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Avoidance of cyclosporine in renal transplantation: effects of daclizumab, mycophenolate mofetil, and steroids.

Cyclosporine (CsA) has been implicated in both acute and chronic graft dysfunction. The addition of humanized IL-2 receptor antibody daclizumab (DZB) to CsA-based immunosuppression decreases the rate of acute renal transplant rejection. Therefore, 45 patients were evaluated in an immunosuppressive protocol that included DZB, mycophenolate mofetil (MMF), and steroids without CsA. This was a prospective, nonrandomized, open-label trial of the efficacy and safety of the treatment. DZB was given intravenously at 2 mg/kg before transplantation and then at 1 mg/kg every 2 wk for four doses, MMF was given orally at 3 g/d, and methylprednisolone/prednisone was given at 7 mg/kg per day and tapered to 15 mg/d at 6 mo. CsA was added to the regimen when patients developed acute rejection episodes or adverse effects to steroids or MMF; 49% of patients were spared CsA maintenance. Patients without CsA had lower serum creatinine at 6 mo and needed fewer medications to control BP. Incidence of biopsyproven rejections was 31% and occurred early (median, 10 d). These rejection episodes occurred earlier in cadaver transplants (median, 7 d) and later in living donor transplants (median, 62 days). Acute rejections occurred at a higher frequency (46% versus 34%) and earlier (6.5 versus 15 d) in patients with delayed graft function compared with patients without delayed graft function. Most of the rejections were moderate and easily reversible. The actuarial 1-yr graft survival was 95% with 100% patient survival.

Acute Disease↗

Application of artificial neural networks to clinical pharmacology.

Drug dosages and drug choices are determined by a knowledge of the drug's pharmacokinetics and pharmacodynamics. Often, insufficient information is available to determine the pharmacokinetics of a drug or which drug will have a desired effect for an individual patient. We propose that a form of nonlinear regression, an artificial neural network, can be used. We have demonstrated this use with 2 examples. In the first example we use a neural network to predict gentamicin peak and trough concentrations from routine therapeutic drug monitoring. In the second example we predict delayed renal allograft function as a guide for induction of immunosuppression therapy. Predictions were made using a multilayer feedforward perceptron and compared to nonlinear mixed effect modeling (NONMEM) and logistic regression. Neural network peak and trough gentamicin predictions were more precise and less biased than control predictions made using NONMEM. Prediction error for peak serum concentrations averaged 16.5% for the neural networks and 18.6% for NONMEM. Prediction error for trough concentrations were 48.3% for neural networks and 59.0% for NONMEM. When used for the prediction of delayed graft function, the neural network correctly predicted immediate graft function 73% of the time and delayed graft function 65% of the time. For those patients predicted to develop delayed graft function, alternate induction using anti-lymphocyte globulin may be indicated. These 2 examples demonstrate how an artificial neural network may be applied to predictions in clinical pharmacology.

Anti-Bacterial Agents↗

Dynamics of erythropoiesis following renal transplantation.

We examined the temporal dynamics of the correction of anemia following renal transplantation in 65 recipients using a sensitive radioimmunoassay for erythropoietin to determine the effects of modern immunosuppressive agents, delayed graft function, and early acute rejection. Pretransplant mean erythropoietin (25.6 +/- 3.3 mU/ml) was only 25% of the expected value at the mean hematocrit of 27.2 +/- 0.7, and erythropoietin correlated positively with hematocrit (r = 0.37, P less than 0.05). Following onset of graft function, erythropoietin increased to 109 +/- 13 mU/ml and then decreased in a negative feedback fashion over the next several months. Delayed graft function was associated with delay in the assumption of this orderly process irrespective of the immunosuppressive regimen used. Cyclosporine A produced a biphasic response despite delayed graft function in recipients with underlying adult polycystic kidney disease. Correction of anemia required resumption of graft function. Onset of acute graft rejection within the first month posttransplantation (14 episodes in 11 patients) abrogated the hematopoietic response until the rejection was successfully reversed. We conclude that a major cause for the anemia of renal failure is subnormal production of erythropoietin. Following transplantation, anemia corrects in an orderly manner with restoration of the normal biofeedback process between erythropoietin and red cell mass. This process is delayed by failure of graft to function initially and interrupted by acute early rejection, re-commencing following successful reversal.

