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De novo use of sirolimus in immunosuppression regimens in kidney and kidney-pancreas transplantation at the University of California, San Francisco.

At UCSF, we have used sirolimus in several immunosuppression regimens and protocols, and this article will summarize our experience in four areas. The purpose of the first study was to assess the efficacy of a sirolimus-based, calcineurin inhibitor-free regimen for the first 3 months after transplantation. Patients were treated with a calcineurin inhibitor-free regimen that consisted of daclizumab, sirolimus, mycophenolate mofetil (MMF), and conventional corticosteroids. Of nine patients, one (case #7) had an acute rejection episode (type IA) at 2 months after transplantation, which was fully reversed with corticosteroids. The second study was a prospective trial of calcineurin inhibitor-free regimen in patients with severe delayed graft function (DGF) (requiring dialysis). The immunosuppression regimen consisted of daclizumab, sirolimus, MMF, and corticosteroids. This immunosuppressive regimen was effective in patients with DGF; however, it was effective only in non-African American (non-AA) patients (AA had a significantly higher acute rejection rate at 1 year than non-AA, 63% vs 23%, P =.025). In some patients sirolimus was associated with a prolonged recovery from DGF. The addition of sirolimus to immunosuppressive agents provide the opportunity for safe steroid withdrawal (at day 5). We participated in a sirolimus-based, multicenter open-label trial of very early corticosteroid withdrawal. Primary renal transplant patients were enrolled in an immunosuppression regimen that consisted of basiliximab, sirolimus (target levels 8 to 15 ng/mL, 0 to 5 months, and 6 to 12 ng/mL, 6 to 12 months) and tacrolimus in a dose of 0.05 mg/kg BID (target levels 6 to 9 ng/mL). Two of 14 enrolled patients had an episode of acute rejection before steroids were withdrawn. No acute rejection episodes have occurred after steroids were withdrawn (6-month follow-up). The regimen of sirolimus and tacrolimus was well tolerated. Wound complications were not noted. Another important use of sirolimus has been its incorporation in the immunosuppressive regimens in kidney-pancreas transplantation. Our current protocol consists of thymoglobulin induction, combined with MMF, sirolimus, and low-dose tacrolimus, for maintenance therapy. Steroids are only utilized during the first 5 to 6 days following the transplant. This steroid-free maintenance regimen has been used in the last 30 enteric-drained, simultaneous pancreas-kidney transplants. Using this immunosuppressive approach, rejection rates are less than 10% for either the kidney or the pancreas.

Acute Disease↗

Daclizumab induction as an immunosuppressive regimen for renal transplant recipients from non-heart-beating donors.

BACKGROUND: Recent reports have demonstrated the efficacy of interleukin-2-receptor blockers in lowering the incidence of early acute rejection. The present study aimed to test the hypothesis that the use of daclizumab induction (DAC) plus low-dose tacrolimus, mycophenolate mofetil, and steroid diminishes the incidence of delayed graft function (DGF) in renal transplants from non-heart-beating donors (NHBD). METHODS: We compared the incidence of DGF and rejection in 185 renal transplants from NHBD treated as follows: Group-I: quadruple sequential therapy with antithymocyte globulin, cyclosporine, azathioprine, and steroids (n=22); Group-II: cyclosporine (8 mg/kg/d) plus azathioprine plus steroid (n=26); Group-III: low-dose cyclosporine (5 mg/kg/d) plus mycophenolate mofetil plus steroid (n=68); Group-IV: low-dose tacrolimus (0.1 mg/kg/d) plus mycophenolate mofetil plus steroid (n=17); and Group-V: DAC plus low-dose tacrolimus plus mycophenolate mofetil plus steroid (n=43). RESULTS: The incidences of DGF were 72.7% in Group-I, 73.1% in Group-II, 69.1% in Group-III, 76.5% in Group-IV, and 44.2% in Group-V. Acute rejection was higher in Group-IV. CONCLUSIONS: The combination of DAC, low-dose tacrolimus, mycophenolate mofetil, and steroids is effective in lowering the incidence of DSF in NHBD kidney transplant recipients without any increase in acute rejection.

