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PubMed2004

A comparative prospective study of two available solutions for kidney and liver preservation.

BACKGROUND: Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation. PATIENTS AND METHODS: From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study. RESULTS: Perfusate volume used was significantly lower in the UW group, being 4,732 +/- 796 mL versus 5,826 + 834 mL in the CEL group (P < 0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 micromol/L, respectively) as compared with CEL (51.3 and 63.4 micromol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P = NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P = NS) and 89.9% versus 90.6% (P = NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P = NS), respectively; PNF rates were 1.9% and 1.7% (P = NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P = NS) and 99.4% versus 97.7% (P = NS). CONCLUSIONS: CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting.

Adenosine↗
PubMed2004

A truncated-dose regimen of daclizumab for prevention of acute rejection in kidney transplant recipients: a single-center experience.

Daclizumab can decrease the incidence of acute rejection (AR) in renal transplant (RTx) recipients. In this prospective study, 52 RTx patients were divided into two groups according to the dose of daclizumab: 1 mg/kg on day 0 and every 14 days for five doses (group 1, n = 30) or a truncated regimen of 2 mg/kg on day 0 and on the day of discharge (group 2, n = 22). The following variables were recorded: demographics; delayed graft function; AR at 3, 6, and 12 months; time to AR; chronic allograft nephropathy (CAN); and serum creatinine. The overall incidences of AR were 23% and 27% (P = 0.76) in groups 1 and 2, respectively, whereas at 6 months they were 21% and 18% (P = 1.0). Median time to AR was 10 days in group 1 and 94 days in group 2 (P = 0.09). The incidence of CAN was 6.6% in group 1 and 13% in group 2 (P = 0.63). These data suggest that the truncated dose of daclizumab is as effective as the standard regimen for AR prophylaxis.

Antibodies, Monoclonal↗
PubMed2005

The relative importance of cytokine gene polymorphisms in the development of early and late acute rejection and six-month renal allograft pathology.

BACKGROUND: Acute rejection episodes and 6-month protocol biopsy acute pathology are highly correlated with long-term outcomes in renal transplant recipients. Recurrent, vascular, and late rejections are particularly deleterious. METHODS: We determined the relative contribution of human leukocyte antigen matching, cytokine genotypes, delayed graft function (DGF), and baseline immunosuppression to the development of acute rejection and allograft pathology in 118 renal transplant recipients. RESULTS: Multivariate logistic regression modeling demonstrated that the adjusted odds ratio and 95% confidence interval for recurrent (> or =2) early rejections (0-3 months) increased linearly for high (H) > intermediate (I) > low (L) interferon-gamma (1.8; 1.1-3.2) and tumor necrosis factor (TNF)alpha (3.0; 1.3-6.9) genotype, whereas every 1 microg/L increase in the cyclosporine A level was protective (0.991; 0.984-0.999). The odds ratio for recurrent late rejections (4-6 months) increased for H > I > L TNFalpha (5.1; 1.8-14.7) genotype and DGF (7.1; 1.6-30.2), whereas H > I/L transforming growth factor-beta1 genotype decreased the relative risk (0.09: 0.02-0.49). Vascular rejection was only predicted by H > I > L TNFalpha phenotype (3.0; 1.2-7.9). The odds ratio for the 6-month Banff Acute Score (6A > or= 4) increased for H > I > L TNFalpha (2.7; 1.1-6.7) and interleukin-10 (3.4; 1.2-6.2) genotype, and DGF (3.4; 1.1-11.5). Treatment of early subclinical rejection decreased the relative risk (0.20; 0.07-0.62). CONCLUSIONS: High transforming growth factor-beta1 producer phenotype seems to be protective against acute inflammation, whereas H and I interferon-gamma, TNFalpha, and interleukin-10 producer genotypes correlate with adverse outcomes. Cytokine genotyping identifies individuals who may benefit from more intensive surveillance and treatment posttransplant.

Adult↗
PubMed2005

High CXCL10 expression in rejected kidneys and predictive role of pretransplant serum CXCL10 for acute rejection and chronic allograft nephropathy.

