Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 1093 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

Table of Contents   
RENAL DATA FROM ASIA-AFRICA  
Year : 2013  |  Volume : 24  |  Issue : 2  |  Page : 403-407
Outcome of deceased donor renal transplantation - A single-center experience from developing country


1 Department of Nephrology and Clinical Transplantation, Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, India
2 Department of Nephrology and Clinical Transplantation; Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, India

Click here for correspondence address and email

Date of Web Publication26-Mar-2013
 

   Abstract 

Renal transplantation (RTx) is considered as the best therapeutic modality for patient suffering from end-stage renal disease (ESRD). Dearth of donor kidneys is a major problem everywhere, and deceased donor renal transplantation (DDRTx) is seen as at least a partial solution. Even so, DDRTx accounts for only less than 4% of RTx in India. We report our 6-year single-center experience on DDRTx vis-à-vis patient/graft survival, graft function in terms of serum creatinine (SCr), rejection episodes, and delayed graft function (DGF). Between January 2005 and March 2011, 236 DDRTx were performed. Majority of the donors were those with brain death due to road traffic/cerebrovascular accidents. The commonest recipient diseases leading to ESRD were chronic glomerulonephritis (42.8%), diabetes (12.7%), and hypertension (10.6%). Mean recipient age was 36.2 ± 14.2 years; 162 were males and 74 were females. Mean donor age was 45.3 ± 17.13 years; 144 were males and 92 were females. Mean dialysis duration pre-transplantation was 18.5 ± 2.5 months. All recipients received single-dose rabbit-anti-thymocyte globulin induction and steroids, calcinueurin inhibitor, and mycophenolate mofetil/azathioprine for maintenance immunosuppression. Delayed graft function was observed in 29.6% patients and 22% had biopsy-proven acute rejection. Over the mean follow-up of 2.18 ± 1.75 years, patient and graft survival rates were 74.57% and 86.8%, respectively, with mean SCr of 1.42 ± 0.66 mg%. DDRTx achieves acceptable graft function with patient/graft survival, encouraging the use of this approach in view of organ shortage.

How to cite this article:
Patel HV, Kute VB, Ghelani GH, Vanikar AV, Shah PR, Gumber MR, Trivedi HL. Outcome of deceased donor renal transplantation - A single-center experience from developing country. Saudi J Kidney Dis Transpl 2013;24:403-7

How to cite this URL:
Patel HV, Kute VB, Ghelani GH, Vanikar AV, Shah PR, Gumber MR, Trivedi HL. Outcome of deceased donor renal transplantation - A single-center experience from developing country. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Nov 15];24:403-7. Available from: http://www.sjkdt.org/text.asp?2013/24/2/403/109618

   Introduction Top


Renal transplantation (RTx) is the best therapeutic modality for end-stage renal disease (ESRD). [1] When compared with dialysis, RTx leads to a longer life, [2] enhances quality of life, [3] and is cost-effective for the health care system. [3],[4] In India, about 175,000 new patients develop ESRD annually and <10% are able to gain access to renal replacement therapy. The rate of renal transplantations performed yearly in India translates to 3.25 per million populations (PMP); the deceased-donation rate is 0.08 PMP/year. [5],[6] This discrepancy between the number of waiting patients and transplantations performed can be reduced by developing deceased donor organ transplantation (DDOT) program. The reasons for such a low rate are multiple, ranging from lack of awareness to socioeconomic reasons. [7] Apart from the medical issues, legal, social, and ethical issues are the key factors in obtaining consent from the relatives of potential deceased donors. [8] We present our experience of DDOT over the last six years.


   Materials and Methods Top


This was a retrospective study of 236 deceased donor renal transplantation (DDRTx) carried out in our institute from January 2005 and March 2011. Both kidneys were procured from all donors and preserved in Histidine-tryptophan-ketoglutarate (HTK) solution. Demographics and post-transplant follow-up including investigations, immunosuppression requirement, rejection episodes, and survival were evaluated.

