- Email: [email protected]
Analysis of 80 Dual-Kidney Transplantations: A Multicenter Experience
Analysis of 80 Dual-Kidney Transplantations: A Multicenter Experience B. Nardo, R. Bertelli, G. Cavallari, E. Capocasale, G. Cappelli, M.P. Mazzoni, L. Benozzi, R. Dalla Valle, G. Fuga, N. Busi, C. Gilioli, A. Albertazzi, S. Stefoni, A.D. Pinna, and A. Faenza ABSTRACT Introduction. The use of kidneys from expanded criteria donors (ECD) is an attractive strategy to enlarge the pool of organs available for transplantation. Considering the fact that ECD organs have a reduced nephron mass, they are preferentially allocated for dual-kidney transplantation (DKT). Authors have reported excellent results of DKT when pretransplant ECD organs are evaluated for histological scores. The aim of this study was to evaluate DKT donor and recipient characteristics for comparison with DKT posttransplant outcomes versus those of recipients of single-kidney transplantations from expanded criteria (edSKT) and ideal donors (idSKT). We analyzed the potential prognostic factors involved in DKT among a population derived from three transplant centers. Materials and methods. Between 2001 and 2007, DKT (n ⫽ 80) were performed based upon the ECD kidney allocation assessed by biopsy. Results. The average donor ages for the DKT, edSKT, and idSKT groups were 68.8 ⫾ 7.8, 65.3 ⫾ 7.2, and 40.1 ⫾ 13.8 years, respectively (P ⬍ .001). The number of human leukocyte antigen mismatches was greater in the DKT group (3.1 ⫾ 1.2, P ⬍ .05). Patient and graft 5-year survival rates were similar among DKT, edSKT, and idSKT recipients, namely, 97.5% versus 95.8% versus 96.9% and 93.7% versus 87.4% versus 86.9%, respectively. Mean serum creatinine values at discharge were lower in the DKT and idSKT recipients (1.5 ⫾ 0.9 and 1.6 ⫾ 0.7 mg/dL; P ⬍ .05) compared with the edSKT group (1.9 ⫾ 0.7 mg/dL). Correlations between supposed prognostic factors and survival among the DKT group noted worse outcomes in reoperation cases (P ⬍ .05). Conclusion. We confirmed that DKT produced successful outcomes. An accurate surgical procedure is particularly important to try to avoid reoperations. In our experience, the use of a biopsy as an absolute criterion to allocate ECD kidneys may be too protective. HE STEADILY INCREASING NUMBER of potential kidney transplant recipients has produced an increased gap between the availability of organs and transplantation demand. In addition to living donor kidney transplantation, the use of organs from “expanded criteria donors” (ECD) has enlarged the organ pool in recent years.1,2 Considering the fact that ECD organs have a reduced nephron mass and therefore a shorter posttransplant graft survival rate, they are preferentially allocated for dual-kidney transplantations (DKT).3 DKT is an effective alternative to single-kidney transplantation; it has been performed in many centers after an accurate pretransplant organ and donor evaluation.4 –7 Allocating ECD organs by histological scores for kidney damage as proposed by
T
Remuzzi et al4 was reported by us among a cohort of recipients population at three transplant centers.8 The aim of this study was therefore to evaluate DKT donor and From the Department of General Surgery and Transplantation University of Bologna (B.N., R.B., G.C., G.F., A.D.P., A.F.), Kidney and Pancreas Transplant Center University of Parma (E.B., M.P.M., L.B., R.D.V., N.B.), Division of Nephrology and Kidney Transplantation University of Modena (G.C., C.G., A.A.), and Division of Nephrology and Kidney Transplantation (S.S.), University of Bologna, Bologna, Italy. Address reprint requests to Bruno Nardo, MD, PhD, Department of General Surgery and Transplantation, Sant’OrsolaMalpighi University Hospital, Via Massarenti 9, 40100, Bologna, Italy. E-mail: [email protected]
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.11.030
Transplantation Proceedings, 43, 1559 –1565 (2011)
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recipient characteristics, to compare posttransplant DKT outcomes with those after single-kidney procedures from expanded criteria (edSKT) or ideal donors (idSKT), and to analyze potential prognostic factors involved in DKT. PATIENTS AND METHODS Study Design We retrospectively examined our regional database, including the kidney transplant centers in Bologna, Modena, and Parma, by retrieving 80 medical records of patients who had received a DKT (group 1 ⫽ DKT) from deceased donors between September 2001 and July 2007. This patient group was compared with 396 records of recipients of a single kidney transplantation (SKT) from a deceased donor in Bologna. These 396 patients were divided into two groups: 229 patients who received kidneys from ideal donors (group 2 ⫽ idSKT) and 169 patients who received organs from expanded criteria donors (group 3 ⫽ edSKT). Only living donor kidney transplantations were excluded from this analysis. Donor and recipient features were compared among the three groups. The donor parameters were: age; gender; cause of death (cerebrovascular/trauma/other); risk factors of hypertension, diabetes mellitus, dyslipidemia and/or smoking habit; cold ischemia time; serum creatinine; creatinine clearance (calculated by the Cockcroft-Gault equation); and biopsy evaluation using the histological score proposed by Remuzzi et al.4 The recipient parameters were: age; gender; time on the waiting list; number of human leukocyte antigen (HLA) mismatch; percentage of panel-reactive antibody (PRA%) at transplant; indication for kidney transplantation (glomerular/tubulointerstitial/policystic/hypertensive/end-stage liver disease/other) and transplant number. We then compared the posttransplant outcomes, considering graft and patient survival rates, as well as a series of other parameters including occurrence of delayed graft function (DGF) defined as need for dialysis within the first week after transplant; acute rejection episodes (confirmed by biopsy); urologic complications (stenosis or fistula); metabolic complications (considered as insurgence of posttransplant diabetes); neoplastic and major infectious complications (necessitating drug treatment or a prolonged hospital stay); early (within 30 days) and late (after 30 days) reoperation rates and causes; length of hospital stay (days); serum creatinine at discharge and at 1-month follow-up and immunosuppressive regimen (double tacrolimus/ triple tacrolimus/double cyclosporine/triple cyclosporine/other). Grafts were considered as nonviable in the following events: transplantectomy, recipient death, and return to a dialysis regimen. Among the DKT group, the loss of one graft was still classified as a functioning kidney graft. Our next study step concentrated on the DKT group seeking to identify adverse prognostic factors correlating with transplant outcomes. The following parameters were analyzed: recipient age (⬎61 vs ⱕ61 years) and gender; indication for kidney transplant; time on waiting list (ⱖ3 vs ⬍3 years); number of HLA mismatches (⬎3 vs ⱕ3); PRA% (ⱖ5% vs ⬍5%); DGF incidence; acute rejection episodes; urologic, metabolic, neoplastic, and infective complications; serum creatinine at discharge (⬎1.4 vs ⱕ1.4 mg/dL); hospital stay; early and late reoperations; and the immunosuppressive regimen.
Expanded Criteria Donors We used the United Network for Organ Sharing (UNOS) definition for ECD: a donor of either over 50 or 60 years of age, but with one or more of the following risk factors: a history of hypertension, cerebrovascular cause of death, or serum creatinine ⬎1.5 mg/dL.
