- Email: [email protected]
Single-Center Experience in Double Kidney Transplantation
Single-Center Experience in Double Kidney Transplantation I. Fontana, A. Magoni Rossi, G. Gasloli, G. Santori, A. Giannone, M. Bertocchi, F. Piaggio, E. Bocci, and Umberto Valente ABSTRACT Use of organs from marginal donors for transplantation is a current strategy to expand the organ donor pool. Its efficacy is universally accepted among data from multicenter studies. Herein, we have reviewed outcomes of double kidney transplantation (DKT) over an 9-year experience in our center. The aim of this study was to evaluate possible important differences between a monocenter versus multicenter studies. Between 1999 and 2008, we performed 59 DKT. Recipient mean age was 63 ⫾ 5 years. Mean HLA-A, -B, and -DR mismatches were 3.69 ⫾ 0.922. Donor mean age was 69 ⫾ 7 years and mean creatinine clearance was 69.8 ⫾ 30.8 mL/min. Proteinuria was detected in three donors (5%). Mean cold ischemia and warm ischemia times were 1130 ⫾ 216 and 48 ⫾ 11 minutes, respectively. The right and left kidney scores were 4.18 ⫾ 2 and 4.21 ⫾ 2, respectively. Thirty patients (51%) displayed good postoperative renal function; 22 (37%), acute tubular necrosis with postoperative dialysis; 3 (5%), acute rejection episodes; 4 (7%), single-graft transplantectomy due to vascular thrombosis; 1 (2%), a retransplantation; 5 (8%), a lymphocele; 3 (5%) vescicoureteral reflux or stenosis requiring surgical correction. Cytomegalovirus infection was detected in five patients (8%). In three patients (5%) displayed de novo neoplasia. Three patients showed chronic rejection (5%), whereas we observed a cyclosporine-related toxicity in 7 (12%). Nine patients (15%) developed iatrogenic diabetes. Patient and graft survivals after 3 years from DKT were 93% and 86.3%, respectively. In this study, we applied successfully a widespread score to allocate organs to single kidney transplantation or DKT. In our experience, the score is suitable for the organ allocation but it may be overprotective, excluding potentially suitable organs for a single transplantation. URING THE LAST YEARS, the shortage of donor organs has rapidly increased the waiting list for kidney transplantation.1 New strategies has been developed to expand the organ donor pool. The kidney transplant activity has increased by harvesting organs from “marginal donors.” The Genoa transplant center has applied a protocol for the double kidney transplantation (DKT) using marginal donor grafts according to the biopsy-based score system proposed by Remuzzi et al.2,3 Herein, we have reviewed the clinical outcomes of DKT performed in a single center during a 9-year period. The aim of this retrospective study was to evaluate DKT clinical outcomes for comparison with current multicenter studies.4
D
PATIENTS AND METHODS From 1999 to 2008, we performed 59 DKTs. Biopsies were performed on all patients with at least one of these risk factors: age
⬎70 years, creatinine clearance ⬍60 mL/min (calculated with the Cockroft-Gault formula), hypertension (on pharmacological treatment), cardiovascular disease (coronary artery disease, stroke, peripheral vascular diseases), diabetes ( pharmacological or insulin treatment), or proteinuria (⬎1 g/d). Biopsies histologically evaluated using the score proposed by Remuzzi et al2 were judged suitable for a single versus a double transplant or sacrifice. The enrollment criteria for DKT were: age over 55 years, good condition of the iliac vessels, adequate dimension of the iliac fossa, and body mass index ⬍32. Selection criteria for DKT were based on ABO compatibility, a negative cross-match, a panel-reactive anti-
