Chapter 4 UNDERSTANDING SUPPORT FOR TISSUE DONATION ACROSS
5.1.2. Living donor kidney transplantation
LDKT accounted for approximately 40% of current kidney transplant activity worldwide [210]. Compared to DDKT, LDKT has been associated with better clinical outcomes. While patients remaining on the waiting list could die due to long waiting time or be excluded from the waiting list due to a decrement in health status, LDKT could shorten their waiting time and increase the probability of successful graft by offering them a more compatible donor. In addition, the LDKT surgery can be scheduled to facilitate the transplant process thanks to planned activities. For example, it can be timed when donor’s health is optimal and the potential transplanted kidney exposed to less damage compared to DDKT. In the UK, one-year and five-year graft survival of LDKT are 98% (95%CI: 98-99) and 92% (95%CI: 91-93%), respectively, in comparison with 94% (95%CI: 94-95) and 87% (95%CI: 86-88%) among DDKT [591]. Survival benefits of LDKT relative to DDKT persist in all age groups [592]. In terms of other outcomes, other studies reported less waiting time and lower risk of rejection for live kidney grafts compared with cadaveric kidney grafts [208,211,593].
Even in case of incompatible transplantation, HLA-incompatible (HLAi) LDKT could achieve better survival outcomes compared to those receiving a DDKT or remaining in the waiting list, and to those remaining in the waiting list only [594]. Spouse-donor kidneys and parental-donor kidneys also had comparable graft-survival despite poor HLA matching in the former case [595]. On the other hand, one UK study found no survival benefit of conducting a direct HLAi transplant compared to matched cases listed for DDKT [596]. The difference in defining studied cohorts were acknowledged as the possible explanation for these findings [596]. Nevertheless, the innovations of desensitized treatments prior to kidney transplantation provide the potential to improve outcomes of incompatible transplantation [597].
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5.1.2.2. Current studies on cost of living donor kidney transplantation
Given the superior survival outcomes as well as the potential to avoid dialysis for a lifetime, LDKT would have better economic benefits compared to other types of RRT.
Although kidney transplantation has been utilised as the optimal treatment for ESRD over decades, only a few studies examined cost of LDKT and DDKT in distinct healthcare systems. Table 5.1 presents a summary of these studies on the cost of LDKT. All costs were adjusted for inflation to 2019 values based on the relevant Consumer price index of their country of origin [598], and then adjusted for purchasing power parity to 2019 US dollars using Organisation for Economic Co-operation and Development (OECD) data [599] (i.e. all costs are presented as 2019 US dollar) to facilitate comparison.
As presented in Table 5.1, among the aforementioned studies that estimated the cost of DDKT and LDKT, two studies were conducted in the US reporting comparable costs of LDKT per year of $37,000 [600] and $27,000 [565], while the other US study reported significantly higher charge for LDKT per year of over $130,000 [589] (2019 US dollar). This difference may be due in part to the use of cost and charge as the measurement of value in terms of money in these studies wherein charge is often higher than cost due to the hospital markup in the US [601]. However, it is noted that none of the three studies provided details of the included costs/charges, which complicates comparison across studies.
Three recent studies - in Spain [602], Canada [184], and the Netherlands [603] - provided more detailed data of LDKT cost (Table 5.1). At 1 year following kidney transplantation, the mean healthcare cost per LDKT case was $51,277 in Spain and
$59,274 in Canada (2019 US dollar). While comparing each cost category in these studies, it is noted that all pre-transplant workup, transplantation, post-transplantation costs were significantly higher in Canada compared to Spain. Moreover, the Canadian study also took the cost incurred by donors into account (such as pre-transplant workup cost, donor graft removal cost, and cost of follow-up to 90 days in living donor) [184], thus making their estimates higher than the estimates in the Spanish study [602]. The Dutch study was the only one that considered other non-RRT costs such as mental health care cost, transportation cost, and healthcare cost spent abroad [603]. The estimated cost of LDKT was $99,876 in the Netherlands (2019 US dollar), representing 25% lower than DDKT [603].
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Table 5.1. Summary of studies on cost of living donor kidney transplantation (all costs are presented in 2019 US dollar)
Study Country Study design Intervention Comparators Cost estimates Conclusion Cost of LDKT
Smith et al.
(2000) [600]
US Data: United States Renal Data System data (USRDS) 1991-1996 Outcome: healthcare payment, including eight categories of costs:
inpatient hospital, outpatient hospital, dialysis, clinic/home health, surgeons, laboratory &
radiology, immunosuppression, and other medical
Perspective: healthcare payer (Medicare)
Sample size: 42,868 DDKT and 13,754 LDKT
LDKT DDKT First year post-transplant DDKT: $58,676
LDKT: $36,588
Five year post-transplant (total):
DDKT: $175,280 LDKT: $142,570
LDKT is cost- saving
compared to DDKT
Inpatient hospital services accounted for
most of
savings of LDKT
Mullins et al. (2003) [589]
US Data: USRDS 1997-1998
Outcome: monthly institutional charges before and after dialysis initiation or transplantation.
