Mean Cold Ischemia Research Articles

The Kidney Not Taken: Single-Kidney Use in Deceased Donors.

The nonuse rate for kidneys recovered from deceased donors is increasing, rising to 27% in 2023. In 10% of these cases, 1 kidney is transplanted but the mate kidney is not. We conducted a retrospective, single-center cohort study from December 2001 to May 2023 comparing single kidneys transplanted at our center (where the contralateral kidney was not used) to kidneys where both were transplanted separately, at least 1 of which was at our center. We performed 395 single deceased-donor kidney transplants in which the mate kidney was not transplanted. Primary reasons for mate kidney nonuse were as follows: no recipient located or list exhausted (33.4%), kidney trauma or injury or anatomic abnormalities (18.7%), biopsy findings (16.7%), and poor renal function (13.7%). Mean donor and recipient ages were 51.5 ± 14.2 and 60 ± 12.6 years, respectively. Mean kidney donor profile index was 73% ± 22%, and 104 donors (26.3%) had kidney donor profile index >85%. Mean cold ischemia was 25.6 ± 7.4 hours, and 280 kidneys (70.7%) were imported. Compared with 2,303 concurrent control transplants performed at our center, primary nonfunction or thrombosis (5.1% single vs 2.8% control) and delayed graft function (35.4% single vs 30.1% control) were greater with single-kidney use (both p < 0.05). Median patient and death-censored graft survival were shorter in the single group (11.6 vs 13.5 years, p = 0.03 and 11.6 vs 19 years, p = 0.003), although the former was at least double median survival on the waiting list. In patients with functioning grafts in the single-kidney group, 1-year mean serum creatinine was 1.77 ± 0.8 mg/dL and estimated glomerular filtration rate was 44.8 ± 20 mL/min/1.73 m 2 . These findings suggest that many mate kidneys are being inappropriately rejected, given the acceptable outcomes that can be achieved by transplanting the single kidney in appropriately selected recipients.

P109 Preliminary identification of immune cells in the perfusate of renal allografts undergoing hypothermic machine perfusion

Aim Renal allografts stored with hypothermic machine perfusion (HPM) have improved outcomes compared to static methods. Passenger immune cells from the allograft have been implicated in acute rejection; improved outcomes with HPM may be due to cell removal by the pump. This study aimed to identify passenger immune cells present in the perfusate of HPM-preserved allografts. Once characterized, future strategies to suppress these cells may prevent acute rejection and improve graft survival. Methods All kidneys placed on HPM prior to transplant from May 2016 to August 2017 were eligible. Perfusate fluid was analyzed using flow cytometry for immune cells and information about the donors was collected. Wilcoxon Scores and Spearman Correlation Coefficient were used in statistical analysis. Results Twenty-seven perfusate specimens were analyzed. Selected donor characteristics: 63.6% male, 36.4% female; 63.6% donation after cardiac death; 54.5% pre-procurement transfusion. The mean HPM and cold ischemia times (CIT) were 9.9 h and 13.9 h respectively, and mean KDPI 36%. Flow cytometry showed a heterogeneous mix of immune cell types in the perfusate, similar to blood. CD15+ granulocytes, CD14+ monocytes, and CD8+ T cells were predominant in the perfusate. Dendritic and natural killer (NK) cells in perfusate were more abundant compared to blood. Conclusions Passenger immune cells, specifically dendritic cells have been implicated in acute rejection. This study showed the perfusate of renal allografts contains an array of immune cells, with a significantly higher percentage of dendritic cells and NK cells, as compared to blood. Future studies would show if HPM removal of these immune cells accounts for improved outcomes. ∗Frequencies of Cell Types in Human Peripheral Blood, www.stemcell.com .