Adrenal Cortex Hormones↗

Results of kidney transplantation in recipients over 70 years of age: experience at a single center.

We performed 41 kidney transplants in patients >70 years (35 single and 6 dual), with a mean recipient age of 72+/-2 years, from January 1990 to December 2001. Mean age of the donors was 69+/-12 years. Immunosuppression used triple therapy with steroids, mycophenolate mofetil, and cyclosporine or tacrolimus. Cold ischemia time was 23+/-3 hours. The incidence of primary nonfunction was 4.8%, and delayed graft function 58.5%. Acute rejection incidence was 12%. The actuarial patient survival rates at 12, 24, and 36 months were 82.5%, 82.5%, and 75%, respectively. Actuarial survival rates of the grafts censuring for death of the recipient with a functioning graft were 89.5%, 86%, and 68%, respectively. Nine of the 18 graft losses were due to recipient death. Overall, renal transplant recipients >70 years showed good results. The principal cause of graft loss was recipient death.

Aged↗

Significance of cytomegalovirus infection in renal transplantation.

The aim of this study was to establish the relationship between vascular lesion chronic allograft nephropathy (CAN) and the presence of cytomegalovirus (CMV) in kidney transplanted patients. We studied 259 consecutive kidney transplant recipients with a minimum follow-up of 6 months; the induction immunosuppressive therapy included a calcineurin inhibitor, mycophenolate mofetil, steroids, and the use of an antilymphocyte serum if the patients developed delayed graft function. CMV early antigen detection (pp65) was performed on a weekly basis between days 30 and 90 post transplantation. Prophylactic treatment was administered in the donor +/recipient-risk group, and preemptive therapy delivered for positive antigenemia namely 3 days of intravenous [IV] gancyclovir [GCV] plus 11 days of oral therapy [in the case of infection], or 14 days of IV GCV [in the case of disease]). An acute kidney allograft rejection episode preceded CMV in 64.3% of the patients, and CMV preceded acute rejection in 35.7% of the cases. We conclude that CMV disease is an independent risk factor for CAN. CMV infection is probably associated with CAN, suggesting that the greater the viral load, the higher the risk of CAN. It may be advisable to perform universal prophylaxis to lower the viral load and CAN.

Cytomegalovirus Infections↗

Obesity favors surgical and infectious complications after renal transplantation.

UNLABELLED: The prevalence of obesity is increasing in the renal transplant population. There are controversial data with respect to posttransplant outcome. We performed a study comparing the incidence of surgical and infectious complications among 40 obese patients (body mass index [BMI] pretransplant > or =30 kg/m2) versus a matched nonobese control group (BMI <30 kg/m2) transplanted at our center between June 1989 and March 2001. RESULTS: There were no differences in patient demographic variables (mean age, gender, cause of renal failure, or percentage of diabetes or hepatitis C virus infection). Donor age, HLA mismatching, sensitization, cold ischemia time, and immunosuppressive regimen were similar in both groups. The mean pretransplant BMI in obese and nonobese patients was 34.1+/-4.0 versus 23.00+/-2.73 kg/m2 (P<.01). The obese group showed a higher incidence of delayed graft function (30% versus 5%, P<.05) and wound infections (12.5%) posttransplant with similar incidences of wound dehiscence, perigraft collections, and graft function at the end of follow up.

Body Mass Index↗

Cadaveric kidney transplantation under prophylactic polyclonal antibody immunosuppression with anti-lymphoblast globulin versus anti-thymocyte globulin.

