & Kidney Transplantation Necker Hospital, Paris Head of the Paris Transplant Group (Inserm) What is the background for this study? Response: The lack of organs for kidney transplantation is a major public health problem across the world, due to its attributable mortality and excess cost to healthcare systems while waitlisted patients are maintained on chronic dialysis. Nearly 5,000 people in the US and 3,500 people in Europe die each year while waiting for a kidney transplant. Yet in the US, over 3,500 donated kidneys are discarded annually, representing almost 18% of the available organs, while the discard rate in France is only 6,8%, though these countries have similar organ allocation systems and offer the same treatments to patients after transplant. We thus compared the use of donated kidneys in the US to France from 2004-2014 in much more depth, using a new approach based on validated analytic methods and computer simulation.  (more…)
Author Interviews, Kidney Disease / 06.06.2019 Interview with: Rita R. Alloway, PharmD, FCCP Research Professor of Medicine Director, Transplant Clinical Research University of Cincinnati College of Medicine, Department of Internal Medicine Division of Nephrology Kidney C.A.R.E. Program (Clinical Advancement, Research & Education) Cincinnati OH 45267 What is the background for this study? Response: Transplant recipients are required to take lifelong immunosuppression to sustain the function of their transplant.  Unfortunately these immunosuppressants have significant side effects.  The most significant of these side effects are worsening kidney function, hypertension, hypercholesterolemia, post transplant diabetes, tremors and headaches.  Researchers focused on improving post transplant outcomes are looking for immunosuppressant regimens with similar efficacy while minimizing harmful side effects. Tacrolimus and steroids are the immunosuppressants associated with the worst side effect profiles.  This study eliminated both of these immunosuppressants and replace tacrolimus with belatacept.  Belatacept is a once monthly intravenous infusion with a more favorable side effect profile compared to tacrolimus.  In addition, since it is a monthly infusion, adherence can improved compared to an oral medication taken twice daily. (more…)
Author Interviews, JAMA, Race/Ethnic Diversity, Surgical Research, Transplantation, Yale / 09.04.2019 Interview with: Sanjay Kulkarni, MD MHCM FACS Associate Professor of Surgery & Medicine Surgical Director – Kidney Transplant Program Medical Director – Center for Living Organ Donors Scientific Director – Yale Transplant Research New Haven, CT 06410 What is the background for this study? Response: The kidney allocation system changed in December of 2014. The aim of the new system was to increase transplant in patients who were highly sensitized (difficult matches based on reactive antibodies) and to improve access to underserved populations. (more…)
Author Interviews, Cost of Health Care, Kidney Disease, Medicare, Transplantation / 07.03.2019 Interview with: Allyson Hart MD MS Department of Medicine, Hennepin Healthcare, University of Minnesota Minneapolis, Minnesota What is the background for this study? What are the main findings? Response: Kidney transplantation confers profound survival, quality of life, and cost benefits over dialysis for the treatment of end-stage kidney disease. Kidney transplant recipients under 65 years of age qualify for Medicare coverage following transplantation, but coverage ends after three years for patients who are not disabled. We studied 78,861 Medicare-covered kidney transplant recipients under the age of 65, and found that failure of the transplanted kidney was 990 percent to 1630 percent higher for recipients who lost Medicare coverage before this three-year time point compared with recipients who lost Medicare on time. Those who lost coverage after 3 years had a lesser, but still very marked, increased risk of kidney failure. Recipients who lost coverage before or after the three-year time point also filled immunosuppressive medications at a significantly lower rate than those who lost coverage on time. (more…)
Author Interviews, Dermatology, JAMA, Kidney Disease, Melanoma, Transplantation / 11.02.2019 Interview with "Kidney Model 9" by GreenFlames09 is licensed under CC BY 2.0. To view a copy of this license, visit: JSextonMD, PhD Department of Nephrology and Kidney Transplantation Beaumont Hospital Royal College of Surgeons in Ireland Dublin, Ireland What is the background for this study? What are the main findings?  Response: Patients who receive a kidney transplant as treatment for end stage kidney disease are at risk of malignancy due to immunosuppression. In contrast to other solid organ transplant types, when kidney transplants fail it is possible for recipients to return to dialysis. Immunosuppression is usually reduced or completely stopped when  the allograft fails due to the risk of infection on dialysis. We decided to investigate what the trajectory of risk for non-melanoma skin cancer and invasive cancers overall (composite group) looked like for patients who have received multiple consecutive kidney transplants with intervening periods of graft failure. We compared cancer risk during periods of allograft failure and periods of functioning kidney transplants.   (more…)
