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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 188-193

Deceased donor transplantation – Our experience in the last 4 years


1 Department of Nephrology, VPS Lakeshore Hospital, Kochi, Kerala, India
2 Department of Nephrology, VPS Lakeshore Hospital and PVSM Hospital, Kochi, Kerala, India
3 Department of Urology, VPS Lakeshore Hospital and PVSM Hospital, Kochi, Kerala, India
4 Department of Anesthesia, VPS Lakeshore Hospital, Kochi, Kerala, India
5 Department of Urology, VPS Lakeshore Hospital, Kochi, Kerala, India
6 Department of Pathology, VPS Lakeshore Hospital, Kochi, Kerala, India
7 Department of Nephrology, PVSM Hospital, Kochi, Kerala, India
8 Department of Transplant Surgery, VPS Lakeshore Hospital, Kochi, Kerala, India
9 Department of Urology, PVSM Hospital, Kochi, Kerala, India
10 Department of Anesthesia, PVSM Hospital, Kochi, Kerala, India

Date of Submission01-Dec-2018
Date of Decision01-Mar-2019
Date of Acceptance05-May-2019
Date of Web Publication17-Sep-2019

Correspondence Address:
Dr. Vilesh Valsalan Kalthoonical
Department of Nephrology, VPS Lakeshore Hospital, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_80_18

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  Abstract 


Background: Kidney transplant is the best treatment option for end stage kidney disease. Deceased donor transplantation has helped in increasing the donor pool for waitlisted dialysis patients. We received seventy deceased donor kidneys through the Kerala Network of Organ Sharing (KNOS) over the past 4 years from August 2013 to August 2017 and transplanted sixty six with good outcome. Pre-implantation biopsy performed in marginal donors helped in decision making to take the kidney and increase the donor pool. Aims and Objectives: 1)To evaluate outcome of renal transplant recipients in deceased donor transplantation. 2)To evaluate the role of pre-implantation biopsy to improve donor selection for better long term outcome. Materials and Methods: Sixty-six deceased donor kidneys were transplanted into the recipients from our pool of 253 patients registered with the KNOS. Four cadaver kidneys were rejected based on pre-implantation biopsy. Fifty-nine transplants were done at VPS Lakeshore and seven were done at PVS Memorial Hospital, Kochi. Donors of age less than 65 years were considered. Pre-tranpslant evaluation of recipients on waiting list including lab and cardiac evaluation with PRA status was done. Cross match was done prior to transplant. Triple immunosuppression including cyclosporine, mychophenolate mofetil and prednisolone with basiliximab as induction agent was used in all cases. Low dose tacrolimus was introduced after the third month in some cases. Pre-implantation biopsy was done in marginal donors for better donor selection. Results: Of the 66 recipients, 52 (78.8%) were males and 14 (21.2%) were females. PRA status was negative in all recipients. Deceased donors <65 years of age were considered. Twenty deceased donor kidneys were biopsied before implantation, of which 16 were implanted. Four kidneys were rejected as one showed glomerulocystic changes . One had extensive thrombus in all glomeruli, one had >56% IFTA changes, and other had 30%–40% IFTA changes. Results at 4 years post-transplant showed graft survival in 55/66 (83.34%) and patient survival in 60/66 (90.91%) cases. Six patients died: two with pneumocystis carinii pneumonia (PCP) (at 9 months/3.3 years post-transplant), one with mucormycosis (at 16 months post-transplant), one with acute coronary syndrome (immediate post-transplant), and two patients with sepsis. The average serum creatinine was < 1.4 mg/dl in 48 (87.2%) cases, 1.4–2.4 mg/dl in 7 (12.7%) cases, and > 2.4 mg/dl in 1 (1.8%) case. The surgical outcome was good in all (100%) patients with no intraoperative surgical complications. Delayed graft function was noted in 18% of patients. Prolonged cold ischemia time was noted in patients with acute tubular necrosis. Six patients had acute rejection, of which two were antibody mediated, and four had acute cellular rejection. One patient had tacrolimus toxicity on biopsy and was shifted to everolimus. Infections included one patient with surgical wound infection, 12 patients with urinary tract infections, one patient with invasive fungal infection, and two patients with PCP. At 4 years, deceased donor transplantation has good graft and patient outcomes. Conclusion: Deceased donor transplantation has good graft outcome which is comparable to live non related donors. It has minimal paper work and less costly than routine live transplant. Pre-implantation biopsy should be considered in marginal donors for appropriate donor selection and avoid organ wastage in doubtful cases. In our study we noted that transplant outcome was better in recipients receiving kidney from with in the city limits because of less cold ischemia time. Hence facilities for early transportation of organs with minimal procedural hurdles to minimize cold ischemia time should be carried out by the concerned authorities. Proactivity from the Government at state, zonal and national level is needed to improve deceased donor pool and cadaver transplantation in India.

