Cadaveric Renal Transplantation : Bombay Hospital Experience

Avinash.T.S, Shankarprasad, Umesh Oza, S.W.Thatte, A.L.Kirpalani, Bichu Shrirang

Abstract Transplantation of human organs is one of the greatest medical breakthroughs of this century. In a developing country such as cadaveric renal transplantation accounts for less than 1% of total renal transplantations. The reasons for such a low rate of cadaveric renal transplantation are many ranging from lack of awareness to socioeconomic reasons. We performed 11 cadaveric renal transplantation in our institute from November 2001 to January 2009. Age of donors ranged from 25 to 65 yrs. Mean cold ischaemic time was 6.5±1.4 hours. No patients had hyperacute rejection. 4 patients (36.5%) had delayed graft function requiring postoperative haemodialysis. Follow-up period ranged from 7 yr to 2 months. During 1 year follow- up 4 patients had (36.6%) acute rejection episodes. Patient survival at 1 year was 77.8%. Graft survival at 1 year was 85%. Mean creatinine at the end of 1 year was 1.9±0.2. Patient survival till current follow-up was 54.6%. Though our study is small, the incidence of delayed graft function requiring postoperative haemodialysis, acute rejection episodes were significantly less and graft survival rate at the end of 1 year was good. Thus cadaveric kidney transplantation is associated with satisfactory patient and graft survival. Creating a positive public attitude, early brain death identification, and certification, prompt consent for organ donation, adequate hospital infrastructure, and support logistics are prerequisites for successful organ transplantation.

Introduction transplantation.1,3 The majority of these ransplantation of human organs is patients are young; their only hope to live T one of the greatest breakthroughs in better is by having organ transplantation. the history of medicine. Kidney Due mainly to nonavailability of organs transplantation offers patients with end- either live related or cadaveric donor most stage renal disease the greatest potential of our patients remain on dialysis only. for increased longevity and enhanced The Indian solid organ transplant quality of life. However, few Indian programme started in the early 1970s. patients are able to benefit from this Since its inception, the programme has medical advance. It is estimated that in rapidly become popular; it is presently India every year over 152,000 people are practiced in over 100 hospitals in all the diagnosed with end-stage renal disease major cities of the country. Despite (ESRD) needing haemodialysis/renal tremendous potential, a cadaveric programme has not developed in many Department of and , Bombay Hospital institute of Medical sciences, . centres. In a developing country such as

Bombay Hospital Journal, Vol. 52 , No. 4 , 2010 473 India cadaveric renal transplantation given ATG. All our patients were on triple accounts for less than 1% of total renal immunosuppression in maintenance 2,5 transplantations. Cadaveric donors can phase. All patients were managed in ICU in provide an effective solution to the immediate postoperative period with problem of organ shortage. We regular monitoring of renal function. retrospectively review the outcomes of our During postoperative period, doppler of cadaveric renal transplants from 2001 transplant kidney was done in all patients through 2009 in our hospital. and kidney biopsy was done as per Material and Methods indication. No protocol biopsies were We retrospectively evaluated the performed. Haemodialysis was done if outcome of 11 patients who had received required. Follow-up period ranged from 4 the cadaveric renal transplants between months to 7 years. Nov. 2001 and Jan 2009 in our hospital. Results Data was collected from medical record Recipient characteristics : Out of 11 section and from the patients who were recipients 4 were male and remaining 7 being followed-up. The analyzed data were female. The age ranged from 21 to 60 included age, sex, cause of ESRD, years. The cause of ESRD was chronic haemodialysis requirements, preoperative glomerulonephritis in 4 patients, and postoperative laboratory evaluation unknown aetiology in 4 patients, diabetic results (including serum electrolytes, nephropathy, nephrotic syndrome and haemoglobin, creatinine, urea and ADPKD in one patient each as shown in albumin), intraoperative data (in surgery T a b l e 1 . A l l p a t i e n t s w e r e o n time, cold and warm ischaemia time, and haemodialysis. Haemodialysis Period packed red blood cell transfusions), varied from 2 - 7 years. 11 patients had postoperative surgical complications, associated hypertension and 1 patient had posttransplantation immunosuppressive Diabetes mellitus as comorbidity. regimens, acute cellular rejection Table 1 : Causes of ESRD in recipients episodes, patient and graft survivals, donor characteristics (age, sex, race, Chronic Glomerulonephritis 4 cause of death, peak serum creatinine Diabetic Nephropathy 1 values). Adult polycystic kidney Disease 1 Patients were accepted for cadaveric Nephrotic Syndrome 1 transplant according to their priority on Unknown aetiology 4 the waiting list maintained in ZTCC, Maharashtra. The harvested kidneys from Total 11 all donors were preserved in HTK solution Donor Characteristics until the completion of the vascular anastomosis. All cadaveric donor kidneys Age of donors ranged from 25 to 64 were transplanted into ABO-compatible years (Mean age was 45 years). Cause of recipients after negative crossmatch test. death was head injury in 6 patients and Carrel's patch used for vascular cerebrovascular accident in remaining 5 anastomosis. DJ stent was kept across the patients. Four organ retrieval was done in vesicoureteric anastomosis in all patients. our hospital and seven kidneys were Recipients received methyl prednisolone received from other hospitals of Mumbai. as induction agent. Few patients were also 3 of the donors had hypertension as