Adolescent↗

Primary immunosuppression with mycophenolate mofetil and antithymocyte globulin for kidney transplant recipients of a suboptimal graft.

BACKGROUND: In renal transplantation the beneficial immunosuppressive effects of cyclosporin (CsA) may be curtailed by its nephrotoxicity, specially in patients receiving a cadaveric allograft from suboptimal donors or at risk of delayed graft function. Mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) have each demonstrated to be potent immunosuppressants in renal transplantation. In a prospective analysis we have studied the results at 6 months of the combination of MMF, ATG and low-dose steroids in patients with low immunological risk receiving a first cadaveric renal allograft from a suboptimal donor or at risk of delayed graft function. METHODS: Patients with preformed reactive antibodies < 500% receiving a first graft from a suboptimal donor (age > or = 40 years, non-heart-beating, acute renal failure, arterial hypertension) or at risk of delayed graft function (cold ischaemia time > or = 24 h) were eligible for this open single-arm pilot trial. From September 1996 to March 1997 we recruited 17 patients. They were treated with MMF 2 g p.o. preoperatively, and after transplantation at 3 g/day; rabbit ATG i.v. at 2 mg/kg preoperatively, and 1.5 mg/kg/day the first day after transplantation, followed by four doses of 1 mg/kg on alternate days; prednisone was given at 0.25 mg/kg/day and reduced progressively to 0.1 mg/kg/day at 3 months. Primary outcomes were incidence of biopsy-proven acute rejection, delayed graft function, opportunistic infections, graft and patient survival, and the need for introduction of CsA treatment. RESULTS: delayed graft function occurred in two cases (12%). Four of 17 patients (24%) had a biopsy-proven acute rejection (2 grade I and 2 grade II) within the first 3 months after transplantation. CsA was added in two cases with grade II biopsy-proven acute rejection, and in one with grade I biopsy-proven acute rejection. In one patient MMF was replaced by CsA because of gastrointestinal intolerance. Mean serum creatinine 6 months after transplantation was 159+/-59 micromol/1. Cytomegalovirus tissue invasive disease occurred in one patient (6%). At 6 months follow-up all patients are alive with functioning allografts. CONCLUSIONS: These preliminary results suggest that in low-immunological-risk patients who receive a suboptimal renal allograft or at risk of delayed graft function, the combination of MMF, ATG, and steroids is an efficient immunosuppressive regime that may avoid the use of CsA in 70% of the recipients.

Adult↗

Laparoscopic donor nephrectomy: impact on an established renal transplant program.

The current disparity of viable organs and patients in need of a transplant has been an impetus for innovative measures. Live donor renal transplantation offers significant advantages compared with cadaveric donor transplantation: increased graft and patient survival, diminution in incidence of delayed graft function, acute tubular necrosis (ATN), and reduction in waiting time. Notwithstanding these gains live donors continue to be underutilized and account for only approximately one quarter of all renal transplants performed in the United States. It has been felt that inherent disincentives to live donation have slowed its growth. These include degree and duration of postoperative pain and convalescence, child care concerns, cosmetic concerns, and time until return to full activities and employment. In an attempt to curtail the disincentives to live donation, laparoscopic live donation (laparoscopic donor nephrectomy; LDN) was developed. The purpose of this study was to compare the results of our first 25 laparoscopic nephrectomies (performed over a 10-month period from September 1998 through July 1999) with the previous 25 standard open donor nephrectomies (ODNs) completed over the past 3 years. We conducted a retrospective review of all donor nephrectomies and recipient pairs performed over the past 3 years. End points included sex, operative time, length of stay, immediate and long-term renal function, and willingness to donate. There were no differences in demographics of the ODN versus the LDN group. The average length of stay was 2.48+/-0.72 days for the LDN versus 4.08+/-0.28 days for the ODN. ODN and LDN have comparable short- and long-term function with no delayed graft function and no complications. Growth of living donor transplant has increased from 16 per cent of all kidney transplants performed in 1995 to 23 per cent in 1999. We conclude that LDN is a viable alternative to the standard donor operation. LDN has had a positive impact on the donor pool by minimizing disincentives to live donation. With the initiation of our laparoscopic program the number of LDNs has increased. Presently the live donor pool is the most viable alternative to significantly increase the number of kidneys for transplantation.