Keywords: Deceased donor, graft survival, patient survival, preimplantation biopsy, rejection


How to cite this article:
Kalthoonical VV, Nainan GK, Abraham GP, Mathew M, George D, Paul R, Sooraj Y S, Thomas PG, Radhakrishnan V, Manavalan FC. Deceased donor transplantation – Our experience in the last 4 years. Indian J Transplant 2019;13:188-93

How to cite this URL:
Kalthoonical VV, Nainan GK, Abraham GP, Mathew M, George D, Paul R, Sooraj Y S, Thomas PG, Radhakrishnan V, Manavalan FC. Deceased donor transplantation – Our experience in the last 4 years. Indian J Transplant [serial online] 2019 [cited 2019 Oct 19];13:188-93. Available from: http://www.ijtonline.in/text.asp?2019/13/3/188/266955




  Introduction Top


Renal transplant is the best modality of renal replacement therapy for patients with chronic kidney disease (CKD). Deceased donor transplantation (DDT) helps in increasing the donor pool.[1] DDT rate in India is now 0.34 per million population, which is about <5% of all kidney transplants in India.[2] The Kerala Network of Organ Sharing (KNOS) through the Mrithasanjeevani programme has helped in propagating awareness and conduct of deceased donor transplantation in Kerala. Out of the total 456 renal DDTs in Kerala state, our unit performed transplants for 66 out of 253 registered recipients during 2013–2017. Marginal donors can be evaluated with preimplantation biopsy and considered for transplant if the biopsy is acceptable, thereby increasing the donor pool. Timely coordination by a dedicated team with well-preserved donor prior to retrieval is key to good outcome.


  Materials and Methods Top


A retrospective analysis of 66 deceased donor transplants (59 transplants at VPS Lakeshore and 7 at PVS Memorial hospital Kochi) between August 2013 and August 2017 was done. Recipients were worked up for fitness for transplant. Cardiac workup included baseline electrocardiography and two-dimensional echocardiography, while coronary angiography was done only if indicated. Data collected were analyzed for age, sex, blood group, dialysis vintage, primary renal disease, comorbidities, preimplantation renal biopsies, surgical outcome, patient and graft survival rates, infections, rejection episodes, and recurrence of primary disease.

All patients in this group were Panel-reactive antibody (PRA) negative. Crossmatch test was carried out by complement-dependent microlymphocytotoxicity test, and the crossmatch result <10% was considered acceptable. Donors >65 years of age were not considered for organ retrieval. The donor kidney was perfused and stored in cold Histidine-tryptophan-ketoglutarate (HTK) solution with an ice pack around.

Immunosuppression

All patients received triple immunosuppression with cyclosporine, mycophenolate mofetil (MMF), and steroids. There was no specific reason for choosing cyclosporine. The unit was using triple immunosuppressives (cyclosporine + MMF + prednisolone) for the last decade prior to this study period and was comfortable with this regimen. Posttransplant diabetes mellitus was high in Tacrolimus (TAC) group, especially with a higher initial dose, which was a matter of concern. TAC levels were not done in Kerala at that time, and it was taking a long time to get reports (at least 1 week). Induction agent used was basiliximab. The first dose was given prior to surgery and second dose on day 4. Six patients received only single dose of basiliximab. All patients were converted to tacrolimus keeping a trough level of low normal (5–6 ng/ml) to avoid hyperglycemia due to initial high dose of tacrolimus. Acute cellular rejection was treated with pulse methylprednisolone 500 mg for 3 days followed by injection antithymocyte globulin (ATG). Acute antibody-mediated rejection was treated with plasmapheresis, intravenous immunoglobulin (IVIg)/rituximab, and, in refractory cases, bortezomib.

