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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↗

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↗

Prophylaxis against herpes infections in kidney transplant patients with special emphasis on CMV.

METHOD: Since 1990, we have treated all kidney transplanted patients with cyclosporin (CsA)+ an initial 10 d antilymphocyte globulin (ALG) course, from September 1995 supplemented with mycophenolate mofetil (MMF). In 170 consecutive transplantations from June 1992 to the end of 1996, aciclovir 3200 mg/d (adjusted for kidney function and in children to age) was given prophylactically for 3 months post-transplantation (Tx), monitored with systematic and frequent tests for HSV and CMV. In case of CMV infection, we gave ganciclovir intravenously (oral ganciclovir from 1996) in doses according to kidney function for 3 months, followed by a further 3 months observation and monitoring period. In case of acute cellular rejection, ganciclovir was given during the 10-d OKT3 course and 1 week further. In case of delayed graft function combined with aciclovir side effects, ganciclovir was given until aciclovir could be reintroduced. RESULTS: 39% were HSV seronegative at Tx. There were no seroconversions or reactivations within the observation period. No mucocutaneous HSV infections was observed. No resistant strains developed. 26% were both HSV and CMV negative at Tx. 52% were CMV negative at Tx. 30% experienced a CMV infection post-transplant. The patients were grouped according to CMV status in the donor (D) and recipient (R) before Tx. We found approximately the same number of patients in the 4 CMV groups D-/R-, D+/R-, D-/R+ and D+/R+. Most infections occurred in the D+/R- group compared to D-/R- (p = 0.009). A significant increase in the number of CMV infections occurred in this subgroup when we gave reduced doses in case of delayed graft function (p = 0.015), from 1994. We observed only 1 CMV disease (in 1992). Serological EBV testing were performed concomitantly. No correlation was seen between CMV and EBV infections. From September 1995 we have treated all transplanted patients (n = 40) with CsA/ALG/MMF. We found no significant increase in CMV infections in this group. CONCLUSIONS: Prophylaxis with aciclovir (combined with ganciclovir during acute rejections and in case of delayed graft function with aciclovir side effects) gives a good protection against HSV and CMV infections and prevents CMV disease effectively. High-dose aciclovir post-transplantation (or shift to ganciclovir) seems to be important to obtain effective prophylaxis. Better immunosuppression with MMF does not result in more CMV infections.

Acyclovir↗

Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation.

Univariate and multivariate analyses have been performed on donor an d recipient variables to determine possible effects on the outcome of 516 primary cadaveric renal transplants performed in our single center from 1989 until 1993. The overall actuarial patient survival at 1 year and 5 years was 94.4% and 87.4%, respectively; the 1 year and 5 year graft survival rates were 88.3% and 77.8%, respectively. A total of 95 grafts were lost; death with function (35%) and chronic rejection (22%) were the major causes. Three variables (HLA-DR mismatch, delayed graft function, and prolonged cold ischemia time) had a significant detrimental effect on both short- and long-term graft survival. Zero HLA-DR mismatched grafts showed significantly enhanced survival over those with 1 HLA-DR mismatch both at 1 year (92.8% vs. 84.5%) and at 5 years (88.3% vs. 73.9%) only if cold ischemia time was less than 26 hours (P=0.0009). Occurrence of delayed graft function significantly lowered graft survival at both 1 year and 5 years (P=0.002), and the incidence was significantly associated with prolonged cold ischemia time (P<0.0001). HLA-A or HLA-B matching, percentage panel reactive antibodies (PRA), and anastomosis time showed no independent effect on long-term survival. The small number of 2 HLA-DR mismatched grafts (n=6) precluded separate analysis of this group. Acute rejection accounted for 12% of losses but had no statistically significant effect on graft survival, even though an increased frequency of rejection episodes was significantly associated with HLA-DR mismatch (P<0.0001). These results would suggest that significant survival benefits may be achieved by prospective HLA matching if cold ischemia times are limited. The efficiency of organ sharing must he improved to make optimal use of a limited resource.

Adolescent↗

Peritoneal dialysis favorably influences early graft function after renal transplantation compared to hemodialysis.