Adult↗

Clinical aspects of sensitization.

1. The incidence of broad sensitization has decreased significantly over the past 8 years, probably due to a decrease in pretransplant blood transfusions. Graft survival rates among broadly sensitized patients have improved over this time period (76% graft survival at 2 years posttransplant for patients transplanted in 1995-1996 compared with 66% for patients transplanted in 1989-1990). This is probably due to an improvement in immunosuppression and a related decrease in the incidence of acute rejection episodes. 2. As has been shown before, blood transfusions, previous pregnancies and failed allografts independently increased the incidence of sensitization. It is clear that certain subgroups of patients are more likely to become sensitized, given antigenic stimulation, as evidenced, for example, by the fact that 52% of patients receiving more than 10 units of blood prior to transplant were relatively unsensitized. Males seem to be less apt than nulliparous females to become broadly sensitized, although this may be due to the lower age of nulliparous females. Asians are the least likely race to become broadly sensitized. Among multiparous Asians who received more than 5 units of blood, 27% were broadly sensitized compared with 35% of comparable Whites and African Americans. 3. The incidence of acute rejection episodes increased with increasing degrees of sensitization. About 46% of first cadaveric allograft recipients with PRA levels greater than 50% had at least one acute rejection episode within 6 months after transplantation compared with 38% of unsensitized individuals. In addition, sensitized individuals were more likely to have an episode of early acute rejection before discharge from the hospital. 4. Induction with antilymphocyte antibody preparation was more commonly used in broadly sensitized patients. However, this therapeutic modality did not reduce the incidence of rejection episodes measured at 6 months posttransplant. In addition, the use of induction therapy for broadly sensitized patients has decreased with the advent of newer immunosuppressive protocols that include Neoral, MMF and FK506. 5. There was an association between the incidence of broad sensitization and delayed graft function. Induction therapy was more commonly used in patients with both delayed graft function and broad sensitization, although the decision to use this therapeutic modality seems to be made based on the presence of broad sensitization rather than the presence of delayed graft function. 6. Choosing the optimal immunosuppressive drug regimen is an important decision in broadly sensitized individuals because of the increase in acute rejections and decrease in overall graft survival in this group. Classic teaching suggests that this group of patients should be administered induction therapy with antilymphocyte antibody preparations. Early data suggests, however, that the combination of Neoral, mycophenolate and prednisone may be the optimal regimen for these individuals with respect to graft survival and that the addition of antibody induction therapy to any of the other commonly used regimens does not improve graft survival (at least up to 3 years after transplantation).

Blood Transfusion↗

The morbidity of prolonged wound drainage after kidney transplantation.

