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[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↗

[Retrospective study of the risk factors of transplant renal artery stenosis].

OBJECTIVE: To investigate the risk factors of transplant renal artery stenosis (TRAS). METHODS: The clinical records of 26 patients undergoing renal transplantation in our hospital between 2000 and 2005 were retrospectively analyzed, whose final diagnosis of TRAS was established on the basis of arteriographic findings. A case-control group of 52 post-renal transplantation patients were sampled by stratified randomization, whose blood pressure and renal graft function were without complications of avascularity or urinary passage. The two groups were matched for the operation time, gender, age, primary diseases, blood type, PRA and HLA matching and use of immunosuppressants. Possible events related to TRAS such as cold ischemia time, acute rejection, delayed graft function and approaches of arterial anastomosis were compared. RESULTS: Fifteen patients (57.7%) with TRAS had a history of acute rejection episode, 7 (26.9%) had delayed graft function, both rates of which were higher than those in the control group (P<0.05). The cold ischemic time and type of arterial anastomosis showed no significant effect on TRAS occurrence (P>0.05). CONCLUSIONS: Post-transplant renal artery stenosis is closely associated with acute rejection and delayed graft function but not with the cold ischemic time or the type of arterial anastomosis.

Adult↗

Evaluation of renal grafts in patients with lupus nephritis as cause of end-stage renal disease.

INTRODUCTION: Kidney transplantation is the best option in end-stage renal disease (ESRD). For many years patients affected with lupus nephritis have had poor graft results. However, this has been changing over recent years with the development of new immunosuppressive drugs and a better comprehension of the natural evolution of the entity. METHODS: We studied 20 patients with lupus nephritis who received 22 kidney grafts: 15 women and five men (n = 11) who were treated with cyclosporine or with tacrolimus (n = 11). Secondary immunosuppression included mycophenolate match (MMF) (n = 13) or azathioprine (n = 9). We analyzed human leukocyte antigen, cold ischemia time, acute tubular necrosis, creatinine, cholesterol, triglycerides, glucose, blood pressure, acute rejection episodes, immunosuppression, infections, disease recurrences, as well as graft and patient survival. RESULTS: After a mean cold ischemia time of 22 +/- 4 hours, nine patients displayed delayed graft function of an average duration 9 +/- 4 days. At 36 +/- 35 months nine grafts were lost: two due to acute rejection; five to chronic allograft nephropathy; and two to venous thrombosis. One patient died of hemorrhagic shock. There were five cytomegalovirus infections. Graft survival was dependent on the type of secondary immunosuppression, incidence of acute rejection episodes and occurrence of delayed graft function. CONCLUSIONS: We found no clinical recurrence of lupus nephritis after transplantation and a low incidence of complications, although there was a trend toward thrombosis. The presence of delayed graft function, episodes of acute rejection, and receiving azathioprine instead of MMF as secondary immunosuppression were associated with poorer graft survival.

Adult↗

[The living kidney donor: laparoscopy versus open surgery].

INTRODUCTION: Living renal donors are an important source of transplanted kidneys due to the number of patients on waiting list is progressively increasing. On the other side, they allow the pre-emptive kidney transplantation. With the aim of reducing donor obstacles such as pain, hospital stay or cosmetic results and in creasing the number of living donors, in 1995 Ratner performed the first laparoscopic nephrectomy (LLDN). By now, LLDN is a routine procedure in more than 200 centres worldwide. METHODS: Literature databases are searched. We have reviewed the data from our experience after performing 50 laparoscopic nephrectomies. RESULTS: Preoperative living donor assessment and contraindications to LLDN do not differ from the open approach. Results are very influenced by the surgeon's situation in the learnig curve. Operating times use to be longer in laparoscopic procedures. The overall complication rate and mortality of LLDN are the same for both of the approaches. Conversion to open-donor nephrectomy has been reported in 0-13% of cases (8% in our data). Postoperative pain and donor estimated blood loss are lower for LLDN, as well as the convalescence period. To avoid the possible negative effects of the laparoscopic technique on kidney graft function a lot of method's variations have been proposed for gaining access and harvesting the kidney, including the hand-assistance techniques, with the aim of minimizing operative time, pneumoperitoneus negative effect on graft function and warm ischemia time (WIT). The higher WIT is not related to delayed graft function or acute rejections when it is less than ten minutes. Delayed graft function does not differ in both approaches and creatinine values from the first month until the third year after transplantation show no differences in randomized studies. CONCLUSIONS: The laparoscopic approach to harvest the allograft from the living donor is a save and effective technique and has the advantage of being less invasive and allowing the donor a shorter convalescence. It has no negative effects on allograft function in the short term follow-up. Further studies are required to evaluate long term donor complications and allograft function and survival.