OBJECTIVES: This retrospective study was undertaken to evaluate and compare the clinical and immunologic outcomes following prophylactic induction treatment with Minnesota anti-lymphoblast globulin (MALG) and Upjohn anti-thymocyte globulin (ATGAM) in cadaver renal transplantation. METHODS: From 1990 to 1994, 63 patients with renal transplants from cadavers received MALG and 77 patients received ATGAM for induction treatment. Most pretransplant parameters were equivalent in both groups. There was no significant difference in the total dose and mean duration of MALG/ATGAM administration. The post-transplant outcome in these groups was compared. RESULTS: There was no difference between the MALG and ATGAM groups with respect to the overall number of rejection episodes, median days to rejection, or the number of steroid-resistant rejection episodes. However, MALG-treated patients experienced a greater number of rejections in the first 60 days postoperatively (P = 0.06). There was no difference in the nadir serum creatinine level in the first 20 postoperative days in the two groups; however, it took fewer days to reach the nadir in the ATGAM group (P = 0.03). The incidence of delayed graft function was higher in the MALG group than in the ATGAM group (38% versus 31%) but not statistically significant. Graft survival at 12 and 24 months was comparable in both groups. However, patient survival was superior at 12 and 24 months in ATGAM-treated transplant recipients (P = 0.03). The mean serum creatinine at 6, 12, and 24 months was similar in both the MALG and ATGAM groups. The mean fall and recovery of CD3, CD4, and CD8 T-lymphocyte subsets while on MALG/ATGAM were similar in both groups. The incidence of infectious complications was greater in the MALG group. CONCLUSIONS: MALG and ATGAM have comparable clinical immunosuppressive effects. Patients receiving ATGAM experienced fewer rejections in the first 2 months, fewer infections, and better survival.

Antilymphocyte Serum↗

Long-term results with cyclosporine monotherapy in renal transplant patients: a multivariate analysis of risk factors.

There is little information on the long-term outcome of patients initially assigned to cyclosporine (CsA) monotherapy and requiring the addition of steroid therapy during follow-up. The aim of this report is to describe our experience with 143 first renal transplant recipients (120 cadaver transplants, 23 living donor transplants) randomized to receive CsA monotherapy as a treatment arm of three consecutive controlled clinical trials. Median follow-up was 86 months. Thirty-four percent of the patients remained on the original CsA monotherapy, whereas the remaining 66% required the addition of steroid therapy. Cumulative patient and graft survivals at 11 years were 0.89 (95% confidence interval [CI], 0.83 to 0.95) and 0.62 (95% CI, 0.52 to 0.72), respectively. The 11-year graft survival for converted patients was 0.53 (95% CI, 0.39 to 0.67). Cumulative graft half-life was 19.9 +/- 3.47 (SE) years. According to the Cox model, variables at transplantation that correlated with a lower 11-year graft survival were yearly increases in age (relative risk [RR], 1. 04; P = 0.039), monthly increases in hemodialysis duration (RR, 1.01; P = 0.029), no blood transfusion before transplantation (RR, 1.99; P = 0.043), CsA administration in a double daily dose (RR, 2.35; P = 0.008), and a cadaver donor transplant (RR, 4.76; P = 0.039). Multivariate analysis of time-dependent variables showed that delayed graft function recovery (RR, 2.20; P = 0.019) and the need to add steroid and/or azathioprine therapy (RR, 5.28; P = 0.000) were also correlated with a lower graft survival. Patients who added steroid therapy developed infections (P < 0.001), cataracts (P < 0.001), cardiovascular complications (P = 0.004), and arterial hypertension (P = 0.024) more frequently than patients remaining on CsA monotherapy. Patients administered CsA in a single daily dose received significantly less CsA over the years (P = 0.0042) than patients administered CsA in two divided doses. They also showed a trend toward greater creatinine clearance levels, although not statistically significant. In conclusion, this analysis showed that in patients assigned to CsA therapy alone, good long-term patient and graft survival probabilities can be obtained. In approximately one third of the patients, the use of steroids could be avoided for up to 11 years, and these patients had a better long-term outcome than those who required the addition of steroid therapy. Finally, in patients administered CsA in a single daily dose, the possibility of reducing CsA dosage probably led to better intrarenal hemodynamics with improving creatinine clearances.

Adult↗

Renal allograft and patient outcome after transplantation: pancreas-kidney versus kidney-alone transplants in type 1 diabetic patients versus kidney-alone transplants in nondiabetic patients.