Charges came from institutional and physician/supplier claims Perspective: healthcare payer (Medicare)
Sample size: 230,769 dialysis patients,
LDKT, Laparoscopic LDKT, and DDKT
Dialysis At 2 year follow-up:
Dialysis: $348,100 DDKT: $319,041
Laparoscopic LDKT:
$267,043
LDKT: $266,099
Dialysis charges exceeded
charges LDKT,
Laparoscopic LDKT, and
LDKT had additional economic benefits
compared to DDKT
Laparoscopic transplantation
may be
potential
165 44,063 transplant patients (181
laparoscopic LDKT, 11,466 LDKT, and 32,416 DDKT)
DDKT after 10, 14, and 18 months, respectively.
Axelrod et al. (2018) [565]
US Data: USRDS, University Health System Consortium, and literature review.
Outcome: mean total medical payment over 10 years, estimated by a discrete event simulation Perspective: healthcare payer (Medicare)
Sample size: a hypothetical cohort of 20,000 patients with ESRD
LDKT, ABOi LDKT, HLAi LDKT Low-KDPI and High- KDPI DDKT
Dialysis Mean total medical payment over 10 years:
Dialysis: $311,149
Low-KDPI DDKT:
$316,655
High-KDPI DDKT:
$352,114
LDKT: $269,610 ABOi LDKT: $388,520 HLAi LDKT: $468,917 Compared to dialysis, LDKT and low-KDPI DDKT were cost- saving, high-KDPI DDKT, ABOi or HLAi LDKT were cost-
effective (at
$100000/QALY threshold)
Kidney
transplantation is cost- effective across all donor types, regardless of marginal organs and innovative LDKT practices
Barnieh et al. (2011) [184]
Canada Data: Southern Alberta Transplant Program, Alberta Health and Wellness, and the Calgary Health Region corporate database (1998- 2006)
LDKT DDKT At 2 year follow-up:
LDKT: $118,547 (95%CI:
110,581-126,512)
Costs of LDKT and DDKT are comparable in Canada
166 Outcome: all direct healthcare-
related costs for both recipients and donors during five distinct periods:
pre-transplant, transplant and post- transplant to 90 days, 1 year, and 2 year.
Perspective: Healthcare payer Sample size: 357 kidney recipients (130 LDKT, 227 DDKT)
DDKT: $121,325 (95%CI:
114,480-128,172)
In which cost for donors:
Living donor: $18,160 (95% CI: 16,873-19,447) Deceased donor: $37,051 (95% CI: 34,479-39,625) Sánchez-
Escuredo et al. (2015) [602]
Spain Data: Hospital Clinic in Barcelona (2011)
Outcome: healthcare costs, including cost of prior-transplant evaluation, cost of surgical intervention, and post-transplant follow-up for 1 year. For Haemodialysis (HD) patients:
dialysis courses, drugs, admissions, medical appointments, and indirect costs (not specified)
Perspective: healthcare payer Sample size: 106 patients, 57 HD and 49 LDKT
LDKT HD LDKT: $51,277 ($13,940
for donors and $37,335 for recipients)
HD: $73,749
Key driver of costs among recipients was hospital stay and among donor was surgical cost.
LDKT represents a saving of $22,471 per patient per year in Spain.
LDKT is cost effective during the first year post- transplantation
Mohnen et al. (2019) [603]
The
Netherlands
Data: Dutch health insurance claims data (2012-2014)
Outcome: total annual health care costs of 5 dialysis modalities (in-
7 RRT
modalities
N/A The average cost in the year of transplantation:
LDKT: $99,876 (SD:
52,626)
CAPD was the most cost- saving option
167 centre HD, home HD, continuous
ambulatory peritoneal dialysis CAPD, automated peritoneal dialysis APD, and mixed dialysis), LDKT, and DDKT. Costs of transplant included donor expenses, pre- and post- transplant care, non-RRT costs (including primary care, mental health, medication, healthcare abroad, travel)
Perspective: N/A
Sample size: 3412 dialysis, 1554 LDKT, 1275 DDKT
DDKT: 135,355 (SD:
49,046)
The average annual cost for dialysis:
In-centre HD: $126,053 (SD: 29,262)
Home HD: $118,479 (SD:17,214)
CAPD: $105,570 (SD:
37,070)
APD: $122,400 (SD:
25,710)
Mixed dialysis: $144,042 (SD: 41,156)
Cost in first year of LDKT
was 25%
lower than that of DDKT
Costs incurred by living donors Klarenbach
et al. (2014) [257]
Canada Data: 7 transplant centres in Canada (2004-2008)
Outcome: out-of-pocket cost, lost wages and home productivity loss.
Perspective: Donor perspective Sample size: 100 living kidney donors
Living kidney donors
N/A The mean total cost was
$3,274 (SD 4,712);
A third of donors incurred cost over $3000, and 15%
incurred cost over $8000
Living
donation had large impact
on some
individuals.