Author Interviews, Johns Hopkins, Kidney Disease, Transplantation / 18.12.2018 Interview with: Chirag R Parikh, M.B.B.S., Ph.D. Director,Division of Nephrology Professor of Medicine School of Medicine, Johns Hopkins University Baltimore, Maryland 21287 What is the background for this study? Response: The initial study idea stemmed from our earlier cohort studies of predictors of delayed graft function after kidney transplantation.  We previously found that kidneys from donors with Acute Kidney Injury (AKI) were more often discarded than kidneys from donors without AKI, and transplanted donor AKI kidneys were at increased risk for delayed graft function. It was important to determine whether that increased risk for delayed graft function also translated into worse long-term outcomes for recipients of kidneys from donors with AKI. (more…)
Annals Internal Medicine, Author Interviews, Hepatitis - Liver Disease, Kidney Disease, Transplantation / 18.07.2018 Interview with: Mark H. Eckman, MD Posey Professor of Clinical Medicine Director, Division of General Internal Medicine Director, Center for Clinical Effectiveness University of Cincinnati Medical Center Cincinnati, OH What is the background for this study? Response: People who are infected with hepatitis C virus and have kidney failure need a kidney transplant. Recent studies have found that it is possible to transplant kidneys from donors who are infected with hepatitis C virus into patients who need a transplant and are already infected with the virus. In addition, drugs are available to cure most patients of hepatitis C virus, including those who have kidney failure. Infected patients who need a kidney transplant have 2 options. One option is to receive an infected kidney and then use drugs after the transplant to cure themselves and the transplanted kidney of the virus. Another option is to use the drugs first to get rid of the virus and then to receive a kidney from a donor who does not have hepatitis C virus infection. For the more than 500,000 patients receiving dialysis for end-stage renal disease (ESRD), less than 4% receive kidney transplants. Because of the limited organ availability, hemodialysis is the final treatment for most patients with ESRD. Of the 10% or so of U.S. patients receiving dialysis who are infected with the hepatitis C virus (HCV), some are willing to accept HCV-infected kidneys, in part, because the wait times for such kidneys are shorter than those for HCV-uninfected kidneys. Because the yearly mortality rate for patients receiving hemodialysis is so high, between 4% and 16%, reducing the time to kidney transplant can have a dramatic effect on both survival and quality of life. Because it may not be possible to do this type of research with actual people, we created a model that allowed us to estimate possible outcomes without using actual people. The model was a computer program that combined the best available information to approximate what might happen to participants in a real-world clinical trial. (more…)
Author Interviews, JAMA, Johns Hopkins, Kidney Disease, Transplantation / 23.01.2018 Interview with: Tanjala S. Purnell, PhD MPH Assistant Professor of Surgery, Epidemiology, and Health Behavior and Society Core Faculty, Epidemiology Research Group in Organ Transplantation Johns Hopkins University Associate Director for Education and Training, Johns Hopkins Center for Health Equity Member, OPTN/UNOS Minority Affairs Committee What is the background for this study?
  • Our study was motivated by the fact that we know live donor kidney transplants are associated with longer life expectancy and higher quality of life than deceased donor kidney transplants or long-term dialysis treatment. We also know that Black and Hispanic adults are more likely than White adults to have end-stage kidney disease but are less likely than White patients to receive live donor kidney transplants.
  • Over the last 2 decades, there have been several transplant education programs implemented within transplant centers and dialysis centers, and legislative policies enacted to improve overall access to live donor kidney transplants for patients. We wanted to see whether these programs and policies resulted in narrowed racial and ethnic disparities in access to live donor kidney transplants in the United States. 