PURPOSE: The consequences of prolonged wound drainage, defined as extravasation of more than 50 ml. fluid daily for more than 1 week through a drain or wound after renal transplantation, have not been well described in the literature. We examine the association of prolonged wound drainage with other clinical events, and its impact on hospitalization, and patient and graft survival. MATERIALS AND METHODS: We prospectively documented prolonged wound drainage in 392 recipients of cadaver and live renal transplants from July 1993 to December 1997. Potential risk factors, associated outcomes within the first 6 months and effect on length of hospital stay due to prolonged wound drainage were determined. RESULTS: Prolonged wound drainage was significantly associated with pre-transplantation weight, weight gain by post-transplantation day 3, delayed graft function and continuous ambulatory peritoneal dialysis on univariate analysis but only with delayed graft function (odds ratio 2.8, 95% confidence intervals 1.4 to 5.6) on multivariate analysis. Post-transplantation lymphoceles (5.2, 9 to 14), wound infection (27, 5.7 to 130) and wound dehiscence (5.8, 1.7 to 20) were associated with prolonged wound drainage. Patients with prolonged wound drainage stayed 8.7 additional days during the first hospitalization and overall 11.3 additional days during the first 6 months after transplantation independent of other co-morbid events, such as delayed graft function, rejection or cytomegalovirus disease. CONCLUSIONS: Prolonged wound drainage is an important post-renal transplantation event that impacts patient outcomes and hospital resource use. Efforts to prevent this complication should be considered.

Adult↗

Delayed endocrine pancreas graft function after simultaneous pancreas-kidney transplantation. Incidence, risk factors, and impact on long-term outcome.

BACKGROUND: The incidence of delayed endocrine pancreas graft function and its impact on long-term outcome after simultaneous pancreas-kidney transplantation are unknown. METHODS: We studied 54 technically successful adult type I insulin-dependent diabetic recipients of cadaver, whole organ, bladder-drained simultaneous pancreas-kidney transplants (mean age, 37.6 years; 65% male, 35% female; 9% pancreas retransplants; 63% on chronic pretransplant dialysis; mean duration of diabetes, 25.1 years). Insulin was administered during the first 2 weeks after transplantation, as needed, to keep blood glucose < 150 mg/dl. Delayed endocrine pancreas graft function was defined as total, cumulative insulin requirement of > 30 U between day 5 and day 10, and/or > 15 U between day 11 and 15. Quadruple immunosuppression was used for all recipients. RESULTS: The incidence of delayed endocrine pancreas graft function was 69%. By univariate analysis, delayed endocrine graft function was associated with pretransplant recipient weight > 80 kg (P = 0.04), donor age > 45 years (P = 0.02), and cardiocerebrovascular (P = 0.06) and nontraumatic causes of donor death (P = 0.02). The incidence of acute pancreas rejection episodes was similar for recipients without and with delayed endocrine pancreas graft function. Pancreas graft survival at 1 and 3 years was 94% and 82% without versus 76% and 59% with delayed endocrine graft function (P = 0.03). CONCLUSIONS: Increased pancreas graft failure after delayed endocrine function was a consequence of insufficient functional reserve (e.g., older donors) rather than increased immunogenicity. Pretransplant reduction of recipient weight and careful donor selection are therefore crucial in order to decrease the incidence of delayed endocrine pancreas graft function and its negative impact on long-term outcome.

Adult↗

Living related kidney donors over 60 years old.

The lack of available cadaveric organs for transplantation has resulted in an increased number of kidney transplants from living donors. During a period of 6 years, 149 kidney transplantations were performed from living related donors in our institute, 33.5% of whom were older than 60 years of age. In this study we examined the survival of patients and grafts as well as the graft function in 50 patients with transplants from donors over 60 years (mean age 65 years) as compared with those of 99 patients with transplants from donors younger than 60 years (mean age 47 years). There were no significant differences in the course of donor nephrectomy, postoperative complications, or remnant kidney function. However, delayed graft function occurred more frequently in recipients of transplants from older donors. Improvement in graft function was also slower in recipients of kidneys from older donors, with significant differences in serum creatinine levels observed during the first 12 months after transplantation. More frequent acute complications and more progressive chronic graft failure, irrespective of the causes, occurred during the 1st post-transplant year in recipients with grafts from older donors. Five-year patient survival (77% vs 92%) and kidney graft survival differed significantly for the same period with worse results for patients receiving grafts from older donors. It may be concluded that kidney grafts from donors older than 60 years -- and especially those older than 70 years -- may be used for living related kidney transplantation, but with precautions.

Adult↗

Effect of rHuEpo therapy in dialysis patients on endogenous erythropoietin synthesis after renal transplantation.

