Declining Influence of Race on the Outcome of Living-Donor Renal Transplantation

A racial disparity in graft survival for renal transplant recipients has been documented for both cadaveric and living-donor transplants. In the present single-center study we analyzed graft survival by race for recipients of living-donor kidney transplants in three eras: 1985-89, 1990-94, and 1995-2000. There was an intensification of the immunosuppressant regimen beginning in 1996, such that all patients received cyclosporine or tacrolimus with mycophenolate and prednisone. Graft survival was analyzed using the Cox proportional hazards model. There were 79 black recipients and 210 white recipients with no difference in mean age, degree of HLA matching, or proportion of recipients with diabetes as the cause of end-stage renal disease. Using all data from 1985 to 2000, graft survival was significantly better for whites vs. blacks adjusted for age, gender, diabetes, era of the transplant, and haplotype match (p = 0.05). However, when analyzed by era, there was a temporal trend for a progressive decrease in the racial disparity in graft survival. In confirmation of this effect, there was a significant race-era interaction (p = 0.01) on multivariable Cox proportional hazards analysis. The most recent data from the United States Renal Data System (USRDS) show a similar decrease in the racial difference in 1-year graft survival. We conclude that the influence of race on living-donor graft survival is diminishing over time.     

Preemptive Renal Transplantation: Why Not?

Dialysis has been the long-established initial choice of treatment for persons with end-stage renal disease. Transplantation before dialysis, or preemptive renal transplantation (PRT), has been controversial because of the paucity of clinical evidence that has clarified the benefits vs. risks of this approach. However, several recent observational analyses indicate that PRT is the optimal strategy to benefit patients requiring renal replacement therapy. This current review will discuss the advantages that are associated with PRT, and will summarize studies that have investigated the impact of the timing of transplantation on outcomes. We will also discuss the utility of PRT from various perspectives, and describe the challenges ahead in expanding the opportunity of PRT for more patients.     

Preemptive Living Donor Renal Transplantation: A Single-Center Experience

Renal transplantation is considered preemptive if it occurs before initiation of dialysis. In our experience and in the literature, preemptive transplantation has been shown not only to reduce the costs of renal replacement therapy but also to avoid the long-term adverse effects of dialysis. Preemptive renal transplantation therefore is associated with better survival of both the allograft and the recipient. Our aim was to evaluate the outcomes of preemptive renal transplantation experience at our center. Since 1985, 1385 renal transplantations have been performed at our center. We retrospectively analyzed the 16/1385 recipients (11 male, 5 female) of overall mean age of 28.5 ± 15 years who underwent preemptive procedures. The causes of end-stage renal failure were focal segmental glomerulosclerosis (n = 5), vesicular ureteral reflux (n = 4), Berger disease (n = 2), polycystic renal disease (n = 2), and others (n = 3). Ten patients were adults, the remaining six, children. The mean creatinine clearance and plasma creatinine levels of the recipients before renal transplantation were 13.5 ± 8.5 mL/min and 6.7 ± 2.4 mg/dL, respectively. All renal transplantations were performed from living related donors. The mean preoperative serum creatinine levels, mean glomerular filtration rate, and creatinine clearance rates of the donors were 0.8 ± 0.1 mg/dL, 61.6 ± 6.5 mL/min, and 112.5 12 mL/min, respectively. Two episodes of acute cellular rejection and one of humoral rejection occurred during a mean follow-up of 48.7 ± 14 months (range = 25-76 months). The two patients who experienced graft losses due to humoral rejection or chronic rejection were retransplanted 2 and 48 months thereafter, respectively. At this time all patients are alive with good renal function. In conclusion, our single-center results are promising for preemptive renal transplantation as the optimal, least-expensive mode of treatment for end-stage renal disease.     

Obesity and Outcome Following Renal Transplantation

Single institution series have demonstrated that obese patients have higher rates of wound infection and delayed graft function (DGF), but similar rates of graft survival. We used UNOS data to determine whether obesity affects outcome following renal transplantation. From the UNOS database, we identified patients who underwent primary kidney-only transplantation between 1997 and 1999. Recipient and donor body mass index (BMI) was categorized as underweight (BMI < 18.5), normal (BMI 18.5-24.9), overweight (BMI 25-29.9), obese (BMI 30-34.9) or morbidly obese (BMI > or = 35). We correlated BMI with intermediate measures of graft outcome and overall graft survival, and created multivariate models to evaluate the independent effect of BMI on graft outcome, adjusting for factors known to affect graft success. The study sample comprised 27,377 recipients. Older age, female sex, African American race and increased comorbidity were associated with obesity (p < 0.001). Compared with normal weight patients, morbid obesity was independently associated with an increased risk of DGF (p < 0.001), prolonged hospitalization (p < 0.001), acute rejection (p = 0.006) and decreased overall graft survival (p = 0.001). Donor BMI did not affect overall graft survival (p > or = 0.07). Recipient obesity is associated with an increased risk of DGF and decreased graft survival following renal transplantation.     

Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

狼疮肾炎终末期肾病患者肾移植临床分析

目的：探讨系统性红斑狼疮肾炎终末期肾病患者行肾移植术治疗的效果和可行性。方法：统计我院2004年1月～2008年12月间,原发病为终末期狼疮肾病的肾移植患者的临床资料和手术后随访情况进行分析。结果：4例患者均为女性,行移植手术时全身病情稳定,无狼疮活动;手术后均使用免疫抑制剂抗排斥反应;术后平均随访时间41.5个月;至今其中3例移植肾功能良好,未发生排异反应,1例移植肾功能异常者经移植肾病理活检证实为慢性排斥反应,4例均无狼疮肾病复发。结论：终末期狼疮肾病患者肾移植效果良好,肾移植治疗终末期狼疮肾病是有效和可行的。     

Prognostic Factors Predicting Poor Outcome in Living-Donor Liver Transplantation for Fulminant Hepatic Failure

Background

Living-donor liver transplantation (LDLT) has been accepted as feasible treatment for fulminant hepatic failure (FHF), although it has generated several debatable issues. In this study, we investigated the prognostic factors predicting fatal outcome after LDLT for FHF.

Living-Donor Kidney Transplantation: Donor-Recipient Function Correlation

Background

With the rising prevalence of living-donor kidney transplantation, evaluation of factors correlated with renal function in the donor-recipient pair constitutes a main goal for kidney transplantation clinicians. Our objective was to analyze the more relevant donor characteristics that contribute to donor and recipient estimated glomerular filtration rates (eGFR) after 1 year.

Fertility Outcome After Renal Transplantation: A Single-Center Experience

BackgroundWomen suffering from kidney disease are more prone to fertility problems, due to uremia. Fortunately, their fertility rate increases dramatically after renal transplantation. This study analyzes the predictors/risk factors of successful pregnancy with live birth outcome while presenting an overview of the 7-year experience of a single center.MethodsThis retrospective cohort study includes 239 women of reproductive age (18–40 years) who underwent renal transplantation in a tertiary Turkish clinic between October 1, 2011, and August 24, 2017. The subjects were invited to take part in a survey questioning their obstetric characteristics and they were assessed in 2 groups: fertile and infertile. Multivariable linear regression analysis was conducted to determine the predictors of a successful pregnancy.ResultsThirty-five 35 patients wished to become pregnant: 12 got pregnant spontaneously, while 21 failed to become pregnant (spontaneously). The mean age of the patients at the survey was 34 ± 7. Regular menstrual cycles after renal transplantation, tacrolimus-mycophenolate mofetil maintenance protocol, and age at transplantation were found to be predictors of spontaneous pregnancy. The duration of peritoneal dialysis was significantly longer in the infertile group (48 vs 12 months).ConclusionEnd-stage renal disease's negative impacts, including menstrual abnormality and fertility problems, can be overcome by successful kidney transplantation with appropriate immunosuppression. Minimizing the duration of peritoneal dialysis, particularly in patients who desire future fertility, may be accepted as a logical management strategy.     

Living-Donor Liver Transplantation for Hepatoblastoma

Hepatoblastoma is the most common malignant liver tumor in children. Recently, liver transplantation has been indicated for unresectable hepatoblastoma. We retrospectively reviewed 14 children with a diagnosis of hepatoblastoma who had undergone living-donor liver transplantation (LDLT) at Kyoto University Hospital. During the period from June 1990 to December 2004, 607 children underwent LDLT. Of these interventions, 2.3% were performed for hepatoblastoma. Based on radiological findings, the pre-treatment extent of disease (PRETEXT) grouping was used for pre-treatment staging of the tumor. There were grade III in seven patients and grade IV in seven patients. Thirteen patients received chemotherapy, and seven underwent hepatectomy 11 times. Immunosuppressive treatment consisted of tacrolimus monotherapy in 11 patients. Actuarial 1- and 5-year graft and patient survival rates were 78.6% and 65.5%. The poor prognostic factors were macroscopic venous invasion and extrahepatic involvement with 1-year and 5-year survival rates of 33.0% and 0%. Pediatric patients without these factors showed an acceptable 5-year survival rate of 90.9%. LDLT provides a valuable alternative with excellent results in children with hepatoblastoma because it allows optimal timing of the liver transplantation, given the absence of delay between the completion of chemotherapy and planned liver transplantation.     