Immunosuppressive regimen

In all patients, immunosuppression given was induction with rabbit-anti-thymocyte globulin (r-ATG) (1.5 mg/kg), and methylprednisolone (MP) 500 mg intravenously. MP was continued for three days postoperatively. Maintenance immunosuppression consisted of prednisolone (20 mg/day tapered to 10 mg/day at one to three months post-transplant and continued thereafter), mycophenolate mofetil (MMF) (2 g/day), and calcineurin inhibitors (CNIs) [cyclosporine (CsA) 5 mg/kg BW/day or tacrolimus 0.08 mg/kg BW/day]. CNI was replaced by sirolimus in the event of toxicity. Doses of CNI were adjusted as per trough levels (C0) by Fluorescence Polarization Immunoassay (FPIA) technology for the first three months, and thereafter tapered to 3 mg/kg BW/day. CNI levels were only assayed in the event of graft dysfunction (due to financial constraints). CsA dosing was adjusted to achieve target C0 concentrations of 200-300 ng/mL during the first three months post-transplantation, 100-250 ng/mL for the next three months, and around 100 ng/mL thereafter. Tacrolimus dosing was adjusted to achieve target C0 concentrations of 10-15 ng/mL for the first three months post-transplantation and 4-8 ng/mL thereafter.

Sirolimus dose was 2 mg/day and maintained at trough levels of 4-8 ng/mL. All patients received prophylaxis against cytomegalovirus (CMV) infection (gancyclovir 1 g thrice a day × 3 months), fungal infections (fluconazole 100 mg once a day × 6 months), and Pneumocystis carinii pneumonia (trimethoprim/sulfamethaxazole 160/800 mg once a day × 9 months).

Post-transplant follow-up

As per our protocol, these patients were followed at weekly intervals for the first three months, fortnightly for the next three months, monthly for the next six months, and three-monthly intervals thereafter. On every visit, renal and liver function status was monitored; complete blood counts and ultrasound Doppler studies were performed.

Diagnosis and treatment of rejection

Recipients underwent renal graft biopsy in the event of graft dysfunction and diagnosed as per the modified Banff classification. [9],[10] Rejections were treated with standard anti-rejection therapy. T-cell rejections were treated with MP, 500 mg × 3 doses ± r-ATG 1.5 mg/kg single dose. B-cell rejections were treated with MP, 500 mg × 3 doses ± plasmapheresis (40 mL/kg per session × 4-8 sessions) + IV immunoglobulins (IVIG), 5 g/day × 5-10 doses ± rituximab, 375 mg/m 2 body surface area (BSA). [11],[12],[13],[14]

Patient survival was defined as the time from transplantation to death, and graft survival was defined as the time from transplant to requirement for hemodialysis. [11],[12] Expanded criteria donor (ECD) included any donor ≥60 years old and donors 50-59 years old with at least two of the following: terminal creatinine >1.5 mg/ dL, history of hypertension, or death by cerebrovascular accident. A wedge biopsy specimen was obtained from donors older than 60 years of age with a history of hypertension or a cerebrovascular accident as the cause of death or with a diagnosis of diabetes mellitus. [12],[13],[14] Using frozen tissue, the biopsy specimen was studied within 1 h after retrieval for percentage of glomerulosclerosis (GS). If it was <15%, a single kidney transplantation (SKT) was performed; if it was 15-50%, dual kidney transplantation (DKT); and if >50% or if there was moderate to severe interstitial and vascular changes, the kidney was discarded. [12],[14]


