Ten kidney paired donation transplantation on World Kidney Day 2013: raising awareness and time to take action to increase donor pool

Abstract

Background: Kidney paired donation (KPD) is feasible for any center that performs living related donor renal transplantation (LRDRTx). Lack of awareness, counseling and participation are important hurdles in KPD patients with incompatible donors. Materials and methods: This is an institutional review board approved study of 10 ESRD patients who consented to participate in the KPD transplantation at our center. All the surgeries were carried out on the same day at the same center on the occasion of World Kidney Day (WKD) (14 March 2013). All recipients had anatomic, functional and immunological similar donors. Results: KPD were performed to avoid blood group incompatibility (n = 8) or to avoid a positive crossmatch (n = 2). None of the patients experienced delayed graft function and surgical complications. At 3 month follow-up, median serum creatinine was 1 (range 0.6 to 1.25) mg/dL and two patients developed allograft biopsy-proven acute rejection and responded to antirejection therapy. Due to impact of our awareness activity, 20 more KPD patients are medically fit for transplantation and waiting for permission from the authorization committee before transplantation. Conclusion: This is a report of 10 simultaneous KPD transplantations in a single day in a single centre on WKD raising awareness of KPD. KPD is viable, legal and rapidly growing modality for facilitating LRDRTx for patients who are incompatible with their healthy, willing LRD.

• End-stage renal disease
• donor pool
• kidney paired donation
• living related donor
• renal transplantation
• World Kidney Day

Introduction

Impressive accomplishments have been made in Indian nephrology, and the expansion of therapeutic facilities in India is hampered by only economic constraints, not lack of expertise. The Indian chronic kidney disease (CKD) registry recently published its first report which showed that of all the stage V CKD cases, a majority (61%) were not on any form of renal replacement therapy (RRT) at the time of reporting, 32% on hemodialysis, 5% on peritoneal dialysis and 2% were being worked up for transplantation.1

India has a renal transplantation (RTx) rate of 3.25 per million of population (PMP) per year and the deceased-donation (DD) rate is 0.08 PMP per year, which is grossly inadequate.1–3 As per the Indian Transplant Registry (data from 48 hospitals), a total of 21,345 kidney transplantation are done in India from 1971 to 2013 out of which 20,569 are from living donors and 776 are from deceased donors. Economic constraints in operating an effective maintenance dialysis program leaves living donor RTx as the only viable option for end-stage renal disease (ESRD) patients in developing countries like India. The commonest cause of donor rejection is ABO incompatibility which eliminates up to one-third of the potential living related donor (LRD) pool. Diabetes, obesity and nuclear family consisting of married couple and their children are other reasons for lack of suitable donors.

Kidney paired donation (KPD) is a rapidly growing modality for facilitating LRDRTx for patients who are incompatible with their healthy, willing LRD. In absence of well-organized deceased donor transplant program, or transplantation with desensitization protocol and ABO incompatible transplantation, KPD promises hope to a growing number of patients suffering from ESRD. Lack of awareness, counseling and participation are important hurdles in KPD patients with incompatible donors. One of the most challenging barriers to KPD across state is the time required for permission from different state government authorization committee. World Kidney Day (WKD) provides a chance to reflect on the success of RTx as a therapy for ESRD that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness.4 We report 10 KPD transplantations in a single day at a single center on WKD 2013. The objective was to bring focus to the tremendous life changing potential of kidney transplantation, raise awareness of the success of organ transplantation and explore the real potential for transforming kidney transplantation into the routine treatment option for ESRD.

Materials and methods

This is an institutional review board approved study of 10 ESRD patients who consented to participate in the KPD transplantation at our center. All the surgeries were carried out simultaneously on WKD (14 March 2013). Transplants for patients from other states were done after permission from their own state and our state government authorization committee. The written informed consent was obtained from all study participants.

Recipient and donor work up

The recipients and donors were initially worked up for transplantation. All potential donors were informed about risks and benefits of KPD as an option prior to initiating evaluation. This allowed sufficient time for the potential donor to consider donation preferences, discuss options with their family and the donor evaluation team, and attenuate feelings of pressure or coercion if KPD is presented later. All recipients had anatomic, functional and immunological similar and suitable donors and they were allowed to meet each other before and after RTx with their mutual consent. All donors were subjected to a diethylene tri-amine penta-acetic acid renal scan before the transplantation and all displayed satisfactory glomerular filtration rate (>40 mL/min on each side). All recipients had complement-dependent cytotoxicity crossmatches and flow cytometry crossmatch negative donor of the same age group (except one with O blood group) as shown in Table 1.

Table 1. Recipient and donor demographic.

