Human T-cell leukemia virus type I infection in various recipients of transplants from the same donor

BACKGROUND: The human T-cell lymphotrophic virus (HTLV) causes adult T-cell leukemia-lymphoma, tropical spastic paraparesis-HTLV type I, and associated myelopathy. METHODS: An analysis was performed of serum samples from a multiorgan donor and the five recipients. Also studied was the donor's family and the partner of one of the renal recipients. Serologic detection of anti-HTLV antibodies was carried out by enzyme immunoassay and Western blot to confirm and discriminate between HTLV types. Analysis of proviral DNA was performed by polymerase chain reaction and sequenced in the long terminal repeat region and the env gene. Peripheral blood mononuclear cell samples from all the recipients of the HTLV-I-positive organs and the donor's mother were studied. RESULTS: Two years after transplantation, three organ recipients positive for antibodies to HTLV-I were detected (two kidney transplants and one liver). All the recipients' serum samples were negative at the time of transplantation except those from the multiorgan donor. The donor's mother was born in Venezuela and was confirmed positive for antibodies to HTLV-I. The remaining family members were negative. HTLV-I DNA sequences were recovered, amplified, and sequenced from all the samples from the HTLV-I-positive recipients and the donor's mother. The homology of HTLV-I sequences was 100% in all cases. CONCLUSIONS: The authors are reporting the first documented case of HTLV-I infection in several transplant recipients sharing the same donor. The donor was infected by vertical transmission. HTLV-I infection has devastating consequences for some immunocompromised organ recipients. This emphasizes the need for a systematic survey of HTLV antibodies in all potential donors.     

Post-transplant Renal Function and Cardiovascular Events Are Closely Associated With the Aortic Calcification Index in Renal Transplant Recipients

Introduction

The aortic calcification index (ACI) is reported to be closely associated with renal dysfunction and cardiovascular events; however, its implication in renal transplant recipients has not been well examined. In this study, we investigated the relationship between pretransplant ACI, ACI progression, post-transplant renal function, and post-transplant cardiovascular events in renal transplant recipients.

Patients and methods

The study from June 1996 to Jan 2012 included 61 renal transplant recipients (living donors, 47; cadaveric donors, 14). The median follow-up period was 60 months. ACI was quantitatively measured on abdominal computed tomography. The relationship between age, dialysis period, estimated glomerular filtration rate (eGFR), and pre- and post-transplant ACI was longitudinally evaluated. Risk factors for post-transplant ACI progression were determined by logistic regression analysis. Patient background and the incidence of post-transplant cardiovascular events were also assessed.

Results

The pretransplant ACI (median 4.2%) significantly correlated with age at transplant, dialysis period, and diabetes mellitus. ACI gradually increased up to 2.8 times at 10 years after transplantation. Post-transplant eGFR significantly correlated with ACI progression in patients with chronic kidney disease of stage ≥3. Logistic regression analyses showed that age at transplantation, post-transplant period, cadaveric donors, and post-transplant chronic kidney disease stage 3 were risk factors for post-transplant ACI progression. The pretransplant ACI was higher (median 66%) in 3 patients who experienced post-transplant cardiovascular events.

Conclusions

ACI progression closely correlates with age and post-transplant renal function. A high pretransplant ACI is a risk factor for post-transplant cardiovascular events in renal transplant recipients.     

Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation

Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I (HTLV-I) carrier. The development of malignancy during immunosuppressive treatment following organ transplantation is one of the late fatal complications. We describe the development of three cases of ATL in eight HTLV-I carriers within 164 living-donor liver transplant recipients undergoing immunosuppressive treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL was diagnosed at 6, 9, and 25 months after living-donor liver transplantation, based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like" nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL cells originated from the recipient, as demonstrated by fluorescence in situ hybridization analysis using sex chromosomal markers. Our observations suggest that immunosuppressive treatment for the prevention of graft rejection after living-donor liver transplantation may induce the development of ATL in an HTLV-I carrier.     