NARDO, BERTELLI, CAVALLARI ET AL
Histological Evaluation Both kidneys of the ECD donor were biopsied and assessed for the amount of damage by the histological score proposed by Remuzzi et al.4 The analysis consists of evaluating changes in each component of the kidney tissue: vessels, glomeruli, tubules, and connective tissue. Each kidney structure received a score of 0 if no changes were observed and up to 3 with marked changes. The vascular score was 3 when the vessel-wall thickness exceeded the luminal diameter or the lumen was occluded; and the glomerular score, 3 when more than 50% of glomeruli were globally sclerotic. The tubular score was 3 when more than 50% of tubules were atrophic, and the connective-tissue score, 3 when more than 50% of the renal parenchyma was replaced by connective tissue. The sum of these scores was defined as the global kidney score, which could range from 0 to 12. We considered organs with a total score from 0 to ⬍4 suitable for edSKT versus 4 to 6, suitable for DKT. A total score of ⬎6 was the reason to discard the kidney.
DKT Program Enrollment Criteria In compliance with our regional Ethics Committee, specific informed consent was obtained from all patients enrolled in the DKT program. Candidate recipients of a DKT in our centers were 55 years of age or older and had acceptable aortoiliac vessels and adequate dimensions of the abdominal cavity allowing placement of two renal grafts. Exclusion criteria were comprised of general contraindications for renal transplantation, high immunization levels, previous surgery on aortoiliac axis vessels, ischemic heart disease with peripheral vasculopathy, chronic hypotension, and anticoagulant therapy. Recipients with large polycystic kidneys and body mass index ⬎ 30 were excluded from the DKT program.
Surgical Procedure Grafts harvested using the standard technique were preserved separately under hypothermic conditions. After bench surgery, the two kidney grafts were implanted sequentially either at the two sides through separate incisions, or both placed in the same side. Apart from this exception, the surgical procedure did not differ significantly from the classic SKT.
Immunosuppressive Therapy All patients were administered induction therapy with basiliximab; thereafter they were maintained on either a double regimen (steroids in scalar dose plus cyclosporine trough level of 350 –500 ng/dL or tacrolimus trough level of 10 ⫾ 5 ng/dL) or a triple regimen (addition of mycophenolate mofetil, everolimus, or rapamycin), seeking to reduce calcineurin-inhibitor nephrotoxicity.
Statistical Analysis The data were described using mean values ⫾ standard deviation or frequencies for comparisons with the chi-square test or the analysis of variance. Graft and patient survival rates were calculated using the Kaplan-Meier method with differences evaluated with the log-rank test. Univariate analysis with log-rank tests were used to identify adverse prognostic factors correlating with transplant outcomes among the DKT group. All analyses were performed using SPSS 13 software (SPSS Inc, Chicago, Ill, USA). Values of P ⬍ .05 were considered to be statistically significant.
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RESULTS Patient Survival
The overall patient survival rates at 1, 3, and 5 years were 98.5%, 97.2%, and 96.6%, respectively. The posttransplant patient survival rates at 1, 3, and 5 years were 97.5%, 97.5%, and 97.5% in the DKT group; 98.6%, 97.8%, and 96.9% in the idSKT group; and 98.8%, 96.4%, and 95.8% in the edSKT group respectively (P ⫽ NS).
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complications (n ⫽ 2), bleeding (n ⫽ 1), or infectious complications (n ⫽ 1) at 14, 14, 6, and 71 days after transplantation, respectively. The most recent serum creatinine values were 1.6, 1.6, 2.6, and 4.7 mg/dL, respectively. Renal dynamic scintigraphy demonstrated three cases of nonfunction of a single graft in patients whose renal function is currently good: namely, serum creatinine values at their most recent follow-up: 1.6, 1.7, and 2 mg/dL. Patient and graft survival curves are shown in Fig 1 and 2.
Graft Survival
The overall graft survival rates at 1, 3, and 5 years were 92.2%, 89.9%, and 88.2%, respectively. The posttransplant graft survival rates at 1, 3, and 5 years for the three groups were 93.7%, 93.7%, and 93.7% in the DKT; 96.9%, 92.5%, and 86.9% in the idSKT; and 91.0%, 88.0%, and 87.4% in the edSKT, respectively (P ⫽ NS). Overall, 56 grafts were lost. In particular, in the DKT group, two patients underwent intraoperative bilateral transplantectomy due to massive vascular thromboses: both are alive and one underwent subsequent SKT several months later. Two patients lost both grafts due to vascular and infectious complications at 7 and 58 days after transplantation. Four patients (5%) underwent single graft transplantectomy due to vascular
Donor Characteristics
The average donor age among the DKT, edSKT, and idSKT groups were 68.8 ⫾ 7.8, 65.3 ⫾ 7.2, and 40.1 ⫾ 13.8 years, respectively (P ⬍ .001). Among the three groups, the distribution of causes of donor death was also different. Traumatic death occurred in 10 cases among the DKT group (12.5%); 33 in the edSKT group (19.7%); and 104 in the idSKT group (45.4%; P ⬍ .001). A cerebrovascular cause of death accounted for 69 DKT donors (86.25%), 130 edSKT donors (77.84%), and 103 idSKT donors (44.95%; P ⬍ .001). Risk factors were more frequent among DKT and edSKT donors (64.07% and 60%, respectively) compared with the idSKT donors (25.76%; P ⬍ .001). While the
Fig 1. Kaplan-Meier actuarial survival analysis showing 5-year patient survival was not significantly different between dual-kidney transplantations (DKT), ideal donor single-kidney transplantations (idSKT), and extended criteria single-kidney transplantations (edSKT, 97.5% vs 96.9% vs 95.8%), respectively (P ⫽ .6 by log-rank test).
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Fig 2. Kaplan-Meier actuarial survival analysis showing 5-year graft survival was not significantly different between dual-kidney transplantations (DKT), ideal donor single-kidney transplantations (idSKT), and extended criteria single-kidney transplantations (edSKT; 93.7% vs 86.9% vs 87.4%), respectively (P ⫽ .2 by log-rank test).
