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Volume: 13 Issue: 5 October 2015

FULL TEXT

ARTICLE
A Single Center Experience With Adult Dual Kidney Transplant

Objectives: Our renal transplant center in South Australian has been at the forefront of dual kidney transplants in Australia. In this study, we reviewed the 17 adult dual kidney transplants performed at our center between 1998 and 2014.

Materials and Methods: We retrospectively reviewed the 17 adult dual kidney transplants performed at our center since 1998 and report data pertaining to donor demographics, preimplant function, and histology of donor kidneys, as well as postoperative outcomes of transplant recipients.

Results: The mean age of donors was 68.5 ± 7.27 years, with 47% presenting with comorbid disease adversely affecting renal function (diabetes or hypertension). Histologic sampling of donor kidneys showed high rates of glomerular obsolescence, scarring, and vascular sclerosis. The mean age of recipients was 57.18 ± 10.93 years, with 10 patients receiving kidneys that were implanted bilaterally in each iliac fossa and 7 patients having both kidneys implanted into 1 iliac fossa. Early surgical com-plications (within the first 2 wk) were found in 6 patients (4 bilateral, 2 unilateral). In patients with bilaterally placed grafts, 2 developed a urinary leak, 1 lost both grafts secondary to renal vein thrombosis, and 1 lost a single graft due to renal vein thrombosis. In patients with unilaterally placed grafts, 1 had wound infection and 1 had double graft loss related to renal vein thrombosis.

Conclusions: Adult dual kidney transplants offer an alternative use of kidneys from marginal donors.


Key words : Renal transplant, Kidney

Introduction

The worldwide shortage of suitable organs available for transplant is an issue of concern in light of the increasing demand. In Australia, the number of deceased-donor organ transplants has steadily increased. Before 2011, our center had performed 14 of the 31 dual organ transplants (45%) in Australia. Recently, the number of dual kidney transplants in Australia has grown as more centers perform adult dual kidney transplants (ADKT) using kidneys from marginal donors. Since 2009, there have been 53 ADKT in Australia compared with 76 total dual-organ transplants in Australia since 1995.1

In the United States, the donor pool has steadily increased; however, this has been greatly outweighed by the even greater annual increase in the number of patients waiting for organs.2 Over the past 10 years, there has been an approximately 60% increase in the number of kidney donors over 65 years old, indicating a greater availability of marginal kidneys. As a result, in the United States, the discard rate for kidneys from donors over the age of 65 years approaches 60%, with biopsy findings being the main reason for discard in 37.34% and anatomic abnormalities being cited in 7.07%.2 In Australia, the overall discard rate after recovery has been 2.99% (9% for kidneys from donors > 65 y) in 2012 and 6.66% (11% for kidneys from donors > 65 y) in 2013.3

Adult dual kidney transplant offers a means to maximize the use of kidneys from older donors and from other marginal donors. In multiple international studies, ADKT has been used with great success, with reports of graft function superior to single kidney transplants (SKT) from expanded criteria donors (ECD).4-8 Furthermore, comparable outcomes have been reported between recipients of ADKT and those of SKT from standard criteria donors.6-8

In this study, we report the experience of ADKT at the Central Northern Adelaide Renal and Transplantation Service, which has been at the forefront of performing ADKT in Australia.

Materials and Methods

Since 1998, our center has performed 17 ADKTs. We retrospectively reviewed these cases and report data pertaining to donor demographics, function and histology of donor kidneys before transplant, and postoperative outcomes of transplant recipients. Donor cause of death and graft and patient survival were extracted from the Australia and New Zealand Organ Donation and Australian and New Zealand Dialysis and Transplantation Registries, as were recipient and donor comorbidities immediately before transplant (diabetes, peripheral vascular disease, coronary vascular disease, cerebral vascular disease, and lung disease). We recorded serum creatinine levels at 1, 3, 6, 12, and 24 months. A multidisciplinary assessment guided the decision to allocate ECD kidneys to recipients of ADKT versus SKT. We factored in several variables, including histologic appearance (diffuse glomerular sclerosis > 20%, fibrosis > 20%, and severe vascular sclerosis), gross morphologic assessment, donor and recipient comorbidities, and donor terminal serum creatinine levels. In general, the donor kidneys were from donors with the following characteristics: age ≥ 54 years old, preexisting hypertension, diabetes mellitus, elevated or rising serum creatinine levels, history of vascular disease, history of systemic disease, or history of medications known to affect the kidneys. Adult dual kidney transplant was considered if the donor creatinine clearance was < 80 mL/min, which was assessed by estimating creatinine level using the best admission serum creatinine level.