Habbous et al. (2018) [604]
Canada Data: Trillium Gift of Life Network database and several databases from Institute for
Living kidney donors
Healthy matched controls
Compared to healthy matched controls, the incremental healthcare
Nephrectomy procedure accounted for
168 Clinical Evaluative Sciences
(2004-2014)
Outcome: healthcare costs in 3 periods (pre-donation evaluation, perioperative period, and 1 year post-transplant)
Perspective: Canadian healthcare payer
Sample size: 1099 living kidney donors and 4396 matched controls
costs of living kidney donors was $14,274 ($13,857-$14,692).
The operative period costs:
$10,247 (95%CI, $10,002-
$10,491)
most costs of care for living kidney donors
Przech et al.
(2018) [210]
Canada Data: 12 transplant centres in Canada (2009-2014)
Outcome: Out-of-pocket and lost productivity costs including lost wages and inability to perform normal activities (since the donor evaluation process to 3 months after donation). Use micro-costing approach via a survey
Perspective: N/A
Sample size: 912 living kidney donors
Living kidney donors
N/A The median total cost:
$1,973 (95%CI: $785-
$4,881).
On average, the total costs were higher in spousal compared to directed non- spousal donors, and in directed donors compared to non-directed donors.
Out-of-pocket and lost productivity costs are substantial in many living donors.
Note: KDPI: Kidney Donor Profile Index, Higher KDPI is associated with a greater risk of rejection. ABOi: blood type ABO incompatible, HLAi:
human leukocyte antigen incompatible. CAD: Canada. 95%CI: 95% confidence interval, SD: standard deviation, N/A: not available. RRT: renal replacement therapies. All costs were adjusted for inflation to 2019 values based on the Consumer price index of their country of origin, and then adjusted for purchasing power parity to 2019 US dollars using Organisation for Economic Co-operation and Development (OECD) data.
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Nevertheless, none of these studies examined productivity losses (including both absenteeism and presenteeism) of the recipients and/or donor due to the transplant surgery, a component of cost which has been shown to be significant in other studies and that could pose a significant financial barrier to the donation (Table 5.1) for some groups. Moreover, although detail was not provided, it is conceivable that the cost of organ acquisition between LDKT and DDKT could vary considerably and be worthy of examination. Thus, there could be differences in costs of transporting the kidneys (DDKT) which become available in a stochastic manner and have time limited viability relative to those of a scheduled living donation. These include not only transport – where for example in DDKT a flight may have to be chartered- but also transplant team costs – having an on-call team (DDKT) compared to that of a scheduled transplant team (LDKT). The distinct features of discussing the donation process with family member of a deceased donor compared to that with the living donor also impose different pressures on healthcare professionals, which might have implications for costs of organ acquisition. Similarly, the evaluation of cost- effectiveness of LDKT (or DDKT) relative to dialysis alone need to be carefully considered. In the absence of transplantation, for example, costs of dialysis should include the capital expense of expanding dialysis capacity - building new dialysis units to accommodate all ESRD patients - rather than simply assuming that current supply can be expanded at no additional cost. Typically in cost–effectiveness analyses, a unit cost is attached to an activity on the assumption of perfectly elastic supply, an assumption that may not in all cases be sustainable. These issues warrant further research.
Although there should not be any costs placed on living donors, some studies have reported the existence of financial barriers to the donors. Table 5.1 presented three studies focusing on cost incurred by living kidney donors in Canada. When considering healthcare costs only, Habbous et al. found that the cost in the perioperative period accounted for 71.8% of total cost of living donor (since donor evaluation up to 1-year post-transplant) [604]. While Canada implements a universal system of healthcare finance and the government covers these operative cost, this is
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not the case in many countries [605] which can be important depending on the perspective adopted by an economic evaluation. Thus, the comparative analysis of RRT modality from a healthcare perspective should take account of entitlements to publicly funded care in the system(s) under consideration – whether for example, travel costs, lost income or concomitant healthcare needs are reimbursed for the donor, at what level and for how long. Two other studies provided comprehensive analyses on financial barriers including out-of-pocket costs, and lost productivity costs (including lost wage, inability to perform normal activities, childcare, care for dependents) [210,257]. These costs varied from $1,973 to $3,274 (2019 US dollar) [210,257]. Nevertheless, none of the studies examined the potential cost in terms of quality of life decrement that may be experienced by the living donor before and after the transplant, a cost that while sometimes referred to as “intangible” has been estimated in other circumstances and may be the key cost from the donor’s perspective.
The aforementioned studies have provided estimates of economic or social costs associated with kidney transplantation in distinct settings. However, most of these studies did not take into account the potential impact of comorbidities or socio- demographic characteristics of recipients/donors [184,589,600,602], or only estimated post-transplant costs but excluded pre-transplant costs [589,600], excluded organ acquisition costs [565,589,600], were conducted in a single-center [602], focused on cost of donors only [604], or did not include inpatient cost data [565]. Moreover, the extent to which components of costs were included is unclear in many studies [565,589,600,604]. Some important cost components borne outside of healthcare such as the transport of kidneys have not been explored. Besides, changes in healthcare utilization such as medication use before and after kidney transplantation are important but not yet fully understood. An analysis of costs in a more detailed manner is therefore necessary. It is unclear if comparable evidence in the UK healthcare system exists, as no publication in this area could be located. Given the significant burden of CKD and ESRD, further research is warranted.