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PubMed2000

The effect of age and prolonged cold ischemia times on the national allocation of cadaveric renal allografts.

BACKGROUND: National sharing of cadaveric renal allografts for perfectly matched kidneys (0 antigen mismatch) has improved outcome in the recipients of these kidneys despite increasing cold storage times. However, there may be limits to outcome improvement of matched kidneys based on age and cold storage time. MATERIALS AND METHODS: To determine if national sharing of kidneys based on matching improves outcome regardless of donor age and cold storage time, we evaluated the United Network for Organ Sharing (UNOS) Scientific Registry for all recipients of cadaveric kidney transplants between January 1, 1990 and July 31, 1998. We divided the recipients into four groups based on donor age and cold storage time. Group 1 comprised young donors (donor age <55 years) with average (<24 h) cold storage time; group 2, young donors with long (>/=24 h) cold storage time; group 3, older donors (donor age >/=55 years) with average cold storage time; and group 4, older donors with long cold storage time. RESULTS: A total of 64,046 recipients were evaluated: 35,061 (55%) in group 1, 21,264 (33%) in group 2, 4308 (7%) in group 3, and 3414 (5%) in group 4. Early graft performance progressively decreased from group 1 to group 4. Delayed graft function (DGF: dialysis requirement in the first 7 days posttransplant) was 18, 29, 33, and 42% (P < 0.0001); serum creatinine at 3 years (in mg/dl) was 1.70 +/- 0.8, 1.73 +/- 0.9, 2. 31 +/- 1.0, and 2.42 +/- 1.1 (P < 0.0001); 1-year graft survival was 87, 84, 79, and 77% (P < 0.0001); and 3-year graft survival was 77, 74, 63, and 62% (P < 0.0001, for groups 1 and 2 vs groups 3 and 4, respectively). The trends in DGF persisted through the groups in 0 antigen mismatched kidneys. CONCLUSIONS: Early function is adversely affected by prolonged cold storage, despite matching, in recipients of younger and older donor kidneys. Long-term function does not appear to be affected by prolonged cold storage. Recipients of kidneys from donors >/=55 years of age have significantly worse short- and long-term outcome and may not benefit from national sharing.

Adolescent↗
PubMed1996

Tissue hydration in kidneys during preservation: a relaxometric analysis of time-dependent differences between cortex and medulla.

Cold preservation of donor organs induces hypothermia-related tissue edema as a result of a reduced activity of the ATP-dependent sodium pump at low temperatures. Hypothermia-induced tissue edema occurs in kidney preservation and is a significant risk factor for delayed graft function (DGF) after transplantation. DGF remains a major problem in kidney transplantation and is significantly associated with preservation injury. The state of hydration of cold-stored organs can be assessed from a biopsy for determination of the wet/dry weight ratio. As a non-invasive method to determine tissue hydration MRI T1 and T2 relaxometry can be used. In this study we have compared changes in tissue hydration in UW-preserved porcine kidneys with increasing cold ischemia times (CIT) using wet/dry weight ratio and MR ralaxometry. The results of the two techniques were correlated to evaluate the use of MR relaxometry. Wet/dry weight ratios of the renal cortex decreased with prolonged CIT (P < 0.01) whereas those of the medulla did not change significantly. T1 values of the cortex decreased with prolonged CIT (P < 0.01). T2 values of the cortex showed a non-significant decline with increased CIT. No significant changes in T1 and T2 were found in the medulla. The correlation between T1 and the wet/dry weight ratio of the cortex was significant (P = 0.05, linear correlation coefficient 0.8698). We conclude that MR relaxometry can be a valuable noninvasive technique to assess tissue hydration in cadaveric donor kidneys before transplantation.

Adenosine↗
PubMed1996

An automated and portable low-flow pulsatile perfusion system for organ preservation.