Outcomes were compared between groups using Pearson product moment correlation analysis or Fisher exact test as appropriate. Continuous variables were analyzed using t tests or 1-way analysis of variance as appropriate (after assumptions of normality were checked) and are presented as means ± SD. Patient and graft survival were analyzed using Cox proportional hazards regression model. We analyzed associations between recipient estimated glomerular filtration rate over time and placement using mixed effects regression models, with patient as a random effect. The small numbers of patients prevented any meaningful adjusted analyses.

The study was approved by the Ethical Review Committee of our center. All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from all patients.

Results

Table 1 shows characteristics of the 17 donors related to demographics and comorbid conditions and describes the morphology, histology, and function of the grafts by graft placement. The most common cause of death was intracranial hemorrhage in 12 donors (70%). Importantly, systemic disease with potential to adversely affect renal function, namely hypertension and diabetes, was found in 8 donors, with 3 donors being affected by both conditions. The mean serum creatinine level was 81.18 ± 28.1 μmol/dL, with 3 donors having a serum creatinine level above 110 μmol/dL. Right kidneys had mean glomerular obsolescence of 20.37%, with left kidneys having 19.69%. The mean degree of scarring was 12.19% for right kidneys and 15% for left kidneys. An important observation was that a high number of grafts had been affected by moderate to severe vascular sclerosis before transplant (66.67%). Furthermore, cystic and atheromatous changes were prevalent among recovered kidneys, with 42.9% and 53.6% of grafts being affected.

All patients who received grafts were recipients of primary grafts. In our center, dual kidney recipients were older with a mean age of 57.18 ± 10.9 years (Table 2). Most recipients were men, with only 6 female patients (35.3%) receiving a dual kidney transplant.

The mean cold ischemia time for first kidney was 15.10 ± 4.20 hours, with the second kidneys being grafted an average of 1.4 hours later (Table 3). Most of the grafts were transplanted into bilateral iliac fossae, with 7 transplants (41%) performed into the same fossa (unilateral). Early surgical complications (within the first 2 wk) were found in 6 patients (4 bilateral, 2 unilateral). In the 4 patients who had bilaterally placed grafts, 2 developed urinary leak, 1 lost both grafts secondary to renal vein thrombosis, and 1 lost a single graft because of renal vein thrombosis. In the 2 patients who had unilaterally placed grafts, 1 had wound infection and 1 had double graft loss related to renal vein thrombosis (Table 4). Patients with unilateral placement had higher overall estimated glomerular filtration rate (P = .01; values calculated using mixed effect reg-ression model) versus patients with bilateral placement; in addition, recipient estimated glomerular filtration rate did not vary significantly over time between the 2 groups (P = .68 for the time-placement interaction; Figure 1).

There were 5 deaths (3 in the bilateral group and 2 in the unilateral group) in 96 patient-years of follow-up. Cox proportional hazards regression model suggested no association between graft survival and placement of kidneys (P = .97). Even with death considered as a competing risk, graft placement was not associated as being a technique failure (P = .79). Only 2 patients returned to dialysis (1 with unilateral transplant and 1 with bilateral transplant); again, this factor was not associated with kidney placement (P = .35). We did not find any statistically significant results even after we adjusted the Cox proportional hazards regression model histologically. Our model suggested no significant association between higher range of glomeruli, scarring, and severe vascular sclerosis and graft failure.
In our patient cohort, the median graft survival was 5 years, with 1-year graft survival shown in 14 patients (survival rate, 0.82), 3-year graft survival in 11 patients (survival rate, 0.76), and greater than 5-year graft survival in 8 patients (survival rate, 0.59). In our patient cohort, the longest surviving graft was 15 years (bilateral placement). The median graft survival with unilateral placement was 3 years and 7 years with bilateral placement.

Discussions

The first reported cases of ADKT by Johnson and associates9 identified suboptimal renal mass as a factor that can be overcome with the use of 2 kidneys from the same donor. In rat models, it has been shown that the use of greater nephron mass to adequately meet the metabolic demand of the recipient leads to improved long-term renal function.10 An initial increase in the transplanted nephron mass has been identified in subsequent human studies to be an important factor in determining graft survival.11,12

The early results with ADKT have indicated better outcomes than with SKT from older donors, as well as from those with comorbid conditions affecting renal function.5,13 Tan and associates8 compared patients who received ADKT based on a combination of histology and clinical parameters with those who received SKT from younger donors and found comparable 8-year patient and graft survival results. In a recent study by Salifu and associates,7 excellent 9-year graft survival was shown (64%) in ADKT recipients, which was comparable to that shown with SKT (60%).7

Recently, a study used the United Network for Organ Sharing database to compare ADKT and SKT recipients from ECD and from standard criteria donors.4 This study showed lower delayed graft function rates in the ADKT patients versus that shown in SKT patients from ECD and comparable overall 3-year graft survival.