UNLABELLED: We have undertaken a prospective study to examine the effect of recombinant human erythropoietin (rHuEpo) therapy during dialysis on Epo levels after renal transplantation and to evaluate the impact of this therapy on the immediate graft function. Between December 1991 and December 1993, 91 renal transplant recipients were studied. There were 34 females and 57 males and the mean age was 38 years. Forty-two patients were treated during dialysis with rHuEpo due to anemia and 49 patients did not receive it. Endogenous Epo (eEpo), hemoglobin concentration, hematocrit level and serum creatinine were determined on days 0, 2, 4, 8, 15, 30, 60 and 180 after transplantation. Ferritin level was determined pretransplant and on day 60. RESULTS: Patients not treated with rHuEpo during dialysis experienced a transient increase in endogenous Epo after renal transplant that was not observed in treated patients (26 +/- 3.3 vs. 9 +/- 1.5 mU/ml, p < 0.001). The eEpo peak was similar in patients with early or delayed graft function (23 +/- 4.3 vs. 32 +/- 5.4 mU/ml, NS). The recovery of the anemia after a successful renal transplant took place in patients treated as well as those not treated with rHuEpo without significant differences. In the treated group, the pretransplant hematocrit level was similar in patients with early or delayed graft function (31 +/- 3.5% vs. 32 +/- 4.8%), but in the untreated group, the hematocrit level was lower in patients with early renal function (28.5 +/- 4% vs. 32 +/- 3%, p < 0.05). However, these patients also had a significantly shorter warm ischemia time (53 +/- 13.8 vs. 64 +/- 14.5 min). Fifty-two percent of the rHuEpo-treated patients and 36% of the untreated patients had delayed graft function. In conclusion, different courses of eEpo levels after renal transplant were observed depending on whether or not patients had been treated with rHuEpo during dialysis. Untreated patients experienced a transient increase which was not observed in the treated group. Immediate or delayed graft function did not modify eEpo levels. No association was found between rHuEpo therapy during dialysis and delayed graft function.

Adolescent↗

Fate of kidneys from the same donor grafted into different recipients: do they behave similarly and are they influenced by donor-related factors?

BACKGROUND: The fate of paired kidneys might be similar and could therefore reflect the influence of donor-related factors on graft outcome. PATIENTS AND METHODS: To verify whether two kidneys retrieved from a single donor and grafted into different recipients have similar short, and middle-term outcomes we investigated the clinical outcome of 103 pairs of cadaveric kidneys grafted into 206 recipients. We evaluated the influence of donor-related factors such as age, sex and cause of death, and of the storage solution and method of harvesting. The incidence of delayed graft function was considered as the short-term outcome and serum creatinine levels at two years as the middle-term outcome. We evaluated the difference from expected frequencies in the incidence of delayed graft function and the incidence of similar serum creatinine levels in each pair of recipients. Univariate analysis of possible risk factors was made by the t-test, chi2 test and Fisher test, as appropriate. Multivariate analysis was done by logistic regression analysis with a forward stepwise variable selection. RESULTS: Delayed graft function was seen in both recipients from the same donor 2.5 times more than the expected frequency (p<0.001). Serum creatinine levels were similar in both recipients with a higher frequency than expected (p<0.01). Multivariate analysis showed that donor-related factors on graft function were age, cause of death and storage solution. CONCLUSIONS: Paired kidneys have similar performances in both the short and the long term. Major donor-related factors in delayed graft function are age and the storage solution. Major donor-related factors in graft function are age and cause of death.

Female↗

[Results of kidney transplantation at the Institute of Urology and Nephrology of the Serbian Clinical Center in Belgrade].