Living donor nephrectomy: open versus laparoscopic technique

The living donor nephrectomy has to be safe and effective, allowing a good graft function in the recipient. In the past, donor nephrectomy was performed only by open technique; more recently this nephrectomy has also been performed by laparoscopic technique. The best technique has not been established in literature. The purpose of this study is to report the results of open and laparoscopic nephrectomy in living donors. MATERIALS AND METHODS. From January 1992 to August 2008, 37 living donor nephrectomies were performed. 23 nephrectomies were achieved by laparoscopic procedure (LDN) and 14 by open technique (ODN). The 2 groups were comparable regarding both donor and recipient characteristics. RESULTS. All laparoscopic nephrectomies were successfully performed without conversion to open procedure. No donor deaths were reported in either groups. 3 complications (13%) in the LDN group and 1 (7.1%) in the ODN group (p=0.6) were observed. Mean operative time was higher in the LDN group (p<0.036). Mean warm and cold ischemia time, resumption of oral intake and hospital stay were shorter in the LDN group (p<0.04)( p<0.03) (p<0.0001), whereas the return to normal occupational life was similar (p<0.52). We had no significant differences in the surgical complication rates, graft and patient survival. CONCLUSIONS. Our experience suggests that both procedures can be used safely and efficiently, and assure a good renal function in the recipient. Laparoscopic nephrectomy, although more difficult, provides post-operative advantages. However, laparoscopic procedure must be performed by experienced centres only to prevent serious complications in the donor.

Parachute Suture Technique with Arteriotomy by using Aortic Punch in Live Related Renal Transplant

Objective: To provide review of our experience in vascular anastomosis technique for kidney transplantation patients. Material and Methods: 100 chronic kidney disease patients 89 males and 11females with mean age 23.5 ± 3 years have been operated for kidney transplantation from January 2011 through April 2015. Vascular part of operation was done using parachute suture technique and arteriotomy by aortic punch. Recipients were prospectively entered into a database and retrospectively reviewed. Data collected included the warm and cold ischemic time, arterial and venous anastomotic time, color Doppler ultrasonography examination of the anastomosis site on 1, 7 postoperative days, mean serum creatinine level on 3, 14 days after the operation and any early or late postoperative complications. Results: Mean kidney warm and cold ischemia time was 7.5 ± 4minutes and 21.5 ± 7minutes respectively. Mean arterial and venous anastomotic time was 7.2 ± 9 minutes and 8 ± 4 minutes respectively. All allografts had single artery. Renal arteries were anastomosed to (53%) common iliac arteries, (40%) external iliac arteries, (6%) internal iliac arteries and just (1%) to lower aorta in recipients; however, allograft renal veins were anastomosed to (95%) common iliac vein and (5%) inferior vena cava recipients. No vascular complications were detected in the early postoperative period by Doppler ultrasonography examination. The mean serum creatinine level on the 3the and 14the days after the operation was 0.9 (range, 0.5-4 mg/dl) and 0.6(range 0.5-1.2 mg/dl) respectively. Slow graft function was diagnosed in 2patients, with a good perfusion of the allografts showed by renal scan. During a mean follow-up of 4 years, we did not encounter any case of renal artery or venous thrombosis or any suspected arterial stenosis. Conclusions: The parachute suture technique is safe and straightforward method for arterial and venous anastomosis in renal transplantation with low complication rates. Using aortic punch for arteriotomy facilitates the arterial anastomosis, which may results in excellent kidney function without stenosis of the renal artery.

Remote Revascularization of Abdominal Wall Transplants Using the Forearm

Primary abdominal wall closure following small bowel transplantation is frequently impossible due to contraction of the abdominal domain. Although abdominal wall transplantation was reported 10 years ago this, technique has not been widely adopted, partly due to its complexity, but largely because of concerns that storing the abdominal allograft until the end of a prolonged intestinal transplant procedure would cause severe ischemia-reperfusion injury. We report six cases of combined small bowel and abdominal wall transplantation where the ischemic time was minimized by remotely revascularizing the abdominal wall on the forearm vessels, synchronous to the intestinal procedure. When the visceral transplant was complete, the abdominal wall was removed from the forearm and revascularized on the abdomen (n = 4), or used to close the abdomen while still vascularized on the forearm (n = 2). Primary abdominal wall closure was achieved in all. Mean cold ischemia was 305 min (300-330 min), and revascularization on the arm was 50 min (30-60 min). Three patients had proven abdominal wall rejection, all treated successfully. Immediate revascularization of the abdominal wall allograft substantially reduces cold ischemia without imposing constraints on the intestinal transplant. Reducing storage time may also have benefits with respect to ischemia-reperfusion-related graft immunogenicity.