average serum creatinine of donors was not significantly different, the mean donor creatinine clearances in the DKT, edSKT, and idSKT groups were significantly different: namely, 75.1 ⫾ 27.5, 85 ⫾ 27.3, and 111.7 ⫾ 33.7 mL/min, respectively (P ⬍ .05). All organs harvested from ECDs underwent a pretransplant biopsy. The average number of glomeruli per sample was 40. In the 80 DKT the average biopsy score of the grafts was 4.4 ⫾ 0.7, while in the edSKT group the mean score was 2.7 ⫾ 1. In particular, in the DKT group, 13/160 kidneys (8.1%) showed more than 20% of glomeruli to be sclerotic and 27/160 (16.8%), severe vascular sclerosis (vessel-wall thickness ⱖ luminal diameter or occlusion of the lumen). These data confirmed the lower histological “quality” of the organs allocated for DKT (P ⬍ .05). Only 14/229 kidney grafts (6%) underwent a biopsy among the idSKT group, with an average score of 2.3 ⫾ 1. Table 1 shows all analyzed donor parameters comparing the three groups. Recipient Characteristics
The mean recipient age was significantly higher among the DKT (61.4 ⫾ 4.5 years) and edSKT (57.5 ⫾ 7.5 years) groups compared with the idSKT group (42.4 ⫾ 12.2 years;
P ⬍ .001). The average time on the waiting list was 3.6 ⫾ 3.2 years for the DKT group; 5.0 ⫾ 8.7 years, for the edSKT group; and 4.2 ⫾ 3.6 years, for the idSKT group (not significant). The number of HLA mismatches as well as pretransplant PRA% was significantly higher among the DKT and idSKT groups when compared with the edSKT group (P ⬍ .05). Differences between the DKT and the two SKT groups were also registered concerning the indication for and number of the transplantation (P ⬍ .05). Detailed comparisons of recipient characteristics among the groups are shown in Table 2. Posttransplant Outcomes
The triple therapy regimen was used more frequently among the DKT and edSKT groups (88.7% and 81.4%) compared with the idSKT (73.4%) respectively (P ⬍ .05). However, the rate of acute rejection episodes was higher in the idSKT group (20.5%) when compared with edSKT and DKT groups (8.8% vs 10%, respectively; P ⫽ .003). Mean serum creatinine at the time of discharge was significantly lower in the DKT and idSKT groups (1.5 ⫾ 0.9 and 1.6 ⫾ 0.7 mg/dL, respectively) when compared with the edSKT group (1.9 ⫾ 0.7 mg/dL). This difference was maintained at
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Age (y) Male gender Cause of death (cerebrovascular/trauma/other) Risk factors (yes) Cold ischemia (h) Serum creatinine (mg/dL) Creatinine clearance (CockcroftGault formula) Biopsy score Glomerular sclerosis (ⱖ20%) Interstizial fibrosis (ⱖ20%) Severe vascular sclerosis*
DKT (n ⫽ 80)
edSKT (n ⫽ 167)
idSKT (n ⫽ 229)
P Value
68.8 ⫾ 7.8 41/39 (51.2%) 69/10/1 (86.2%/12.5%/1.2%) 48/32 (60%) 17 ⫾ 3.9 1.0 ⫾ 0.5 75.1 ⫾ 27.5
65.3 ⫾ 7.2 92/75 (55%) 130/33/4 (77.8%/19.7%/2.3%) 107/60 (64%) 16.5 ⫾ 4.3 0.9 ⫾ 0.3 85 ⫾ 27.3
40.1 ⫾ 13.8 129/100 (56.3%) 103/104/22 (44.9%/45.4%/9.6%) 59/170 (25.7%) 16.2 ⫾ 4.3 0.9 ⫾ 0.3 111.7 ⫾ 33.7
⬍.001 NS ⬍.001
4.4 ⫾ 0.7 13/160 (8.1%) 6/160 (3.7%) 27/160 (16.8%)
2.7 ⫾ 1 6/167 (3.5%) 4/167 (2.3%) 16/167 (9.5%)
2.3 ⫾ 1 N/A N/A N/A
⬍.05 ⬍.05 NS ⬍.05
⬍.001 NS NS ⬍.05
DKT, dual-kidney transplantation; edSKT, single transplantation using kidney from expanded criteria donor; idSKT, single transplantation using kidney from ideal donor; N/A, not applicable; NS, not significant. *Vessel-wall thickness ⱖ the luminal diameter or lumen occlusion.
1 month after the transplant (1.6 ⫾ 0.7, 1.7 ⫾ 0.8, and 1.9 ⫾ 0.8 mg/dL, respectively; P ⬍ .05). The incidence of DGF was lower (P ⬍ .05) in the idSKT (28.8%) compared with the edSKT groups (47.9%). A low incidence of posttransplant diabetes was registered in the idSKT and edSKT groups (4.8% and 6%) compared with the DKT group (10%; P ⫽ .004). Neoplastic, urologic, and infectious complications as well as reoperation rates and hospital stays did not differ among the groups. In particular, in the DKT group the urologic complication rate was 13.7% (three stenoses and eight ureteral fistulae) with 8/11 requiring surgical reexplorations. There were six other surgical reoperations for intestinal perforation (n ⫽ 2), bleeding (n ⫽ 3), and lymphocele (n ⫽ 1). Detailed comparisons of posttransplant outcomes among the groups are reported in Table 3. Prognostic Factors in DKT
Table 4 reports the univariate analysis of prognostic factors for patient and graft survival rates using the log-rank test. The only significant parameters were the early and late reoperation rates (P ⬍ .05). In contrast, recipient prognostic factors that were already reported as negative, such as
the older age, DGF incidence, high PRA% at transplant, and ⬎3 HLA mismatches, showed no significant correlation with graft or patient survival rates. DISCUSSION
In the last few years, several studies have examined the feasibility and outcomes of DKT.1,4 –7 In this domain, our study represents one of the largest experiences with a long follow-up period. In particular, unlike most published studies, we have stratified the analysis into three groups to prevent potentially misleading effects that can occur when edSKTs and idSKTs are combined. Furthermore, in our study, the retrospective analysis sought to identify prognostic factors for DKT patient and graft survival rates. In our experience, long-term graft and patient survival rates were similar for the three types of kidney transplant recipients. This lack of differences in short- and long-term graft survival rates between edSKT and DKT transplants has also been documented in many other reports, including the recent UNOS data analysis by Gill et al.9 In our series, data have appeared that require considerations. Concerning the analysis of the donor characteristics,
Table 2. Baseline Recipient Characteristics
Age (y) Male gender Time on waiting list (y) Number mismatch HLA-A, -B, -DR (1–6) PRA% Indication for kidney transplant (glomerular/tubulointerstitial/ policystic/ hypertensive/ESKD/other) Transplant number (1st/2nd)
DKT (n ⫽ 80)
edSKT (n ⫽ 167)
idSKT (n ⫽ 229)
P Value
61.4 ⫾ 4.5 55/25 (68.7%) 3.6 ⫾ 3.2 3.1 ⫾ 1.2
57.5 ⫾ 7.5 110/57 (65.8%) 5 ⫾ 8.7 2.6 ⫾ 1.1
42.4 ⫾ 12.2 150/79 (65.5%) 4.2 ⫾ 3.6 2.5 ⫾ 1.1
⬍.001 NS NS ⬍.05
5.9 ⫾ 16.9 33/8/12/14/13/0 (41.2%/10%/15%/17.5%/ 16.2%/0%)
3.3 ⫾ 9.3 71/14/37/24/16/5 (42.5%/8.3%/22.1%/14.3%/ 9.5%/2.9%)
5.5 ⫾ 12.5 100/32/32/11/35/19 (43.6%/13.9%/13.9%/4.8%/ 15.2%/8.2%)
⬍.05 ⬍.05
79/1 (98.7%/1.2%)
150/17 (89.8%/10.1%)
195/34 (85.1%/14.8%)
⬍.05
DKT, dual-kidney transplantation; edSKT, single transplantation using kidney from expanded criteria donor; idSKT, single transplantation using kidney from ideal donor; PRA, panel-reactive antibodies; ESKD, end-stage kidney disease without diagnostic histology.
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NARDO, BERTELLI, CAVALLARI ET AL Table 3. Comparison of Early Posttransplant Outcomes Data Between the Three Study Groups DKT (n ⫽ 80)
edSKT (n ⫽ 167)
P Value
idSKT (n ⫽ 229)
DGF rate 30/50 (37.5%) 81/86 (47.9%) 66/163 (28.8%) Acute rejection episodes 8/72 (10%) 15/152 (8.8%) 47/182 (20.5%) Urologic complications 11/69 (13.7%) 25/142 (14.8%) 27/202 (11.8%) Posttransplant diabetes 8/72 (10%) 10/157 (6%) 11/218 (4.8%) Neoplastic complications 5/75 (6.2%) 4/163 (2.4%) 4/225 (1.7%) Major infectious 10/70 (12.5%) 15/152 (9%) 21/208 (9.2%) complications Early reoperations (ⱕ30 d) 13/67 (16.2%) 18/149 (10.7%) 33/196 (14.4%) Late reoperations (⬎30 d) 9/71 (11.2%) 17/150 (10.1%) 21/208 (9.2%) Hospital stay (d) 22.1 ⫾ 12.1 23.9 ⫾ 11.9 21.9 ⫾ 12.1 Serum creatinine at discharge 1.5 ⫾ 0.9 1.8 ⫾ 0.7 1.6 ⫾ 0.7 (mg/dL) Serum creatinine 1-mo 1.6 ⫾ 0.7 1.9 ⫾ 0.8 1.7 ⫾ 0.8 posttransplant (mg/dL) 7/45/0/26/2 16/86/10/50/5 33/88/21/80/7 Immunosuppressive regimen (double FK/triple FK/double (8.7%/56.2%/0%/32.5%/2.5%) (9.5%/51.4%/5.9%/29.9%/2.9%) (14.4%/38.4%/9.1%/34.9%/3%) cyclosporine/triple cyclosporine/other)
⬍.05 ⬍.05 NS ⬍.05 NS NS NS NS NS ⬍.05 ⬍.05 ⬍.05
DKT, dual-kidney transplantation; edSKT, single transplantation using kidney from expanded criteria donor; idSKT, single transplantation using kidney from ideal donor; DGF, delayed graft function.
