Foreign Speaker Symposium at 10th Biennial PSN Conference 2015

Transforming transplantation
for better patient outcomes

ISLAMABAD: Everolimus has a key role to play in addressing current unmet needs in transplantation by targeting the causes of short and long-term graft loss. Everolimus based regimens are associated with significantly less CMV & BKV infections, less de novo malignancies, and better cardiovascular profile. This was stated by Prof. Lionel Rostaing from France while speaking at 10th Biennial Pakistan Society of Nephrology Conference organized by Pakistan Society of at local hotel in Islamabad recently.

Prof. Lionel Rostaing

There was a Special segment dedicated to Renal Transplantation on 1st March by the name of “Foreign Speaker Symposium”, where a number of International and National Speakers took part and shared their experience.Leading Nephrologist and Transplant Surgeons & Physicians from different cities and peripheries attended the session.
The session was moderated by Dr. Nayyer Mehmud from Shifa International Hospital Islamabad, whereas Prof. Jaffer Naqvi from Karachi and Prof. Nisar Anwer from Peshawar were the Chairman and Co-chairman of the session. Speakers likeProfessor Lionel Rostaing (France), Dr. Jeongkye Hywang (Korea), Prof. Rezvi Sherrif (Sri Lanka), Prof. Tahir Aziz, Dr. Maimoona Jawed and Dr. Shahab Zahid Khan highlighted different aspects of Transplant Management.

Dr. Uffaq Zara, Prof. Sameeh J. Khan, Prof. Lionel Rostaing and
Dr. Faisal M.B Rehman photographed in the Foreign Speaker
Symposium during 10th Biennial PSN Conference
held at Islamabad recently.

Dr. Hywang discussed the surgical aspects of renal transplant, while Prof. Sherrif elaborated the pre-requisites of running a successful cadaveric transplant program with respect to the vast data he brought from Sri Lanka. Prof. Tahir Aziz, being an Immunologist, presented the clinical utility of anti-bodies in renal transplant. Other topics included Secondary Hyperparathyroidism in Renal Transplant recipients, and CNI reduction in renal transplantation.

The main topic that became limelight of the event was delivered by Professor Lionel Rostaing; MD Ph.D., Consultant in Clinical Transplantation – Toulouse, France. His topic was Everolimus-based Immunosuppression – The Current Standard of Care. Prof. Rostaing obtained his PhD from Toulouse University in 2000. Since 2008 he is the Medical Director of the Organ Transplant Program of Toulouse University Hospital. His main field of clinical and basic research includes viral infections in dialysis and in organ transplant patient. He has authored or co-authored some 64 articles and more than 430 papers. Professor Rostaing is a member of several professional and scientific organizations.
The discussion started with latest advancements with regards to Patient Management in Transplantation. Comparing Transplantation with hemodialysis, he showed that Kidney transplantation improves quality of life and reduces the risk of mortality. The survival benefit of kidney transplantation over hemodialysis applies even to the use of marginal donor kidneys. Much of this success has been attributed to calcineurin inhibitors, cyclosporine and tacrolimus, and their ability to reduce acute rejection rates.

Dr. Nayyer Mahmud, Dr. Maimoona Jawed, Prof. Rizvi Sherrif, Dr. Jeongkye Hywang, Prof. Tahir Aziz,
Prof. Lionel Rostaing and others speaking in the Foreign Speaker Symposium during
10th Biennial PSN Conference held at Islamabad recently.