Author Interviews, Kidney Disease, Transplantation / 04.04.2017 Interview with: Amanda Miller, MD, FRCPC Dalhousie University Transplant Nephrology What is the background for this study? What are the main findings? Response: Earlier studies have shown that there may be a higher risk of kidney transplant failure if a kidney donor is smaller than their recipient. This may be due to increased strain on the relatively smaller transplanted kidney. Very few studies have investigated outcomes associated with donor and recipient weight mismatch measured directly by differences in body weight however. There is also a suggestion that sex mismatch between kidney donor and recipient may lead to worse outcomes post-transplant, however results from earlier studies have been controversial and conflicting. The combined effect of weight and sex matching/mismatching between kidney donor and recipient (two very important and physiologically relevant factors) has not been rigorously studied previously. Thus, the aim of this study was to determine if receiving a kidney transplant from a smaller donor of the opposite sex would impact transplant outcomes. Accounting for other transplant variables, we demonstrated that if a kidney transplant recipient is more than 30 kg (66 pounds) heavier than the donor there is a 28% increased risk of the transplant failing compared to equally weighted donors and recipients. If the kidney is from a smaller donor of the opposite sex, the risk of transplant failure is further increased to 35% for a male receiving a kidney from a female donor, and 50% for a female receiving a kidney from a male donor. This risk is high and is similar to that when a recipient receives a kidney transplant from a donor who has diabetes; a known risk factor for kidney failure in the non-transplant population. (more…)
Author Interviews, Cancer Research, Immunotherapy, NEJM, Transplantation / 19.01.2017 Interview with: Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021 What is the background for this study? What are the main findings? Response: The immune check point inhibitors are novel anti cancer agents being used rapidly in various cancers. Many cancers don’t allow our natural immune system to attack the cancer. These immunotherapy agents “activate” the immune system to attack the cancer. These agents have been reported to cause multiple end organ side effects as noted by this recent NYT article. We also recently reported the known renal effects of immunotherapy. In the kidney transplant patient who is on immunosuppressive agents, the physicians need to keep the immune system suppressed to preserve the kidney. When one of these agents are used for a cancer in a kidney transplant patient, prior reports have suggested severe rejection episodes and loss of the transplanted kidney. Our case in the NEJM is the first report of a preventive strategy used to allow for simultaneous treatment of cancer and preventive rejection of the kidney. We used a regimen of steroids and sirolimus( an anti-proliferative agent that is used to treat cancer and also is an immunosuppresant) along with the immunotherapy. The cancer started regressing and the kidney did not reject. (more…)
Author Interviews, Kidney Disease, Lancet, Transplantation / 28.11.2016 Interview with: Prof. Dr. med. Christian Hugo Head, Division of Nephrology Medical Clinic III Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Dresden What is the background for this study? Response: At the end of 2007, the harmony trial was designed predominantly based on the one year results of the ELITE-Symphony trial, demonstrating that low dose tacrolimus, mycophenolate mofetile, and steroids together with monoclonal interleukin-2-receptor (CD 25 antigen) antibody induction therapy has superior efficacy in renal transplant patients compared to all other regimens (low or normal dose cyclosporine or sirolimus) tested. While these advantages of the low dose tacrolimus protocol were so convincing to become the new gold standard of immunosuppressive therapy within the next few years (see KDIGO guide lines for renal transplantation in 2009), the low dose tacrolimus treatment arm also demonstrated increased incidence rates regarding post-transplantation diabetes mellitus (PTDM, at that time called new onset of diabetes after transplantation - NODAT) compared to the low cyclosporine treatment arm. Previous studies had also demonstrated a detrimental association between NODAT and cardiovascular events and mortality, the leading cause of death in renal transplant recipients. Corticosteroid-free or rapid withdrawal regimens were relatively encouraging regarding influencing NODAT rates but only at the price of an increased rate of T cell mediated acute rejections. (more…)