From the Department of Transplantation, San Martino University Hospital, Genoa, Italy. Address reprint requests to Iris Fontana, MD, Department of Transplantation, San Martino University Hospital, L.go R. Benzi 10, 16132 Genoa, Italy. E-mail: [email protected]
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.03.063
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1108
Transplantation Proceedings, 42, 1108 –1110 (2010)
DOUBLE KIDNEY TRANSPLANTATION
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Table 1. The Percentage of Posttransplant Immunosuppressive Treatment for Patients (n) in Each Follow-up Time
CyA ⫹ S ⫹ MMF CyA ⫹ MMF CyA ⫹ S FK ⫹ S ⫹ MMF FK ⫹ S RAPA ⫹ S ⫹ CyA RAPA ⫹ S ⫹ MMF RAPA ⫹ S MMF ⫹ S S
HD (n ⫽ 58)
3 mo (n ⫽ 56)
6 mo (n ⫽ 55)
1 y (n ⫽ 46)
2 y (n ⫽ 42)
3 y (n ⫽ 26)
4 y (n ⫽ 15)
5 y (n ⫽ 13)
69 0 2 22 2 0 3 0 2 0
64 2 4 21 4 0 4 0 2 0
65 2 4 20 4 0 4 0 2 0
53 2 7 20 7 4 4 0 2 2
50 3 9 18 6 6 6 0 0 3
43 0 19 19 8 4 4 4 0 0
31 0 23 23 7 0 7 7 0 0
31 0 23 23 8 0 8 8 0 0
HD, hospital discharge; CyA, cyclosporine; MMF, mycophenolate mofetil; FK, tacrolimus; RAPA, rapamycin; S, steroids.
body less than 20%, and the best possible HLA-A, -B, and -DR match. Mean donor age was 69 ⫾ 7 years, and mean blood creatinine level was 1.09 ⫾ 1.4 mg/dL. Donor mean creatinine clearance was 69 ⫾ 60.4 mL/min. Mean left kidney weight was 218.75 ⫾ 144 g, while the right kidney was 217.5 ⫾ 124 g. During residence in the intensive care unit (ICU), an amine was used in 51 donors (86%): dopamine (n ⫽ 43; 73%), noradrenaline (n ⫽ 17; 29%), dobutamine (n ⫽ 14; 24%), or isoproteronol (n ⫽ 1; 2%). During ICU residence, seven patients (12%) displayed at least one episode of hypotension. The main donor risk factors were: hypertension on pharmacological therapy (59%), cardiovascular diseases (31%), smoking (10%), dyslipidemia on pharmacological therapy (7%), vascular diseases (7%), diabetes on insulin or pharmacological therapy (7%), past acute myocardial infarction (3%), hyperthyroidism on pharmacological therapy (2%), gotta in pharmacological therapy (2%), or obesity (2%). The mean right kidney score was 4.18 ⫾ 2 (mean glomerular sclerosis 0.98; mean tubular atrophy 0.96; mean interstitial fibrosis 1; and mean wall thickening 1.23). The mean left kidney score was 4.21 ⫾ 2 (mean glomerular sclerosis 0.98; mean tubular atrophy 1; mean interstitial fibrosis 1.13; and mean wall thickening 1.23).
Mean HLA-A, -B, and -DR mismatch was 3.84 ⫾ 1.8. Recipient mean age was 63 ⫾ 5 years, and body surface area, 1.84 ⫾ 0.4 m2. During the procedure, the two grafts were transplanted sequentially in the iliac fossa via separate double-J incisions bilaterally. Mean cold ischemia time was 1091 ⫾ 444 minutes for the right and 1148 ⫾ 437 minutes for the left kidney. Mean warm ischemia time was 48 ⫾ 22 minutes for right and 49 ⫾ 24 minutes for the left kidney. In most cases (69%), immunosuppressive treatment on discharge was based on cyclosporine (CsA), mycophenolate mofetil (MMF) and steroids; in 22% of patients, it was based on tacrolimus (FK), mycophenolate mofetil (MMF), and steroids. During follow-up, the percentage of patients with CsA ⫹ MMF ⫹ Steroid and FK ⫹ MMF ⫹ Steroid therapy was gradually reduced with use of rapamycin immunosuppression (Table 1).