However, despite dramatic reductions in acute rejection rates over time, long-term graft survival rates have not improved to an appreciable extent. A number of factors have been postulated that contribute to the lack of improvement in graft survival, including donor factors, recipient factors, human leukocyte antigen matching, and death with a functioning allograft, delayed graft function, calcineurin inhibitor toxicity, chronic allograft nephropathy, and infectious nephropathy (BK virus).
Because of the known contribution of calcineurin inhibitors to nephrotoxicity, there has been much interest in finding the optimal agent and/or regimen. While many studies demonstrated improved renal function with reduced dose calcineurin inhibitor use, or an early benefit on renal function with tacrolimus use when compared to cyclosporine, improvements in long-term graft function were not demonstrated. Additionally, there are numerous differences in the adverse event profile of cyclosporine and tacrolimus. Many outside factors differentiate the calcineurin inhibitors and influence their contribution to nephrotoxicity, including therapeutic drug monitoring strategy, dosing strategy, drug-drug interaction, pharmacogenetics, and non-adherence. These medication-related variables make nephrotoxicity and decline in allograft function very difficult to predict in practice. The lack of surveillance biopsies also makes differentiation of outcomes related to calcineurin inhibitor use and non-medication related factors difficult in practice.
Despite advances in immunosuppressive therapy, long-term renal-transplantation outcomes have not significantly improved over the last decade. The nephrotoxicity of calcineurin inhibitors (CNIs) is an important cause of chronic allograft nephropathy (CAN), the major driver of long-term graft loss.
Prof. Rostaing has an experience of modulating individualized immunosuppressive protocols and based on his own clinical experience he refers to Everolimus as being a core solution to much of the problems associated with graft rejection.
Everolimus is a proliferation signal inhibitor with a mechanism of action that is distinct from CNIs. The efficacy and tolerability of everolimus in renal-transplant recipients have been established in a wide range of clinical trials. Importantly, synergism between everolimus and the CNI cyclosporine (CsA) permits CsA dose reduction, enabling nephrotoxicity to be minimized without compromising efficacy.

One of the participant of the 10th Biennial PSN Conference being
presented certificate during the Foreign Speaker Symposium

Currently, everolimus is being investigated in regimens where reduced exposure CNIs are used from the initial post-transplant period to improve renal function and prevent CAN. By inhibiting the proliferation of smooth muscle cells, everolimus may itself delay the progression or development of CAN. Although everolimus is associated with specific side effects, these can generally be managed. By targeting the main causes of short- and long-term graft loss, everolimus has a key role to play in renal transplantation.
Evidence from clinical trials supports the efficacy and tolerability of everolimus in renal‑transplant recipients. He utilized clinical trial data to prove that everolimus can facilitate CNI reduction/halving without compromising efficacy. By facilitating CNI reduction, and inhibiting smooth-muscle proliferation, everolimus may prevent the progression or development of CAN, which has been investigated in the A2309, MECANO and ASCERTAIN (A2413) trials. Everolimus has a key role to play in addressing current unmet needs in transplantation by targeting the causes of short and long-term graft loss.
Everolimus plus reduced CNIs, compared to a regime based on mycophenolic acid (MPA) plus full-dose CNIs, results in the same renal function at 1 and 2 years post-transplant, with the same magnitude of albuminuria. In addition, everolimus plus low doses of CNIs are associated with significantly less CMV infection and less BKV infection compared to a regimen of MPA + CNI.

Grouped photograph taken during 10th Biennial PSN Conference shows
Dr. Shahzad Saleem, Dr. Uffaq Zara, Dr. Faisal M.B Rehman
and other memebers of Novartis I&D Team.

Finally, the association of everolimus plus low doses of CNI, compared to MPA plus CNI, is associated i) with a significantly better cardiovascular profile, particularly a significant decrease in left-ventricular hypertrophy, and ii) with less de novo malignancies mTOR-inhibitors (sirolimus, everolimus) can be used as immunosuppressive agents either with or without calcineurin-inhibitors (CNIs). However, the combined use of sirolimus and CNIs leads to nephrotoxicity. Recent studies show that it was possible to safely use everolimus combined with CNI reduction (cyclosporine or tacrolimus). The daily dose of everolimus was ≈50% lower when it was combined with cyclosporine compared to when it was used with tacrolimus. In maintenance KT patients, the trough levels used are aimed at 4–8 ng/mL for everolimus, 50–75 ng/mL for cyclosporine, and 2–4 ng/L for tacrolimus. (PR)

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