BACKGROUND: Several experimental models have shown that CXCL10 is required for initiation and development of graft failure caused by both acute and chronic rejection. METHODS: CXCL10 expression and distribution was investigated in tissue specimens obtained from 22 patients suffering from acute rejection (AR) or chronic allograft nephropathy (CAN) by using in situ hybridization. Furthermore, pretransplantation sera of 316 cadaveric kidney-graft recipients were tested retrospectively for serum CXCL10 levels by a quantitative sandwich immunoassay. RESULTS: Bioptic specimens obtained from patients with CAN were characterized by wide CXCL10 expression not only at level of infiltrating inflammatory cells but also of vascular, tubular, and glomerular structures. In addition, assessment of pretransplant serum CXCL10 levels in 316 graft recipients and stratification of patients in three groups according to serum CXCL10 levels (<100 pg/mL, n=163; 100-150 pg/mL, n=69; >150 pg/mL, n=84) showed highly significant differences in 5-year survival rates for the two extreme groups (95.7% vs. 79.7%, P=0.0002). Accordingly, patients who developed severe, early AR (277.14+/-65.08 p=0.004) and those who developed CAN also showed increased pretransplant serum CXCL10 levels (193.2+/-36.9, P=0.03). Multivariate analysis demonstrated that among the analyzed variables, CXCL10 (relative risk [RR] 2.801) and delayed graft function (RR 3.728) had the highest predictive power of graft loss. CONCLUSIONS: These results suggest that pretransplant serum CXCL10 levels greater than 150 pg/mL confer an increased risk of early, severe, AR and subsequent CAN, finally resulting in renal-allograft failure. This finding might be used for the individualization of immunosuppressive therapies.

Biomarkers↗
PubMed2005

A radical scavenger, edaravone, protects canine kidneys from ischemia-reperfusion injury after 72 hours of cold preservation and autotransplantation.

BACKGROUND: Cold ischemia-reperfusion (I/R) injury is a prominent cause of delayed graft function after kidney transplantation. Reactive oxygen species play a crucial role in I/R injury. Edaravone is a synthetic radical scavenger that has been used in acute stroke. Some animal experiments have revealed its beneficial effects against I/R injury, but its effects after cold preservation and transplantation of canine kidneys are unknown. METHODS: Female hybrid dogs weighing 11 to 13 kg were used. Under anesthesia, the left kidney was harvested. After 72 hr of preservation in cold histidine-tryptophan-ketoglutarate solution, autotransplantation was performed in the right iliac fossa, with contralateral nephrectomy. Animals were divided into control and treatment groups (n=6 per group). In the treatment group, edaravone was administered intravenously at harvest and at reperfusion (3 mg/kg) and in addition was added to the preservation solution (50 microM). RESULTS: Animal survival at 2 weeks was four of six in the control group and six of six in the treatment group. Compared with controls, treated animals had higher mean urine output, higher mean glomerular filtration rate, improved tubular cell function, lower mean serum creatinine, and lower renal vascular resistance. Biopsy specimens from treated animals showed less tubular cell damage and decreased P-selectin expression in endothelial cells. Lipid peroxidation of renal tissue and urinary excretion of 8-hydroxy-2'-deoxyguanosine were suppressed by the treatment. CONCLUSIONS: Edaravone reduced cold I/R injury in canine renal transplantation. The agent has the potential to ameliorate preservation injury in clinical transplantation.

Animals↗
PubMed2005

Long-term patient and graft survival in the eurotransplant senior program: a single-center experience.

BACKGROUND: The Eurotransplant Senior Program (ESP) was launched in 1999, targeted to increase the supply of donor kidneys to the elderly. This program requires local allocation of kidneys from cadaveric donors >>65 years to recipients >>65 years. METHODS: Of all patients >>65 years who received a kidney transplant in 1999-2002 at our center, 59 patients were transplanted through the ESP protocol (ESP group), and 44 patients received a transplant from a younger donor (EuroTransplant Kidney Allocation System, ETKAS group). Recipients were followed for up to 5.3 years using the Austrian Dialysis and Transplant Registry. Outcomes studied included all-cause mortality and allograft loss. RESULTS: Age, sex, and comorbid conditions did not differ by group. Donor age was higher (69 vs. 36 years; P < 0.001) and cold ischemia time shorter in the ESP group (10 vs. 15 hr; P < 0.001). Number of HLA mismatches was greater in the ESP group (3.8 vs. 3.0; P = 0.003). ESP patients were more likely to receive induction therapy and less likely to receive cyclosporine A. Primary nonfunction, delayed graft function, operative mortality, rate of acute rejection episodes, and length of stay did not differ by group. Although serum creatinine at discharge was higher in ESP patients (1.7 vs. 1.4 mg/dL; P < 0.001), 4-year mortality (hazard ratio [HR] = 0.68; 95% CI: 0.31-1.49) and graft loss (HR = 0.61; 95% CI: 0.29-1.28) tended to be less. CONCLUSIONS: Long-term patient and graft survival were comparable between elderly patients who received their organ via the ESP and the regular ETKAS algorithm.