Age Factors↗

Kidney transplantation from elderly donors: a prospective randomized study comparing celsior and UW solutions.

AIM: The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. RESULTS: The warm ischemia time was 42.4 +/- 11 minutes among Celsior vs 46.9 +/- 17.9 minutes in the UW cohort (P = NS). The cold ischemia time was 18 +/- 4.5 hours in Celsior and 19 +/- 6.5 hours in UW (P = NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P = NS). Mean serum creatinine levels and mean daily urinary output were also similar. One- and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.

Adenosine↗

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↗

Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion.

BACKGROUND: Ischemia/reperfusion (I/R) injury after organ transplantation is a major cause of delayed graft function. Following I/R, locally produced CXC chemokines attract and activate granulocytes, which in turn promote graft damage. METHODS: We examined the involvement of granulocyte recruitment via the CXCR2 pathway in a rat model of 4 hours cold ischemia followed by kidney transplantation. Serum creatinine and intragraft granulocyte infiltration were monitored in the early phase posttransplant. A CXCR2 inhibitor, repertaxin, was given to recipients before transplantation (at -24 hours or -8 hours or -2 hours), immediately before reperfusion and 2 hours later. RESULTS: An increase of granulocyte chemoattractant CINC-1/interleukin-8 (IL-8) mRNA expression after I/R both in syngeneic and allogeneic transplantation was associated with a marked infiltration of granulocytes in renal tissue. In syngeneic transplantation, Lewis rats given 15 mg/kg repertaxin 24 hours before surgery had granulocyte graft infiltration and serum creatinine levels significantly reduced in respect to vehicle-treated animals. Intermediate effects were observed with 5 mg/kg, whereas the dose of 30 mg/kg had toxic effects. We found that reducing the pretreatment time to 8 hours before surgery was still effective. Prevention of granulocyte infiltration and serum creatinine increase was also obtained in allogeneic transplantation, when Brown Norway recipients of Lewis kidneys were given 15 mg/kg repertaxin starting 8 hours before surgery. CONCLUSION: Repertaxin treatment of the recipient animal was effective in preventing granulocyte infiltration and renal function impairment both in syngeneic and in allogeneic settings. The possibility to modulate I/R injury in this rat model opens new perspectives for preventing posttransplant delayed graft function in humans.

Animals↗

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↗

ICAM-1 antisense oligodesoxynucleotides prevent reperfusion injury and enhance immediate graft function in renal transplantation.

BACKGROUND: Ischemia-reperfusion injury after organ transplantation is a major cause of delayed graft function. We showed earlier that antisense oligodesoxynucleotides (ODN) for intercellular adhesion molecule-1 (ICAM-1) ameliorate reperfusion injury after acute ischemia. This study tested the hypothesis that antisense ODN for ICAM-1 prevents ischemia-reperfusion injury and facilitates immediate graft function in a rat autotransplantation model. METHODS: Both kidneys were removed from male Lewis rats and re-implanted the left kidney after 30 minutes of cold ischemia time. The warm ischemia time was 60 minutes. Sham operated, uninephrectomized animals served as controls for renal function and histology. ICAM-1 antisense ODN (5 mg/kg), reverse ODN, or saline-vehicle were administered to donor animals i.v. six hours before autotransplantation. Glomerular filtration rate (insulin clearance), and serum creatinine concentrations were measured 24 hours post-transplantation. Tubular necrosis severity was assessed by histological grading scale. ICAM-1 expression was determined by immunohistochemistry and Western blot. RESULTS: Antisense ODN decreased ICAM-1 expression and leukocyte infiltration significant. Antisense ODN-treated animals showed significantly less tubular necrosis, than controls. Serum creatinine of antisense ODN-treated animals (N = 6) was 0.55 +/- 0.02 mg/dl compared to 1.92 +/- 0.07 mg/dl in reverse ODN-treated controls (N = 6; P < 0.01), 24 hours after transplantation. Antisense ODN-treated animals had normal GFR (0.93 +/- 0.07 ml/min/kidney wt) compared to sham-operated animals (0.95 +/- 0.09 ml/min/kidney wt), while autotransplanted animals treated with reverse ODN or saline-vehicle were all anuric. The ischemia-reperfusion-induced up-regulation of MHC class II was totally prevented by antisense ODN. CONCLUSIONS: ICAM-1 inhibition ameliorates ischemia-reperfusion injury and prevents delayed graft function. Antisense ODN-treatment of donors or donor organs for ICAM-1 may be useful for the prevention of reperfusion injury in human renal transplantation.