While machine preservation reduces the incidence of delayed graft function in renal transplant recipients, it is only used in 10% of kidney transplantations. The performance of our portable, low-flow-pulsatile organ perfusion system was examined in a canine kidney autotransplantation model. Grafts were stored for 72 h by simple cold preservation in University of Wisconsin (UW) solution, or by high or low-flow machine preservation After preservation, the grafts were autotransplanted and the animals were followed for 15 days. Graft function was better in machine-preserved kidneys. Tissue biochemistry indicated that machine preservation resulted in higher levels of adenine nucleotides and better histological integrity than the cold storage. While histology and biochemistry of machine-preserved groups were similar, electromicroscopy of high-flow grafts showed mild accumulation of intravenous debris and endothelial swelling. This study shows that a simplified machine perfusion technique is effective for organ preservation.

Animals↗
PubMed1993

Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation.

We studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37 male/21 female) consecutive renal allograft recipients were entered in this trial. Treatment results were compared with 56 patients treated with intravenous cyclosporin (CyA). In all patients concomitant medication consisted of steroids and azathioprine, followed by oral CyA. Following rabbit ATG, T cells (WT31) quickly disappeared from the peripheral blood and a return to greater than 100/mm3 was observed at a median of 7 (range 3-21) days. Graft survival was the same in both groups, as was the incidence of primary nonfunction. The rate of acute rejection was significantly lower in the rabbit ATG-treated patients (12% vs 50%). We conclude that a single shot of rabbit ATG is an attractive, easy, and cost-effective induction scheme with a low incidence of delayed graft function and acute rejection episodes. A relatively high incidence of vascular thrombosis of the graft, however, warrants further study before this treatment regimen can be generally applied.

Adolescent↗
PubMed1992

Monoclonal antibodies in renal transplantation: a review.

OKT3 is the first anti-CD3 monoclonal antibody available for treatment in humans. Over the last few years it has proven to be a very powerful immunosuppressive agent in renal transplantation. Clinical studies have shown that OKT3 is superior to high-dose steroids as first-line treatment for acute renal allograft rejection. Furthermore, it is comparable to antithymocyte globulin (ATG) in treating steroid-resistant rejection and is also effective as rescue treatment in ATG- and antilymphocyte globulin-(ALG-) resistant rejection. Despite its excellent rejection-reversal rate, OKT3 treatment is followed by a substantial percentage of re-rejections, most of which respond well to steroids. In the early post-transplantation period, a prophylactic course of OKT3 is very effective in preventing acute rejections, and in this respect it is probably equivalent to ATG. Indirect evidence exists that a prophylactic course of OKT3 may be beneficial in immunologically high-risk patients and in patients with delayed graft function. However, more clinical studies are required to answer the question whether OKT3 should be given as induction treatment, as first-line treatment, or as rescue treatment. To answer this question, the side effects of OKT3 should also be taken into account. First-dose-related side effects, although frequent and disturbing, are usually transient and seldom life-threatening, provided overhydration has been corrected and steroids have been given before the first administration. These side effects are attributed to the release of cytokines as a result of T-cell activation or lysis. After exposure of patients to OKT3 an increased incidence of infections and malignancies has been reported. However, it is not yet clear whether this is due to OKT3 as such, or whether it merely reflects the total burden of immunosuppression. Xeno-sensitization represents an important limitation to OKT3 treatment, although a second or third course can still be effective in patients with low antibody titers. The precise immunosuppressive mechanism of anti-CD3 monoclonal antibodies is yet unknown. Monitoring of patients treated with OKT3 revealed CD3 and/or T-cell antigen receptor depletion and immunological incompetence of remaining T cells. More clinical data are required to establish the correct dose and duration of OKT3 treatment. In conclusion, OKT3 is a powerful immunosuppressive agent but its real value in renal transplantation remains to be determined. A practical approach may be to reserve it for the treatment of steroid-resistant rejections.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1996

A novel dextran 40-based preservation solution.