Inadequate involvement of nephrologist/dialysis physicians in transplantation: based on the findings of a survey of transplant recipients

The number of kidney transplantations(KTx) performed annually in Japan remains small even after enactment of the "Organ Transplant" law. One of the reasons for this paucity of KTx might be because most nephrologists or dialysis physicians who provide medical care to potential transplant candidates have little knowledge of KTx and are seldom involved in the care of recipients and donors. The extent to which Japanese physicians participate in KTx has not been well studied. We sent questionnaires to the 212 kidney transplant recipients who have received an allograft at Tokyo Women's Medical University and conducted a survey to examine the extent to which nephrologists or dialysis physicians are involved in KTx. There were 149 recipients, consisting of 95 males and 54 females with an average age of 46.5 years, who responded to the questionnaire. Only 23% of the patients had considered KTx before dialysis access placement. Lack of information on KTx was suspected for this delay in considering KTx. In fact, only 18% of patients were informed about KTx by their nephrologists before starting dialysis and as many as 49% did not receive any information at all. Forty-eight percent of the patients were not provided with the information even on registration for a cadaveric transplant list by their physicians. Only 20% of the patients received some information about KTx through their nephrologists. On the other hand, nearly 100% of patients think it is essential for nephrologists or dialysis physicians to provide information on KTx especially before the initiation on dialysis access. In addition, almost all of the patients would prefer nephrologists or a dialysis physician to participate in the care of transplant patients from the stage of preoperative evaluation through the post-transplant follow-up period. In conclusion, nephrologists or dialysis physicians have not provided information on KTx to their patients appropriately and most of the transplant recipients expect them to participate in KTx. Nephrologists and dialysis physicians need fundamental knowledge about KTx so that they can provide appropriate information to patients with end-stage renal disease.     

Which renal transplant patients should receive cytomegalovirus immune globulin? A cost-effectiveness analysis.

Our study objective was to determine the cost-effectiveness of prophylaxis with cytomegalovirus immune globulin for preventing CMV-associated disease in renal transplant patients. We used a decision analytic model applied to 5 groups of renal transplant recipients at varying risks of developing CMV-associated disease. We obtained the rates of developing CMV-associated disease, graft rejection, and mortality, and the effectiveness of CMV-IG from the published literature. We used actual variable costs of CMV-IG, hospitalization, dialysis, and outpatient follow-up. The incremental cost of administering CMV-IG compared with withholding it ranged from $29,800 per life saved for the highest risk group, CMV-seronegative recipients of kidneys from CMV-seropositive cadaveric donors, to $1.68 million per additional life saved for the lowest risk group, CMV-seronegative recipients of grafts from CMV-seronegative donors. The outcome was somewhat sensitive to the effectiveness of CMV-IG in preventing CMV-associated disease but not sensitive to wide variations in CMV-IG costs, dialysis costs, outpatient costs, and the probability of graft rejection. Our conclusion is that prophylaxis with CMV-IG is very worthwhile for renal transplant recipients at high risk of CMV-associated disease and is possibly worthwhile for some patients at lower risk. The cost-effectiveness of other strategies for preventing CMV-associated disease, such as prophylaxis with acyclovir, CMV vaccine, or unselected immune globulin, should be compared with CMV-IG.     

Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis

BACKGROUND: Waiting time on dialysis has been shown to be associated with worse outcomes after living and cadaveric transplantation. To validate and quantify end-stage renal disease (ESRD) time as an independent risk factor for kidney transplantation, we compared the outcome of paired donor kidneys, destined to patients who had ESRD more than 2 years compared to patients who had ESRD less than 6 months. METHODS: We analyzed data available from the U.S. Renal Data System database between 1988 and 1998 by Kaplan-Meier estimates and Cox proportional hazards models to quantify the effect of ESRD time on paired cadaveric kidneys and on all cadaveric kidneys compared to living-donated kidneys. RESULTS: Five- and 10-year unadjusted graft survival rates were significantly worse in paired kidney recipients who had undergone more than 24 months of dialysis (58% and 29%, respectively) compared to paired kidney recipients who had undergone less than 6 months of dialysis (78% and 63%, respectively; P<0.001 each). Ten-year overall adjusted graft survival for cadaveric transplants was 69% for preemptive transplants versus 39% for transplants after 24 months on dialysis. For living transplants, 10-year overall adjusted graft survival was 75% for preemptive transplants versus 49% for transplants after 24 month on dialysis. CONCLUSIONS: ESRD time is arguably the strongest independent modifiable risk factor for renal transplant outcomes. Part of the advantage of living-donor versus cadaveric-donor transplantation may be explained by waiting time. This effect is dominant enough that a cadaveric renal transplant recipient with an ESRD time less than 6 months has the equivalent graft survival of living donor transplant recipients who wait on dialysis for more than 2 years.     

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.     

Human T-lymphotropic virus type I (HTLV-I): risk of transmission with transfusion

PATHOGENIC ROLE: The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus discovered, is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and of HTLV-I associated myelopathy or tropical spastic paraparesis (HAM/TSP) and has a widespread but uneven worldwide distribution. HTLV-I has a high seroprevalence in Southern Japan, the Caribbean basin and Sub-Sahara Africa. Blood transfusion, intravenous drug use, breast feeding and sexual contacts are major routes of contamination. IMPLICATIONS FOR BLOOD TRANSFUSION: The screening of blood donors for antibody to HTLV-I became systematic in 1989 in French West Indies and in 1991 in Continental France. This review deals with the transfusional implications of the HTLV-I, which belongs to the group of the blood-borne viruses: the prevalence of transfusion-linked HTLV-I infection before the implementation of the specific preventive measures, the parameters influencing the risk of transfusional contamination (the type of blood products, the age of the blood product with regards to its collection date, the proviral load of the blood donor), the prognosis of HTLV-I infection in patients contaminated by transfusion, the prophylactic strategies of transfusion contamination and the residual risk of infection through HTLV-I-infected risk blood products.     

肾移植176例死亡分析

目的：分析探讨肾移植受者的死亡情况和死亡在因。方法：总结1977年10月至1999年6月1039例尸体肾移植患者的临床资料。术后患者死亡率的计算按Kaplan-Meier乘积极限法进行。对可能影响移植受者死亡的因素，加供受者性别和年龄、移植次数、移植前透析时间、移植前输血量、淋巴细胞毒交叉试验、冷缺血时间、肾功能延迟恢复、急慢性排斥反应、免疫抑制药物治疗以及术后并发症等因素进行log-rank单因素和Cox模型多因素分析。结果：截至1999年12月，1039例中存活863例，死亡176例。总的术后1、5、10及15年累计死亡率分别为6．9％、19．7％、32．1％和34．7％，感染、心脑血管疾病和肝功能衰竭分别占38．1％、21．6％和14．8％。在全部死亡病例中，移植肾有功能者占75．0％，而移植后1年以上的死亡患者中移植物有功能者占87．5％。对可能影响患者死亡的诸多变量进行单因素和多因素的综合分析显示：移植年代、移植前透析时间、免疫抑制药物治疗、慢性排斥反应、术后肺炎以及心脑血管疾病并发症等6个因素与肾移植术后患者的死亡相关（P＜0．001）。结论：移植1年后患者死亡率以平均每年2．5％的速度递增。感染、心脑血管疾病和肝功能衰竭是引起死亡的3个主要原因。接受移植的年代、移植前透析时间、免疫抑制药物治疗、慢性排斥反应、术后肺炎以及心脑血管疾病并发症等是肾移植受者死亡的重要影响因素。     

Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates

An increasing number of cadaveric kidney transplants are now performed with organs from donors who would have been deemed unsuitable in earlier times. Although good allograft outcomes have been obtained with these marginal donor transplants, it is unclear whether recipients of marginal kidney transplants achieve a reduction in long-term mortality as do recipients of "ideal" kidneys. Patients with end-stage renal disease registered on the cadaveric renal transplant waiting list between January 1, 1992, and June 30, 1997, were studied for mortality risks according to three outcomes: wait-listed on dialysis treatment with no transplant (WLD); transplantation with marginal donor kidney (MDK); and "ideal" or optimal donor kidney transplantation (IDK). Thirty-four percent of wait-list registrants had received a cadaveric kidney transplant by June 30, 1998. Of these, 18% received a marginal kidney that had one or more of the following pretransplant factors: donor age >55 yr, non-heartbeating donor, cold ischemia time >36 h, and donor hypertension or diabetes mellitus of > 10 yr duration. Five-year graft and patient survival was 53% and 74% for MDK recipients compared with 67% (P< 0.001) and 80% (P< 0.001) for IDK recipients. Adjusted annual death rate and estimated remaining life time was 6.3%, 4.7%, and 3.3% and 15.3 yr, 20.4 yr, and 28.7 yr for WLD, MDK, and IDK groups, respectively. The average increase in life expectancy for MDK recipients compared with the WLD cohort was 5 yr, although this benefit varied from 3 to 10 yr depending on the recipient's characteristics. It is concluded that transplantation of a marginal kidney is associated with a significant survival benefit when compared with maintenance dialysis.     

Antibodies to hepatitis C virus in kidney transplantation.

Ninety patients on dialysis, 241 cadaveric kidney donors and 27 cadaveric kidney recipients with a follow-up of 2 years, have been investigated as for anti-HCV positivity by means of 3 tests. As for patients on dialysis and cadaveric donors, the prevalence was 32 and 4%, respectively. As for transplanted patients, it must be noted that 4 negative recipients from positive donors seroconverted, but without any change in hepatic enzymes, while in 2 or 9 anti-HCV-positive recipients, hepatic enzymes increased after transplantation. Seroconversion in patients transplanted from a negative donor was not significantly different. We conclude that, according to their experience, anti-HCV positivity in the donors is not associated with a significant risk of infection in recipients of cadaveric grafts.     

Renal transplantation after prolonged dwell peritoneal dialysis in children

Thirty-three children received a total of 38 renal transplants (18 living related donor, and 20 cadaveric) after being on CAPD and/or CCPD (PDPD). Ten patients (12 transplants) were converted to hemodialysis pre-transplant in order to be free of the risk of peritonitis and off antibiotics, whereas 23 patients (26 transplants) were on PDPD at the time of transplant. The latter group of patients are described in greater detail. Within this group there was one episode of catheter colonization with Flavobacterium, and only three patients developed ascites post-transplant. Of the 26 transplants, catheters were removed at the time of transplant in the 13 LRD allografts but left in situ for a mean of 3.8 weeks in the 13 cadaveric transplant recipients. Peritoneal dialysis was required post-transplant in seven patients (two LRD recipients requiring a new catheter placement) without complications. Our policy of removing PD catheters at the time of transplant in LRD recipients and prior to hospital discharge in cadaveric transplant recipients has resulted in the avoidance of additional hospitalizations in 19 of the 26 transplants and avoided extra surgery in 11 of the 13 LRD transplants. We conclude that children who have been on PDPD are suitable candidates for renal transplantation and that the early removal of PD catheters, including removal at the time of transplantation in LRD recipients, is associated with a significant reduction in operative procedures for the patients.     