BACKGROUND: Delayed graft function (DGF) and acute renal failure (ARF) after renal transplantation negatively influence short- and long-term graft outcome. Peritoneal dialysis as pretransplantation dialysis modality was reported to influence favorably the recovery of renal function immediately after kidney transplantation. It has been hypothesized that fluid status was the factor explaining this better outcome. This hypothesis was tested in this study by multivariate analysis, also including other factors related to DGF and ARF. METHODS: The records of peritoneal dialysis (PD; n=40) and hemodialysis (HD; n=79) patients receiving a first cadaveric kidney transplantation at the University Hospital Gent were analyzed. RESULTS: DGF and ARF were observed in 33 (27 HD and 6 PD, P=0.03) and 14 (14 HD and 0 PD, P=0.01) patients, respectively. The number of days needed to reach a serum creatinine 50% below that before transplantation (T1/2(SCr)), was correlated with cold ischemia time (CIT) (P<0.001) and body weight gain (BWG) (P<0.01) and was inversely correlated with urinary output in the first 24 hr (P<0.001), fluid load (P<0.001), and central venous pressure (P<0.001). A multivariate model with CIT (P<0.001), PD as pretransplantation dialysis mode (P=0.01), urinary output in the first 24 hr (P=0.001), BWG (P=0.05), and fluid load (P=0.01) resulted in an R2 of 0.32 (P<0.001). Using Cox regression analysis, the relative risk for a prolonged T1/2(SCr) increased with 4%/hr CIT (P=0.01) and with 1%/kg BWG (P=0.02). Fluid load decreased the relative risk with 5%/liter (P<0.001) and PD as pretransplantation modality favorably modified the relative risk by a factor of 1.6 (P=0.01). CONCLUSION: PD as pretransplantation dialysis modality can reduce the incidence and the severity of delayed recovery of renal function after renal transplantation. This protective effect was independent from CIT, and fluid status, two other major influencing factors.

Acute Kidney Injury↗

A good alternative to reduce the kidney shortage: kidneys from nonheartbeating donors.

BACKGROUND: Because of the shortage of kidneys available for transplantation, we began in 1985 to harvest kidneys from non-heartbeating (NHB) donors. METHODS: We compared the results of a group of 66 kidney recipients from NHB donors (NHB group) with 122 kidney recipients from heartbeating donors (HB group). We analyzed, in the NHB group, the influence of ischemia times in graft survival and we tested the best cut-offs by receiver operating characteristic curves. We also studied, using a univariate and multivariate Cox hazard model, the capacity of different variables to predict graft loss. RESULTS: Patient and graft survival were similar in both groups during the follow-up. The percentage of delayed graft function was the only significant difference between both groups (NHB group 62% vs. HB group 32%; P=0.0001). Delayed graft function, in the NHB group, is influenced by the warm ischemia time, which is directly related to the number of days to achieve a serum creatinine<300 mmol/L (P=0.0001). The best cut-off times in this group were 45 min for warm ischemia time and 22 hr for cold ischemia time. Recipients have a greater likelihood of losing the graft beyond those limits (P=0.017, relative risk: 7.3). The incidence of acute rejection was similar in both groups, and it was the only predictor factor of graft loss in the complete series of patients (P=0.0001), in the NHB group (P=0.007), and in the HB group (P=0.02). CONCLUSIONS: Reducing the incidence of acute rejection and shortening ischemia time are conditions needed to guarantee a long graft survival of kidneys from NHB donors.

Adult↗

[Clinical value of "zero-hour" biopsy in kidney transplantation].

We have performed 115 "zero-hour" biopsies of transplanted kidneys since 1994. Donor kidneys were divided into five groups, based on the morphological findings of "zero-hour" biopsies. No morphological abnormalities were found in 38.26% of the cases (group 1). Arteriolosclerosis was present in 22.61% of donor kidneys (group 2). Specific morphological alterations, i.e. acute tubular necrosis (24.35%), tubulointerstitial nephritis (5.22%) or glomerulonephritis (9.56%) were detectable in the remaining cases (groups 3-5). During an average of 644 days after transplantation clinical and histological follow-up were performed. According to our observations: 1. Higher creatinine was found in patients with grafts with arteriolosclerosis (group 2). 2. There were more non-viable grafts and longer periods of delayed graft function in patients with acute tubular necrosis (group 3). 3. Higher serum creatinine, more frequent rejections with the need of secondary hemodialysis were observed in patients who received a kidney with "zero-hour" biopsy of tubulointerstitial nephritis (group 4). 4. The only complication observed in patients with glomerulonephritis donor kidneys was delayed functioning of the graft (group 5). Biopsies did not cause complication in any of our patients. In conclusion, "zero-hour" biopsies can be useful and safe tools to predict early graft function. Besides, "zero-hour" biopsies help histological interpretation of consecutive graft re-biopsies.