Although the University of Wisconsin (UW) solution has become the standard solution for the preservation of kidneys for transplantation, the importance of the colloid hydroxyethylstarch (HES), one of the key compounds of the UW solution, has been questioned repeatedly. It is now established that HES is not necessary for routine kidney preservation. However, colloids may still be advantageous in UW like solutions for the purpose of multiorgan procurements and the preservation of organs from marginal donors. It has been shown in various experimental models that dextran 40 may successfully substitute for HES. Dextran 40 is not only cheaper but also has a variety of biological effects that may be beneficial during the graft reperfusion phase. The aim of this clinical study was to examine the efficacy of a dextran 40-based preservation solution (Dex-PS) for its use in human kidney graft preservation and to compare the transplantation results with kidneys preserved with UW solution. A total of 87 kidneys were preserved with Dex-PS and matched with 87 kidneys preserved with UW solution. Both groups were comparable in terms of donor and recipient characteristics and both had a high proportion of kidneys from nonheart-beating donors. Patient survival and graft survival after 1 year were 95% and 86% for the Dex-PS group and 94% and 90% for the UW group, respectively (P = NS). Primary nonfunction, delayed graft function, postoperative need for dialysis, and follow-up of serum creatinine were statistically comparable between these two groups. We conclude that dextran 40 can safely replace HES in UW solution for the purpose of clinical kidney preservation. There were no statistically detectable differences in graft performance between the kidneys preserved with UW and those preserved with Dex-PS.

Adenosine↗
PubMed1996

A prospective randomised study of the effect of nicardipine on ischaemic renal injury in renal allografts.

In a prospective double-blind trial, 127 kidneys were randomised to receive Eurocollins (n = 65) or Eurocollins plus nicardipine (n = 62) as a second flush solution at the time of organ retrieval. Delayed graft function occurred in 18 of 65 control kidneys (28%) and in 20 of 62 nicardipine kidneys (32%; P = 0.7, Fischer's exact test). The mean (SD) serum creatinine at 6 weeks was 197 (138) mumol/l in the Eurocollins group and 195 (159) mumol/l in the nicardipine group (P = 0.95). Eighteen recipients (28%) in the controlled Eurocollins group experienced a rejection episode in the first 6 weeks post-transplant compared to 17 (27%) in the nicardipine group (chi 2 with Yates' correction = 0.027; P = > 0.95). In this study, the addition of nicardipine to the kidney perfusion fluid did not have a beneficial effect on kidney function following transplantation.

Adolescent↗
PubMed1995

Developing the ideal immunosuppressive protocol by internal audit.

To identify the best immunosuppressive protocol in a centre where five different regimens are employed, 227 consecutive renal recipients who were transplanted over a 2.5-year period were studied. The five different regimens employed were cyclosporin monotherapy, dual therapy (cyclosporin and prednisolone), triple therapy (cyclosporin, azathioprine, prednisolone), antithymocyte globulin (ATG) followed by dual therapy and ATG followed by triple therapy. Recipients were chosen for the different regimens according to HLA mismatch, positive donor crossmatch due to IgM, regraft and delayed graft function. The group with the lowest risk, cyclosporin monotherapy, had the highest acute rejection rate, with only 13% free of acute rejection (in comparison to triple immunosuppression, P = 0.024, chi-square test). The overall infection rate and graft success rate were similar between the different groups.

Adult↗
PubMed1993

Non-immunological risk factors in paediatric renal transplantation.

In paediatric renal transplantation, non-immunological risk factors account for about one-third of graft losses. Recurrence of original disease is observed mainly in primary hyperoxaluria and glomerulopathies such as steroid-resistant nephrotic syndrome and membranoproliferative glomerulonephritis. In both glomerulopathies, 20% of grafts are lost from recurrence. Vascular thrombosis is, in most series, the second cause of graft loss in children, particularly in young recipients or with young donors (under 5 years of age). Non-compliance with treatment is a common non-immunological factor in adolescent recipients, which may trigger a severe rejection process resulting in graft loss. The role of factors related to graft preservation and intra- and post-operative management (ischaemia time, delayed graft function) or to cytomegalovirus infection is less obvious in our series. Prevention of vascular thrombosis and of non-compliance is most important in order to improve the results of paediatric renal transplantation.