Pretransplantation systolic blood pressure and the risk of delayed graft function in young living-related renal allograft recipients

Delayed graft function (DGF) is associated with decreased long-term renal allograft survival, however, the entire mechanism of action of DGF has not yet been established. The goal of this study was to determine possible risk factors for DGF in young living-related renal allograft recipients. We retrospectively analyzed the outcome of 142 renal transplant recipients (115 men and 27 women; mean age, 29.7 +/- 9.43 years; 114 living-related donors and 28 cadaveric donors). Data recorded for each patient and donor included gender, age at transplantation, duration of pretransplantation dialysis (recipients only), body mass index, number of human leucocyte antigen mismatches, panel-reactive antibodies, donor creatinine clearance, body weight, systolic and diastolic blood pressure levels, lipid profile, and biochemical parameters. Having obtained the transplant from a cadaveric donor (P<.000, odds ratio [OR]=17.556, confidence interval [CI]=5.961-51.743) and a pretransplantation systolic blood pressure level in the recipient of <120 mm Hg (P<.021, OR=3.600, CI=1.214-10.672) were possible risk factors for DGF. When only living-related recipients were considered, the systolic blood pressure level was significantly associated with DGF. We concluded that a pretransplantation systolic blood pressure level <120 mm Hg is a risk factor for DGF and that preoperative blood pressure control and intervention may help to decrease the risk of DGF.     

Pregnancy in women receiving renal dialysis or transplantation in Japan: a nationwide survey.

BACKGROUND: Since a report on the first successful pregnancy of a woman on long-term haemodialysis in Japan in 1977, there has been a growing number of case reports on successful pregnancy in patients on dialysis. We undertook a nationwide survey on pregnancy in women on renal replacement therapy in 1996. METHODS: A preliminary questionaire was sent to 2504 dialysis units and 143 renal transplant units in Japan. For each reported pregnancy, a more detailed questionaire was sent to collect nephrological, obstetric and neonatal information. RESULTS: There were 172 pregnancies (0.44%) reported in 38889 women on dialysis, with 90 successful pregnancies (0.23%), and 194 pregnancies reported in 852 female renal transplant recipients. Detailed pregnancy information was collected from 74 women on dialysis and 194 renal transplant recipients. Of the 74 pregnancies in the women on dialysis, 36 (48.6%) resulted in surviving infants, nine (12.2%) in neonatal death, nine (12.2%) spontaneous abortions and 14 (18.9% elective abortions were reported. The outcome of six pregnancies (8.1%) was unknown. Of 194 pregnancies in renal transplant recipients, 159 (82.0%) resulted in surviving infants, two (1.4%) in neonatal death and 28 (14.4%) in spontaneous or elective abortion. In five cases the pregnancy outcome was not reported. No congenital anomalies were reported, except two infants with mental retardation and one with epilepsy. CONCLUSION: The current survey revealed that the rate of successful pregnancy in women on dialysis has improved. More than half of the pregnancies resulted in infant survival. But, premature birth is a major problem for the children of women on dialysis and there is a higher rate of neonatal death. There are significant differences in gestational age, birth weight, frequency and severity of prematurity and rates of neonatal death between pregnancies of women undergoing dialysis and those who are renal transplant recipients.     

Impact of renal transplantation on survival in end-stage renal disease patients with elevated body mass index

BACKGROUND: Cadaveric renal transplantation is associated with a survival advantage compared with dialysis patients remaining on the renal transplantation waiting list, but this advantage has not been confirmed in obese end-stage renal disease (ESRD) patients. METHODS: Using data from the USRDS, we studied 7521 patients who presented with ESRD from 1 April 1995 to 29 June 1999 and later enrolled on the renal transplantation waiting list with body mass indices (BMI) >or=30 kg/m(2) at the time of presentation to ESRD, and followed until 6 November 2000. Recipients of preemptive renal transplantation or organs other than kidneys were excluded. Cox non-proportional hazards regression models were used to calculate adjusted, time-dependent hazard ratios (HR) for time to death in a given patient during the study period, controlling for renal transplantation, demographics and comorbidities (Form 2728). RESULTS: The incidence of mortality was 3.3 episodes per 100 patient-years (PY) in cadaveric renal transplantation and 1.9/100 PY in living donor renal transplantation compared with 6.6 episodes/100 PY in all patients on the transplant waiting list. In comparison to maintenance dialysis, both recipients of solitary cadaveric kidneys (HR 0.39, 95% CI 0.33 to 0.47), and recipients of living donor kidneys (HR 0.23, 95% CI 0.16 to 0.34) had statistically significant improved survival. A benefit of cadaveric renal transplantation did not apply to patients with BMI >or=41 kg/m(2) (HR 0.47, 95% CI, 0.17 to 1.25, P = 0.13). CONCLUSIONS: Obese patients on the renal transplant waiting list had a significantly lower risk of mortality after renal transplantation compared with those remaining on dialysis.     