	Recipient					Donor
No	Weight (Kg)	Age (years)	ABOgroup	Original disease	HD (months)	Weight (Kg)	Age (years)	ABO group	HLA match
1	51	50	A	CGN	2	49	44	B	1
2	60	42	B	Diabetic nephropathy	7	51	37	A	1
3	55	50	B	CGN	12	50	40	A	0
4	46	28	A	Single kidney	15	48	25	B	3
5	64	34	A	Hypertension	30	55	34	O	0
6	50	41	B	Hypertension	3	50	38	A	1
7	27	15	B	Single kidney	2	50	54	O	0
8	62	28	O	Hypertension	8	45	27	B	1
9	49	50	O	Hypertension	9	55	44	A	0
10	45	50	A	ADPKD	5	45	38	O	1

CGN, chronic glomerulonephritis; ADPKD, autosomal dominant polycystic kidney disease.

Recipient and donor matching

Patient number 5 and 10 were sensitized due to multiple pack cell blood transfusions and their wives as donors. Patient number 5 had positive anti-human, globulin-enhanced, complement-dependent cytotoxicity crossmatch of 90 with his wife as potential kidney donor. He failed to respond to desensitization treatment and hence was kept in this list of KPD transplants. Patient number 10 with ESRD due to autosomal dominant polycystic kidney disease (ADPKD) underwent bilateral pre-transplantation nephrectomy for recurrent urinary tract infection not responding to therapeutic and prophylactic antibiotics. He was at high risk of infection with desensitization treatment and hence was not administered the same. Patients 8 and 9 were hard-to-match due to non-“O” donor and “O” recipient blood-type combinations. The 27-year-old wife with blood group “B” of patient 8 donated kidney to 15-years-old patient 7, in turn patient 8 received “O” blood group kidney from 54-years-old donor of patient 7.

Surgical details

On World Kidney Day, 14 March 2013, 10 transplantation surgeries were started from 7.30 am in morning and anastomosis of last patient was completed at 7.40 pm same day. A team of 15 surgeons, 10 anesthesiologist, 10 nephrologists, 2 immunopathologists, a transplant co-coordinator and other paramedical staff carried out the 10 transplantations. Eight donors had laparoscopic donor nephrectomy (five left sided, three right sided) and two had open donor nephrectomy (one right side and one left side). All donors had single renal artery and single renal vein except one donor with dual renal veins. Warm ischemia time (WIT), cold ischemia time (CIT) and anastomosis time (AT) are shown in Table 2. One pediatric recipient underwent simultaneous right nephroureterectomy. Immunosuppressive therapy constituted induction with methylprednisolone, 500 mg × 3 days and rabbit-antithymocyte globulin (1.5 mg/kg, single dose) with prednisolone and tacrolimus-based immunosuppression for maintenance therapy. All patients received prophylaxis against cytomegalovirus, fungal and Pneumocystis infections.

Table 2. Surgical details.

Patient No	Warm ischemia time (minutes, seconds)	Cold ischemia time (minutes)	Anastomosistime(minutes, seconds)	Intra-operative urineoutput (mL)
1	2; 51	60	20; 0	300
2	1; 46	53	35; 43	500
3	1; 26	15	25; 48	1200
4	2; 15	90	30; 0	600
5	1; 46	58	20; 0	1000
6	2; 56	30	38; 0	300
7	2; 0	50	40; 18	650
8	3; 23	9	14; 24	300
9	2; 29	22	14; 23	1100
10	3; 0	49	23; 16	600

Results

Recipient and donor demographic characteristics (Table 1)

All the KPDs were carried out smoothly and precautions to avoid mixing-up of donor kidneys at all levels were taken care of. A total of 5 KPD pairs, 3 conventional (2 balanced, 1 unbalanced) and 2 unconventional pairs of KPD transplantations were performed in 10 recipients. They were performed to avoid blood group incompatibility (n = 8) or to avoid a positive crossmatch (n = 2) (median panel-reactive antibodies >80%). All recipients were male, with a mean age of 39 (range 15–50) years. Original disease leading to ESRD were chronic glomerulonephritis (CGN) (n = 2), diabetic nephropathy (DN) (n = 1), hypertensive nephropathy (n = 4), single unit kidney (n = 2) and ADPKD (n = 1). Five recipients were residents of states other than Gujarat [Rajasthan (n = 1), Madhya Pradesh (n = 2), Uttar Pradesh (n = 1) and Haryana (n = 1)]. The mean age of donors was 34 (range 27–55) years, 1 was male and 9 were females. The relationships between the intended donors and recipients were spousal (n = 9) and extended family [uncle] (n = 1) with mean HLA match of 0.8 (median 1; range 0–3). Donor ABO blood group type was A (n = 4), B (n = 3) and O (n = 3). Recipient ABO type was A (n = 4), B (n = 4) and O (n = 2). The mean hemodialysis (HD) duration before RTx was 9.3 months (median; 2 months, range 2–30 months). The median waiting time between enrollment and successful exchange transplantation was 1 month (range 1–9 months).