Animals↗

Use of anti-CD25 monoclonal antibody in combination with rapamycin to eliminate cyclosporine treatment during the induction phase of immunosuppression.

BACKGROUND: Cyclosporine and tacrolimus are associated with drug-induced renal dysfunction that may exacerbate recovery from ischemic injuries during the first month posttransplant. We sought to use anti-CD25 (anti-interleukin-2 receptor) monoclonal antibodies in combination with sirolimus (rapamycin) to avoid cyclosporine therapy during the early postoperative period in six renal transplant recipients deemed to be at high risk for delayed graft function. METHODS: Six consecutive patients deemed to be at high risk for delayed graft function were treated with rapamycin (2-12 mg/day), anti-CD25 monoclonal antibodies, and steroids, withholding inception of cyclosporine therapy until the serum creatinine fell below 3.0 mg/dl. RESULTS: During the first 2 months posttransplant, none of the patients displayed clinical or histopathological evidence of acute allograft rejection episodes, cytokine release syndrome, or hypersensitivity reactions. None of the patients received even empiric bolus or high-dose steroid therapy for a presumed rejection episode. All patients recovered renal graft function within 8 weeks posttransplant. To date all patients have stable renal graft function. Five patients have serum creatinine levels between 0.8 to 1.3 mg/dl at 6 months and the other patient has a serum creatinine level of 1.7 mg/dl at present follow-up of 2 months posttransplant. CONCLUSION: During the early posttransplant period anti-CD25 monoclonal antibodies combined with rapamycin and steroids offer a promising baseline therapy to avoid cyclosporine exposure and facilitate recovery from ischemic/reperfusion injuries.

Adult↗

Renal transplantation in recipients over the age of 60: the impact of donor age.

BACKGROUND: Kidneys from older donors exhibit a series of changes characterized by glomerular, vascular, and tubular senescence. These changes may be aggravated by atherosclerosis, hypertension, or diabetes, which are highly prevalent in older individuals. METHODS: We analyzed the outcome after transplantation in 230 recipients over the age of 60, who received transplants between February 1990 and December 1996. We assessed the 1- and 5-year patient and graft survival, the quality of renal function, tacrolimus levels, the incidence of rejection, and the incidence of delayed graft function, and compared the outcomes in recipients of kidneys from donors over the age of 60 (group 1, n = 40) with those in recipients of kidneys from donors under the age of 60 (group 2, n = 190). There were no differences between the two groups in terms of recipient sex, race, age, and cold ischemia time. Immunosuppression was with tacrolimus and steroids in 61% of cases; in the remainder of the patients, a third agent, either azathioprine, cyclophosphamide (for 1 week), or mycophenolate mofetil was administered as well. The median follow-up was 31.5 months (range: 1-86). RESULTS: In recipients over the age of 60 receiving tacrolimus-based immunosuppression, overall patient survival at 1 and 5 years was 90% and 76%, and was not significantly compromised in recipients receiving a kidney from a donor over the age of 60. The overall 1-and 5-year actuarial graft survival was 84% and 64%; in recipients from donors over the age of 60, it was 73% and 52%, whereas in recipients of kidneys from donors under the age of 60, it was 87% and 66% (P<0.05). Most of the effect on graft survival was seen by 1 year. The mean serum creatinine was 2.6+/-2.7 mg/dl, without any difference between the two groups. Although the incidence of delayed graft function was higher in recipients of kidneys from donors over the age of 60, this difference did not reach statistical significance. CONCLUSIONS: Although the overall outcomes of transplantation in older recipients remain reasonable, the inferior outcomes with older donor kidneys call into question proposals to utilize older donor kidneys preferentially in older recipients.

