Surgical Complications in En Bloc Renal Transplantation M.A. Moreno de la Higuera Díaza,*, N. Calvo Romeroa, I. Pérez-Floresa, M. Calvo Arévaloa, B. Rodríguez Cubilloa, A. Shabakaa, V. López de la Manzanaraa, Á. Gómez Vegasb, J. Blázquez Izquierdob, and A.I. Sánchez-Fructuosoa a
Nephrology and bUrology Departments, Hospital Clinico San Carlos, Madrid, Spain
ABSTRACT En bloc pediatric transplantation (EBPT) began with the aim of increasing the donor pool due to the existing high demand for donors. At its inception, it was considered a type of suboptimal transplantation due to its association with a high incidence of vascular, urologic, and immunologic complications. The main objective of this study was to update information on EBPT with the largest case series that exists on a worldwide scale. In a retrospective study, the results obtained from brain-dead donors (BDDs; n ¼ 770) were compared to those of EBPT (n ¼ 100) from January 1990 to December 2012. The median of follow-up was 12.8 years (interquartile range 8.1 to 17.2). The variables collected for analysis were demographic factors (age and sex of recipients, age and weight of donors), renal function, graft survival, recipient survival, surgical complications (thrombosis, lymphocele, urologic complications, and renal artery stenosis and need for revascularization with angioplasty and/or stents). Subsequently in a second analysis, we studied the association between graft survival, thrombosis, angioplasty, stents, and appearance of lymphoceles with the different factors that were considered to be related in accordance with published literature and our own experience. Graft loss due to surgical complications was more frequent in EBPT than in BDD (15% vs 2.2 % in BDD; P < .001), and interstitial fibrosis and tubular atrophy were more frequent in BDD (13% vs 2%; P < .001). EBPT offers a good survival rate after overcoming the possible surgical complications that may arise.
T
HE DISPARITY between the number of patients with end-stage renal disease on the kidney transplant waiting list and the availability of deceased donor organs continues to grow. The prolonged waiting time for kidney transplantation and associated longer periods on dialysis have been associated with significant morbidity and mortality [1], although attempts have been made to maximize the donor pool, including the use of expanded criteria donors, donation following cardiac death [2], and dual kidney transplantation from expanded criteria donors [3,4]. The optimal use of pediatric donors has been less clear. En bloc pediatric transplantation (EBPT) began with the aim of increasing the donor pool due to the existing high demand for donors. At its inception, it was considered a type of suboptimal transplantation due to its association with a high incidence of vascular, urologic, and immunologic complications [5e7]. Nevertheless, in recent years several studies have shown that even transplantation of suboptimal ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 48, 2953e2955 (2016)
kidneys offers a higher benefit in regards to patient survival as compared to remaining on dialysis. There are no single-center cohort studies in the literature involving pediatric transplantation that equals the sample size and follow-up time of this study. Thus, the main objective of this study was to update information on EBPT with the largest case series that exists on a worldwide scale. We hypothesized that EBPT is an optimal type of transplantation with results that are comparable to classical transplantation with adult brain-dead donors (BDDs). Our main objective was to demonstrate the validity of EBPT as an optimal type of renal transplantation, comparable to the rest of known optimal transplantation types. *Address correspondence to Maria Ángeles Moreno de la Higuera Díaz, Hospital Clínico San Carlos, NefrologiaeTrasplante, Profesor Martin Lagos, S/N, 28040, Madrid, España. E-mail:
[email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.09.014
2953
2954
MORENO DE LA HIGUERA DÍAZ, CALVO ROMERO, PÉREZ-FLORES ET AL
Table 1. Demographic Features of Renal Transplant Recipients From Brain-Dead Donors (BDD) and En Bloc Pediatric Transplantation (EBPT)
Donor age (y)* Recipient age (y)* Donor gender (% males) Recipient gender (% males) Time on dialysis (mo)† Type of dialysis (%) Hemodialysis Peritoneal dialysis Predialysis Cause of renal failure First renal transplantation (%)
BDD (n ¼ 770)
EBPT (n ¼ 100)
P
42.9 (16.9) 49.7 (13.2) 60.4 63
1.8 (0.8) 46.6 (13.4) 68.1 69
<.001 .032 .152 .239
26.1 (12.5e54.4)
17.2 (7.2e60.5)
82.9 73 14 16 3.1 11 No significant differences 84.7 88
.003 .001
.506 .380
*Mean (standard deviation). † Median (interquartile range).