Aged↗
PubMed2005

Serum sCD30 in monitoring of alloresponse in well HLA-matched cadaveric kidney transplantations.

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (P<0.01). However, steroid-resistant rejection was associated with increasing posttransplant sCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.

Antigens, CD↗
PubMed2006

Comparison of histidine-tryptophan ketoglutarate solution and University of Wisconsin solution in prolonged cold preservation of kidney allografts.

Although University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation, Histidine-Tryptophan Ketogluatarate (HTK) solution has been increasingly used. This study compared HTK or UW for cold static storage of kidney allografts. In all, 149 renal transplants were performed with cold ischemic times (CI) greater than 16 hr (UW 87, HTK 62) and a subset analysis was performed with CI over 24 hr (HTK 31, UW 38). Data from receiving renal transplant centers focused on delayed graft function (DGF), patient and allograft survival. In CI greater than 16 hr, graft and patient survival were comparable. HTK cohort had lower DGF. In CI greater than 24 hr, there was no difference in patient survival, a trend towards improved graft survival in HTK, and decreased rate of DGF in HTK. This data suggests that UW and HTK have at least similar efficacy in kidney preservation at longer ischemic times.

Adenosine↗
PubMed2006

Early cyclosporine C0 and C2 monitoring in de novo kidney transplant patients: a prospective randomized single-center pilot study.

BACKGROUND: C2 monitoring of cyclosporine (CsA) has been promoted as improving the results of organ transplantation. No randomized, controlled studies in de novo kidney transplant recipients are available. METHODS: Between June 2003 and August 2004, 160 consecutive cadaveric kidney recipients allocated to CsA, mycophenolate and steroids were randomized to either C0 or C2 monitoring of CsA for the first 3 weeks posttransplant. Both levels were measured, keeping the other level blinded until 3 weeks. Altogether, 1451 double measurements were done. The target C0 was 200-300 microg/L and C2 1500-2000 microg/L. From the fourth week on, only C0 monitoring was used. Median follow up time was 505 days. RESULTS: The overall 3-month rejection rate was 7.5% in Group C0 vs. 10.8% in Group C2 and the one-year graft survival rates were 92.5% vs. 94.6% (NS). Rate of delayed graft function was similar in the groups. Plasma creatinine tended to be higher in group C2 at 3 weeks, but not thereafter. During the first three weeks posttransplant, the mean CsA dose was 57%, mean C2 levels were 55%, and mean C0 levels were 98% higher in group C2 than in group C0 (P < 0.00001). CONCLUSION: This pilot study showed no advantages of C2 monitoring but led to significantly higher CsA doses and blood levels than C0 monitoring.

Adult↗
PubMed2006

Surgical aspects of third and subsequent renal transplants performed by the extraperitoneal access.

BACKGROUND: We reviewed our experience with third, fourth, and fifth renal transplants performed by the extraperitoneal access. METHODS: The charts of 21 third and subsequent transplants performed extraperitoneally were reviewed. Surgical aspects, the occurrence of rejection episodes, delayed graft function (DGF), graft and patient survival were evaluated and compared with 1560 first transplants in adults with nonmanipulated fossa performed in the same period. RESULTS: Transfusion was necessary in 52% of the retransplants and in 5.7% of the first transplants (P<0.0001). Mean operative time was 327 min for retransplants and 212 min for first transplants (P<0.0001). Surgical complications occurred in 4 patients (19%): two arterial thrombosis and two ureteral obstructions. DGF occurred in 11 patients (52%) among retransplants and in 453 (29%) among first transplants (P=0.028). Acute rejection occurred in 7 (33.3%) retransplants and in 530 first transplant patients (33.9%). The mean serum creatinine among retransplant patients 30 days and one year after transplantation was 2.5 mg/dl and 1.8 mg/dl. One-year graft survival was 57.1% (75% for live and 46% for cadaver donors) for retransplants and 86% for first transplant patients (P<0.0001). CONCLUSION: Third and subsequent transplants performed extraperitoneally are more time-consuming and require more transfusions in the perioperative period. A higher but acceptable incidence of arterial thrombosis and urinary obstruction were observed. One-year graft survival was better with live donor grafts, but was still lower when compared with first transplants using the same surgical technique.