RESULTS
Thirty patients (51%) displayed good postoperative renal function; 22 (37%), acute tubular necrosis with postoperative dialysis; 3 (5%), acute rejection episodes; 4 (7%), single-graft transplantectomy due to vascular thrombosis; 1
Fig 1. Kaplan-Meier plots for patient (A) and graft (B) survival after double kidney transplantation (DKT). Dotted staircase lines show confidence intervals for the corresponding survival function.
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(2%), retransplantation for poor function. Mean hospitalization time was 20 ⫾ 13 days. Posttransplant hypertension on pharmacological treatment was observed in 25 patients (42%); 17 (29%) had one or more urinary tract infections; diabetes in 11 (19%); dyslipidemia in 10 (17%); osteoporosis in 7 (12%); cytomegalovirus infections in 6 (10%); cholelithiasis in 5 (8%); and hyperparathyroidism in 5 (8%). CsA-related toxicity was observed in seven kidney recipients (12%). Six patients (10%) had a lymphocele and 2 (3%), vescicoureteral reflux or stenosis that required surgical correction. Chronic allograft nephropathy was documented by biopsy in four patients (7%). Chronic rejection, which occurred in one patient (2%), recovered with steroid based therapy. A de novo neoplasm was observed in three patients (5%); Kaposi’s sarcoma, bladder cancer, and soft tissue tumor. Among these subjects, one died because of cancer. Seven patients (12%) experienced no posttransplant disease or complication. Mean creatinine level at discharge, 3, 6, 12, 36, 48, and 60 months among surviving grafts were 1.5 ⫾ 1.2, 1.43 ⫾ 0.8, 1.5 ⫾ 0.8, 1.6 ⫾ 1, 1.65 ⫾ 1.1, 1.67 ⫾ 1.3, 1.47 ⫾ 1.2 and 1.42 ⫾ 1 mg/mL, respectively. Patient survivals at 1, 6, 24, and 36 months were 100%, 98.3%, 96.1%, and 93% (Fig 1A), with graft survivals of 93.2%, 91.5%, 89.3%, and 86.3% (Fig 1B), respectively.
FONTANA, MAGONI ROSSI, GASLOLI ET AL
DISCUSSION
Our single-center experience demonstrated DKT to be a safe approach to the organ shortage to reduce the waiting list times of patients with end-stage kidney disease. Our results were similar to previous multicenter studies.3–5 In this study, we applied the score proposed by Remuzzi et al to allocate organs to single or DKT.2,3 In our experience, the score was suitable for organ allocation but, as suggested by other groups,4 it may be overprotective, with the result of excluding potentially suitable organs for single transplantations. REFERENCES 1. Moore PS, Famey AC, Sundberg AK, et al: Experience with dual kidney transplants from donors at the extremes of age. Surgery 140:597, 2006 2. Remuzzi G, Cravedi P, Pema A, et al: Long term outcome of renal transplantation from older donors. N Engl J Med 354:343, 2006 3. Remuzzi G, Grynyò J, Ruggenenti P, et al: Early experience with dual kidney transplantation in adults using expanded donor criteria. Double Kidney Transplant Group (DKG). J Am Soc Nephrol 10:2591, 1999 4. Bertelli R, Nardo B, Capocasale E, et al: Multicenter study on double kidney transplantation. Transplant Proc 40:1869, 2008 5. Bunnapradist S, Gritsch HA, Peng A, et al: Dual kidneys from marginal adult donors as a source for cadaveric renal transplantation in the United States. J Am Soc Nephrol 14:1031, 2003
D
PATIENTS AND METHODS From 1999 to 2008, we performed 59 DKTs. Biopsies were performed on all patients with at least one of these risk factors: age
