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 International Preceptor ship 
Program launched in Pakistan

A collaborative academic activity by
AFIU Pakistan & Toulouse Hospital France

RAWALPINDI: Armed Force Institute of Urology recently conducted a Clinical Preceptorship Program in its premises at Rawalpindi. The beauty of this preceptorship was the involvement of multiple Transplant Institutes of the region like AFIU, Shifa International Hospital, Combined Military Hospital, Fauji Foundation and KRL Hospital. This was initiated and lead by Brig. Umair Ahmed, Head of Nephrology Department at AFIU in collaboration with Toulouse University & Hospital France. Prof. Lionel Rostaing who is a well-known researcher and an eminent Transplant Nephrologist and Chairman of Kidney Transplant Unit, Toulouse Hospital in France was invited to share his experience of the latest protocols of immunosuppressive drugs being used in Renal Transplantation.

 

Prof. Lionel Rostaing

The two days scientific meeting was inaugurated by the Chief Guest, Maj. Gen. Arshad Mahmood,Commandant & Advisor Consultant of Urology and Transplantation. In his welcome address he thanked the Guest of Honour Prof. Lionel Rostaing and the participants.This was followed by his introductory presentation where in he elaborated the efforts of AFIU is providing the best possible healthcare services to its dependent population.  He then discussed in detail the establishment of AFIU where in 1979,they performed first ever renal transplant and by the end of year 1985 a land mark of one hundred Kidney Transplants had been achieved. The success of this programme was because of the extreme hard work and dedication of their transplant team despite many hurdles like unavailability of proper infrastructure and lack of professionally trained Transplant Surgeons.Currently they are performing four to five transplants per month which are all Live Related Kidney Transplants.


Maj. Gen. Arshad Mahmood

Speaking about the difficulty in cadaveric transplantation he said these are the same as faced by other institutes in Pakistan which mainly accounts for organ shortage due to ignorance. HOTA was established in 2010 and due to limited human resource and awareness, the deceased donor program could not be established in Pakistan. To overcome these obstacles AFIU has started an awareness programme aboutdeceased donor program.  AFIU has started organizing seminars andmaking presentationwith the aim to communicate the message to medical colleges anduniversities.

Brig. Umair Ahmed Siddiqui was the next speaker and topic of his presentation was AFIU Organizational Framework and Transplant Program. AFIU, he said, operates under legal framework known as HOTA. The 1st Nephrologist was Brig. Dr. Shaheen Moin, now heading Bahria Medical and Dental College in Karachi. CPSP recognized Military Hospital Rawalpindi in 1995 and AFIU in 1999 with full accreditation.


Dr. Brig. Umair Ahmed Siddiqui

AFIU organizational framework consist of Commandant,Deputy Commandant, Department of Anesthesia headed by Brigadier Hamid, Department of Nephrology withtwo postgraduate trainees Nephrologist and the department of Urology which is headed by Major Gen. Arshad himself and a dialysis center, where as military hospital in Rawalpindi has a nephrology ward and Dialysis Centre as well.


The mission of AFIU is to provide outdoor services, indoor patient hemodialysis facilities, kidney transplant and management of pre and post-transplantation. Armed Forces Institute of Urology provides training to future nephrologists and armed forces nursing officers in the subject of nephro-urology and after completion of their training, they are placed in Nephrology wards and Dialysis centers.  AFIU also provides training to Dialysis Technicians, which is the paramedical arm of AFIU. A yearly audit is carried out in AFIU where all the Nephrologists and Urologists from Pakistan meet and share their experiences on a yearly basis.



Group photograph of some of the participants of Clinical Preceptorship Program.

After this the complete protocol, starting from pre- transplant to post-transplant were discussed in detail. The recommended vaccination and drug levels done were also shared with the participants. The presentation was concluded by sharing their vision for future in which the main emphasis was to optimize the number of dialysis equipment to ensure adequate dialysis dose as per ISN norms.To establish collaboration with international center for CPD and research and to ensure provision of dedicated renal histopathologist and electron microscope at AFIP.


Dr. Col. Zahid Farooque,currently working in CMH Peshawar as a nephrologist,shared two years data of AFIU as he was part of the Transplant team.The 1st renal Transplant was performed in CMH Rawalpindi by Dr. Col. Hamid Mukhtar Shah. On 20th January 1996 AFIU was established and after that the Renal Transplants were performed in AFIU. In August 2013 a transplant registry was maintained and software was developed since thetransplant data is recorded in AFIU. The data recorded from September 2013 till September 2015 consists of 63 patients out which 44 patients underwent kidney transplantation.


Dr. Col. Zahid Farooque

Mean age and gender of the donors and recipient were shared with the donors according to the SOP of AFIU are 1st degree relatives of the patients. Sisters are at the top of donor list with a percentage of 42.9 followed by brothers and wives.  AFIU transplant population is quiet young and so Chronic GN is the commonest cause in our data. AFIUhad seven transplants in patients with diabetes mellitus and in 33% of cases the cause remained unknown. The presentation was concluded with the need to establish the cadaveric renal transplantation procedures.

Prof.  Lionel Rostaing presenting shield to Major General Arshad Mahmood.
Brig Dr. Umair Ahmed Siddique is also seen in the picture.