474 Bombay Hospital Journal, Vol. 52 , No. 4 , 2010 comorbidity. The serum creatinine value of end of 1 year was 1.9±0.4mg%. Patient donors varied from 0.8-1.2 mg/dl. The survival at 1 year was 77.8% (2 patients Mean cold ischaemic time was 6.5±1.8 hrs. died with functioning graft). One patient Immunosuppression died due to sudden cardiac arrest. One patient died due to fungal sepsis. Graft For induction Methylprednisolone 1g survival at 1 year was 85.8%. 7 patients w a s u s e d i n a l l o u r p a t i e n t s (73.6%) had > 1 episode of infection which intraoperatively followed by tapering dose included UTI, pneumonia and fungal of oral prednisolone. Anti Thymocyte infection. Globulin was used in 6 patients as Table 3 : Outcome compared to other studies in induction. All our patients were on triple India1,2 immunosuppression regimen during Results Chennai Ahmedabad Bombay Hospital maintenance phase. Regimen included experience=68 experience=38 experience=11

C y c l o s p o r i n e / t a c r o l i m u s w i t h (1 year follow (6 months (1 year follow up) Mycophenolate and prednisolone as up) follow up) shown in Table 2. Delayed 17.6% 68% 36.5% graft Table 2 : Maintenance immunosuppressive regimen function Name of Drug No. of patients Acute 26.4% 16% 35.5% rejection

Steroid All patients Patient 88.2% 90% 77.2% survival MMF All patients Graft 73.5% 85% 85.5% Cyclosporine 7 survival (Death censored graft survival) Tacrolimus 4 Discussion Postoperative Complications Though our study is small results are No patient had postoperative vascular comparable to other series. Graft survival complications. One patient had prolonged and patient survival rate at the end of 1 ileus, one had wound infection who year were satisfactory. Infection rate was recovered with conservative management. slightly high. The shortcomings of this one patient developed lymphocoele for analysis included its retrospective nature, which marsupalisation was done. small number of patients, limited data Graft Rejection and Survival from the early patients who underwent None of our patients had hyperacute cadaveric kidney transplantation, and rejection. 4 patients (36.5%) had delayed being a single-centre study. We have not graft function requiring postoperative used protocol kidney biopsies, hence it is haemodialysis. Three were dialysed once possible that organ rejection rate was and the other patient required two under reported. Donation from brain stem sessions of dialysis. No protocol biopsies dead patients is 17% in India compared were performed. All rejection episodes with 50% in the United States and 75% in were documented by biopsy, which was Europe. Survey conducted in Chennai to performed when clinically indicated or for examine social attitudes toward organ elevated serum creatinine levels. During 1 donation showed that more than half the year follow-up, kidney biopsy was done in people who responded to survey expressed 8 patients. 4 patients (36.5%) had acute “some degree of familiarity” with the 1,4 rejection episodes. Mean creatinine at the concept of brain death. More than 70%