even if the registered graft and patient survival rates were comparable to those in other studies that have used routine pretransplant biopsy and were clearly superior to reports from centers that do not routinely perform histological analysis of the graft,5 our experience suggested that the current system that uses biopsies as the absolute criterion to allocate ECD kidneys as dual rather than single transplants might be too protective. On the basis of the excellent long-term results of DKT in our series, we believe that a careful evaluation of the opportunity to discard kidneys on
exclusive consideration of the reported bioptical score is necessary. It is noteworthy that seven patients who had only one functioning graft at follow-up displayed surprisingly good outcomes in terms of renal function. With the aim of avoiding kidney discards of organs, which could be potentially useful for DKT, we assume that in the near future, biopsy results will probably not just be considered alone, but in connection with the donor’s clinical data such as age, creatinine, creatinine clearance, and particularly clinical history of diabetes and hypertension. Unfortunately, this
Table 4. Regression Analysis for Graft and Patient Survival
Age (⬎61 vs ⱕ61 y) Gender (M/F) Indication for kidney transplant (glomerular/tubulointerstitial/policystic/ hypertensive/ESKD) Time on waiting list (ⱖ3 vs ⬍3) Number of HLA mismatches (⬎3 vs ⱕ3) PRA% (ⱖ5 vs ⬍5%) DGF (yes/no) Rejection episodes (yes/no) Urologic complications (yes/no) Posttransplant diabetes (yes/no) Neoplastic complications (yes/no) Infective complications (yes/no) Serum creatinine at discharge (⬎1.4 vs ⱕ1.4) Hospital stay (d) Early reoperations (yes/no) Late reoperations (yes/no) Immunosuppressive regimen (double FK/triple FK/double Cs/triple Cs/other)
n per Class
P Value for GS
P Value for PS
40/40 55/25 33/8/12/14/13
NS NS NS
NS NS NS
36/44 29/49 15/57 30/50 8/72 11/69 8/72 5/75 10/70 21/44
NS NS NS NS NS NS NS NS NS NS NS ⬍.05 ⬍.05 NS
NS NS NS NS NS NS NS NS NS NS NS ⬍.05 ⬍.05 NS
13/67 9/71 7/45/0/26/2
PRA, panel reactive antibodies; DGF, delayed graft function; Cs, cyclosporine; ESKD, end-stage kidney disease; GS, graft survival; PS, patient survival; HLA, human leukocyte antigen; NS, not significant.
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retrospective analysis rests upon an insufficient number of cases to derive conclusions about this point. However, prospective studies analyzing donor clinical data in large populations may help to elucidate useful criteria for allocation of ECD kidneys. A recent study by Snanoudj et al reported the significance of the donor-estimated GFR as a prognostic criterion to allocate ECD kidneys as single or dual transplantations.10 With regard to the recipient characteristics, as predicted, we registered a higher mean age among the DKT and edSKT groups. Older recipients are more likely to have comorbidities, thus experiencing a higher risk of death with a functioning graft and being more susceptible to infections and adverse drug reactions.11 In our analysis of prognostic significance, however, there was no statistically significant correlation between the older age of DKT recipients (⬎61 years) and less successful outcomes. Furthermore, the HLA mismatch number was significantly greater among the DKT versus the other two groups. However, in contrast with other reports,4,6 it did not correlate with transplantation outcomes. Consistent with this observation, the OPTN/ UNOS reported no correlation between mismatch number and graft survival rate.9 Concerning posttransplantation outcomes, no differences were registered among the groups in the incidence of complications— urologic, infective, neoplastic, and reoperation rates. As in the UNOS report,9 but differing from a previous report,12 we registered a lower rate of rejection episodes among the DKT and edSKT versus idSKT group, which may be partially explained by the reduced immunologic activity among older recipients13 and the more frequently used, triple regimen in these groups. Moreover, a lower PRA% level was registered among edSKT recipients. In contrast with the higher incidence of acute rejection episodes, recipients of idSKT showed a lower incidence of DGF compared with the edSKT group, which can be partially explained by the better quality of the grafts. However, no significant difference in the incidence of DGF was observed between DKT and idSKT groups. Since patient age at the time of transplantation was the most frequent risk factor for posttransplant diabetes,14 the greater incidence registered in the DKT group could be explained by their higher mean age. Univariate analysis of potentially adverse prognostic factors correlating with graft or patient survival rates in the DKT group appeared to be the only significant parameter for the reoperation rate. In contrast, frequently considered negative prognostic factors, such as the DGF incidence, high PRA%, and HLA mismatches ⬎3,15 showed no significant correlation with graft or patient survival rates. Recent reports have noted a reduced impact of these prognostic factors in older recipients, as seen among those in the DKT cohort.16,17 In conclusion, this study confirmed that the DKT technique offers excellent early and long-term outcomes with regard to graft and patient survival rates. Even though DKT
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is characterized by a higher recipient mean age and longer operative time, its complication rate was comparable to that of idSKT. Kidney graft allocation, however, has to be accurate. The use of biopsy protocols is necessary for a complete evaluation of ECD organs to optimize resource allocation. Nevertheless, in our opinion, the use of a biopsy as the absolute criterion in allocating ECD kidneys to DKT might be too protective, whereas a correlation with donor clinical data may be more appropriate. Prospective longitudinal studies in the future may help to elucidate which donor features are useful criteria for ECD kidneys allocation. REFERENCES 1. Stratta RJ, Sundberg AK, Rohr MS, et al: Optimal use of older donors and recipients in kidney transplantation. Surgery 139:324, 2006 2. Metzger RA, Delmonico FL, Feng S, et al: Expanded criteria donors for kidney transplantation. Am J Transplant 3:114, 2003 3. Remuzzi G, Grynyo J, Ruggenenti P, et al: Early experience with dual kidney transplantation in adults using expanded donor criteria. J Am Soc Nephrol 10:2591, 1999 4. Remuzzi G, Cravedi P, Perna A, et al: Long-term outcome of renal transplantation from older donors. N Engl J Med 354:343, 2006 5. Lee RS, Miller E, Marsh CL, et al: Intermediate outcomes of dual renal allografts: the University of Washington experience. J Urol 169:855, 2003 6. Moore PS, Farney AC, Sundberg AK, et al: Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors. Transplantation 83:1551, 2007 7. Stratta RJ, Rohr MS, Sundberg AK, et al: Increased kidney transplantation utilizing expanded criteria deceased organ donors with results comparable to standard criteria donor transplant. Ann Surg 239:688, 2004 8. Bertelli R, Nardo B, Capocasale E, et al: Multicenter study on double kidney transplantation. Transplant Proc 40:1869, 2008 9. Gill J, Cho YW, Danovitch GM, et al: Outcomes of dual adult kidney transplants in the United States: an analysis of the OPTN/ UNOS database. Transplantation 85:62, 2008 10. Snanoudj R, Rabant M, Timsit MO, et al: Donor-estimated GFR as an appropriate criterion for allocation of ECD kidneys into single or dual kidney transplantation. Am J Transplant 9:2542, 2009 11. Basar H, Soran A, Shapiro R, et al: Renal transplantation in recipients over the age of 60: the impact of donor age. Transplantation 67:1191, 1999 12. Salifu MO, Norin AJ, O’Mahony C, et al: Long term outcomes of dual kidney transplantation—a single center experience. Clin Tranplant 23:400, 2009 13. Martins PN, Pratschke J, Pascher A, et al: Age and immune response in organ transplantation. Transplantation 79:127, 2005 14. Kasiske BL, Snyder JJ, Gilberston D, et al: Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 3:178, 2003 15. Pessione F, Cohen S, Durand D, et al: Multivariate analysis of donor risk factors for graft survival in kidney transplantation. Transplantation 75:361, 2003 16. Oniscu GC, Brown H, Forsythe JL, et al: How old is old for transplantation? Am J Transplant 4:2067, 2004 17. Keith DS, Demattos A, Golconda M, et al: Effect of donor recipient age match on survival after first deceased donor transplantation. J Am Soc Nephrol 15:1086, 2004