Adolescent↗
PubMed2001

Renal ischemia--reperfusion injury: an inescapable event affecting kidney transplantation outcome.

Ischemia--reperfusion (I-R) injury has been shown to be a common cause of late and irreversible complications during a variety of standard medical and surgical procedures. The pathogenesis of events which follow the I-R involves both injured endothelium and activated leukocytes and their interaction. In kidney transplantation, an I-R injury occurs in situations such as graft harvesting, cold storage and surgery. Clinical consequences of I-R injury have been considered to be delayed graft function and acute rejection in the short term and chronic rejection late after transplantation. Here we focused on current knowledge of pathophysiology of renal I-R injury in kidney transplantation and on possibilities of experimental therapy.

Graft Rejection↗
PubMed1997

[Femoral arteriovenous fistula and transplant malfunction after allogeneic kidney transplantation. A case report].

This case report deals with the clinical history of a 52-year-old woman who suffered from delayed graft function and ischaemic pain after a technically successful renal transplantation. The past history of the patient revealed that coronary catheters had repeatedly been used for investigation and treatment of myocardial infarctions. The clinical investigation reported here revealed a typical auscultatory result with an arteriovenous (AV) fistula in the right upper limb. After performing a digital arterial angiography, an AV fistula between the femoral artery and vein was demonstrated. Operative occlusion of the fistula increased the perfusion of the kidney graft and the right limb. The patient recovered without wound infection and could leave the hospital with the transplanted kidney functioning well. This case report demonstrates that persistence of AV fistulas after angiographic investigations is rare. Operative occlusion of these lesions should be performed before kidney transplantation to avoid steal phenomena and disturbed would healing.

Angiography, Digital Subtraction↗
PubMed1999

[Perioperative incidence of transfusions after allogenic kidney transplantation].

The requirement of blood transfusions was evaluated in a two compartment (retrospective/prospective) study in our renal transplantation program. Between July 1st, 1993 and December 31st, 1994 (observation period 1) we retrospectively investigated 110 patients with end stage renal disease and anemia undergoing kidney transplantation. Between January 1st, 1995 and December 31st, 1996 (observation period II) the requirement of blood transfusions was followed prospectively in 134 patients after allogenic renal transplantation. The amount of blood drawn for preoperative diagnostic investigations was in observation period 1 significantly higher (280 ml) than in observation period II (150 ml) (p = 0.02). For postoperative diagnostic tests in observation period II significantly less blood (240 ml) was needed than in observation period 1 (510 ml) (p = 0.01). The intraoperative blood loss was similar in both periods (170 ml vs. 190 ml; p = 0.6). The need for closer graft observation was the reason for significantly increased amount of blood transfusions in patients with delayed graft function. The number of blood transfusions was significant lower in patients with primary graft function (p = 0.0001). There was no correlation between blood transfusions and the use of ATG/OKT3, surgical complications and reoperations. With an improved management of blood drawing for diagnostic tests after allogenic kidney transplantation the number of perioperative blood transfusions can be reduced significantly.

Adolescent↗
PubMed2004

Effect of University of Wisconsin organ-preservation solution on haemorheology.