Single-Center Experience in Double Kidney Transplantation

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.

Living Donor Nephrectomy: Open versus Laparoscopic Technique

Background The living donor nephrectomy has to be safe and effective, allowing a good graft function in the recipient. In the past, donor nephrectomy was performed only by open technique; more recently this nephrectomy has also been performed by laparoscopic technique. The best technique has not been established in literature. The purpose of this study is to report the results of open and laparoscopic nephrectomy in living donors. Materials and Methods From January 1992 to August 2008, 37 living donor nephrectomies were performed. 23 nephrectomies were achieved by laparoscopic procedure (LDN) and 14 by open technique (ODN). The 2 groups were comparable regarding both donor and recipient characteristics. Results All laparoscopic nephrectomies were successfully performed without conversion to open procedure. No donor deaths were reported in either groups. 3 complications (13%) in the LDN group and 1 (7.1%) in the ODN group (p=0.6) were observed. Mean operative time was higher in the LDN group (p&lt;0.036). Mean warm and cold ischemia time, resumption of oral intake and hospital stay were shorter in the LDN group (p&lt;0.04)(p&lt;0.03) (p&lt;0.0001), whereas the return to normal occupational life was similar (p&lt;0.52). We had no significant differences in the surgical complication rates, graft and patient survival. Conclusions Our experience suggests that both procedures can be used safely and efficiently, and assure a good renal function in the recipient. Laparoscopic nephrectomy, although more difficult, provides post-operative advantages. However, laparoscopic procedure must be performed by experienced centres only to prevent serious complications in the donor.

Segmental Liver Transplantation from Non-Heart Beating Donors—An Early Experience with Implications for the Future

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11), median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n=2). The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2-8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10-36) follow-up all children are alive and well with functioning grafts. Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.

Living Donor Renal Transplantation in Catalonia: Overall Results and Comparison of Survival With Cadaveric Donor Renal Transplantation

Objectives To describe the general characteristics of living-donor renal transplantation (LRT) in Catalonia, and to compare results with those of the cadaveric donor renal transplant (CRT). Results Four hundred seventy-three LRTs have been performed in Catalonia since 1965. Transplantations carried out between 1980 and 2003, according to the RMRC data, were reviewed. The most frequent degrees of kinship are parents–children (48%), spouses (22%), and siblings (18%). Around 68% of the donors were women. Around 56% of recipients were men. The transplant was advanced in approximately 30% of the cases. The mean cold ischemia was 2 hours. Seven percent showed delayed graft function (DGF). Forty-nine percent of the patients had glomerular filtration >60 mL/min after 1 year. Patient survival at 1, 5, 10, and 20 years were 99%, 97%, 93%, and 82% in LRT; and 96%, 90%, 80%, and 62% in CRT ( P < .00001). Graft survivals over the same periods were 91%, 76%, 58%, and 32% in LRT, and 85%, 69%, 49%, and 23% in CRT ( P = .00008). The graft mean life was 12 years (LRT) and 10 years (CRT). Graft survivals, censoring deaths over the same periods, were 93%, 79%, 62%, and 39% in LRT, and 89%, 77%, 62%, and 37% in CRT ( P = .3). Mean life was 14 years in both cases. The recipients mean age was 31 (LRT), and 44 years (CRT), whereas the donor mean age was 51 (LRT), and 42 years (CRT). Conclusions LRT results were excellent both regarding DGF and patient and graft survivals. They were not comparable to CRT due to the different characteristics of the recipients. LRT is a good solution to reduce waiting lists.