   Results Top


Out of 236 DDRTx performed, 68.64% (n = 162) were males and 31.36% (n = 74) were females, with a mean age of 36.2 ± 14.2 years. The commonest diseases leading to ESRD were chronic glomerulonephritis (42.8%), diabetic nephropathy (12.7%), and hypertension (10.6%). There were 7.6% (n = 18) non-heart-beating donors (NHBD) and 31.7% ECDs. Totally 7.6% (n = 18) patients received dual kidneys. Mean donor age was 45.3 ± 17.13 years; 61% (n = 144) were males and 39% (n = 92) were females. Main cause of brain death was road traffic/cerebrovascular accident. Mean dialysis duration pre-transplantation was 18.5 ± 2.5 months, and mean third-party infusions were 13 ± 3. Regarding geographic location, 17.8% (n = 42) recipients belonged to states other than Gujarat. These were Rajasthan (8.9%, n = 21), Maharashtra (3.8%, n = 9), Madhya Pradesh (1.7%, n = 4), and other states of India. Mean cold ischemia time (CIT) was 6.1 ± 2.2 h, and a total of 29.6% (n = 70) patients developed delayed graft function (DGF). Over a mean follow-up of 2.18 ± 1.75 years, patient and graft survival rates were 77.08% and 86.8%, respectively, with mean serum creatinine (SCr) of 1.42 ± 0.66 mg/dL. Totally 24.6% (n = 58) patients died; 48.3% deaths (n = 28) were due to gram-negative sepsis, 10.3% (n = 6) due to fungal infections and CMV disease each, 8.6% (n = 5) due to staphylococcal pneumonia with acute respiratory distress, 10.3% (n = 6) due to acute myocardial infarction, and 12.1% deaths (n = 7) were due to cerebrovascular stroke. Immunosuppression regimen consisted of CsA (33.8%, n = 80), tacrolimus (50%, n = 118), sirolimus (16.1%, n = 38), MMF (75%, n = 177), and azathioprine (15.2%, n = 36). Totally 22.5% (n = 53) had biopsy-proven acute rejection (BPAR). Acute B-cell mediated rejections were noted in 8% (n = 19), acute T-cell mediated rejections in 9.7% (n = 23), combined acute T- and B-cell mediated rejections in 4.3% (n = 11), chronic T-cell mediated rejection in 2.1% (n = 5), and chronic B-cell mediated rejection in 0.8% (n = 2), and unexplained interstitial fibrosis with tubular atrophy (IFTA) was noted in 1.3% (3) patients. Majority of the acute rejections were observed in the first year and 84.9% (n = 45) patients responded to anti-rejection therapy.


   Discussion Top


DDOT is still low in India despite the need and tremendous potential. Our DDOT program can be considered fairly successful for the Indian context due to active steps taken by our institute in the form of increased public awareness on need for organ donation, participation of general hospitals in identification of potential donors, reduction in transplantation cost, early brain death identification, committed and integrated rapid response team capable of transporting potential donor to hospital in a timely manner, improvement in transportation, communication network, successful organ retrieval, adequate hospital infrastructure and support logistics, inclusion of ECD, and positive support from the local government and non-governmental organizations. [7],[8],[12],[14],[15],[16],[17],[18]

In India, where DDOT accounts only for around 4% of total transplants, discarding marginal kidneys would hamper the program. In this study, ECD comprised 31.7% of DDOT. In the circumstances of organ shortage, DDOT with ECD is a feasible option.

Individual centers in India have reported their transplant outcomes. In a study by Mani et al, 1-year and 4-year graft survival rates of 88 DDOT in Chennai were 72% and 63%, respectively, and patient survival was hardly different from graft survival. The inability of most of the patients to afford monoclonal anti-bodies for immunosuppression might be the reason for the inferior 1-year survival results in this study. [16]

Five-year patient and graft survival rates of 68 DDOT in Chennai were 61.7% and 58.8%, respectively, with BPAR in 26.4%, DGF in 50%, and CIT of 5.6 ± 3.2 h, respectively. Short-term graft survival was reduced because of a high 1-year post-transplantation mortality, with most of these deaths caused by sepsis or multiple organ failure. Risk factors for early graft loss were re-transplantation, longer CIT, and AR episodes. [17]

The 1-year allograft and patient survival rates of 100 DDOT from four major centers in Chennai were 82% and 86%, respectively, and 2-year allograft and patient survival rates were 74% and 80%, respectively. [18] In a study by Feroz et al from our center, 1-year patient and graft survival rates for 38 DDOT were 90% and 85%, respectively, with BPAR in 17%, DGF in 68% and CIT of 6.9 ± 3.8 h, respectively. [7] In India, 1-year graft survival rates in good centers are approximately 80% in DDOT. [5]

One-year and 2-year survival rates of DDRTx were 89.6% and 76.5%, respectively. [19] One-year graft survival in our patients was 92.3%, and 3-year graft survival was at least 55%; mean CIT was 8.1 h. One-year and 3-year graft survival rates were 92.3% and 55%, respectively; mean CIT was 8.1 h. [20] This shows that we also had a outcome similar to that of other series (3-year graft survival 55%-75%). [21],[22] The survival rates of patients receiving an allograft from a deceased donor, including both non-extended criteria and extended criteria donors, were 84% and 70%, respectively. [23],[24]