Presentations were followed by lively discussion on post-transplant infections and a suggestion was made to start with an induction therapy to prevent acute rejection. All patients who appeared to have sepsis were not given the induction therapy. The cost of ATG is higher than Basiliximab. The mean age of the recipient was sixty years and they go for stress test. Responding to a question Prof. Rostaing said that BKVprophylaxisis not given in their institute. Dr. Zahid Nabi from KRL hospital was asked about the induction protocol to which he responded by saying that he used Basiliximab for induction in his entire patients and valgancyclovir for CMV. Resultantly, there is no acute rejection and no deaths and 0% CMV in his patients, while 60 – 70 % donors were CMV positive. AFIU, it was stated was preparing a strategy to start with induction therapy with public sector and private sector without differentiating the two arms. Level asked for Everolimus were 4-7 ng/ml for Everolimus, Cyclosporine 50 – 75mg and with tacrolimus it is 4ng/ml.


Discussion on importance of induction in Kidney Transplantation in progress.

Brigadier Tahir Aziz was invited as subject expert of Immunology from Shifa International Hospital to discuss about the Immunological Tests in Transplantation. According to him, a prospective cross match must be performed.The cross match may be undertaken by carrying out a laboratory cross match test or, in selected cases, by performing a virtual cross match.  Patients with a complex antibody profile or incompletely defined antibody profile should be prospectively cross matched using flow cytometric techniques and/or complement dependent cytotoxicity (CDC).  If a virtual cross match is performed, a retrospective laboratory cross match test should be performed using serum collected within 24-48 hours prior to transplantation. Laboratory cross match tests should distinguish between donor T cell and B cell populations; they must detect clinically relevant IgG HLA class I and class II donor specific antibodies, and distinguish these from IgM.  The report must include appropriate advice on the cross match results in the context of the patient’s antibody profile.


Dr. Brig. Tahir Aziz

Dr. Zahid Nabi talked about donor selection and outcomes from KRL Hospital. He was of the view that donor selection and outcomes are basically supply and demand issues because there are scenarios where one can accept a donor and in certain cases one will probably say ‘NO’. So, unfortunately we are not running a successful program because there is a big gap in supply and demand.As in some cases Donors are being rejected due to multiple reasons.Donor selection is a big task and should be based on case to case scenarios, rather than just putting some sort of protocol which could deny many recipients of donors. 

 

Dr. Zahid Nabi

The process starts with medical evaluation, personal medical history with significant medical conditions, kidney specific personal history, the medication history, family history, social history and outcomes of physical examination, with a special emphasis on body mass index. Then comes the laboratory workup, primarily basic lab tests and then followed by special lab tests. He concluded his presentation addressing the issueswhich are related to kidney donation whichare categorized in Immediate and long term risk. There was aninteresting debate over the selection of donors when in the end Dr. Zahid Nabi asked if the donor is twenty years old and recipients is sixty years, would his son be a good donor?

Dr. Lionel Rostaingdelivered his talk on CNI reduction protocols. His talk started with the brief explanation of Immune system and mechanism of action of different immunosuppressants and their target sites. Prof. Rostaing stressed on the nephrotoxicity that is caused by CNI in different transplant protocols. He talked about the combined regimen of mTOR inhibitor and CNI reduction protocols with the benefit of long term graft function. It was emphasized that early conversion from CNI-based immunosuppression to Everolimus-based immunosuppression is of benefit in Kidney Transplant patients mainly in those patients who have the best renal function at conversion; whereas very late conversion to mTOR-I-based immunosuppression might be too late.

 Lt. Col. Khalid Mahmood Raja from CMH Lahore, Mr. Saad Ullah Salari
and an other guest photographed during the meeting.

The data regarding cardiovascular risk profile was also presented. In one study it showed that mTOR inhibitor prevents pathogenesis of atherosclerosis by preventinglipid accumulation in tissues, stabilising atherosclerotic plaques by selective clearance of macrophages, inhibiting local inflammatory responses in smooth muscle cells. These effects may increase in hypercholesterolaemia and hypertriglyceridemia. In another study, it showed that mTOR inhibitor improves left Ventricular Hypertrophy when converted from CNI based regimen.


In a Spanish cohort study, it showed that mTOR also results in less CMV infections with Lower incidences of BKV and CMV infections with EVR regimens vs. MPA. The presentation ended with management of side effects of Everolimus, by keeping its level to the lower side.

Dr. Humaira Nasir, Assistant Professor and Consultant Pathologist from Shifa International Hospital, deliveredher talk on C4d Staining. C4d is a magic marker and the positivity favors antibody mediated rejection.However it may be seen in the absence of morphologic features of rejection and results should be interpreted by taking into account the DSA and endothelial activation markers as well.


Dr. Humaira Nasir

The second presentation by Prof. Rostaing was on transplanting the highly sensitized patients.For HLA matching, the only relevant matching is DQ (and DR) matching with assessment at pre-transplant of donor-specific alloantibody (DSA) by Luminex. Also, the effect of reducing or discontinuing maintenance immunosuppression on kidney graft survival first year post transplant. He concluded his presentation by quoting from KIDIGO guidelines where he recommended including induction therapy with a biologic agent as part of the initial immunosuppressive regimen in all kidney transplant recipients. He also recommended that an interleukin 2 receptor antagonist (1L2-RA) be the first-line induction therapy. He suggested using a lymphocyte depleting agent, rather than an anti-1L2 receptor antibody, for kidney transplant recipients at high immunological risk.


A view of the reception desk at Clinical Preceptorship Program 
held at Armed Force Institute of Urology, Rawalpindi.

At the end of the meeting, mementoes were presented. Brig. Dr Umair and Major General Arshad Mahmood presented Shields of honor to Prof Rostaing for his valuable contributions to the scientific deliberations. Prof. Rostaing presented mementoes to the other speakers.  It was decided to continue to conduct such preceptorship programs on a regular basis. The possibility of a paired-knowledge exchange program was also discussed between the two countries. The organizers also commended Novartis Pharmaceuticalsfor being a Strategic Partner by sponsoring this academic activity.

 

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