Despite recent advances and improved outcome, pancreas transplantation remains controversial. The purpose of this review was to study renal allograft outcome after simultaneous pancreas-kidney transplants (SPK, n = 61), kidney-alone transplants in type I diabetic patients (KA-D, n = 63), and kidney-alone transplants in nondiabetic patients (KA-ND, n = 80). Patients were matched for donor age, donor gender, donor race, interval from donor admission to procurement, DR mismatch, and recipient gender. The mean renal allograft cold ischemic time and recipient age were lower in the SPK group. Patient survival was highest in the KA-ND group (99% and 86% at 1 and 5 years, respectively), intermediate in the SPK group (90% and 78% at 1 and 5 years, respectively), and lowest in the KA-D group (89% and 66% at 1 and 5 years, respectively) (P = 0.004). similarly, renal allograft survival was higher in the KA-ND (89% and 63% at 1 and 5 years, respectively) and SPK (82% and 69% at 1 and 5 years, respectively) groups compared with the KA-D group (76% and 49% at 1 and 5 years, respectively) (P = 0.07). This difference disappeared when renal graft survival was censored for death, which probably reflects the selection bias. Actuarial pancreas graft survival was 76% and 62% at 1 and 5 years, respectively. Acute rejection (AR) was more frequent in the SPK group than in the KA-D and KA-ND groups (41% v 16% v 29%; P = 0.007). Delayed graft function (DGF), on the other hand, occurred more frequently in the KA-D group than in the KA-ND and SPK groups (66% v 55% v 38%; P = 0.08). Death as a result of a cardiovascular event occurred more frequently in the KA-D group. Cardiovascular death and renal graft failure occurred earlier in the SPK group. Cox regression analysis revealed a 1.6 and 1.8 times higher risk of renal graft failure in the SPK group when the donor was > or = 40 years old or female and a five times higher risk of graft failure in the KA-ND group in the presence of AR. Graft survival in patients with AR/DGF was lower than that in patients with no AR/no DGF in both the KA-D (71% and 63% v 100% and 100% at 1 and 5 years, respectively; P = 0.03) and KA-ND (90% and 56% v 100% and 100% at 1 and 5 years, respectively; P = 0.001) groups. Acute rejection did not affect graft survival in the SPK group. In the absence of AR, DGF had no effect on graft survival in any of the groups. Although the selection bias in favor of pancreas transplantation does not allow for definitive conclusions, our results show that outcome after SPK transplantation is acceptable and factors that influence the outcome after this procedure may be different from the ones affecting KA-D recipients.

Actuarial Analysis↗

Posttransplantation acute tubular necrosis: risk factors and implications for graft survival.

Previous studies aimed at identifying the causes, risk factors, and outcome of kidney transplant recipients with delayed graft function (DGF) have yielded controversial results. We retrospectively analyzed the causes and risk factors for DGF in 263 cadaveric kidney transplantations from November 1988 to March 1997 in one center. Causes of DGF were assessed by postoperative graft evolution and graft biopsy. Univariate and multivariate analysis were used to investigate the risk factors for DGF induced by acute tubular necrosis (ATN). Seventy-six patients (29%) had DGF, which was caused by ATN in 70 patients (92.1%) and acute rejection (AR) in 6 patients (7.9%). Therefore, we focused on risk factors and consequences for ATN-induced DGF. In monofactorial analysis, ATN was significantly associated with greater weight and presence of an atheromatous disease in both donor and recipient. Other risk factors for ATN were older age of donor, recipient American Society of Anesthesiology (ASA) physical status category IV, cold ischemia time (CIT), and transplantation using the right kidney. The multivariate analysis showed that donor and recipient weight, donor age, transplantation using the right kidney, preservation in Eurocollins solution, ASA score, and CIT were associated with ATN. The incidence of rejection and renal function were not different at 3 months or 1 and 5 years. ATN is the main cause of DGF in kidney transplant recipients. ATN is caused by donor and recipient vascular background, grafting the right kidney, and CIT. ATN does not appear to have an adverse effect on long-term kidney function.