The criteria for allocation of donor kidneys to ADKT varies. Early reports have suggested the use of clinical parameters to determine the allocation of ECD kidneys for use in ADKT, namely, age ≥ 59 years and donor creatinine clearance ≤ 90 mL/min.14 Alternatively, Andres and associates15 suggested the use of a pregraft renal biopsy to identify the degree of glomerulosclerosis as a criterion for determining the use of donor kidneys in SKT or ADKT when donor age is above 60 years. Remuzzi and associates16 further refined this concept and introduced the use of a scoring system based on histologic findings from preimplant biopsies. The scoring system graded each of the following: degree of vessel wall thickness, glomerular sclerosis, tubular atrophy, and renal parenchymal scarring. The total score for each component was used to guide allocation decisions. A donor kidney with a score of ≤ 3 was fit for SKT, kidneys with scores of 4 to 6 were fit for ADKT, and kidneys with scores ≥ 7 were discarded. In a study published in 2006, Remuzzi and associates6 showed that this histologic scoring system was the only positive predictor of long-term graft survival in patients over 60 years of age who received either a SKT or ADKT.

In our center, marginal donor kidneys are accepted if the donor is greater than 70 years old without any medical conditions that are known to adversely affect kidney function, such as hyper­tension or diabetes, or is below 70 years old with any one of hypertension, diabetes, or vascular disease. All kidneys from marginal donors are assessed with any one or more of the following examinations: pre­donation radiologic imaging, surgical assessment at the time of organ recovery to look for gross renal arterial and parenchymal disease, or histologic assessment by wedge biopsy to look for glomerular obsolescence, fibrosis, and severe vascular sclerosis. If the glomerular obsolescence is < 20%, then our center uses the organ for SKT; at 20% to 30%, it is used for ADKT; kidneys with glomerular obsolescence above 30% are discarded. In our series, we had 1 kidney donation after cardiac death and 16 kidney donations before cardiac death.

Our results show that 4 of the 17 patients who underwent ADKT lost one or both grafts in a relatively short period. Of the 6 patients who presented with postoperative complications, 1 patient died from complications related to a fungal pneumonia and dehiscence of the transplant wound but with working grafts. Early graft loss related to vein thrombosis occurred in 5 patients, 3 who had bilaterally placed grafts and 2 who had unilaterally placed grafts. The occurrence of important surgical complications in 6 of 17 patients is higher than expected, with 4 of 10 from the bilateral group compared with 2 of 7 from the unilateral group. This may be related to age of the recipients, comorbid disease, cold ischemia time, and the technical difficulty of the surgical procedure related to quality of the donor kidneys. The surgical procedures are long, particularly when the kidneys are placed separately in each iliac fossa, and it is possible that fatigue may play a role.

The decision to allocate marginal donor kidneys to ADKT or SKT is made after assessing several variables, including histologic appearance, gross morphology, donor and recipient comorbidities, and donor terminal serum creatinine level. We believe that the use of both histologic and clinical parameters is the ideal combination for determining allocation of ECD kidneys to ADKT or SKT. Similar combinations of clinical variables and histologic findings have been used to allocate ECD kidneys in a number of studies with excellent graft function and survival.4,7,8

In our center, wedge biopsies are used to assess donor kidneys. This is in contrast to Remuzzi and associates6 who reported the use of core biopsies during preimplant donor kidney assessment. Wedge biopsies are more likely than core biopsies to result in an adequate sample for histologic assessment, although it could lead to overrepresentation of the degree of glomerular scarring and underrep-resentation of the degree of intimal fibrosis.17,18 This difference in biopsy modality may explain the difference in outcomes between our center and those of others from around the world. Extended criteria donors are an important source of organs for transplant. Although studies have shown a significant survival advantage compared with dialysis patients on the waiting list, our study shows that these ECD kidneys when given to older transplant recipients are not without complications. Placing both kidneys into the same iliac fossa, if technically possible, seems to be associated with less complications and is certainly a shorter operation.


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Volume : 13
Issue : 5
Pages : 408 - 412
DOI : 10.6002/ect.2015.0025


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From the Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare. We acknowledge the help in statistics provided by Blair Sydney Grace.
Corresponding author: Santosh Antony Olakkengil, Central Northern Adelaide Renal and Transplantation Service, L9 East Wing, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia
Phone: +61 08 8222 0956
Fax: +61 08 8222 0970
E-mail: Santosh.Olakkengil@health.sa.gov.au