Adult↗

Regional vs. national renal sharing organizations: pros and cons.

Delayed graft function, defined as the need of dialysis in the first week after transplantation, neither due to immunological nor technical causes, determines a poor outcome of renal grafts. Delayed graft function is related to the cold ischemia time, which is shorter in local allocation programs. These, however, do not assure an optimal HLA-A,B,DR matching that can be provided by national allocation organizations. We reviewed 160 cadaveric kidney grafts performed in our local transplant network. Owing to the long waiting list caused by organ shortage, we were able to ensure both a high-grade histocompatibility and short cold ischemia times. The mean HLA-B,DR mismatch was 1.17. Cold ischemia time was < 24 h in 85% of cases. The incidence of DGF was 23.1%. In our experience a regional sharing program in the case of organ shortage provides good graft outcome (86.9% graft survival at 1 yr) with low incidence of delayed graft function.

Cadaver↗

Prevention of OKT3 nephrotoxicity after kidney transplantation.

In our experience the use of OKT3 as prophylaxis in renal transplantation has been associated with an increased incidence of both delayed graft function and thromboses of graft vessels. OKT3 nephrotoxicity might have been favored by restriction of perioperative fluid infusion to prevent pulmonary edema and by the use of very high dose (30 mg/kg) of methylprednisolone (mPDS) before the first OKT3 injection to reduce the release of cytokines. This led us to modify our perioperative management in three ways: (1) hydration status was optimalized; (2) the calcium-channel blocker diltiazem, considered beneficial for recovery of graft function, was administered on the day of transplantation; and (3) the dose of mPDS given before the first OKT3 injection was fixed at 8 mg/kg. Comparison of two consecutive series of patients (group 1, control patients, N = 172; group 2, managed as described above, N = 173) showed that: (1) the incidence of delayed graft function fell from 52% in group 1 to 22% in group 2 (P < 0.0001): (2) the incidence of pulmonary edema was not significantly increased in group 2 (3.5% vs. 1.7% in group 1, P = 0.5); and (3) the frequency of intragraft thrombosis fell from 7.6% in group 1 to 1.2% in group 2 (P = 0.0034). Multivariate analysis showed that the volemia/diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the reduced occurrence of delayed graft function and graft vessels thrombosis, respectively. We conclude that a combined strategy of appropriate dosage of steroids before the first OKT3 injection, administration of a calcium-channel blocker and optimalization of volemia is safe and efficiently prevents against OKT3 nephrotoxic effects.

Adult↗

Outcome of renal transplantation in children with low urinary tract abnormality.

INTRODUCTION: Patients with end-stage renal disease and lower urinary tract abnormality are often considered high risk for renal transplantation. METHODS AND SUBJECTS: To examine the degree of risk, we studied patients who received renal transplants between 1985 and 2003. Forty eight patients had congenital lower urinary tract anomalies and 168 patients comprised a control group without these anomalies. RESULTS: Mean age and distribution of sex were not significantly different between the case and the control group. Among patients with anomalies, 8% had delayed graft function; 75%, acute rejection; and 39.5%, chronic rejection. Among the controls 2.3% had delayed graft function; 59%, acute rejection; and 35%, chronic rejection. None of these differences was significant. Mean survival time was 6 years in affected patients and 7.3 years in the control group (P = .7). Among patients with anomalies the rate of graft survival in the first year after transplantation was 90%; and those in the third, fifth, and seventh years, 76%, 65%, and 40%, respectively. For the controls, the graft survivals were 88% at 1 year; 73% at 3 years; 70% at 5 years; and 49% at 7 years after transplantation. CONCLUSION: This study showed that a history of lower urinary tract anomalies had no effect on graft function. Graft survival was not different among these patients compared with patients free of these anomalies.

Acute Disease↗