Marginal donors

Donors with a short history of diabetes mellitus with <500 mg/day proteinuria, hypertension, renal calculus, age >60 years, age >55 years with a history of cerebrovascular accident, and patients with prolonged cold ischemia were considered as marginal donors.

Marginal donors underwent preimplantation kidney biopsy. Wedge biopsy from the donor kidney was taken at the time of retrieval and sent for histopathological grading on a frozen section, and the biopsy site was sutured with prolene sutures. The biopsy report was available within 2 h, well within the waiting period of crossmatch report. The biopsy was graded as per scores based on the presence of interstitial fibrosis, tubular atrophy, vascular involvement, and glomerulosclerosis.[3]

Pre-implantation scoring [Figure 1] was done as per the algorithm proposed by Perico et al.[3]
Figure 1: Pre-implantation scoring algorithm proposed by Perico et al

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Postoperative evaluation

Ultrasonography (USG) of the transplant kidney was done on postoperative day 1, once before discharge and in between if delayed graft function (DGF) occurred. Cyclosporine levels were checked on day 5 and the drug dose was adjusted. Follow-up in the outpatient department with blood investigations was carried out twice weekly for 2 weeks, once weekly for 4 weeks, and then once monthly. In case of deranged renal function test, decreasing urine output and urinary abnormalities such as proteinuria, blood workup, and USG transplant kidney were done along with renal biopsy, when indicated.


  Results Top


In the present study, 66 patients underwent deceased donor renal transplantation from August 2013 to August 2017. The increased awareness in the general public through media and steps taken by the KNOS led to the rise in the number of deceased donor transplants in the state. In our series, six, 17, 17, 21, and five transplants were done in 5 years.

Among the 66 recipients [Table 1], 52 (78.8%) were males and 14 (21.2%) were females. The ages of recipients were as follows: < than 20 years in 1 recipient; 20–40 years in 21 recipients; 40–60 years in 38 recipients, and >65 years in 6 recipients. The etiology of CKD was as follows: diabetic nephropathy in 38 recipients, immunoglobulin A nephropathy in 7 recipients, focal segmental glomerulosclerosis (FSGS) in 2 recipients, polycystic kidney disease in 1 recipient, and others had CKD unidentified. Dialysis vintage was 15 ± 5 months. The recipients had the following blood groups: O blood group: 27, B blood group: 19, A blood group: 15, and AB blood group: 5. Two recipients had a second transplant with deceased donor kidney. All were Hepatitis C Virus (HCV) negative.
Table 1: Recipient characteristics

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The mean age of donors [Table 2] was 34.46 ± 11 years. Donor age groups were as follows: age <20 years in 2 recipients, 20–40 years in 39 recipients, 40–60 years in 28 recipients, and above 60 years in 1 recipient. Twenty deceased donor kidneys were biopsied before implantation, of which 16 were implanted. The four rejected kidneys showed glomerulocystic changes, extensive thrombus in all glomeruli, and one had >56% IFTA changes and other had 30%–40% IFTA changes [Figure 2] and [Figure 3]. Patients with >20% IFTA were not considered for both single and double kidney transplants. There was no bleeding from the site of biopsy nor complications. One patient had an aneurysm at the biopsy site on USG which resolved over time without intervention.
Table 2: Donor characteristics

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Figure 2: Cadaver donor kidney preimplantation biopsy on frozen hematoxylin and eosin stain shows extensive thrombus in all glomeruli in a 46yearold woman with baseline creatinine of 1.2 mg/dl

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Figure 3: Cadaver donor kidney preimplantation biopsy on frozen hematoxylin and eosin stain shows glomerulocystic changes in an 18yearold boy with baseline creatinine of 1.4 mg/dl

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In the 66 deceased donor transplants, 28 donors were in house, 19 donors were within city limits, and 11 donors were out of city limits. The mean cold ischemia time was 220 ± 90 min. Double J stents were placed in all cases and removed after 6 weeks. DGF defined as need of dialysis in the 1st week of transplant was seen in 12 patients. Three patients with DGF underwent biopsy which showed acute tubular necrosis (ATN). Nine of the 12 patients had recovered with good graft function. There was no case of primary nonfunction of graft.