⬎70 years, creatinine clearance ⬍60 mL/min (calculated with the Cockroft-Gault formula), hypertension (on pharmacological treatment), cardiovascular disease (coronary artery disease, stroke, peripheral vascular diseases), diabetes ( pharmacological or insulin treatment), or proteinuria (⬎1 g/d). Biopsies histologically evaluated using the score proposed by Remuzzi et al2 were judged suitable for a single versus a double transplant or sacrifice. The enrollment criteria for DKT were: age over 55 years, good condition of the iliac vessels, adequate dimension of the iliac fossa, and body mass index ⬍32. Selection criteria for DKT were based on ABO compatibility, a negative cross-match, a panel-reactive anti-
From the Department of Transplantation, San Martino University Hospital, Genoa, Italy. Address reprint requests to Iris Fontana, MD, Department of Transplantation, San Martino University Hospital, L.go R. Benzi 10, 16132 Genoa, Italy. E-mail: [email protected]
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.03.063
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1108
Transplantation Proceedings, 42, 1108 –1110 (2010)
DOUBLE KIDNEY TRANSPLANTATION
1109
Table 1. The Percentage of Posttransplant Immunosuppressive Treatment for Patients (n) in Each Follow-up Time
CyA ⫹ S ⫹ MMF CyA ⫹ MMF CyA ⫹ S FK ⫹ S ⫹ MMF FK ⫹ S RAPA ⫹ S ⫹ CyA RAPA ⫹ S ⫹ MMF RAPA ⫹ S MMF ⫹ S S
HD (n ⫽ 58)
3 mo (n ⫽ 56)
6 mo (n ⫽ 55)
1 y (n ⫽ 46)
2 y (n ⫽ 42)
3 y (n ⫽ 26)
4 y (n ⫽ 15)
5 y (n ⫽ 13)
69 0 2 22 2 0 3 0 2 0
64 2 4 21 4 0 4 0 2 0
65 2 4 20 4 0 4 0 2 0
53 2 7 20 7 4 4 0 2 2
50 3 9 18 6 6 6 0 0 3
43 0 19 19 8 4 4 4 0 0
31 0 23 23 7 0 7 7 0 0
31 0 23 23 8 0 8 8 0 0
HD, hospital discharge; CyA, cyclosporine; MMF, mycophenolate mofetil; FK, tacrolimus; RAPA, rapamycin; S, steroids.
body less than 20%, and the best possible HLA-A, -B, and -DR match. Mean donor age was 69 ⫾ 7 years, and mean blood creatinine level was 1.09 ⫾ 1.4 mg/dL. Donor mean creatinine clearance was 69 ⫾ 60.4 mL/min. Mean left kidney weight was 218.75 ⫾ 144 g, while the right kidney was 217.5 ⫾ 124 g. During residence in the intensive care unit (ICU), an amine was used in 51 donors (86%): dopamine (n ⫽ 43; 73%), noradrenaline (n ⫽ 17; 29%), dobutamine (n ⫽ 14; 24%), or isoproteronol (n ⫽ 1; 2%). During ICU residence, seven patients (12%) displayed at least one episode of hypotension. The main donor risk factors were: hypertension on pharmacological therapy (59%), cardiovascular diseases (31%), smoking (10%), dyslipidemia on pharmacological therapy (7%), vascular diseases (7%), diabetes on insulin or pharmacological therapy (7%), past acute myocardial infarction (3%), hyperthyroidism on pharmacological therapy (2%), gotta in pharmacological therapy (2%), or obesity (2%). The mean right kidney score was 4.18 ⫾ 2 (mean glomerular sclerosis 0.98; mean tubular atrophy 0.96; mean interstitial fibrosis 1; and mean wall thickening 1.23). The mean left kidney score was 4.21 ⫾ 2 (mean glomerular sclerosis 0.98; mean tubular atrophy 1; mean interstitial fibrosis 1.13; and mean wall thickening 1.23).
Mean HLA-A, -B, and -DR mismatch was 3.84 ⫾ 1.8. Recipient mean age was 63 ⫾ 5 years, and body surface area, 1.84 ⫾ 0.4 m2. During the procedure, the two grafts were transplanted sequentially in the iliac fossa via separate double-J incisions bilaterally. Mean cold ischemia time was 1091 ⫾ 444 minutes for the right and 1148 ⫾ 437 minutes for the left kidney. Mean warm ischemia time was 48 ⫾ 22 minutes for right and 49 ⫾ 24 minutes for the left kidney. In most cases (69%), immunosuppressive treatment on discharge was based on cyclosporine (CsA), mycophenolate mofetil (MMF) and steroids; in 22% of patients, it was based on tacrolimus (FK), mycophenolate mofetil (MMF), and steroids. During follow-up, the percentage of patients with CsA ⫹ MMF ⫹ Steroid and FK ⫹ MMF ⫹ Steroid therapy was gradually reduced with use of rapamycin immunosuppression (Table 1).