Adolescent↗
PubMed2006

Expression of MHC class I-related Chain B (MICB) molecules on renal transplant biopsies.

BACKGROUND: MICA and MICB (MHC class I-related chain A and B) are polymorphic genes that encode molecules related to MHC class I and are expressed on epithelial cells in response to stress. Incompatible donor MIC antigens can stimulate antibody production in transplant recipients. This study was designed to determine MICB expression in kidney pretransplant and any subsequent changes in expression following transplantation and to correlate changes with inflammatory markers and clinical events. METHODS: Paired renal biopsies obtained from living donor (n=10) and cadaveric allografts (n=50) before and 7 days posttransplant were stained for MICB, leukocytic infiltration, and HLA class II antigens. RESULTS: Variable tubular MICB expression was evident in donor biopsies [high 6/60 (10%), low/negative 13/60 (22%), intermediate 41/60 (68%)]. Following transplantation, MICB was up-regulated on renal tubules of 17/60 (28%) biopsies and was associated with MHC class II antigen induction (P=0.02) and leukocyte infiltration (P=0.01). Acute tubular necrosis leading to delayed graft function (DGF) and acute rejection (AR) cause cellular stress within the transplanted kidney. We found a strong association between up-regulation of MICB and cellular stress, 15/17 biopsies with up-regulated MICB expression had AR and/or DGF (P=0.003). CONCLUSIONS: This is the first study demonstrating variable levels of MICB expression in kidneys before transplantation and induction of MICB expression following renal transplantation. MICB expression is associated with HLA class II antigen induction, leukocytic infiltration of the graft and cellular stress in the transplanted kidney. Expression of MICB could contribute significantly to the alloimmune response in mismatched donors and recipients.

Adult↗
PubMed2006

Association of high pretransplant sIL-6R plasma levels with acute tubular necrosis in kidney graft recipients.

BACKGROUND: Delayed graft function is primarily caused by acute tubular necrosis (ATN). We studied in renal transplant recipients with posttransplant graft biopsy whether an up-regulated immune system in the recipient immediately before transplantation affects the risk of developing ATN and might be relevant for the pathogenesis of ATN. METHODS: In a retrospective study, we analyzed pretransplant and early posttransplant soluble interleukin (sIL)-1RA, interleukin (IL)-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta2, interferon (IFN)-gamma, and neopterin plasma levels in patients with ATN (n=26). Matched patients with acute rejection (AR) (n=26) or normal posttransplant biopsy (n=26) served as controls. RESULTS: Pretransplant sIL-6R was higher (P=0.0004) and pretransplant TGF-beta2 lower (P=0.002) in patients with ATN than in patients with normal biopsy. ROC curves showed that high pretransplant sIL-6R has a high sensitivity (77%) and high specificity (64%) for ATN (P=0.002). Posttransplant plasma sIL-6R continued to be higher in ATN patients than in patients with normal biopsy (P=0.001). Patients with acute rejection showed pre- and posttransplant sIL-6R and TGF-beta2 plasma levels similar to those of patients with normal biopsy (P=NS). CONCLUSION: High pretransplant sIL-6R plasma levels are associated with an increased risk of ATN and might contribute to the development of ATN early posttransplant. Our data suggest that preactivation of the recipient's immune system increases the risk of ATN.

Acute Disease↗
PubMed2006

High pretransplant parathyroid hormone levels increase the risk for graft failure after renal transplantation.