Impact of cadaveric renal transplantation on survival in patients listed for transplantation

The aim of this study was to assess the magnitude of the survival benefit of renal transplantation compared with dialysis in patients selected for transplantation in Scotland. Longitudinal study of survival and mortality risk in all adult patients (1732) listed for a first transplant between January 1, 1989, and December 31, 1989, in Scotland. A time-dependent Cox regression analysis adjusted for comorbidity, sociodemographic and geographic factors, primary renal disease, time on dialysis, and year of listing compared the risk of death for patients receiving a first cadaveric transplant versus all patients on dialysis listed for transplantation. After adjustment for the covariates, the relative risk (RR) of death during the first 30 days after transplantation was 1.35 (95% confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR = 1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI, 0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long-term risk of death was present in all patients undergoing transplantation, irrespective of their age group or primary renal disease. Similar results were seen when survival with a transplant was censored for graft failure. The projected life expectancy with a transplant was 17.19 yr compared with only 5.84 yr on dialysis. Despite an initial higher risk of death, long-term survival for patients who undergo transplantation is significantly better compared with patients who are listed but remain on dialysis. A successful transplant triples the life expectancy of a listed renal failure patient.     

Adult T cell leukemia in hemodialysis patients from the Kagoshima district, an area in which human T cell leukemia virus type I is highly endemic

We report 2 cases of adult T cell leukemia (ATL) from hemodialysis (HD) patients with chronic renal failure (CRF) in the Kagoshima district, an endemic area of human T cell leukemia virus type I(HTLV-I) in Japan. The positivity of antibodies to ATL-associated antigen(anti-ATLA) in HD patients, regardless of whether or not blood transfusions were given, has been higher than in healthy persons in the district (p less than 0.01). ATL is considered to break out from HTLV-I carriers. Further study should be conducted to clarify the relationship between HTLV-I infection and CRF, and moreover, attention should be directed not only to treatment of HD but accompanying ATL as well, particularly in HTLV-I-endemic areas.     

Observations regarding the use of sirolimus and tacrolimus in high-risk cadaveric renal transplantation

BACKGROUND: Balancing the risk of acute rejection (AR) with drug-induced toxicities complicates the selection of the optimal immunosuppressive regimen, especially in the high-risk renal transplant recipient. This study was designed to determine the optimal dosage combinations of tacrolimus and sirolimus in a high-risk cadaveric renal transplant population. METHODS: Primary cadaveric renal transplant recipients were randomly assigned to receive either standard tacrolimus (trough levels of 10-15 ng/mL) plus reduced sirolimus (trough levels of 5-10 ng,mL) (Group I) or to receive reduced tacrolimus (trough levels of 5-10 ng,mL) plus standard sirolimus (trough levels of 10-15 ng/mL) (Group II). All patients received Thymoglobulin induction and steroids. RESULTS: Thirty-nine (16 in Group I and 23 in Group II) high-risk renal transplant recipients (100% cadaveric donors, 79% African-American recipients, and 59% delayed graft function) are the subjects of this report. At 6 months, the patient survival rate was 94 and 100% and the graft survival rate was 94 and 83% in Groups I and II, respectively. The incidence of biopsy-proven AR was 6 and 5% in Groups I and II, respectively. Eight patients (50%) in Group I required discontinuation of tacrolimus, seven because of biopsy-proven tacrolimus nephrotoxicity and one secondarily to interstitial pneumonitis. Wound complications were the most frequent adverse event reported in both groups. CONCLUSIONS: The combination of tacrolimus and sirolimus was associated with a low risk of AR in this cohort of high-risk renal transplant recipients. However, 50% of patients who received standard tacrolimus and reduced sirolimus combination had to be discontinued from the regimen because of biopsy-proven nephrotoxicity. These preliminary results provide evidence that sirolimus should not be added to tacrolimus without dosage adjustments. We have discontinued recruitment of patients to the standard tacrolimus and reduced sirolimus combination and we have tightened our criteria for selection of marginal donor kidneys with our high-risk renal transplant recipients.     