Post-transplant outcome data

Immediately after the transplantation brisk urine output (>0.5–1 liter/hour) was observed in all the patients. None of the patients experienced delayed graft function and surgical complications. On third post-transplant day, median serum creatinine was 1 (range 0.7 to 1.22) mg/dL. Patient 5 who was sensitized and patient 7 developed allograft biopsy-proven combined acute cellular/humoral rejection and acute cellular rejection, respectively, and responded to standard antirejection therapy. At 3-month follow-up, median serum creatinine was 1 (range 0.6 to 1.25) mg/dL.

Discussion

World Kidney Day is meant to raise the awareness of kidney diseases. The barriers to universal transplantation as the therapy for ESRD include the economic limitations which, in some countries, place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high-income countries, the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise.4

From our personal experience in our country, despite legal permission for KPD from transplantation human organ act amendment 2011, one of the most challenging barriers to KPD at this time is the time required for permission from different state government authorization committee rather than financial reimbursement for donor evaluation as in the United States and prohibit the participation of patients in KPD from different states. The most of the limitation is not a willingness to participate in KPD, but rather barriers to execution.

KPD is underutilized in India and should be promoted with various awareness activities. There is no published data about total number of KPD done in India other than single-center reports.5,6 The report is particularly significant given that in a developing country like India, transplantation, especially living donor transplantation, in addition to survival benefit, makes most economic sense. Any strategy that increases the living donor pool therefore needs to be publicized. Our experience should be reported to help advance KPD in India and worldwide.

Recent study results are valuable for encouraging participation of KPD pairs and transplant centers in national KPD program.5–23

Our single-center experience has demonstrated that KPD is feasible, successful and, if applied to larger donor pools, capable of expanding access to RTx.6 In our center, we have performed a total of 115 KPD transplantations. We have performed only one three-way exchange8 and remaining were two-way exchanges. On 13 February 2013, we have also performed the first successful three-way KPD transplantation resulting in transplantation of highly sensitized patient and hard-to-match patient with AB donor from India.8 We have not performed any chain and non-directed donation.

In KPD from an old donor to a young recipient, it may be argued that elderly donors provide an inferior quality kidney. If an old donor–recipient pair is matched to a young donor–recipient pair, the young recipient may feel disadvantaged and may not be willing to exchange with an older donor. However, the findings of two registries (Australian registry and US renal data system) regarding impact of living donor age in outcome of RTx are of major relevance to solve this issue.10,11 Living donor age between 18 and 64 years has minimal effect on allograft survival.10 Living kidney donors, who are up to 30 years older than their recipients, provide kidneys of excellent quality. KPD should not be prohibited due to high donor–recipient age difference, when size of donor pool is small as in single-center KPD program.

One of the greatest obstacles to the implementation of regional or national KPD is the need for the donor to travel to their matched recipient’s hospital. The effects of prolonged CIT could be perceived as barrier to long-distance transportation of living donor kidneys. The finding from United Network for Organ Sharing/Organ Procurement and Transplantation Network data suggests that transport of live donor organs may be a feasible alternative to donor travel in KPD regions where CIT can be limited to 8 hours.12

We have earlier also compared the outcomes of KPD (n = 34) versus living related donor renal transplantation (LRDRTx) (n = 190) patients on regular follow-up, at our institute. There was similar graft survival, patient survival and rejection rates of KPD versus LRDRTx over 2 years post-transplantation, encouraging the use of this approach for national KPD program.7 In our short-term comparison, despite greater HLA mismatches, thymoglobulin induction and maintenance immunosuppression with prednisolone, tacrolimus, mycophenolate may have contributed similar graft survival and rejection rate in KPD and living related donor RTx.7,13

The waiting time in KPD is short as compared to deceased donor transplantation14 which could save the cost of maintenance dialysis and associated morbidity and mortality. ESRD patients have more willingness for KPD versus list exchanges.15

Transplant surgeons and economists should join forces to implement efficient, effective KPD systems. Kidney exchange will require innovations in how to arrange, coordinate and conduct surgeries, and in how to assemble and organize efficient clearinghouses. Therefore, KPD is a natural area of collaboration between surgeons and economists.

Each transplant center should have counseling for KPD, a KPD registry and peer mentorship program to increase participation from KPD. The wider participation from compatible donors can be increased by providing young donor or better human leukocyte antigen (HLA)-matched donor.16,17 The advantages of better HLA matches are less immunosuppression requirement, lower infective morbidity and better survival. Broader implementation of KPD would lead to more than 1000 additional live donor kidney transplants every year.18 All transplant centers should work together toward national KPD program and frame uniform acceptable allocation policy.

Conclusion

We present a report of 10 simultaneous KPD transplantations in a single day at a single center on World Kidney Day, raising awareness of KPD. Our report will provide motivation for others and give hope to those patients with renal disease for whom kidney transplantation does not seem easily possible. Our results show that KPD is viable, legal and rapidly growing modality for facilitating LRDRTx for patients who are incompatible with their healthy, willing living donor.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.