BACKGROUND: Calcium (Ca), phosphate (P), and parathyroid hormone (PTH) are important variables influencing the risk for cardiovascular disease in dialysis patients. We studied the influence of long-standing Ca-P disregulation on renal transplant survival. METHODS: Pretransplant PTH, Ca, P, total protein (TP), albumin, and alkaline phosphatase (AP) values were gathered in all 407 patients that received a renal transplant in our center between January 1, 2000 and July 1, 2004. Other variables expected to influence the risks were included. RESULTS. In the Cox proportional hazards analysis the risk for graft failure censored for death was significantly influenced by pretransplant PTH concentration (P = 0.008) and donor type (P < 0.001). The influence of PTH on the risk for patient death was not significant. The risk for acute rejection was studied but PTH level did not have a significant influence on this risk (P = 0.055). The risk for delayed graft function was not influenced by PTH level. CONCLUSION: Serum PTH levels have an independent influence on the risk for graft failure censored for death. Efforts to improve calcium-phosphate-PTH homeostasis in patients on the waiting list for renal transplantation should be encouraged also to improve graft survival.

Aged↗
PubMed2006

Successful renal transplantation in high-risk small children with a completely thrombosed inferior vena cava.

BACKGROUND: Inferior vena cava (IVC) thrombosis is generally a contraindication to renal transplantation in small children because of the technical difficulty and limitations in allograft venous outflow drainage that risk graft thrombosis. METHODS: The records of six consecutive children (9.9-27.4 kg) with end-stage renal disease and thrombosed IVCs were reviewed. Small deceased donor renal allografts were utilized in all cases where immediate posttransplant venous renal outflow would theoretically not exceed the drainage capacity of the iliac or adjacent pelvic collateral veins. RESULTS: There is 100% patient survival with two patients returning to dialysis at seven and three years posttransplantation. There were no surgical complications or delayed graft function. Postoperatively, progressive renal vein and simultaneous iliac venous enlargement was observed in five of six recipients concomitant with renal allograft enlargement. In these patients, maximum renal volume achieved was between 152 and 275 ml and last recorded Schwartz glomerular filtration rates ranged from 67 to 118 ml/min. The sixth allograft had an early, severe rejection episode that limited renal growth and attainment of good renal function. All patients demonstrated resumption of growth rates commensurate with age but without significant catch-up growth. CONCLUSION: A small deceased donor kidney can provide freedom from dialysis and better quality of life for small children with IVC thrombosis during an age when dialysis treatment is difficult and the complications of the thrombosed IVC may compromise life. Good renal function was attained in patients without rejection episodes. In those with rejection, our approach allowed for patient growth during allograft function, providing a bridge for a repeat transplant.

Adolescent↗
PubMed2007

Comparison of laparoscopic versus hand-assisted live donor nephrectomy.

BACKGROUND: The aim of the present study was to compare hand-assisted laparoscopic live donor nephrectomy with the classic laparoscopic method, using meta-analytical techniques. METHODS: A literature search was performed for studies comparing hand-assisted laparoscopic nephrectomy with classic laparoscopic nephrectomy for live kidney donation between 1999 and 2005. The following end points were evaluated: operative time, warm ischemia time, intraoperative adverse events, donor and recipient postoperative complications, and length of hospital stay. RESULTS: Nine comparative studies matched the selection criteria, reporting on 376 patients, of whom 202 (53.7%) had hand-assisted laparoscopic nephrectomy and 174 (46.3%) had the classic laparoscopic technique. Conversion to open surgery was 2.97% in the hand-assisted group and 4.60% in the laparoscopic group (P=0.35). Total operative and warm ischemia times were significantly shorter for hand-assisted laparoscopy by 30.03 minutes (P=0.02) and 1.14 minutes (P<0.001), respectively. The intraoperative blood loss was less for the hand-assisted laparoscopy group by 34.16 mL (P=0.008), although intraoperative (3.46% vs. 7.47%; P=0.24) and postoperative (5.94% vs. 10.34%; P=0.30) donor complications and recipient complications (including delayed graft function and primary nonfunction, 8.41% vs. 7.42%; P=0.32) were similar between the hand-assisted and laparoscopic groups. CONCLUSION: Hand-assisted laparoscopic nephrectomy appeared to have the same donor and recipient complication rate with standard laparoscopy but offered substantial advantages in terms of shortened operative and warm ischemia time as well as decreased intraoperative bleeding.

Adult↗
PubMed2004

Observations regarding the use of sirolimus and tacrolimus in high-risk cadaveric renal transplantation.