Renal transplantation done safely without prior chronic dialysis therapy

The complications, cost, and inconvenience associated with pretransplant hemodialysis and peritoneal dialysis would be minimized if transplantation were instituted without prior dialysis. That preuremic transplantation is safe and efficacious in patients with immanent end-stage renal disease has not been established. All 1742 consecutive primary renal transplants performed at the University of Minnesota during the 16.5 year period from January 1968 through July 1984 were reviewed to determine whether graft and patient survival were adversely affected by transplantation prior to dialytic therapy. In the overall group of primary renal transplants, no differences in actuarial graft or patient survival were noted with or without prior dialysis. Likewise, outcome was not affected by the pretransplant dialysis status in recipients of allografts from HLA-identical mismatched living-related donors. However, in cadaveric transplantation graft function appeared to be adversely affected by transplantation prior to dialysis, with 52% vs. 66% two-year graft function for nondialyzed vs. chronically dialyzed recipients, respectively (P = 0.15). Patient survival was significantly (P = .04) decreased in the nondialyzed group, with 66% vs. 80% two-year survival in the chronic dialysis group. However, nearly all of the nondialyzed, cadaveric recipients were diabetic. The outcome of transplantation was found to be identical in these patients, as compared with chronically dialyzed diabetic recipients of cadaveric grafts. Thus, the apparent detrimental effect of predialytic transplantation in the cadaver group was due to the preponderance of diabetics in the nondialyzed group. Since July 1984, a single-armed therapeutic trial of combination therapy with azathioprine, prednisone, antilymphoblast globulin (ALG), and cyclosporine has been undertaken, Since that time, 36 primary graft recipients were transplanted prior to dialysis. Of these 36, 35 currently have a functioning graft. Thus, transplantation prior to chronic dialysis is safe irrespective of donor source, or choice of immunosuppressive agents.     

Why should we implement living donation in renal transplantation?

BACKGROUND: Renal transplantation started with living donor transplants. However, after the introduction of cyclosporine, the improved results of kidney transplants from cadaveric donors have raised controversy regarding the use of living donors. There are various reasons as to why some transplant centers tend to refuse living donation: first of all, the possibility that unilateral nephrectomy can be harmful to a healthy individual. SUBJECTS AND METHODS: By reviewing the medical literature on the various aspects of living donation, postoperative mortality in connection with living donation has been calculated to be 1:3,000. RESULTS: Long-term follow-up investigations of donors demonstrated that the risk of progressive renal failure, hypertension, and proteinuria was not increased by nephrectomy per se, but other causes were responsible for that in occasional patients. From these studies, one can conclude that unilateral nephrectomy is not harmful to a healthy individual. In addition, there are other valid reasons to expand living donation: 1) the need for cadaveric donor kidneys for transplantation far exceeding the supply; 2) the better kidney quality from living donors due to the shorter ischemia time, the lack ofagonal phase and cytokines release that follows brain death; 3) the continuing improved results of kidney transplants from living donors in comparison with those from cadaveric donors in the cyclosporine era also. This appears to be true also for kidney transplants from unrelated living donors in spite of complete incompatibility with recipients. 4) Pre-emptive transplantation, based on living donors, not only avoids the risks, cost, and inconvenience of dialysis, but is also associated with better graft survival than transplantation after a period of dialysis, particularly within the live donor cohort. CONCLUSIONS: In conclusion, living donor transplants should be part of any transplant center's activity. To encourage living donation, every center should have a formal recipient family education program in conjunction with national organ donation campaigns.