MATERIALS AND METHODS In a retrospective study, the results obtained from BDDs were compared to those of EBPT from January 1990 to December 2012. Only those donors who were older than 8 months old and weighed more than 8 kg were accepted for EBPT. The variables collected for analysis were demographic factors (age and sex of recipients, age and weight of donors), renal function, graft survival, recipient survival, and surgical complications (thrombosis, lymphocele, urologic complications, renal artery stenosis, and need for revascularization with angioplasty and/or stents). Subsequently in a second analysis, we studied the association between graft survival, thrombosis, angioplasty, stents, and appearance of lymphoceles with the different factors that were considered to be related in accordance with published literature and our own experience: surgeon and surgical technique, use of prophylactic heparin, donor age and weight, and recipient age. The surgical technique performed for all cases of EBPT consisted of an extraperitoneal approach of the iliac vessels, starting with a terminolateral anastomosis to the external iliac vein in the distal end of the inferior vena cava after closure of its proximal end at bench surgery, where the aortic patch is also prepared. Afterward, a terminolateral anastomosis of the external iliac artery to the renal arteries with its aortic patch is completed following the Schneider technique. Finally, an extravesicular ureteroneocystostomy is performed separately for both ureters following the Woodruff technique and placing a double J ureteric stent in each ureter for 15 days and then removed if no complications arise.
RESULTS
We analyzed 770 BDD renal transplants and 100 EBPT renal transplants. The median of follow-up was 12.8 years (interquartile range 8.1 to 17.2). The mean age of recipients from BDD was 49 13.2 years, and that of recipients from EBPT was of 46.6 13.4 years. The baseline demographic features of both cohorts are represented in Table 1. Renal function was significantly better in EBPT compared to BDD throughout the follow-up period. Graft loss due to surgical complications was more frequent in EBPT (15% vs 2.2% in BDD; P < .001), and
interstitial fibrosis and tubular atrophy were more frequent in BDD (13% vs 2%; P < .001). The surgical complication in EBPT was vascular thrombosis in 100% of the cases. Patient survival was similar (79.1% vs 84.3%; P ¼ .319 after 12 years of follow-up). Graft survival in EBPT was 82% and 78.7% after 1 year and 12 years, respectively, and in BDD it was of 88.9% and 69.2%, respectively, showing no statistically significant differences between groups (P ¼ .222). In 6 cases, there was evidence of thrombosis of one of the kidneys, and in all cases, the other graft continued growing throughout the follow-up period with a sufficient renal function (serum creatinine <1.5 mg/dL). Angioplasty was required in 16% of EBPT, with 9 requiring stent placement. The incidence of lymphoceles was 7%, which was not significantly different from the incidence of lymphoceles described in BDD. A significant association between incidence of thrombosis and surgeon involved was observed (P ¼ .045). There was no statistically significant association with donor age or weight, recipient age, or use of heparin. DISCUSSION
There are controversial results in the literature regarding en bloc renal transplantation. However, over time an increasing number of study groups that has considered these grafts optimal for en bloc transplantation in adult recipients [8]. This study represents the largest single-center cohort of EBPT in adults, with the longest follow-up found in the literature of transplantation. In general, most authors recommend en bloc implantation when the donor age is less than 3 years, weight is less than 15 kg, and the kidney measures less than 6 cm. Vascular complications are inherent to the use of smallcaliber vessels. Many techniques have been described for performing EBPT [9]. The technique used in our center is performed for its practical simplicity and in an attempt to avoid turbulences in the proximal arterial end that could predispose for arterial thrombosis. Thrombosis of only one of the grafts occurred in 6 cases of this series, and probably due to the potential growing and development of these kidneys, the single grafts survived out in these recipients [10]. Historically, several risk factors for vascular thrombosis have been identified, namely, cold ischemia time, acute rejection episodes, recipients of black race, having a history of previous transplants, and a body mass index greater than or equal to 25 [11]. In our study, we only obtained a significant association between thrombosis and the responsible surgeon (P ¼ .045), as has been described in previous studies [12], and we did not obtain significant differences with donor age and weight, with recipient age, or the use of prophylactic heparin. Several authors referred to the need of a meticulous surgical technique [13], which in the light of the results obtained in this study is essential.