CAMPATH PRECONDITIONING AND TACROLIMUS MONOTHERAPY WITH SUBSEQUENT WEANING IN RENAL TRANSPLANT RECIPIENTS

O144 Aims: After elucidating the mechanisms of alloengraftment, we proposed a strategy of tolerogenic immunosuppression that facilitates these mechanisms. Two principles were applied: recipient pretreatment and the minimal use of post-transplant immunosuppression. In an earlier series, kidney recipients were preconditioned with Thymoglobulin and given post-transplant monotherapy with tacrolimus. Methods: Between November 2002 and September 2003, we substituted 30 mg Campath 1-H for Thymoglobulin in 96 adult kidney recipients (mean age 50.3 ± 16.4 years; range 17 - 82). Thirteen (13.5%) were undergoing retransplantation, and 20 (20.8%) had a PRA >20%. Mean HLA mismatches were 3.7 ± 1.6. There were 59 (61.5%) cadaver donors (mean cold ischemia 20.9 ± 7.3 hours) and 37 (38.5%) live donors. Mean donor age was 41.4 ± 15.9 years (range 1 – 72). Post-transplant immunosuppression was with tacrolimus monotherapy (target levels 10 mg/ml), with dose spacing to every other day or longer at various times after about four months. Results: With a mean follow up of 8.7 ± 2.4 months, the patient and graft survival rates are 97% and 95%, respectively, with a mean serum creatinine of 1.5 ± 0.6 mg/dl. Only one patient (1%) in the cohort has had acute rejection (steroid responsive) prior to weaning. Weaning was attempted in 73 (76%) and is ongoing in 69 (72%) patients. Four (5.5%) developed rejection after attempted weaning. Thirty-eight (40%) are on every other day tacrolimus, 30 (31%) are on three times a week tacrolimus, and one (1%) is on every third day tacrolimus. The incidence of delayed graft function was 10.4%. The incidence of CMV disease and diabetes was 0%. One (1%) patient developed PTLD. Conclusions: Although the follow up is still short, we conclude that the use of Campath 1-H for pretreatment has significantly improved the efficacy of our tolerogenic regimen of immunosuppression.

THYMOGLOBULIN PRECONDITIONING AND TACROLIMUS MONOTHERAPY WITH SUBSEQUENT WEANING IN RENAL TRANSPLANT RECIPIENTS: AN UPDATE

O142* Aims: We have suggested that the heavy conventional immunosuppression used for organ transplantation subverts the seminal tolerogenic mechanism of clonal exhaustion-deletion and thereby contributes to long-term drug dependence. Methods: This self-defeating effect was avoided in 175 adult kidney recipients (mean 49.9 ± 14.3 years) treated between July 2001 and September 2003; 43 (24.6%) had adjunct donor bone marrow cell infusion. Two therapeutic principles were applied: (1.) recipient pretreatment (with 5 mgm/kg Thymoglobulin); (2.) minimal post-transplant immunosuppression (with tacrolimus monotherapy, initial target trough 10 ng/ml). Twenty-five (14.2%) patients were undergoing retransplantation, and 34 (19.4%) had a PRA >20%. Mean HLA mismatches were 3.1 ± 1.7. One hundred kidneys (57%) were cadaveric (mean cold ischemia 25.6 ± .7 hours) and 75 (43%) were live donated. Mean donor age was 39.9 ± 6.3 years (range 1-66). Post-transplant doses of tacrolimus were spaced to every other day or longer at various times after four months. Results: With a mean follow up of 16.9 ± 7.1 months, the actuarial one and two patient survival is 97% and 95% with graft survival of 91% and 84%. Mean current serum creatinine is 1.95 ± 1.14 mg/dl. The incidence of preweaning acute clinical rejection was 34.9% (6.3% steroid resistant). Weaning was attempted in 149 cases (85.1%) and interrupted by rejection in 45 (30.2%). Currently, 111 (63.4%) patients are at various stages of weaning: 25 (14.2%) every other day, 44 (25.1%) three times a week, 28 (16%) two times a week, and 14 (8%) once a week. Ten percent of patients had asymptomatic CMV infection and there was one BK infection, but the incidence of CMV disease, diabetes, and PTLD was 0%. Conclusions: With significant numbers of highly weaned patients beyond the two-year mark, we continue to apply this strategy of immunosuppression, which is neither drug nor organ specific.