In conventional cold-storage organ preservation, the donor organ is flushed with University of Wisconsin (UW) solution at 0-4 degrees C. The initial flush is used to wash out blood from the microcirculation to allow optimal preservation with the UW solution. The component hydroxyethyl starch (HES) of UW is known to cause relatively high viscosity and a possible interaction with blood, i.e. increased red blood cell (RBC) aggregation. The aim of this study was to investigate the influence of the HES component on the viscosity of UW and the aggregation behaviour of blood during washout. Viscosity aspects were measured with a cone-plate rheometer. HES-induced RBC aggregation was studied by means of an optical aggregation measuring device. The experiments were carried out with rat whole blood and mixtures of rat whole blood with UW-solution and UW without HES (UWmod), at 4 degrees C. The viscosity of blood at 4 degrees C is two-times higher than at 37 degrees C; the UW/blood mixture at 4 degrees C is 1.3-times more viscous than blood at 37 degrees C; the 4 degrees C UWmod/blood mixture equals the viscosity of blood at 37 degrees C. The UW/blood mixture shows a ninefold increased aggregation compared with whole blood. These aggregates are larger than the diameter of the sinusoids in the rat liver. A mixture of whole blood and UWmod shows a lower aggregation than blood. Apart from an increased viscosity, HES in UW causes increased RBC aggregation. The aggregates are larger than the diameter of the sinusoids. Initial washout could be optimised by pre-flushing to improve the viability of the liver and to decrease delayed graft function.

Adenosine↗
PubMed2004

Severe gastrointestinal complications after 1,515 adult kidney transplantations.

We studied, retrospectively, the occurrence of severe gastrointestinal (GI) complications after kidney transplantation. After 1,515 consecutive adult kidney transplantations performed on 1,445 patients during 1990-1999 at our centre, 147 (10%) severe post-transplantation GI complications were found. Ten percent of the complications were fatal. The median follow-up time was 6.2 years. The main complications were gastroduodenal ulcers and colon complications. GI malignancy developed in 13 patients (0.9%). The complication rate for the first post-transplantation year was 4.8%. Delayed graft function, high age and polycystic kidney disease were risk factors. Five-year patient survival rate was significantly lower in patients with a first-year complication than in those with later or no GI complications (68% vs 88%). Graft survival with deaths censored was the same in both groups. In conclusion, severe GI complications during the first post-transplantation year remain a high risk factor also for long-term patient survival.

Adolescent↗
PubMed1999

Dual renal transplant from a non-heart beating donor.

In September 1998, a 48 year old male underwent bilateral renal transplantation from a 51 year old non-heart beating donor (NHBD) with ischemic heart disease. The grafts exhibited delayed graft function, otherwise short term results have been good, with a three month serum creatinine of 80 mumol/l, three month GFR of 79 ml/min per 1.73 m2 BSA, and no episodes of acute rejection. We advocate dual transplantation when sub-optimal NHBD kidneys are otherwise in danger of being discarded.

Cadaver↗
PubMed2000

Increasing urinary IL-6 levels announce kidney graft rejection.

Acute rejection (AR) is the recipient's inflammatory response to the grafted organ. Within the graft-infiltrating cells, a high ratio of IL-6 producing cells can be found, indicating local IL-6 production. Therefore, in cases of kidney transplantation, urinary (u) IL-6 should be detectable. In order to establish the dynamics and diagnostic relevance, uIL-6 levels were determined daily by Quantikine IL-6 immunoassay (R & D Systems, Minneapolis, Minn.) in 101 kidney graft recipients (n = 1915 urine samples) during their post-transplant hospital stay. Immunosuppression consisted of azathioprine, steroids, cyclosporine and an intraoperative high-dose single antithymocyte globulin (ATG)-Fresenius bolus (9 mg/kg). In all the uncomplicated courses (n = 31) mean uIL-6 level was determined, after a post-transplant peak of 174 pg/ml, to be between 4 and 8 pg/ml. In contrast, delayed graft function (n = 16) was always associated with very high uIL-6 levels (> 200 pg/ml), dropping down only with commencement of graft function. Steroid-sensitive AR (n = 14) was consistently associated with significantly increasing uIL-6 levels prior to antirejection therapy (from 23 to 82 pg/ml). In cases of steroid-resistant AR, following antirejection therapy with methylprednisolone (5 days 5 mg/kg), there was no obvious trend towards normalization, indicating the persistence of inflammation (mean uIL-6 peak prior to OKT3 or ATG therapy: 99 pg/ml). In addition, AR-associated uIL-6 levels were found to be of much greater diagnostic relevance than AR-associated serum IL-6 levels. In bacterial urinary tract infections (n = 20), increased uIL-6 levels (peak 53 pg/ml) coincided with the commencement of antibiotic therapy. In mild cytomegalovirus diseases (n = 8), the development of leukocytopenia was associated with a slight increase of uIL-6 (peak 26 pg/ml), showing graft involvement. All increased uIL-6 values returned towards baseline after successful treatment. Thus, uIL-6 provides information about the intragraft inflammatory situation. Its determination is simple, expressive, non-invasive and can be recommended.