T
Remuzzi et al4 was reported by us among a cohort of recipients population at three transplant centers.8 The aim of this study was therefore to evaluate DKT donor and From the Department of General Surgery and Transplantation University of Bologna (B.N., R.B., G.C., G.F., A.D.P., A.F.), Kidney and Pancreas Transplant Center University of Parma (E.B., M.P.M., L.B., R.D.V., N.B.), Division of Nephrology and Kidney Transplantation University of Modena (G.C., C.G., A.A.), and Division of Nephrology and Kidney Transplantation (S.S.), University of Bologna, Bologna, Italy. Address reprint requests to Bruno Nardo, MD, PhD, Department of General Surgery and Transplantation, Sant’OrsolaMalpighi University Hospital, Via Massarenti 9, 40100, Bologna, Italy. E-mail: [email protected]
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.11.030
Transplantation Proceedings, 43, 1559 –1565 (2011)
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recipient characteristics, to compare posttransplant DKT outcomes with those after single-kidney procedures from expanded criteria (edSKT) or ideal donors (idSKT), and to analyze potential prognostic factors involved in DKT. PATIENTS AND METHODS Study Design We retrospectively examined our regional database, including the kidney transplant centers in Bologna, Modena, and Parma, by retrieving 80 medical records of patients who had received a DKT (group 1 ⫽ DKT) from deceased donors between September 2001 and July 2007. This patient group was compared with 396 records of recipients of a single kidney transplantation (SKT) from a deceased donor in Bologna. These 396 patients were divided into two groups: 229 patients who received kidneys from ideal donors (group 2 ⫽ idSKT) and 169 patients who received organs from expanded criteria donors (group 3 ⫽ edSKT). Only living donor kidney transplantations were excluded from this analysis. Donor and recipient features were compared among the three groups. The donor parameters were: age; gender; cause of death (cerebrovascular/trauma/other); risk factors of hypertension, diabetes mellitus, dyslipidemia and/or smoking habit; cold ischemia time; serum creatinine; creatinine clearance (calculated by the Cockcroft-Gault equation); and biopsy evaluation using the histological score proposed by Remuzzi et al.4 The recipient parameters were: age; gender; time on the waiting list; number of human leukocyte antigen (HLA) mismatch; percentage of panel-reactive antibody (PRA%) at transplant; indication for kidney transplantation (glomerular/tubulointerstitial/policystic/hypertensive/end-stage liver disease/other) and transplant number. We then compared the posttransplant outcomes, considering graft and patient survival rates, as well as a series of other parameters including occurrence of delayed graft function (DGF) defined as need for dialysis within the first week after transplant; acute rejection episodes (confirmed by biopsy); urologic complications (stenosis or fistula); metabolic complications (considered as insurgence of posttransplant diabetes); neoplastic and major infectious complications (necessitating drug treatment or a prolonged hospital stay); early (within 30 days) and late (after 30 days) reoperation rates and causes; length of hospital stay (days); serum creatinine at discharge and at 1-month follow-up and immunosuppressive regimen (double tacrolimus/ triple tacrolimus/double cyclosporine/triple cyclosporine/other). Grafts were considered as nonviable in the following events: transplantectomy, recipient death, and return to a dialysis regimen. Among the DKT group, the loss of one graft was still classified as a functioning kidney graft. Our next study step concentrated on the DKT group seeking to identify adverse prognostic factors correlating with transplant outcomes. The following parameters were analyzed: recipient age (⬎61 vs ⱕ61 years) and gender; indication for kidney transplant; time on waiting list (ⱖ3 vs ⬍3 years); number of HLA mismatches (⬎3 vs ⱕ3); PRA% (ⱖ5% vs ⬍5%); DGF incidence; acute rejection episodes; urologic, metabolic, neoplastic, and infective complications; serum creatinine at discharge (⬎1.4 vs ⱕ1.4 mg/dL); hospital stay; early and late reoperations; and the immunosuppressive regimen.
Expanded Criteria Donors We used the United Network for Organ Sharing (UNOS) definition for ECD: a donor of either over 50 or 60 years of age, but with one or more of the following risk factors: a history of hypertension, cerebrovascular cause of death, or serum creatinine ⬎1.5 mg/dL.
NARDO, BERTELLI, CAVALLARI ET AL
Histological Evaluation Both kidneys of the ECD donor were biopsied and assessed for the amount of damage by the histological score proposed by Remuzzi et al.4 The analysis consists of evaluating changes in each component of the kidney tissue: vessels, glomeruli, tubules, and connective tissue. Each kidney structure received a score of 0 if no changes were observed and up to 3 with marked changes. The vascular score was 3 when the vessel-wall thickness exceeded the luminal diameter or the lumen was occluded; and the glomerular score, 3 when more than 50% of glomeruli were globally sclerotic. The tubular score was 3 when more than 50% of tubules were atrophic, and the connective-tissue score, 3 when more than 50% of the renal parenchyma was replaced by connective tissue. The sum of these scores was defined as the global kidney score, which could range from 0 to 12. We considered organs with a total score from 0 to ⬍4 suitable for edSKT versus 4 to 6, suitable for DKT. A total score of ⬎6 was the reason to discard the kidney.
DKT Program Enrollment Criteria In compliance with our regional Ethics Committee, specific informed consent was obtained from all patients enrolled in the DKT program. Candidate recipients of a DKT in our centers were 55 years of age or older and had acceptable aortoiliac vessels and adequate dimensions of the abdominal cavity allowing placement of two renal grafts. Exclusion criteria were comprised of general contraindications for renal transplantation, high immunization levels, previous surgery on aortoiliac axis vessels, ischemic heart disease with peripheral vasculopathy, chronic hypotension, and anticoagulant therapy. Recipients with large polycystic kidneys and body mass index ⬎ 30 were excluded from the DKT program.
Surgical Procedure Grafts harvested using the standard technique were preserved separately under hypothermic conditions. After bench surgery, the two kidney grafts were implanted sequentially either at the two sides through separate incisions, or both placed in the same side. Apart from this exception, the surgical procedure did not differ significantly from the classic SKT.