RESULTS
Thirty patients (51%) displayed good postoperative renal function; 22 (37%), acute tubular necrosis with postoperative dialysis; 3 (5%), acute rejection episodes; 4 (7%), single-graft transplantectomy due to vascular thrombosis; 1
Fig 1. Kaplan-Meier plots for patient (A) and graft (B) survival after double kidney transplantation (DKT). Dotted staircase lines show confidence intervals for the corresponding survival function.
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(2%), retransplantation for poor function. Mean hospitalization time was 20 ⫾ 13 days. Posttransplant hypertension on pharmacological treatment was observed in 25 patients (42%); 17 (29%) had one or more urinary tract infections; diabetes in 11 (19%); dyslipidemia in 10 (17%); osteoporosis in 7 (12%); cytomegalovirus infections in 6 (10%); cholelithiasis in 5 (8%); and hyperparathyroidism in 5 (8%). CsA-related toxicity was observed in seven kidney recipients (12%). Six patients (10%) had a lymphocele and 2 (3%), vescicoureteral reflux or stenosis that required surgical correction. Chronic allograft nephropathy was documented by biopsy in four patients (7%). Chronic rejection, which occurred in one patient (2%), recovered with steroid based therapy. A de novo neoplasm was observed in three patients (5%); Kaposi’s sarcoma, bladder cancer, and soft tissue tumor. Among these subjects, one died because of cancer. Seven patients (12%) experienced no posttransplant disease or complication. Mean creatinine level at discharge, 3, 6, 12, 36, 48, and 60 months among surviving grafts were 1.5 ⫾ 1.2, 1.43 ⫾ 0.8, 1.5 ⫾ 0.8, 1.6 ⫾ 1, 1.65 ⫾ 1.1, 1.67 ⫾ 1.3, 1.47 ⫾ 1.2 and 1.42 ⫾ 1 mg/mL, respectively. Patient survivals at 1, 6, 24, and 36 months were 100%, 98.3%, 96.1%, and 93% (Fig 1A), with graft survivals of 93.2%, 91.5%, 89.3%, and 86.3% (Fig 1B), respectively.
FONTANA, MAGONI ROSSI, GASLOLI ET AL
DISCUSSION
Our single-center experience demonstrated DKT to be a safe approach to the organ shortage to reduce the waiting list times of patients with end-stage kidney disease. Our results were similar to previous multicenter studies.3–5 In this study, we applied the score proposed by Remuzzi et al to allocate organs to single or DKT.2,3 In our experience, the score was suitable for organ allocation but, as suggested by other groups,4 it may be overprotective, with the result of excluding potentially suitable organs for single transplantations. REFERENCES 1. Moore PS, Famey AC, Sundberg AK, et al: Experience with dual kidney transplants from donors at the extremes of age. Surgery 140:597, 2006 2. Remuzzi G, Cravedi P, Pema A, et al: Long term outcome of renal transplantation from older donors. N Engl J Med 354:343, 2006 3. Remuzzi G, Grynyò J, Ruggenenti P, et al: Early experience with dual kidney transplantation in adults using expanded donor criteria. Double Kidney Transplant Group (DKG). J Am Soc Nephrol 10:2591, 1999 4. Bertelli R, Nardo B, Capocasale E, et al: Multicenter study on double kidney transplantation. Transplant Proc 40:1869, 2008 5. Bunnapradist S, Gritsch HA, Peng A, et al: Dual kidneys from marginal adult donors as a source for cadaveric renal transplantation in the United States. J Am Soc Nephrol 14:1031, 2003