Adult↗

Early immunologic and nonimmunologic predictors of arterial hypertension after renal transplantation.

We followed up a cohort of 680 renal transplant recipients receiving cyclosporine (CsA) immunosuppression with the aim of establishing an early-risk profile for early and late hypertension (HT) after renal transplantation (RTx), specifically comparing the predictive role of immunologic and nonimmunologic markers of graft prognosis. HT was defined as the need for antihypertensive drugs. The prevalence of HT was 65% at the time of RTx, increased to a peak of 78% at the end of the first year, and stabilized between 71% and 73% thereafter. Multivariate analysis identified HT at the time of RTx, basal renal disease, and grafting the right kidney as independent predictors of HT 3 months after RTx. The risk profile for HT 12 months after RTx included HT present at RTx, grafting the right kidney, markers of early ischemia-reperfusion injury (delayed graft function, cold and warm ischemia), and transplant from an elderly or female donor. Polytransfusion before RTx was associated with a decreased risk for HT, but retransplantation, increased reactivity against the lymphocyte panel, poor HLA compatibility, and early acute rejection did not portend an increased risk for the complication under study. The CsA schedule (dose, trough levels) correlated poorly with the blood pressure status of the patients, but simultaneous graft function was independently associated with late HT. In conclusion, the early predictive profile for HT after RTx includes, preferentially, nonimmunologic markers of graft prognosis. Hyperfiltration damage may be a significant pathogenic mechanism for this complication of RTx.

Adolescent↗

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion.

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.

Biopsy↗

Reduced incidence of acute renal graft failure in patients treated with peritoneal dialysis compared with hemodialysis.

In a case-control study performed in two centers, the incidence of delayed graft function (DGF), defined as the necessity to perform dialysis after transplantation, was analyzed according to prior treatment with continuous ambulatory peritoneal dialysis (CAPD; n = 117) or hemodialysis (HD; n = 117). The patients were matched for age, sex, HLA compatibility, and cold ischemia time. The patients were followed up for 6 months to monitor renal graft function (serum creatinine [Screa] level immediately after transplantation, at 6 weeks, at 6 months) and postoperative complications. No significant differences were found in the warm ischemia time of the graft or previous time on dialysis. DGF occurred in 27 CAPD patients (23.1%) and 59 HD patients (50.4%; P < 0.0001). The decline in Screa level after transplantation was faster in CAPD patients: the time for Screa level to decrease 50% after transplantation (T1/2Screa) was reached after 5.0 +/- 6.6 days in the CAPD group compared with 9.8 +/- 11.5 days in the HD group (P < 0.0001). A greater number of patients developed acute rejection episodes in the CAPD group (P < 0. 05), but Screa level was not different in the two groups 6 weeks and 6 months after transplantation. No differences were observed in infectious or surgical complications. This study shows that immediate renal function after transplantation is better in CAPD patients and that peritoneal dialysis should be considered as a first choice for pretransplantation therapeutic modality.

Adult↗

"Old-for-old" cadaveric renal transplantation: surgical findings, perioperative complications and outcome.

OBJECTIVE: To evaluate the surgical findings and outcome of locally allocated, blood-group-compatible but HLA-unmatched cadaveric kidneys in first renal transplantation of donor/recipient pairs aged 65 years and above (Eurotransplant Senior Program=ESP). METHODS: 26 patients of the study group (donor age 70.4 +/- 3.6/recipient age 67.7 +/- 2.8) were compared to 30 controls aged 60 and above (mean recipient age 62.6 +/- 2.3/mean donor age 43.8 +/- 15.3). For controls kidney allocation included HLA matching. RESULTS: Cold ischemic time (ESP vs. controls 501 vs. 883 min; p<0.05) and mean number of HLA mismatches (4.2 +/- 1.36 vs. 1.6 +/- 1.62; p<0.05) differed significantly. Delayed graft function was lower in the study group (12% vs. 43%; p<0.05), rejection episodes in the ESP group were numerous but did not differ significantly from the controls (46% vs. 30%; p=0.21). More intraoperative complications and a higher incidence of donor organ arteriosclerosis (p<0.05) were seen in the ESP group. Three-year graft survival uncensored and censored for death with functioning graft did not differ, even though mean creatinine and creatinine clearance differed significantly beginning at month three. Three-year patient survival (55% vs. 81%) differed in favour of the control group, even though the difference was not significant due to small number of patients. CONCLUSION: "Old-for-old" kidney transplantation with local allocation yields graft survival rates comparable to HLA-matched young grafts and is a good approach to extend the donor and recipient pool. Careful patient selection is advised.