Immunosuppressive Therapy All patients were administered induction therapy with basiliximab; thereafter they were maintained on either a double regimen (steroids in scalar dose plus cyclosporine trough level of 350 –500 ng/dL or tacrolimus trough level of 10 ⫾ 5 ng/dL) or a triple regimen (addition of mycophenolate mofetil, everolimus, or rapamycin), seeking to reduce calcineurin-inhibitor nephrotoxicity.
Statistical Analysis The data were described using mean values ⫾ standard deviation or frequencies for comparisons with the chi-square test or the analysis of variance. Graft and patient survival rates were calculated using the Kaplan-Meier method with differences evaluated with the log-rank test. Univariate analysis with log-rank tests were used to identify adverse prognostic factors correlating with transplant outcomes among the DKT group. All analyses were performed using SPSS 13 software (SPSS Inc, Chicago, Ill, USA). Values of P ⬍ .05 were considered to be statistically significant.
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RESULTS Patient Survival
The overall patient survival rates at 1, 3, and 5 years were 98.5%, 97.2%, and 96.6%, respectively. The posttransplant patient survival rates at 1, 3, and 5 years were 97.5%, 97.5%, and 97.5% in the DKT group; 98.6%, 97.8%, and 96.9% in the idSKT group; and 98.8%, 96.4%, and 95.8% in the edSKT group respectively (P ⫽ NS).
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complications (n ⫽ 2), bleeding (n ⫽ 1), or infectious complications (n ⫽ 1) at 14, 14, 6, and 71 days after transplantation, respectively. The most recent serum creatinine values were 1.6, 1.6, 2.6, and 4.7 mg/dL, respectively. Renal dynamic scintigraphy demonstrated three cases of nonfunction of a single graft in patients whose renal function is currently good: namely, serum creatinine values at their most recent follow-up: 1.6, 1.7, and 2 mg/dL. Patient and graft survival curves are shown in Fig 1 and 2.
Graft Survival
The overall graft survival rates at 1, 3, and 5 years were 92.2%, 89.9%, and 88.2%, respectively. The posttransplant graft survival rates at 1, 3, and 5 years for the three groups were 93.7%, 93.7%, and 93.7% in the DKT; 96.9%, 92.5%, and 86.9% in the idSKT; and 91.0%, 88.0%, and 87.4% in the edSKT, respectively (P ⫽ NS). Overall, 56 grafts were lost. In particular, in the DKT group, two patients underwent intraoperative bilateral transplantectomy due to massive vascular thromboses: both are alive and one underwent subsequent SKT several months later. Two patients lost both grafts due to vascular and infectious complications at 7 and 58 days after transplantation. Four patients (5%) underwent single graft transplantectomy due to vascular
Donor Characteristics
The average donor age among the DKT, edSKT, and idSKT groups were 68.8 ⫾ 7.8, 65.3 ⫾ 7.2, and 40.1 ⫾ 13.8 years, respectively (P ⬍ .001). Among the three groups, the distribution of causes of donor death was also different. Traumatic death occurred in 10 cases among the DKT group (12.5%); 33 in the edSKT group (19.7%); and 104 in the idSKT group (45.4%; P ⬍ .001). A cerebrovascular cause of death accounted for 69 DKT donors (86.25%), 130 edSKT donors (77.84%), and 103 idSKT donors (44.95%; P ⬍ .001). Risk factors were more frequent among DKT and edSKT donors (64.07% and 60%, respectively) compared with the idSKT donors (25.76%; P ⬍ .001). While the
Fig 1. Kaplan-Meier actuarial survival analysis showing 5-year patient survival was not significantly different between dual-kidney transplantations (DKT), ideal donor single-kidney transplantations (idSKT), and extended criteria single-kidney transplantations (edSKT, 97.5% vs 96.9% vs 95.8%), respectively (P ⫽ .6 by log-rank test).
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Fig 2. Kaplan-Meier actuarial survival analysis showing 5-year graft survival was not significantly different between dual-kidney transplantations (DKT), ideal donor single-kidney transplantations (idSKT), and extended criteria single-kidney transplantations (edSKT; 93.7% vs 86.9% vs 87.4%), respectively (P ⫽ .2 by log-rank test).
average serum creatinine of donors was not significantly different, the mean donor creatinine clearances in the DKT, edSKT, and idSKT groups were significantly different: namely, 75.1 ⫾ 27.5, 85 ⫾ 27.3, and 111.7 ⫾ 33.7 mL/min, respectively (P ⬍ .05). All organs harvested from ECDs underwent a pretransplant biopsy. The average number of glomeruli per sample was 40. In the 80 DKT the average biopsy score of the grafts was 4.4 ⫾ 0.7, while in the edSKT group the mean score was 2.7 ⫾ 1. In particular, in the DKT group, 13/160 kidneys (8.1%) showed more than 20% of glomeruli to be sclerotic and 27/160 (16.8%), severe vascular sclerosis (vessel-wall thickness ⱖ luminal diameter or occlusion of the lumen). These data confirmed the lower histological “quality” of the organs allocated for DKT (P ⬍ .05). Only 14/229 kidney grafts (6%) underwent a biopsy among the idSKT group, with an average score of 2.3 ⫾ 1. Table 1 shows all analyzed donor parameters comparing the three groups. Recipient Characteristics
The mean recipient age was significantly higher among the DKT (61.4 ⫾ 4.5 years) and edSKT (57.5 ⫾ 7.5 years) groups compared with the idSKT group (42.4 ⫾ 12.2 years;
P ⬍ .001). The average time on the waiting list was 3.6 ⫾ 3.2 years for the DKT group; 5.0 ⫾ 8.7 years, for the edSKT group; and 4.2 ⫾ 3.6 years, for the idSKT group (not significant). The number of HLA mismatches as well as pretransplant PRA% was significantly higher among the DKT and idSKT groups when compared with the edSKT group (P ⬍ .05). Differences between the DKT and the two SKT groups were also registered concerning the indication for and number of the transplantation (P ⬍ .05). Detailed comparisons of recipient characteristics among the groups are shown in Table 2. Posttransplant Outcomes
The triple therapy regimen was used more frequently among the DKT and edSKT groups (88.7% and 81.4%) compared with the idSKT (73.4%) respectively (P ⬍ .05). However, the rate of acute rejection episodes was higher in the idSKT group (20.5%) when compared with edSKT and DKT groups (8.8% vs 10%, respectively; P ⫽ .003). Mean serum creatinine at the time of discharge was significantly lower in the DKT and idSKT groups (1.5 ⫾ 0.9 and 1.6 ⫾ 0.7 mg/dL, respectively) when compared with the edSKT group (1.9 ⫾ 0.7 mg/dL). This difference was maintained at
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Age (y) Male gender Cause of death (cerebrovascular/trauma/other) Risk factors (yes) Cold ischemia (h) Serum creatinine (mg/dL) Creatinine clearance (CockcroftGault formula) Biopsy score Glomerular sclerosis (ⱖ20%) Interstizial fibrosis (ⱖ20%) Severe vascular sclerosis*
DKT (n ⫽ 80)
edSKT (n ⫽ 167)
idSKT (n ⫽ 229)
P Value
68.8 ⫾ 7.8 41/39 (51.2%) 69/10/1 (86.2%/12.5%/1.2%) 48/32 (60%) 17 ⫾ 3.9 1.0 ⫾ 0.5 75.1 ⫾ 27.5
65.3 ⫾ 7.2 92/75 (55%) 130/33/4 (77.8%/19.7%/2.3%) 107/60 (64%) 16.5 ⫾ 4.3 0.9 ⫾ 0.3 85 ⫾ 27.3
40.1 ⫾ 13.8 129/100 (56.3%) 103/104/22 (44.9%/45.4%/9.6%) 59/170 (25.7%) 16.2 ⫾ 4.3 0.9 ⫾ 0.3 111.7 ⫾ 33.7
⬍.001 NS ⬍.001
4.4 ⫾ 0.7 13/160 (8.1%) 6/160 (3.7%) 27/160 (16.8%)
2.7 ⫾ 1 6/167 (3.5%) 4/167 (2.3%) 16/167 (9.5%)
2.3 ⫾ 1 N/A N/A N/A
⬍.05 ⬍.05 NS ⬍.05
⬍.001 NS NS ⬍.05
DKT, dual-kidney transplantation; edSKT, single transplantation using kidney from expanded criteria donor; idSKT, single transplantation using kidney from ideal donor; N/A, not applicable; NS, not significant. *Vessel-wall thickness ⱖ the luminal diameter or lumen occlusion.