BACKGROUND: Balancing the risk of acute rejection (AR) with drug-induced toxicities complicates the selection of the optimal immunosuppressive regimen, especially in the high-risk renal transplant recipient. This study was designed to determine the optimal dosage combinations of tacrolimus and sirolimus in a high-risk cadaveric renal transplant population. METHODS: Primary cadaveric renal transplant recipients were randomly assigned to receive either standard tacrolimus (trough levels of 10-15 ng/mL) plus reduced sirolimus (trough levels of 5-10 ng,mL) (Group I) or to receive reduced tacrolimus (trough levels of 5-10 ng,mL) plus standard sirolimus (trough levels of 10-15 ng/mL) (Group II). All patients received Thymoglobulin induction and steroids. RESULTS: Thirty-nine (16 in Group I and 23 in Group II) high-risk renal transplant recipients (100% cadaveric donors, 79% African-American recipients, and 59% delayed graft function) are the subjects of this report. At 6 months, the patient survival rate was 94 and 100% and the graft survival rate was 94 and 83% in Groups I and II, respectively. The incidence of biopsy-proven AR was 6 and 5% in Groups I and II, respectively. Eight patients (50%) in Group I required discontinuation of tacrolimus, seven because of biopsy-proven tacrolimus nephrotoxicity and one secondarily to interstitial pneumonitis. Wound complications were the most frequent adverse event reported in both groups. CONCLUSIONS: The combination of tacrolimus and sirolimus was associated with a low risk of AR in this cohort of high-risk renal transplant recipients. However, 50% of patients who received standard tacrolimus and reduced sirolimus combination had to be discontinued from the regimen because of biopsy-proven nephrotoxicity. These preliminary results provide evidence that sirolimus should not be added to tacrolimus without dosage adjustments. We have discontinued recruitment of patients to the standard tacrolimus and reduced sirolimus combination and we have tightened our criteria for selection of marginal donor kidneys with our high-risk renal transplant recipients.

Cadaver↗
PubMed2004

Renal transplants from non-heart beating paracetamol overdose donors.

INTRODUCTION: Non-heart beating donors (NHBD) are widely encouraged to avert the critical shortage in the kidney donor pool. Ischaemic injury at the time of cardiac arrest in the NHBD is more pronounced and therefore the kidneys resulting are considered marginal. This review describes our experience with four kidneys from two controlled NHBDs who were exposed to paracetamol intoxication and subsequently were treated with mannitol prior to organ donation. MATERIALS AND METHOD: Two patients with fulminant liver failure following paracetamol overdose were referred as 'withdrawal of treatment' NHBD. As the two patients had developed hepatic encephalopathy they were treated with mannitol to reduce intra-cerebral oedema. The two donors were oligoanuric for at least 24 h prior to cardiac arrest. Following cardiac arrest, in situ perfusion was carried out and the kidneys were removed. One pair of kidneys were machine perfused while the second pair of kidneys were cold stored prior to transplantation. RESULTS: Pre-transplant assessment of NHBD kidneys resulted in three of four kidneys being transplanted. The NHBD kidneys exhibited a period of delayed graft function (DGF). The early transplant biopsies showed evidence of diffuse cytoplasmic vacuolation. These histological features disappeared with time and the renal function improved until the time of discharge. DISCUSSION: Non-heart beating donor kidneys are considered marginal and the effect of mannitol and paracetamol drug intoxication will induce reversible sub-lethal injury. A period of dialysis is inevitable in clearing the reactive intermediates of mannitol and paracetamol. The kidneys behaved as traditional controlled NHBD at time of discharge.

Acetaminophen↗
PubMed2005

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury.

BACKGROUND: Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients. PATIENTS AND METHODS: Twenty-two cadaveric liver transplant recipients were randomized to receive either TG (1.5 mg/kg/dose) during the anhepatic period and QOD x2 doses or no TG. No differences in recipients' demographics were present and donor characteristics were similar in terms of age, cause of death, and cold ischemia time. Maintenance immunosupression consisted of Tacrolimus (or Cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage and 1 h after re-vascularization. Post-operative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary non-function and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft non-function and no need for re-transplantation. The incidence of acute rejection was similar between the two groups. Patients in the TG group had significant decreases in alanine aminotransferase test at day 1 compared to the control group (p = 0.02). There were also near significant decreases of total bilirubin at day 5 and shorter length of hospitalization. Liver biopsy (at procurement, when cold, and post-reperfusion) of TG group demonstrated a trend for increased central ballooning. CONCLUSION: The TG allowed for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function. Further studies on the degree of apoptosis in the liver biopsy post-reperfusion are underway.

Adult↗