Age Factors↗

Tumour necrosis factor levels during acute rejection and acute tubular necrosis in renal transplant recipients.

Plasma tumour necrosis factor levels were measured serially in 16 patients following renal transplantation, and in 10 patients on haemodialysis and in 12 patients on peritoneal dialysis. The patients on peritoneal dialysis had lower plasma TNF levels than the patients on haemodialysis. There was a decrease in TNF levels immediately following renal transplantation; this is probably related to the bolus doses of methylprednisolone administered intra-operatively. Patients with acute rejection had higher levels of TNF than non-rejecting patients. The increase in TNF levels in rejecting patients was observed 2 days before the clinical manifestation of acute rejection. There was a marked decrease in TNF levels in rejecting patients in response to treatment with steroids. Patients with delayed graft function had higher levels of TNF on the first post-operative day compared to patients with immediate function. These changes in plasma TNF levels following renal transplantation have important clinical and therapeutic implications.

Acute Disease↗

Dual kidney transplantation: older donors for older recipients.

BACKGROUND: Dual kidney transplantation, the transplantation of both donor kidneys into a single recipient, allows increased use of expanded criteria donors (eg, older donors with a history of hypertension) to alleviate the disparity between available donors and potential recipients. We evaluated outcomes in our dual kidney transplant program that started in 1995. STUDY DESIGN: A retrospective comparison of donor and recipient data between recipients of dual (n = 41) versus single (n = 199) cadaveric renal transplants from February 1, 1995, to March 22, 1998, was performed. Dual kidney transplantation was selectively performed when the calculated donor admission creatinine clearance was less than 90 mL/min and the donor age was greater than 60 years, or if the donor had an elevated terminal serum creatinine. Every attempt was made to age- and size-match the donor and recipients. RESULTS: Recipients of dual kidneys had donors who were older than single kidney donors (59 +/- 12 versus 42 +/- 17 years respectively, p < 0.0001) and had more hypertension (51% versus 29%, p = 0.024). Average urine output was lower in the dual versus single kidney group (252 +/- 157 versus 191 +/- 70 mL/hr, p = 0.036). Donors for dual kidney recipients had a lower donor admission creatinine clearance of 82 +/- 28 mL/min versus 105 +/- 45 mL/min in the single kidney group (p = 0.005). Recipients of dual versus single kidneys were older (58 +/- 11 versus 47 +/- 12 years, p > 0.0001). Dual versus single kidney recipients had similar serum creatinines up to 2 years posttransplant (1.6 +/- 0.3 versus 1.6 +/- 0.7 mg/dL at 2 years, p = NS) and a comparable incidence of delayed graft function (24% versus 33%, p = NS) and 3-month posttransplant creatinine clearance (54 +/- 23 versus 57 +/- 25 mL/min, p = NS). One-year patient and graft survival for single kidney transplantation was 97% and 90%, respectively, and 98% and 89% for dual kidney transplantation (p = NS). CONCLUSIONS: Dual kidney donors were significantly older, had more hypertension, lower urine outputs, and lower donor admission creatinine clearance. Despite these differences, dual kidney recipients had comparable postoperative function, outcomes, and survival versus single kidney recipients. We believe selective use of dual kidney transplantation can provide excellent outcomes to recipients of kidneys from older donors with reduced renal function.

Adult↗

Nutrition in the critical care settings of renal diseases.