Arteriosclerosis↗

Long-term graft outcome is not necessarily affected by delayed onset of graft function and early acute rejection.

BACKGROUND: Both acute rejection episodes and delayed graft function (DGF) have been shown to be associated with decreased 1-year renal allograft survival. In our center, the incidence and the intensity of acute rejection episodes have been reduced by cyclosporine-based triple-drug therapy. We have also shown that DGF alone is not a risk factor for long-term graft survival. METHODS: We have now investigated whether an acute rejection episode together with DGF significantly effects long-term graft outcome. This study involved 862 first cadaveric renal allografts and 182 regrafts. RESULTS: The incidence of DGF was 33% after first transplants and 44% after retransplants. The overall incidence of acute rejection episodes was 23% in first grafts and 28% in regrafts. After first grafts, there were no statistically significant differences in graft survival rates and half-lives between the early graft function (EGF) and DGF groups with or without acute rejection. In regrafts, graft survival was significantly higher in the EGF group without acute rejection than in the DGF group with acute rejection. However, if all other causes except chronic rejection were censored, the half-life in the EGF group without acute rejection was 17.3 years in first grafts, and in the DGF group with acute rejection, that number was 11.5 years in first grafts; for regrafts, the half-life was 12.3 years and 6.1 years, respectively. CONCLUSIONS: Acute rejection together with DGF could contribute to initial damage to the graft, and this might lead to later chronic allograft failure. In our study, this effect was evident only in the case of retransplants.

Acute Disease↗

Factors influencing long-term primary cadaveric kidney transplantation--importance of functional renal mass versus avoidance of acute rejections--the Toronto Hospital experience 1985-1997.

1. The 5-year actuarial graft, patient and functional graft survival rates were analyzed in 743 consecutive primary cadaveric kidney transplants from The Toronto Hospital between January 1985-December 1997. 2. Recipient age > or = 55 years, male recipient sex, recipient diabetes mellitus, CIT > 36 hours and delayed graft function were found to significantly decrease patient survival. 3. Recipient age > or = 55 years, sensitization to HLA antigens (peak PRA > 50%), donor/recipient HLA antigen mismatches, CIT > 36 hours, delayed graft, function and 6-month SCr > 200 mumol/L were found to significantly decrease graft survival. 4. Acute rejection episodes had no significant impact on overall 5-year patient or graft survival. 5. The observation that serum creatinine > 200 mumol/L had a major adverse influence on long-term outcome reflects the importance of functional renal mass on graft survival.

Adult↗

Histological factors of 1-h biopsy influencing the delayed renal function and outcome in cadaveric renal allografts.