Renal biopsy was done in nine patients post-transplant, of which three had ATN and seven had acute rejection [Table 3]. Two patients had antibody-mediated rejection with loss of one graft inspite of treatment with plasmapheresis, IVIg, and rituximab. Four patients had cellular rejection and were treated with pulse methylprednisolone and ATG (totally 7 had rejection, 2 had antibody mediated rejection, while 4 had cellular rejection and one had both cellular and antibody mediated rejections) [Table 3]. None of the patients had thrombotic microangiopathy.
Table 3: Complications

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Results at 4 years posttransplant showed graft survival (11/66 [83.34%]) and patient survival (60/66 [90.91%]). Six patients died: two with pneumocystis carinii pneumonia (PCP) (9 months/3.3 years posttransplant), one patient with invasive aspergillosis (16 months posttransplant), one with acute coronary syndrome (immediate posttransplant), and two patients with sepsis [Table 3]. Among patients surviving at 4 years, the average serum creatinine was <1.4 mg/dl in 48 (87.2%) patients, 1.4–2.4 mg/dl in 7 (12.7%) patients, and >2.4 mg/dl in 1 (1.8%) patient. The surgical outcome was 100% with no intraoperative surgical complications. One patient had recurrence of primary disease (FSGS) which was treated with plasmapheresis and Angiotensin receptor blocker (ARB).

Sixteen patients had urinary tract infection (UTI), and three patients had multi drug resistant UTI requiring antibiotic colistin [Table 3]. Diabetes mellitus was the native kidney disease in eight patients with UTI, and the rest were of unknown etiology. One patient had surgical wound infection treated with antibiotics. Two patients had PCP (9 months and 3.3 years post transplant), and both died inspite of treatment. One patient had invasive aspergillosis (16 months post transplant) involving the paranasal sinuses with extension to the frontal lobe. He was treated with liposomal amphotericin B and voriconazole but died. Two patients died of sepsis.


  Discussion Top


Deceased donor transplantation

DDT program has helped in increasing the donor pool for CKD patients waiting for transplant. In our series, there has been a steady rise in the number of DDTs in Kerala from 2013 to 2016. The drop in deceased donor transplants in the year 2017 was due to procedural delay, i.e., cumbersome procedure in declaring brain death as per the new rules laid by the state government. The procedure includes need of presence of four doctors, of which two have to be from any of the government hospitals, with video recording of the apnea test and nerve conduction study to maintain transparency of the brain death declaration. Nonavailability of resources and time taken to arrange for the above have led to an increase in cold ischemia time and reversal of consent in some cases.

Marginal donors

The DDT rate in India is among the lowest in the world[2] with more demand than supply, making it imperative to look for the increasing donor pool. Marginal donors with proper evaluation including preimplantation biopsy have rendered an acceptable option. In our series, we included the following:

Preimplantation biopsy

Preimplantation biopsy helped in securing 16 vital donors which would have otherwise been rejected. In one case of a young 18-year-old donor with a history of road traffic accident with creatinine 1.4 mg/dl on arrival to the hospital, which would have been otherwise implanted, was rejected based on biopsy finding of glomerulocystic changes. Preimplantation biopsy should be considered in marginal donors with a short history of diabetes mellitus with proteinuria <500 mg/dl and hypertension and in the elderly. It is a useful tool with a dedicated expert renal pathologist in house.[4]

Horseshoe donor kidney

One deceased donor had horse shoe shaped kidney, with the right kidney having two arteries and single vein and the left kidney having four arteries and two veins with the isthmus [Figure 4] and [Figure 5]. Due to multiple arteries on the left, the right kidney with part of the left was transplanted to a single recipient [Figure 6]. The graft is functioning well with a creatinine of 1.5 mg/dl.[5]
Figure 4: Horseshoe-shaped kidney as received from a deceased donor

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Figure 5: Due to multiple arteries on the left, the right kidney with part of the left was transplanted to a single recipient

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Figure 6: Computed tomography (kidneys, ureters, and bladder plain) image of the implanted, modified horseshoe-shaped kidney

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Donor kidney with calculus

One deceased donor kidney had two calculi measuring 5 mm each in the upper and lower poles.