Analysis of Variance↗
PubMed2000

Early results of a non-heartbeating donor (NHBD) programme with machine perfusion.

Freeman Hospital, Newcastle upon Tyne restarted their non-heartbeating donor (NHBD) programme in September 1998 using machine perfusion, due to early poor results with conventional cold storage (45% graft survival, phase II). Since then, 15 NHBD kidneys have been transplanted. The retrieval protocol consisted of in situ perfusion with a double balloon triple lumen cannula in Maastricht category II male donors age range 13-59 years. Mean primary warm ischaemic time was 24.8 min (range 10-44). All kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of total GST (maximum acceptable limit of 200 units/l) and intrarenal vascular resistance (IRVR) was recorded. Fifteen of the 22 kidneys (68.62%) were transplanted. Delayed graft function (DGF) was seen in ten recipients (66.6%), two kidneys had immediate function (IF), one organ was exported, two recipients died of unrelated causes and a further seven kidneys were discarded (two had high tGST, two were infected and three had poor flow characteristics). In phase III, a success rate of 91.7% was thus achieved, which was better than the phase II period (P = 0.027, Fisher 2-tail test). Machine perfusion has been successfully introduced in phase III to the Newcastle NHBD programme and facilitates viability assessment of NHBD kidneys.

Adolescent↗
PubMed2001

Initial clinical experience with interleukin-2 receptor antagonist induction in combination with tacrolimus, mycophenolate mofetil and steroids in simultaneous kidney-pancreas transplantation.

Since 1996, our standard immunosuppressive protocol for simultaneous kidney-pancreas transplantation (SKPT) has been tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids without antibody induction. When basiliximab and daclizumab, monoclonal antibodies directed against the interleukin-2 receptor (IL-2R), became available, we selectively added these agents to our standard protocol. The purpose of this prospective, open-label study was to evaluate the safety and efficacy of IL-2 receptor antagonists in SKPT. From April 1998 to August 1999, 35 SKPTS were performed. One patient with delayed graft function received Thymoglobulin and was excluded; 17 received no induction, and 17 received IL-2R antagonists (9 basiliximab, 8 daclizumab) as induction. Demographic- and transplant characteristics were similar between the two groups. At 6 months, patient survival was 88 % (15/17) in the induction arm compared to 100 % (17/17) in the no-induction arm, P = NS. The 2 causes of death were sepsis and hemolytic uremic syndrome, and both patients died with functioning grafts. Death-censored pancreas and kidney graft survival rates in the induction and the no-induction groups were 88 % vs. 100 % respectively, in both groups. The incidence of acute rejection (kidney or pancreas) at 6 months did not differ between the two groups (35 % in both groups). Biopsy proven pancreas and kidney acute rejections were 35 % vs. 24 % and 12 % vs. 12 % in the induction- and no-induction groups, respectively. The incidences of major infection and readmission did not differ between groups. TAC trough levels and mean daily doses of TAC, MMF and steroids did not differ between the two groups at 1, 3, and 6 months. The incidence of event-free survival (no death, rejection, or graft loss) at 6 months was 59 % (10/17) in the induction and 65 % (11/17) in the no-induction group. Basiliximab and daclizumab appear to be safe in SKPT. However, the preliminary results of this study do not demonstrate a significant benefit in either reducing the incidence of acute rejection or improving outcomes at 6 months. Larger studies with longer follow-up are needed to confirm these findings.

Adrenal Cortex Hormones↗