UNLABELLED: Over the period 1980-1992 256 kidney transplantations were carried out in the Institute of Urology and Nephrology, Clinical Centre, Belgrade: 105 (41%) from cadaveric and 151 (59%) from alive related donors. The first kidney transplantation was performed in our Institution in 1974; however, in the first decade only 27 kidney transplantations were performed. Since 1987, thanks to an increasing number of living kidney donors, the number of transplantations continually increased, and after that period an average of 30 kidney transplantations are performed annually (Figure 1). The aim of the study was to establish the survival of patients and grafts, and factors influencing this survival, as well as to determine the causes of patients' death and graft loss. All the patients were followed-up in our outpatient department within at least 5 years to maximum 17 years. Drug combination therapies were changed in the observation period. From 1983 cyclosporin A (CyA) was added to azathioprine (Aza) and prednisolone (Pr). An increasing number of patients with high immunological risks necessitated the strongest initial immunosuppressive treatment with ALG in addition to Aza and Pr. CyA in a dose of 8 mg/kg b.w. was introduced when serum creatinine concentration fell below 300 mumol/L. The triple treatment including CyA, Aza and Pr was the most common maintenance immunosuppressive therapy in our patients. RESULTS: One and five years survived 95% and 75% of patients, and 84% and 52% of grafts. In assessing the impact of donor source, the year of transplantation, and age of donors we obtained the following results: Living related grafts survived better than cadaver grafts, especially during the first posttransplantation year (Figure 2). Furthermore, graft survival rates from 1987 to 1992 were significantly better than those from early period i.e. 1980 to 1986 (Figure 3). The significantly worse survival rate for grafts from donors older than 60 was noted than for grafts from younger donors. Searching for factors influencing the survival, non immunological and immunological differences between donors and recipients were analyzed. Our analysis showed that 50 living related donors were older than 60. In addition, the majority of them were 20 years older than their graft recipients. Two and more HLA mismatches were observed in 46% of our transplant patients, and 20 patients were highly sensitized. However, the immunological risks were higher in living related transplantations: different ABO blood groups, historical positive cross match reaction between donors and recipients (Table 1). A multivariate analysis using Cox proportional hazards model was performed to determine the important independent predictors of graft survival, and it revealed the following factors (Table 2): number of acute rejections, graft function at the end of the first month and until the end of the first posttransplant year, donors' age, and age and sex differences between donors and recipients. The occurrence of acute rejection at any time had a significant negative effect on graft survival. Since better HLA matching is likely to mean less early rejection it could be concluded that HLA matching influenced graft function and survival in our patients. Absence of acute rejection and delayed graft function or acute tubular necrosis were associated with an improvement of the graft function based on serum creatinine concentration, indicating that delayed graft function also influenced graft survival. The relative risk of graft loss was 2 times higher for patients receiving graft from donors older than 60. Until December 1997, when our analysis was done, of 256 kidney transplant patients 156 lost their grafts. The major causes of graft loss (Table 3) in the early period from 1980 to 1986 were non immunological such as acute tubular necrosis, vascular thrombosis and patients death with functioning graft. (ABSTRACT TRUNCATED)

Adolescent↗

Extension of the organ pool in kidney transplantation: first year experience of the Israel Transplant Center.

BACKGROUND: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors. OBJECTIVE: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation. METHODS: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring > 1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor's death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts. RESULTS: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n = 13, 9.3%) or DGF (n = 25, 17.9%). On regression analysis, donor age > 50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors > 50 years old, 21 (37.5%) developed either PNF (n = 9) or DGF (n = 12). CONCLUSIONS: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from "aged" donors may help to choose appropriate donors from that pool.

Adolescent↗

Long-term graft survival after transplantation with kidneys from uncontrolled nonheartbeating donors.