Author Interviews, Exercise - Fitness, Transplantation / 15.10.2014 Interview with: Elvira Cicognani PhD Department of Psychology School of Psychology and Education, University of Bologna Piazza Aldo Moro, 90 - Cesena, Italy - Viale Berti Pichat, 5 - Bologna, Italy Medical Research: What are the main findings of the study? Dr. Cicognani: The study is part of a larger project of the Italian National Transplant Center (Centro Nazionale Trapianti, CNT), started in 2008, in collaboration with Istituto Superiore di Sanità, Centro Studi Isokinetic, University of Bologna, Cimurri Impresa e Sport and Patients’ associations. The general aim is to encourage transplant patients to practice physical activity and even sport activity, in view of its benefits in enhancing recovery and quality of life after transplantation. In this study we assessed Health-related quality of life on 118 active kidney transplant patients practicing different sports at low to moderate intensity and compared them with those of 79 sedentary kidney transplant patients and with 120 active healthy control subjects. Active transplant patients reported higher levels of quality of life than sedentary patients on most dimensions of quality of life and similar to active healthy controls. In brief, practicing sports may allow patients to achieve a level of quality of life similar to the general population of active individuals. (more…)
Author Interviews, Kidney Disease, Lancet, Transplantation / 28.07.2014 Interview with Dr. Richard Haynes Clinical Trial Service Unit and Epidemiological Studies Unit Roosevelt Drive, Headington Oxford OX3 Medical Research: What are the main findings of the study? Dr. Haynes: The main result from this analysis is that alemtuzumab-based induction therapy (ie, alemtuzumab followed by low-dose mycophenolate and tacrolimus with steroid avoidance) reduced biopsy-proven acute rejection by about half during the first 6 months after transplantation among a wide variety of different types of participant, compared to standard basiliximab-based induction therapy (basiliximab followed by standard dose mycophenolate, tacrolimus and steroids). This reduction was achieved despite the lower doses of tacrolimus used and there was no excess of infection observed. (more…)
Author Interviews, Kidney Disease, Transplantation / 15.07.2014

Dr Hallvard Holdaas Consultant in Nephrology National Hospital of Oslo, Interview with: Dr Hallvard Holdaas Consultant in Nephrology Department of Transplant Medicine Oslo University Hospital Rikshospitalet, Oslo Norway. Medical Research: What are the main findings of the study? Dr. Holdaas: Most studies examining long-term risk for living kidney donors have included  comparators from the background population with hypertension, diabetes mellitus, reduced renal function, cancer and other concomitant diseases; or for the few studies with more “healthy” comparators the follow-up time have been restricted. In our study we compared living donors to a healthy non-donor population which would have qualified as donors themselves, with median follow-up of 15.1 years for the donors. The relative risk for the living donors compared to a healthy control was 11.38 for endstage renal disease (ESRD), 1.4 for cardiovascular death and 1.3 for all-cause mortality (Mjoen et al., 2014). (more…)
Wake Forest / 23.05.2013 eInterview with Dr. Giuseppe Orlando, M.D., Ph.D.  Instructor, General Surgery Specialty Areas: Transplant Urology, Kidney Transplantation, Pancreas Transplantation, Transplant Immunology, Transplant Immunosuppression, Transplant Surgery Wake Forest Baptist Medical Center Medical Center Boulevard, Winston-Salem, NC eInterview with Dr. Giuseppe Orlando, M.D., Ph.D.

Instructor, General Surgery Specialty Areas: Transplant Urology, Kidney Transplantation, Pancreas Transplantation, Transplant Immunology, Transplant Immunosuppression, Transplant Surgery Wake Forest Baptist Medical Center Medical Center Boulevard, Winston-Salem, NC 27157.  What are the main findings of the study? Dr. Orlando: Our study shows that we can use discarded kidneys from deceased human donors as platform for kidney regeneration investigations. As of now, we are using porcine models, after having developed smaller scale models (mainly in rodents, as it normally occurs in health science ie we need to provide the proof of concept in small animals before scaling up to larger animals which, for obvious reasons, are clinically more relevant). In regenerative medicine we know that cells do not survive if they are not seeded on supporting platforms which we call "scaffolds". There are several types of scaffolds, but probably the most effective are the ones that we can produce from animal/human organs. Basically, every organ consists of a cellular component which is endowed within the framework of the so-called extracellular matrix. When we strip cells out of an organ, what remains is the acellular extracellular matrix. Quite strikingly, the acellular organ in question maintains the same shape and volume that it had before stripping. What counts is that the so-obtained scaffold contains most information that cells require to grow, be viable and exert their function. It looks like this happens also for discarded human kidneys which may represent the most promising platform for our research (more…)