During the bench surgery, a pediatric cystoscope was inserted, and stones were fragmented using holmium YAG laser and then implanted with good graft function.[6]

Donor with Klebsiella bacteremia

One donor had Klebsiella bacteremia which was sensitive to all groups of antibiotics on culture, and hence, donor kidney was retrieved after administering the appropriate antibiotic to the donor and the same antibiotic was given to the recipients pre- and post transplant. Both recipients had a stable postoperative course with good graft function.[7]

Donor kidney with stripped cortex and accidentally incised cut on cortical surface

The cut area was sutured with prolene, and on the stripped area, a patch was applied. There was a small lymphocele in this patient which resolved over time.

Donor kidney with atheromatous thrombus in renal artery

In this case, donor artery thrombectomy was done, and postoperative heparin was given with achievement of good global perfusion.

Six-year-old donor

The surgeon on bench dissection had initially planned to do en bloc anastomosis, but due to adequate size of kidneys and prior normal renal function, two kidneys were anastomosed to two different recipients. Both the recipients had good graft function at the end of 1 year and 3 years.

Single-dose basiliximab

Six patients received single-dose basiliximab due to financial problems stated after transplant. These patients in 1-year follow-up period are having mean creatinine value of 1.2 mg/dl. This group of patients will put insight on whether single-dose basiliximab is enough in certain group of patients, which needs further evaluation and long-term follow-up.[8]

Cold ischemia time

In our series, 28 donors were in house with minimal cold ischemia time and had better outcomes. Out-of-city limit donors had less coordination with prolonged cold ischemia time, directly affecting graft outcome with loss of one graft where the cold ischemia time was 13 h.[9]


  Conclusion Top


DDT increases donor pool with satisfactory patient and graft outcomes. We strongly recommend that preimplantation biopsy should be considered in marginal donors to increase the donor pool. A dedicated team with timely coordination and good donor maintenance is key to long-term successful graft outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

We acknowledge the immense support from the hospital administration and contribution of the Departments of Urology, Anesthesia, Cardiology, Neurology, Neurosurgery, and transplant coordinators of our hospitals and also the transplant coordinators and transplant teams of other hospitals, and salute the families of deceased donors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, et al. Systematic review: Kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant 2011;11:2093-109.  Back to cited text no. 1
    
2.
Abraham G, Vijayan M, Gopalakrishnan N, Shroff S, Amalorpavanathan J, Yuvaraj A, et al. State of deceased donor transplantation in India: A model for developing countries around the world. World J Transplant 2016;6:331-5.  Back to cited text no. 2
    
3.
Perico N, Ruggenenti P, Scalamogna M, Remuzzi G. Tackling the shortage of donor kidneys: How to use the best that we have. Am J Nephrol 2003;23:245-59.  Back to cited text no. 3
    
4.
Kari JA, Ma AL, Dufek S, Mohamed I, Mamode N, Sebire NJ, et al. Can pre-implantation biopsies predict renal allograft function in pediatric renal transplant recipients? Saudi Med J 2015;36:1299-304.  Back to cited text no. 4
    
5.
Yun S, Woo HD, Doo SW, Kwon SH, Noh H, Song D. Transplantation of a horseshoe kidney found during harvest operation of a cadaveric donor: A case report. J Korean Med Sci 2014;29:1166-9.  Back to cited text no. 5
    
6.
Vasdev N, Moir J, Dosani MT, Williams R, Soomro N, Talbot D, et al. Endourological management of urolithiasis in donor kidneys prior to renal transplant. ISRN Urol 2011;2011:242690.  Back to cited text no. 6
    
7.
Outerelo C, Gouveia R, Mateus A, Cruz P, Oliveira C, Ramos A, et al. Infected donors in renal transplantation: Expanding the donor pool. Transplant Proc 2013;45:1054-6.  Back to cited text no. 7
    
8.
Cunningham KC, Hager DR, Fischer J, D'Alessandro AM, Leverson GE, Kaufman DB, et al. Single-dose basiliximab induction in low-risk renal transplant recipients. Pharmacotherapy 2016;36:823-9.  Back to cited text no. 8
    
9.
Ponticelli CE. The impact of cold ischemia time on renal transplant outcome. Kidney Int 2015;87:272-5.  Back to cited text no. 9
    


    Figures

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