BACKGROUND: Notwithstanding the widely acknowledged organ-donor shortage coupled with the expanded waiting list for organs, many transplant programs have been reluctant to use kidneys from nonheartbeating donors. Some reasons expressed by those programs include a higher rate of delayed graft function, additional dialysis requirements, more medication usage, and inferior graft survival rates. To refute the common misperceptions, we reviewed our 4-year experience with 31 nonheartbeating donor kidneys recovered from uncontrolled donors (Maashticht classification) at our institution. METHODS: After cardiac arrest and declaration of death, all donors underwent intravascular and intraperitoneal cooling. Immediately after bilateral en bloc nephrectomy, kidneys were placed on the Waters MOX pulsatile preservation machine. Preservation parameters were monitored hourly, using pharmacologic agents (Stelazine, dexamethasone, Humulin R) as indicated by those parameters. RESULTS: The nonheartbeating donors ranged in age from 15 to 53 years, 83% were males, and 60% of deaths were caused by trauma. For the 21 recovered and transplanted at our center, delayed graft function occurred with 16 kidneys; there was no primary nonfunction. There was no obvious correlation between functional status and donor age. It was noted that the immediate-function kidneys had shorter warm ischemia and total preservation times compared with the delayed graft function group. Nineteen of the 21 grafts continue to function. All patients are surviving. CONCLUSIONS: This series suggests that to obtain excellent results with nonheartbeating donor kidneys certain principles should be followed: use machine preservation to resuscitate and evaluate viability, choose immunologically low-risk recipients, avoid immediate exposure to immunophilin antagonists, and perform biopsy frequently for allograft dysfunction to exclude low-grade rejection.

Adolescent↗

Assessment of non-heart-beating donor (NHBD) kidneys for viability on machine perfusion.

UNLABELLED: The shortage of organs has resulted in renewed interest in organs from non-heart-beating donors (NHBD). Viability assessment of such organs may reduce the incidence of delayed graft function and primary non-function. In Phase III of the NHBD programme, introduction of machine perfusion enabled the assessment of these marginal donors. Since then the graft survival has been 88.4% compared with the previous phase where machine perfusion or viability assessment was not done (45.5%). The parameters used were total glutathione S-transferase (GST) in the perfusate, the intrarenal vascular resistance (IRVR) and flow characteristics over time. METHODS: All NHBD kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of the above-mentioned parameters. RESULTS: Forty-two local NHBD kidneys were retrieved and one kidney was imported, of which 19 donors (i.e. 38 kidneys) were of the uncontrolled (category II) donors. After viability assessment on machine perfusion; two kidneys were discarded due to positive tests for syphilis, four kidneys had high total GST levels, five kidneys due to high IRVR and poor flow characteristics and one did not flush on retrieval. Three kidneys were exported after viability tests. In 28 NHBD kidney recipients, immediate graft function was seen in two kidneys, 22 (84.6%) developed delayed graft function. One kidney had primary non-function, and two recipients lost their grafts, due to chronic rejection and renal vein thrombosis. There were two deaths, unrelated to transplantation. Graft survival was achieved in 88.4% (23/26 graft survival in phase III) of cases. CONCLUSION: Machine perfusion and assessment of NHBD kidneys has been successfully introduced to the Newcastle NHBD programme. This approach, using renal transplants from largely category II donors produced a success rate of 88.4% which was significantly better than the phase II period (45.5%) of the program (p=0.023, Fisher 2 tail test).

Humans↗

Inferior outcome of cadaveric kidneys preserved for more than 24 hr in histidine-tryptophan-ketoglutarate solution. Leuven Collaborative Group for Transplantation.