In our study, over a mean follow-up of 2.18 ± 1.75 years, patient and graft survival rates were 74.57% and 86.8%, respectively. We had high 1-year post-transplantation mortality with most of these deaths caused by sepsis. It is possible that triple drug immunosuppressive regimen with r-ATG induction, unhygienic living conditions, delayed presentation and diagnosis, tropical climate, limited availability and expense of diagnostic tools, and financial constraints for treatment in majority of patients may have contributed to the high infection rate, similar to that reported in other studies. [16],[25],[26],[27]

Infection, long duration of dialysis before transplant, ECD, increased DGF, and socio-economic factors pervasively influenced access to health care, and therefore may have contributed to high 1-year post-transplantation mortality, with most of these deaths being caused by sepsis. [28],[29],[30] Renal allograft recipients in developing countries may be more prone to infections, which are the most common cause of post-transplant mortality. [31]

The shortcoming of this analysis included its retrospective single-center evaluation and variable immunosuppressive regimens. In the circumstances of organ shortage, DDRTx has a potential to expand the donor pool and shorten the waiting list for RTx, especially in a developing country like India. Our study demonstrates DDRTx achieves acceptable graft function with patient/graft survival, encouraging the use of this approach.


   Acknowledgments Top


We are indebted to Ms. Priyardarshini Shah and Ms. Shobhanarani Sengunthar for data acquisition and analysis.

 
   References Top

1.Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999;341:1725-30.  Back to cited text no. 1
[PUBMED]    
2.Evans RW, Manninen DL, Garrison LP Jr, et al. The quality of life of patients with end-stage renal disease. N Engl J Med 1985;312:553-9.  Back to cited text no. 2
[PUBMED]    
3.Laupacis A, Keown P, Pus N, et al. A study of the quality of life and cost-utility of renal transplantation. Kidney Int 1996;50:235-42.  Back to cited text no. 3
[PUBMED]    
4.Abraham G, Jayaseelan T, Matthew M, et al. Resource settings have a major influence on the outcome of maintenance hemodialysis patients in South India. Hemodial Int 2010;14: 211-7.  Back to cited text no. 4
[PUBMED]    
5.Chugh KS. Five decades of Indian nephrology: A personal journey. Am J Kidney Dis 2009;54:753-63.  Back to cited text no. 5
[PUBMED]    
6.Khanna U. The economics of dialysis in India. Indian J Nephrol 2009;19:1-4.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7.Feroz A, Dabhi M, Gumber M, et al. Cadaveric renal transplantation: Our experience at the Institute of Kidney Diseases and Research Center, Institute of Transplantation Sciences, Ahmedabad. Transplant Proc 2007;39:721-2.  Back to cited text no. 7
[PUBMED]    
8.Vathsala A. Improving cadaveric organ donation rates in kidney and liver transplantation in Asia. Transplant Proc 2004;36:1873-5.  Back to cited text no. 8
[PUBMED]    
9.Racusen LC, Colvin RB, Solez K, et al. Antibody-mediated rejection criteria -vAn addition to the Banff′97 classification of renal allograft rejection. Am J Transplant 2003;3: 708-14.  Back to cited text no. 9
[PUBMED]    
10.Solez K, Colvin RB, Racusen LC, et al. Banff′05 Meeting Report: Differential Diagnosis of Chronic Allograft Injury and Elimination of Chronic Allograft Nephropathy (′CAN′). Am J Transplant 2007;7:518-26.  Back to cited text no. 10
[PUBMED]    
11.Chon WJ, Brennan DC, Murphy B, Sheridan AM. Acute renal allograft rejection: Treatment. Available from: http://www.uptodate.com [Last updated on 2011 Feb 15].  Back to cited text no. 11
    
12.Goplani KR, Kute VB, Vanikar AV, et al. Expanded criteria donor kidneys for younger recipients: Acceptable outcomes. Transplant Proc 2010;42:3931-4.  Back to cited text no. 12
[PUBMED]    
13.Sung RS, Guidinger MK, Lake CD, et al. Impact of the expanded criteria donor allocation system on the use of expanded criteria donor kidneys. Transplantation 2005;79:1257-61.  Back to cited text no. 13
[PUBMED]    
14.Goplani KR, Firoz A, Ramakrishana P, et al. Deceased donor organ transplantation with expanded criteria donors: A single-center experience from India. Transplant Proc 2010;42:171-4.  Back to cited text no. 14
[PUBMED]    
15.Abraham G, Shroff S, Nayak KS, et al. Deceased-donor renal transplantation program in India. Kidney Int 2010;77:378-80.  Back to cited text no. 15
[PUBMED]    
16.Mani MK. Review article, development of cadaver renal transplantation in India. Nephrology 2002;7:177-82.  Back to cited text no. 16
    