Bombay Hospital Journal, Vol. 52 , No. 4 , 2010 475 were willing to carry a donor card. The b r a i n d e a t h i d e n t i f i c a t i o n a n d most significant finding was that the certification, prompt consent for organ proportion of people who were willing to donation, as well as adequate hospital donate their eyes was substantially higher infrastructure and support logistics are than the proportion of people who were required to increase the number and willing to donate solid organs after death. outcome of cadaver transplantations. The survey's results pointed to the References significant success of the campaign for eye donations. Such a campaign could serve 1. M. R. Prabhakar and P. Soundararajan, et al : Cadaveric Renal Transplantation : The Chennai as an example for a similar effort to raise Experience Transplantation Proceedings, 2008; awareness about the need for organ 40:1104-1107. donation. When asked about whether 2. Feroz A, Dabhi M, Gumber M, et al : Cadaveric financial incentives and employment renal transplantation : Our experience at the opportunities influenced the rate of Institute of Kidney Diseases and Research Centre, cadaveric organ donation, most Institute of Transplantation Sciences, Ahmedabad. Transplant Proc 2007; 39:721. respondents said that they would be more likely to donate an organ if these were 3. Modi GK, Jha V : The incidence of end stage renal disease in India : A population based study. Kid Int provided. 2006; 70:2131. Conclusion 4. Government of India. Transplantation of Human Organs Act, 1994. Central Act 42 of 1994. Available Cadaveric kidney transplantation is at: http://www.medindia. net/tho/thobill.asp. still evolving in India. The rate of organ 5. Shroff S, Navin S, Abraham G, et al : Cadaver organ donation is low. Creating a positive public donation and transplantation-an Indian perspective. attitude toward organ donation, early Transplant Proc 2003; 35:15.

ALLOPURINOL FOR CHRONIC STABLE ANGINA : OLD DRUG, NEW TRICKS? Stable angina, a chronic coronary syndrome, has received much less attention despite being the most frequent initial presentation of coronary heart disease. This condition is unusual among manifestations of coronary heart disease by being more common in women. Generally regarded as having a favourable prognosis, progression to an acute coronary syndrome (with its associated risks) is by no means unusual in higher-risk groups, such as in patients with recent onset angina. allopurinol, the standard treatment for gout, could also be useful in the treatment of patients with stable angina. Allopurinol not only increased total exercise time but also the time to ST-segment depression and the time to symptoms. The specific antianginal drugs, ß blockers, nitrates, calcium-channel blockers, nicorandil and the sinus-node inhibitor ivabradine variously improve the balance between myocardial oxygen supply and demand through reduction of heart rate, blood pressure, myocardial wall stress or contractility, coronary vasodilation or different combinaitons of haemodynamic effects. Xanthine oxidase inhibition by allopurinol is yet another non-haemodynamic action that could be exerting its putative anti-ischaemic effects by various mechanisms, including preventing the deleterious effects of oxidative stress on endothelial dysfunction and energy supply. The proposed mechanism of action of trimetazidine, a partial inhibitor of fatty-acid oxidation (a pFOX inhibitor), is to partly switch myocardial energy production from fatty acid to glucose oxidation, as occurs during ischaemia. A Cochrane analysis showed that trimetazidine is effective in the treatment of stable angina. Another drug, ranolazine, has recently been licensed for angina in Europe and the USA. Although further work is needed to confirm allopurinol’s putative anti-ischaemic effects and to better understand its mechanism of action, allopurinol joins a growing list of compounds that tests the conventional wisdom on what constitutes antianginal therapy. RENJITH ANTONY, HENRY J DARGIE, THE LANCET, 2010; 375 : 2126, 2127

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