1 month after the transplant (1.6 ⫾ 0.7, 1.7 ⫾ 0.8, and 1.9 ⫾ 0.8 mg/dL, respectively; P ⬍ .05). The incidence of DGF was lower (P ⬍ .05) in the idSKT (28.8%) compared with the edSKT groups (47.9%). A low incidence of posttransplant diabetes was registered in the idSKT and edSKT groups (4.8% and 6%) compared with the DKT group (10%; P ⫽ .004). Neoplastic, urologic, and infectious complications as well as reoperation rates and hospital stays did not differ among the groups. In particular, in the DKT group the urologic complication rate was 13.7% (three stenoses and eight ureteral fistulae) with 8/11 requiring surgical reexplorations. There were six other surgical reoperations for intestinal perforation (n ⫽ 2), bleeding (n ⫽ 3), and lymphocele (n ⫽ 1). Detailed comparisons of posttransplant outcomes among the groups are reported in Table 3. Prognostic Factors in DKT
Table 4 reports the univariate analysis of prognostic factors for patient and graft survival rates using the log-rank test. The only significant parameters were the early and late reoperation rates (P ⬍ .05). In contrast, recipient prognostic factors that were already reported as negative, such as
the older age, DGF incidence, high PRA% at transplant, and ⬎3 HLA mismatches, showed no significant correlation with graft or patient survival rates. DISCUSSION
In the last few years, several studies have examined the feasibility and outcomes of DKT.1,4 –7 In this domain, our study represents one of the largest experiences with a long follow-up period. In particular, unlike most published studies, we have stratified the analysis into three groups to prevent potentially misleading effects that can occur when edSKTs and idSKTs are combined. Furthermore, in our study, the retrospective analysis sought to identify prognostic factors for DKT patient and graft survival rates. In our experience, long-term graft and patient survival rates were similar for the three types of kidney transplant recipients. This lack of differences in short- and long-term graft survival rates between edSKT and DKT transplants has also been documented in many other reports, including the recent UNOS data analysis by Gill et al.9 In our series, data have appeared that require considerations. Concerning the analysis of the donor characteristics,
Table 2. Baseline Recipient Characteristics
Age (y) Male gender Time on waiting list (y) Number mismatch HLA-A, -B, -DR (1–6) PRA% Indication for kidney transplant (glomerular/tubulointerstitial/ policystic/ hypertensive/ESKD/other) Transplant number (1st/2nd)
DKT (n ⫽ 80)
edSKT (n ⫽ 167)
idSKT (n ⫽ 229)
P Value
61.4 ⫾ 4.5 55/25 (68.7%) 3.6 ⫾ 3.2 3.1 ⫾ 1.2
57.5 ⫾ 7.5 110/57 (65.8%) 5 ⫾ 8.7 2.6 ⫾ 1.1
42.4 ⫾ 12.2 150/79 (65.5%) 4.2 ⫾ 3.6 2.5 ⫾ 1.1
⬍.001 NS NS ⬍.05
5.9 ⫾ 16.9 33/8/12/14/13/0 (41.2%/10%/15%/17.5%/ 16.2%/0%)
3.3 ⫾ 9.3 71/14/37/24/16/5 (42.5%/8.3%/22.1%/14.3%/ 9.5%/2.9%)
5.5 ⫾ 12.5 100/32/32/11/35/19 (43.6%/13.9%/13.9%/4.8%/ 15.2%/8.2%)
⬍.05 ⬍.05
79/1 (98.7%/1.2%)
150/17 (89.8%/10.1%)
195/34 (85.1%/14.8%)
⬍.05
DKT, dual-kidney transplantation; edSKT, single transplantation using kidney from expanded criteria donor; idSKT, single transplantation using kidney from ideal donor; PRA, panel-reactive antibodies; ESKD, end-stage kidney disease without diagnostic histology.
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NARDO, BERTELLI, CAVALLARI ET AL Table 3. Comparison of Early Posttransplant Outcomes Data Between the Three Study Groups DKT (n ⫽ 80)
edSKT (n ⫽ 167)
P Value
idSKT (n ⫽ 229)
DGF rate 30/50 (37.5%) 81/86 (47.9%) 66/163 (28.8%) Acute rejection episodes 8/72 (10%) 15/152 (8.8%) 47/182 (20.5%) Urologic complications 11/69 (13.7%) 25/142 (14.8%) 27/202 (11.8%) Posttransplant diabetes 8/72 (10%) 10/157 (6%) 11/218 (4.8%) Neoplastic complications 5/75 (6.2%) 4/163 (2.4%) 4/225 (1.7%) Major infectious 10/70 (12.5%) 15/152 (9%) 21/208 (9.2%) complications Early reoperations (ⱕ30 d) 13/67 (16.2%) 18/149 (10.7%) 33/196 (14.4%) Late reoperations (⬎30 d) 9/71 (11.2%) 17/150 (10.1%) 21/208 (9.2%) Hospital stay (d) 22.1 ⫾ 12.1 23.9 ⫾ 11.9 21.9 ⫾ 12.1 Serum creatinine at discharge 1.5 ⫾ 0.9 1.8 ⫾ 0.7 1.6 ⫾ 0.7 (mg/dL) Serum creatinine 1-mo 1.6 ⫾ 0.7 1.9 ⫾ 0.8 1.7 ⫾ 0.8 posttransplant (mg/dL) 7/45/0/26/2 16/86/10/50/5 33/88/21/80/7 Immunosuppressive regimen (double FK/triple FK/double (8.7%/56.2%/0%/32.5%/2.5%) (9.5%/51.4%/5.9%/29.9%/2.9%) (14.4%/38.4%/9.1%/34.9%/3%) cyclosporine/triple cyclosporine/other)
⬍.05 ⬍.05 NS ⬍.05 NS NS NS NS NS ⬍.05 ⬍.05 ⬍.05
DKT, dual-kidney transplantation; edSKT, single transplantation using kidney from expanded criteria donor; idSKT, single transplantation using kidney from ideal donor; DGF, delayed graft function.