COMPLICATIONS IN EN BLOC RENAL TRANSPLANTATION
We consider urologic complications to be so low in our cohort as well as in other cohorts due to the placement of double J ureteric stents and the independent insertion of each ureter into the urinary bladder [14]. EBPTs are more liable to develop renal artery stenosis. Few authors describe this complication in their series. In our study, the incidence of renal artery stenosis is mildly lower, 16%. However, it still has a significantly higher incidence compared to adult renal transplantation. In all cases, renal artery stenosis was satisfactorily resolved with angioplasty and/or stent placement, with no repercussion on the renal function of patients, like all the articles mentioned before. In this series, we found no significant association between this complication and the surgical procedure. CONCLUSIONS
EBPT is a valid option for renal transplantation and has a comparable survival to BDD. The transplants present excellent renal function in the long run and a lower incidence of rejection, interstitial fibrosis, and tubular atrophy compared to BDD. EBPT offers a good survival rate after overcoming the possible surgical complications that may arise. An adequate donor and recipient selection is essential, with an attempt to prioritize young patients with a normal body mass index that would help to minimize surgical complications and because they would probably benefit more on the long run from the excellent survival of these grafts. REFERENCES [1] Lentine KL, Hurst FP, Jindal RM, Villines TC, Kunz JS, Yuan CM, et al. Cardiovascular risk assessment among potential kidney transplant candidates: approaches and controversies. Am J Kidney Dis 2010;55(1):152e67. [2] Sanchez-Fructuoso AI, Prats D, Torrente J, PerezContin MJ, Fernandez C, Alvarez J, et al. Renal transplantation
2955 from non-heart beating donors: a promising alternative to enlarge the donor pool. J Am Soc Nephrol 2000;11(2):350e8. [3] Sanchez-Fructuoso AI, Prats D, Naranjo P, Fernandez C, Aviles B, Herrero JA, et al. Renal transplantation from suboptimal donors. Transplant Proc 1998;30(5):2272e3. [4] Sanchez-Fructuoso AI, Prats D, Naranjo P, Fernandez C, Aviles B, Barrientos A. Renal transplantation from older donors: a single center experience. Transplant Proc 1998;30(5): 1793e4. [5] Gourlay W, Stothers L, McLoughlin MG, Manson AD, Keown P. Transplantation of pediatric cadaver kidneys into adult recipients. J Urol 1995;153(2). 322e5. [6] Neumayer HH, Huls S, Schreiber M, Riess R, Luft FC. Kidneys from pediatric donors: risk versus benefit. Clin Nephrol 1994;41(2):94e100. [7] Yagisawa T, Kam I, Chan L, Springer JW, Dunn S. Limitations of pediatric donor kidneys for transplantation. Clin Transplant 1998;12(6):557e62. [8] Mahdavi R, Arab D, Taghavi R, Gholamrezaie HR, Yazdani M, Simforoosh N, et al. En bloc kidney transplantation from pediatric cadaveric donors to adult recipients. Urol J 2006;3(2):82e6. [9] Hernandez Sanchez JE, Gomez Vegas A, Blazquez Izquierdo J, Grimalt Alvarez J, Perez Contin MJ, Rabadan Marina M, et al. En bloc transplantation of pediatric donor kidneys to adult receptors. Arch Esp Urol 2007;60(2):137e46. [10] Merkel FK. Five and 10 year follow-up of En Bloc small pediatric kidneys in adult recipients. Transplant Proc 2001;33(1-2): 1168e9. [11] 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(2):256e61. [12] Sanchez-Fructuoso AI, Prats D, Perez-Contin MJ, Marques M, Torrente J, Conesa J, et al. Increasing the donor pool using en bloc pediatric kidneys for transplant. Transplantation 2003;76(8):1180e4. [13] Ratner LE, Cigarroa FG, Bender JS, Magnuson T, Kraus ES. Transplantation of single and paired pediatric kidneys into adult recipients. J Am Coll Surg 1997;185(5):437e45. [14] Beltran S, Kanter J, Plaza A, Pastor T, Gavela E, Avila A, et al. One-year follow-up of en bloc renal transplants from pediatric donors in adult recipients. Transplant Proc 2010;42(8):2841e4.