17.Prabahar MR, Soundararajan P. Cadaveric renal transplantation: The Chennai experience. Transplant Proc 2008;40:1104-7.  Back to cited text no. 17
[PUBMED]    
18.Shroff S, Navin S, Abraham G, et al. Cadaver organ donation and transplantation - an Indian perspective. Transplant Proc 2003;35:15-7.  Back to cited text no. 18
[PUBMED]    
19.Cho WH, Kim HT, Sohn CY, Joo SH, Park SB, Kim HC. Cadaveric Donor Kidney Transplantation: Review of 39 Cases. Transplant Proc 2000;32:1833-4.  Back to cited text no. 19
[PUBMED]    
20.Yazdani M, Izadpanahi MH, Gharaati MR, Tadayonn F. Cadaveric kidney transplantation: Five years experience at a single center. Transplant Proc 2007;39:904-6.  Back to cited text no. 20
[PUBMED]    
21.Bresnahan BA, McBride MA, Cherikh WS, Hariharan S. Risk factors for renal allograft survival from pediatric cadaver donors: An analysis of united network for organ sharing data. Transplantation 2001;72:256-61.  Back to cited text no. 21
[PUBMED]    
22.Hariharan S, McBride MA, Bennett LE, Cohen EP. Risk factors for allograft survival from older cadaver donors. Transplantation 1997;64: 1748-54.  Back to cited text no. 22
[PUBMED]    
23.Port FK, Dykstra DM, Merion RM, Wolfe RA. Trends and results for organ donation and transplantation in the United States, 2004. Am J Transplant 2005;5:843-9.  Back to cited text no. 23
[PUBMED]    
24.McCullough KP, Keith DS, Meyer KH. Kidney and pancreas transplantation in the United States, 1998-2007: Access for patients with diabetes and end-stage renal disease. Am J Transplant 2009;9:894-906.  Back to cited text no. 24
    
25.Jha V, Chugh KS. Posttransplant infections in the tropical countries. Artif Organs 2002;26: 770-7.  Back to cited text no. 25
[PUBMED]    
26.Jha V, Chugh S, Chugh KS. Infections in dialysis and transplant patients in tropical countries. Kidney Int 2000;57:S85-93.  Back to cited text no. 26
    
27.Kher V. End-stage renal disease in developing countries. Kidney Int 2002;62:350-62.  Back to cited text no. 27
[PUBMED]    
28.Goldfarb-Rumyantzev A, Hurdle JF, Scandling J, et al. Duration of end-stage renal disease and kidney transplant outcome. Nephrol Dial Transplant 2005;20:167-75.  Back to cited text no. 28
[PUBMED]    
29.Shoskes DA, Cecka JM. Deleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejection. Transplantation 1998;66:1697-701.  Back to cited text no. 29
[PUBMED]    
30.Rao PS, Ojo A. The alphabet soup of kidney transplantation: SCD, DCD, ECD-fundamentals for the practicing nephrologist. Clin J Am Soc Nephrol 2009;4:1827-31.  Back to cited text no. 30
[PUBMED]    
31.Samhan M, Al-Mousawi M, Hayati H, et al. Results in 158 consecutive cadaveric renal transplantations. Transplant Proc 2005;37: 2965-6.  Back to cited text no. 31
[PUBMED]    

Top
Correspondence Address:
Himanshu V Patel
Department of Nephrology and Clinical Transplantation, IKDRC-ITS, Civil Hospital Campus, Asarwa, Ahmedabad 380016, Gujarat
India
Login to access the Email id


DOI: 10.4103/1319-2442.109618

PMID: 23538375

Rights and Permissions




 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Acknowledgments
    References
 

 Article Access Statistics
    Viewed1645    
    Printed44    
    Emailed0    
    PDF Downloaded364    
    Comments [Add]    

Recommend this journal