even if the registered graft and patient survival rates were comparable to those in other studies that have used routine pretransplant biopsy and were clearly superior to reports from centers that do not routinely perform histological analysis of the graft,5 our experience suggested that the current system that uses biopsies as the absolute criterion to allocate ECD kidneys as dual rather than single transplants might be too protective. On the basis of the excellent long-term results of DKT in our series, we believe that a careful evaluation of the opportunity to discard kidneys on
exclusive consideration of the reported bioptical score is necessary. It is noteworthy that seven patients who had only one functioning graft at follow-up displayed surprisingly good outcomes in terms of renal function. With the aim of avoiding kidney discards of organs, which could be potentially useful for DKT, we assume that in the near future, biopsy results will probably not just be considered alone, but in connection with the donor’s clinical data such as age, creatinine, creatinine clearance, and particularly clinical history of diabetes and hypertension. Unfortunately, this
Table 4. Regression Analysis for Graft and Patient Survival
Age (⬎61 vs ⱕ61 y) Gender (M/F) Indication for kidney transplant (glomerular/tubulointerstitial/policystic/ hypertensive/ESKD) Time on waiting list (ⱖ3 vs ⬍3) Number of HLA mismatches (⬎3 vs ⱕ3) PRA% (ⱖ5 vs ⬍5%) DGF (yes/no) Rejection episodes (yes/no) Urologic complications (yes/no) Posttransplant diabetes (yes/no) Neoplastic complications (yes/no) Infective complications (yes/no) Serum creatinine at discharge (⬎1.4 vs ⱕ1.4) Hospital stay (d) Early reoperations (yes/no) Late reoperations (yes/no) Immunosuppressive regimen (double FK/triple FK/double Cs/triple Cs/other)
n per Class
P Value for GS
P Value for PS
40/40 55/25 33/8/12/14/13
NS NS NS
NS NS NS
36/44 29/49 15/57 30/50 8/72 11/69 8/72 5/75 10/70 21/44
NS NS NS NS NS NS NS NS NS NS NS ⬍.05 ⬍.05 NS
NS NS NS NS NS NS NS NS NS NS NS ⬍.05 ⬍.05 NS
13/67 9/71 7/45/0/26/2
PRA, panel reactive antibodies; DGF, delayed graft function; Cs, cyclosporine; ESKD, end-stage kidney disease; GS, graft survival; PS, patient survival; HLA, human leukocyte antigen; NS, not significant.
DUAL-KIDNEY TRANSPLANTATIONS
retrospective analysis rests upon an insufficient number of cases to derive conclusions about this point. However, prospective studies analyzing donor clinical data in large populations may help to elucidate useful criteria for allocation of ECD kidneys. A recent study by Snanoudj et al reported the significance of the donor-estimated GFR as a prognostic criterion to allocate ECD kidneys as single or dual transplantations.10 With regard to the recipient characteristics, as predicted, we registered a higher mean age among the DKT and edSKT groups. Older recipients are more likely to have comorbidities, thus experiencing a higher risk of death with a functioning graft and being more susceptible to infections and adverse drug reactions.11 In our analysis of prognostic significance, however, there was no statistically significant correlation between the older age of DKT recipients (⬎61 years) and less successful outcomes. Furthermore, the HLA mismatch number was significantly greater among the DKT versus the other two groups. However, in contrast with other reports,4,6 it did not correlate with transplantation outcomes. Consistent with this observation, the OPTN/ UNOS reported no correlation between mismatch number and graft survival rate.9 Concerning posttransplantation outcomes, no differences were registered among the groups in the incidence of complications— urologic, infective, neoplastic, and reoperation rates. As in the UNOS report,9 but differing from a previous report,12 we registered a lower rate of rejection episodes among the DKT and edSKT versus idSKT group, which may be partially explained by the reduced immunologic activity among older recipients13 and the more frequently used, triple regimen in these groups. Moreover, a lower PRA% level was registered among edSKT recipients. In contrast with the higher incidence of acute rejection episodes, recipients of idSKT showed a lower incidence of DGF compared with the edSKT group, which can be partially explained by the better quality of the grafts. However, no significant difference in the incidence of DGF was observed between DKT and idSKT groups. Since patient age at the time of transplantation was the most frequent risk factor for posttransplant diabetes,14 the greater incidence registered in the DKT group could be explained by their higher mean age. Univariate analysis of potentially adverse prognostic factors correlating with graft or patient survival rates in the DKT group appeared to be the only significant parameter for the reoperation rate. In contrast, frequently considered negative prognostic factors, such as the DGF incidence, high PRA%, and HLA mismatches ⬎3,15 showed no significant correlation with graft or patient survival rates. Recent reports have noted a reduced impact of these prognostic factors in older recipients, as seen among those in the DKT cohort.16,17 In conclusion, this study confirmed that the DKT technique offers excellent early and long-term outcomes with regard to graft and patient survival rates. Even though DKT
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is characterized by a higher recipient mean age and longer operative time, its complication rate was comparable to that of idSKT. Kidney graft allocation, however, has to be accurate. The use of biopsy protocols is necessary for a complete evaluation of ECD organs to optimize resource allocation. Nevertheless, in our opinion, the use of a biopsy as the absolute criterion in allocating ECD kidneys to DKT might be too protective, whereas a correlation with donor clinical data may be more appropriate. Prospective longitudinal studies in the future may help to elucidate which donor features are useful criteria for ECD kidneys allocation. REFERENCES 1. Stratta RJ, Sundberg AK, Rohr MS, et al: Optimal use of older donors and recipients in kidney transplantation. Surgery 139:324, 2006 2. Metzger RA, Delmonico FL, Feng S, et al: Expanded criteria donors for kidney transplantation. Am J Transplant 3:114, 2003 3. Remuzzi G, Grynyo J, Ruggenenti P, et al: Early experience with dual kidney transplantation in adults using expanded donor criteria. J Am Soc Nephrol 10:2591, 1999 4. Remuzzi G, Cravedi P, Perna A, et al: Long-term outcome of renal transplantation from older donors. N Engl J Med 354:343, 2006 5. Lee RS, Miller E, Marsh CL, et al: Intermediate outcomes of dual renal allografts: the University of Washington experience. J Urol 169:855, 2003 6. Moore PS, Farney AC, Sundberg AK, et al: Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors. Transplantation 83:1551, 2007 7. Stratta RJ, Rohr MS, Sundberg AK, et al: Increased kidney transplantation utilizing expanded criteria deceased organ donors with results comparable to standard criteria donor transplant. Ann Surg 239:688, 2004 8. Bertelli R, Nardo B, Capocasale E, et al: Multicenter study on double kidney transplantation. Transplant Proc 40:1869, 2008 9. Gill J, Cho YW, Danovitch GM, et al: Outcomes of dual adult kidney transplants in the United States: an analysis of the OPTN/ UNOS database. Transplantation 85:62, 2008 10. Snanoudj R, Rabant M, Timsit MO, et al: Donor-estimated GFR as an appropriate criterion for allocation of ECD kidneys into single or dual kidney transplantation. Am J Transplant 9:2542, 2009 11. Basar H, Soran A, Shapiro R, et al: Renal transplantation in recipients over the age of 60: the impact of donor age. Transplantation 67:1191, 1999 12. Salifu MO, Norin AJ, O’Mahony C, et al: Long term outcomes of dual kidney transplantation—a single center experience. Clin Tranplant 23:400, 2009 13. Martins PN, Pratschke J, Pascher A, et al: Age and immune response in organ transplantation. Transplantation 79:127, 2005 14. Kasiske BL, Snyder JJ, Gilberston D, et al: Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 3:178, 2003 15. Pessione F, Cohen S, Durand D, et al: Multivariate analysis of donor risk factors for graft survival in kidney transplantation. Transplantation 75:361, 2003 16. Oniscu GC, Brown H, Forsythe JL, et al: How old is old for transplantation? Am J Transplant 4:2067, 2004 17. Keith DS, Demattos A, Golconda M, et al: Effect of donor recipient age match on survival after first deceased donor transplantation. J Am Soc Nephrol 15:1086, 2004