The morphological characteristics of a kidney biopsy specimen taken 1 h after reperfusion of blood into the graft (1-h biopsy) during a cadaveric transplant operation were studied. The aim of the 1-h biopsy is to evaluate the pre-transplant risk factors for the delayed graft function, assess the renal function of the graft, and predict long-term graft survival. The total number of 1-h biopsies was 113, consisting of 86 male and 27 female donors. The mean age of the donors is 39.5 +/- 17.3 yr. Arteriosclerosis (AS) and tubulo-interstitial injury (TI) were both estimated using a semi-quantitative scale. AS score was graded into four categories, according to the severity of the thickening of interlobular artery: 0: none, 1: mild, 2: moderate and 3: severe. No biopsy revealed severe AS of grade 3. The TI score was graded from 0 to 5, according to the morphological injury: 0: none, 1-2 non-specific tubulo-interstitial injury (NSTI), and 3-5 compatible with acute tubular necrosis (ATN) in terms of pathological diagnosis. The mean ages of donors showing as AS of score 0, 1, and 2 were 30.6 +/- 14.6, 49.7 +/- 13.5, and 56.9 +/- 6.30, respectively. The mean donor age of the AS 1 group and AS 2 group was significantly lower than for the AS 0 group. The lowest serum creatinine values after operation (best Cr) of recipients with AS scores of 0, 1, and 2 were 1.31 +/- 0.45, 1.60 +/- 0.70, and 1.84 +/- 0.71 mg/dL, respectively; the best Cr of AS scores of 1 and 2 was significantly higher than in the AS score 0 group. The mean creatinine level at the final point of the AS 0 group was significantly lower than in the combined AS 1 and AS 2 group (serum creatinine 1.44 +/- 1.03 vs 1.87 +/- 1.53 mg/dL: p < 0.01). The duration of severe hypotension less than 50 mmHg or 80 mmHg was significantly shorter in the NSTI group than in the ATN group (less than 50 mmHg was 29.7 +/- 124 vs 72.5 +/- 174, less than 80 mmHg 105 +/- 234 vs 193 +/- 261 min: p < 0.01). The post-operative (po) day expressing diuresis in excess of 1000 mL of urine per d was 8.28 +/- 17.5 and 13.7 +/- 23.3 (p < 0.01) in the NSTI and ATN group, respectively. The po-d of the last hemodialysis and the po-d showing serum creatinine less than 2.0 mg/dL in NSTI and ATN group was 7.74 +/- 17.4 and 13.3 +/- 23.2 (p < 0.01), and 25.0 +/- 30.5 and 38.0 +/- 35.2 (p < 0.01), respectively. We concluded that 1-h renal biopsy is useful for assessing the outcome of renal allograft. AS of a donor kidney is one of the most important risk factors for both short and long-term outcome of the graft. The TI score was useful to predict the outcome of delayed graft function.

Adult↗

The UNOS Scientific Renal Transplant Registry--1991.

Based upon data reported to the UNOS Scientific Renal Transplant Registry between October 1987 and November 1991: 1. One-year graft survival rates were 79%, 73% and 62% for recipients of first (20,864), second (3,217), and multiple (673) cadaver donor transplants, respectively. 2. One-year graft survival rates were 94%, 89%, and 90% for first transplant recipients of kidneys from HLA-identical siblings (970), parents (1,487), and 1-haplotype-mismatched siblings (1,206), respectively. 3. Half-lives calculated after the first year were 7 years for cadaver donor transplants, 11 years for parent, 12 years for 1-haplotype sibling and, 27 years for HLA-identical sibling-donor first transplants. 4. The 1-year first transplant survival rate has improved from 78% in 1987-88 to 80% in 1990-91 transplants (p = 0.001). There has been an attendant decline in the percentage of broadly sensitized patients transplanted from 15% in 1987 to 8% in 1990 (p less than 0.01), which may have contributed to rising survival rates. 5. There has been a remarkable improvement in the 1-year graft survival of retransplanted patients from less than 70% in 1987-88 to 78% in 1990 (p less than 0.001). This improvement has been most notable in broadly sensitized patients and those with delayed graft function. 6. Diabetics who received a pancreas and kidney transplant (995) had 81% 1-year graft survival compared to 77% for those who received a kidney transplant only (p less than 0.002). 7. One-year graft survival rates decreased significantly in recipients of kidneys from donors aged under 16 or over 45. Survival was less than 70% when the donor was under 5 or over 60 compared to 81% when the donor was aged 16-45 (p less than 0.001) for recipients of first cadaver transplants. Delayed graft function occurred in 40% of cases when the donor was over 60 and 28% of cases when the donor was under 5. When function was delayed, survival was 50% for these marginal kidneys compared to 68% for younger adult kidneys with delayed function (p less than 0.001). Rejection also had a greater impact on survival of kidneys from donors under 5 or over 60. 8. The 1-year graft survival rate for 2,504 first transplant recipients of cadaver kidneys from young male victims of traffic accidents was 85%. The 1-year graft survival of 2,670 patients given kidneys from older female donors who died of cerebrovascular accidents was 73% (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