BACKGROUND: During recent years, an increasing number of transplant centers within the Eurotransplant organization have used histidine-tryptophan-ketoglutarate (HTK) solution instead of University of Wisconsin (UW) solution as their preferred cold storage solution for abdominal organ preservation. We report on our single-center experience on the outcome of imported kidneys preserved with either HTK or UW solution in relation to the duration of cold ischemia time (CIT). METHODS: Between July 1989 and July 1997, 323 cadaveric kidneys preserved with UW or HTK and imported as a result of an exchange within the Eurotransplant organization were transplanted at our institution. CIT was <24 hr in 216 kidneys (UW: n=174, HTK: n=42) and > or =24 hr in 107 kidneys (UW: n=67, HTK: n=40). Renal functional outcome was evaluated by comparing delayed graft function and initial non-function rates, daily urinary output, the evolution of serum creatinine, and creatinine clearance at 1, 3, 5, 7, and 14 days and at 1, 3, 6 and 12 months, and graft survival at 1 year after transplantation in relation to the type of cold storage solution and CIT < or > or =24 hr. RESULTS: Whereas the incidence of delayed graft function did not differ significantly between kidneys preserved for less than 24 hr in UW (18.6%) or HTK (26.2%), this rate increased to 50% in HTK kidneys compared to 23.9% in UW kidneys when CIT exceeded 24 hr (P=0.006). Mean serum creatinine and creatinine clearance values were better at 1 and 5 days postoperatively in kidneys preserved <24 hr with UW as compared to HTK (P<0.05). After 24 hr of CIT, HTK-preserved kidneys showed an impaired renal function, not only in the immediate postoperative phase but also at 1, 3, 6, and 12 months after transplantation (P<0.05). Graft survival at 1 year was 92.9% in UW vs. 87.5% in HTK kidneys preserved for <24 hr (NS), and 91% vs. 77.4% when CIT exceeded 24 hr (P=0.059). CONCLUSIONS: From these single-center findings, it can be concluded that UW is superior to HTK in kidney preservation, particularly when CIT exceeds 24 hr.

Adenosine↗

Ten-year experience in the use of double balloon catheter for kidney procurement from non-heart beating donors in cadaveric kidney transplantation.

One-hundred-and-twenty patients underwent first cadaveric kidney transplantation from the non-heart beating donors. All of the organs were procured with the use of double balloon catheter for in situ cooling. The mean warm ischemic time and cold ischemic time were 10.7 +/- 17.0 minutes and 18.9 +/- 11.4 hours, respectively. One- and 5-year graft survival rates were 85.0 and 72.7%, respectively. Among 120 recipients, 30 (25%) grafts functioned immediately (immediate function), 82 (68.3%) grafts functioned after varying length of oliguric periods (delayed function) and 8 (6.7%) grafts never functioned (non-function). The mean age of the donors in the group of immediate function (31.5 +/- 16.1 yr) was significantly lower than those of other two groups. The mean warm ischemic time in the group of immediate function (6.0 +/- 11.2 min) was significantly shorter than that of delayed function. However, there was no significant difference in donor hypotensive episode, types of preservation fluid and cold ischemic time between the groups. The conclusion is that the ultimate result of cadaveric kidney transplant from the non-heart beating donors with the use of double lumen catheter is acceptable despite a relatively high incidence of delayed graft function.

Adolescent↗

Patient death or renal graft loss within 3 yr of transplantation in a county hospital: importance of poor initial graft function.

Our purpose was to study the factors predictive of graft loss or patient death within 3 yr of renal transplant in a county population. 363 renal transplants performed between 1984 and 1991 at the Harbor-UCLA Medical Center were reviewed. There were 16 recipients (4%) who died and 76 (21%) who lost their grafts within 3 yr. Known causes of death were cardiac (44%), infection (38%) and malignancy (6%). There was a higher proportion of diabetics (44%), hypertensives (69%) and those with a past cardiac history (38%). There was also a high delayed graft function rate (56%). Of the 76 grafts that failed in the first 3 yr, 14% were due to noncompliance, 20% to grafts that never functioned, 9% to technical problems, 21% to acute rejection, 9% to recurrent disease and 26% to chronic rejection. The noncompliance group were younger (mean 34 yr), and more likely to be a first transplant (90%) and be non-white (82%). The rejection group was significant for high delayed graft function rate (84%) and frequent and early rejection (76% at least one rejection). We conclude that fair organ allocation requires a balance between equity and utility, but patient death or graft loss within 3 yr benefits neither the patient or society. Patient survival may be improved with diligent cardiac evaluation, particularly in older patients and diabetics. Patient education and monitoring for noncompliance is essential, particularly in young first-time recipients. Maneuvers to decrease delayed graft function are essential to improve long-term results.

Adolescent↗