Acute catabolic events during the course of renal dysfunction lead to exacerbation of nutritional abnormalities often present in these patients. Whether the renal failure is acute or chronic, the nutritional management of these patients is extremely challenging. Traditional methods of nutritional assessment must be extrapolated to include the effects of the renal dysfunction and renal replacement therapy being used. Cases of patients with acute renal failure, chronic renal failure with an acute insult, pancreas-kidney transplant recipient with delayed graft function, and a liver transplant recipient who developed renal failure are reviewed with emphasis on the nutritional management during the course of illness. Monitoring techniques are reviewed, and comparisons are made to other nutrition support protocols.

Acute Kidney Injury↗

Should I accept this kidney?

BACKGROUND: Transplant candidates frequently ask whether they should, based on information available at the time, accept a cadaver kidney or wait for a potentially better one. METHODS: We analyzed 937 first and second cadaver transplants done between January 1, 1984 and December 31, 1997 to determine if information available at the time an offer is made could be used to predict long-term graft survival. RESULTS: By Cox regression, risk factors for worse long-term graft survival were older donor age, cardiovascular or cerebrovascular cause of donor death, and delayed graft function (DGF). HLA-ABDR mismatch was marginally significant. Whether DGF will occur is not known at the time of an offer, but risk factors can be determined; we found these to be older donor age and > 10% panel-reactive antibodies (PRA) at transplantation (by Cox regression). Using these variables (PRA, ABDR mismatch, donor age, and donor cause of death) known at the time of an offer, we calculated the relative risk of worse long-term graft survival for each subgroup (Table 3 in manuscript). In general, older age and donor death from cardiovascular or cerebrovascular disease were associated with worse outcome. Kidneys from donors of < 50 yr had the best outcome, irrespective of match. CONCLUSION: The data provided can be used to help guide patients as to whether they are better off accepting an offered kidney or waiting for a potentially better one. If an offer is declined, the next kidney may have a potentially worse outcome.

Adolescent↗

Failure of ganciclovir prophylaxis to completely eradicate CMV disease in renal transplant recipients treated with intense anti-rejection immunotherapy.

Ganciclovir prophylactic regimens have been shown to be effective in renal transplant recipients at risk for primary (donor seropositive/recipient seronegative) and secondary (recipient seropositive) cytomegalovirus (CMV) disease. However, in addition to serologic factors, the type and intensity of the administered immunosuppression is a strong risk factor for CMV disease. Since January 1995, we have utilized a potent immunosuppressive protocol selectively in recipients at high risk for immunologic graft loss, defined as retransplant recipients, recipients with delayed graft function, non-Caucasian recipients, and recipients suffering from acute rejection. Between January 1995 and December 1996, 110 consecutive renal transplants were performed in recipients who were either CMV seropositive or received an allograft from a CMV-seropositive donor. All recipients received ganciclovir prophylactic therapy for 3 months post-transplant. Group I (N = 43) consisted of recipients at high-immunologic risk for graft loss as defined above. These recipients were treated with an intense anti-rejection immunotherapeutic regimen consisting of Cellcept, Neoral, and prednisone, with the frequent addition of antilymphocyte antibody therapies and intravenous methylprednisolone. The remaining 67 recipients (group II) were treated with a less intense immunotherapeutic regimen consisting of azathioprine, Neoral, and prednisone. The incidence and severity of CMV disease and the patient and allograft survival were compared. The incidence of CMV syndrome was greater in group I (28%) compared with group II (7%), and was statistically significant (p < 0.05). The 1-yr patient and graft survival were similar, 95 and 91%, respectively, for group I compared with 97 and 97%, respectively, for group II. These data suggest that 3 months of ganciclovir prophylactic therapy is significantly less effective for the prevention of CMV disease in renal transplant recipients at high risk for acute rejection treated with an intense immunotherapeutic regimen. These data suggest that more effective prevention of CMV disease in these high-risk recipients will require the addition of other anti-viral agents, such as immunoglobulin preparation to the prophylactic regimen.

Adult↗