Renal Vein Lengthening Using Gonadal Vein Reduces Surgical Difficulty in Living-Donor Kidney Transplantation

Background  

During living-donor kidney transplantation, to maximally decrease donor injury, the right kidney with lower glomerular filtration rate often is selected as the donor kidney. However, the renal vein of the right kidney is relatively short for transplantation. The gonadal vein is essentially useless and is easily accessed during the donor nephrectomy.     

Pre-Transplant Inosine Monophosphate Dehydrogenase Activity is Associated with Clinical Outcome After Renal Transplantation

Mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase (IMPDH) activity, is usually administered as a standard dose of 1 g b.i.d. after renal transplantation. Because MMF dose reductions are associated with inferior outcome, we investigated pre-transplant IMPDH activity, MMF dose reductions and outcome. IMPDH activity was determined in isolated peripheral mononuclear cells immediately prior to renal transplantation. We observed considerable inter-individual variability in pre-transplant IMPDH activity (9.35 +/- 4.22 nmol/mg/h). Thirty of 48 patients (62.5%) with standard MMF dose (1 g b.i.d.) had dose reductions within 3 years post-transplant; these patients also had significantly lower IMPDH activity. The area under the receiver-operating characteristics curve (AUC-ROC) for prediction of dose reduction within 6 months post-transplant was 0.75 (95% CI, 0.61-0.89; p < 0.004). IMPDH activity above the cut-off value, MMF dose reduction and age of recipient were significant contributors for the occurrence of acute rejection in the multivariate logistic regression. Patients with high IMPDH activity and MMF dose reduction had the highest rejection rate (81.8% vs. 36.4%; p < 0.01). Conclusion: Patients with low IMPDH activity experienced more complications of MMF therapy. High pre-transplant IMPDH activity and MMF dose reductions were associated with rejection. Determination of IMPDH activity prior to transplantation may help to improve MMF therapy after renal transplantation.     

Syngeneic Living-Donor Liver Transplantation for Hemangioendothelioma: A Clinical Model for Studying Liver Regeneration

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.     

Valacyclovir Prophylaxis Versus Preemptive Valganciclovir Therapy to Prevent Cytomegalovirus Disease After Renal Transplantation

Both preemptive therapy and universal prophylaxis are used to prevent cytomegalovirus (CMV) disease after transplantation. Randomized trials comparing both strategies are sparse. Renal transplant recipients at risk for CMV (D+/R−, D+/R+, D−/R+) were randomized to 3-month prophylaxis with valacyclovir (2 g q.i.d., n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia (≥2000 copies/mL by quantitative PCR in whole blood) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. The 12-month incidence of CMV DNAemia was higher in the preemptive group (92% vs. 59%, p < 0.001) while the incidence of CMV disease was not different (6% vs. 9%, p = 0.567). The onset of CMV DNAemia was delayed in the valacyclovir group (37 ± 22 vs. 187 ± 110 days, p < 0.001). Significantly higher rate of biopsy-proven acute rejection during 12 months was observed in the preemptive group (36% vs. 15%, p = 0.034). The average CMV-associated costs per patient were $5525 and $2629 in preemptive therapy and valacyclovir, respectively (p < 0.001). However, assuming the cost of $60 per PCR test, there was no difference in overall costs. In conclusion, preemptive valganciclovir therapy and valacyclovir prophylaxis are equally effective in the prevention of CMV disease after renal transplantation.     

Outcome After Myocardial Revascularization and Renal Transplantation: A 25-Year Single-Institution Experience

BACKGROUND AND OBJECTIVE: Cardiac disease is a common cause of death in renal transplant recipients. This study retrospectively analyzes the results of myocardial revascularization procedures in these patients and makes recommendations for managing coronary atherosclerosis in patients with renal disease who already have a transplanted kidney or who may receive a kidney transplant. METHODS: Patients who had myocardial revascularization (coronary artery bypass grafting [CABG] or percutaneous transluminal coronary angioplasty [PTCA]) and renal transplantation at the authors' institution between 1968 and 1994 were analyzed. Patient, procedural, and institutional variables were used for actuarial analyses of survival, as well as multivariate analyses of risk factors for death. RESULTS: Eighty-three of 2989 renal transplant patients required myocardial revascularization either before or after their transplant, and diabetes mellitus was the cause of renal failure in 42% of these patients. Standard coronary angiography, CABG, and PTCA techniques were used without periprocedural renal allograft loss. Actuarial patient survival was 89%, 77%, and 65% at 1, 3, and 5 years after the last procedure (transplantation or revascularization). Cardiac disease was the most common mode of death. Early-phase risk factors for death by multivariate analysis included hypertension and revascularization before 1989. Late-phase risk factors for death included diabetes mellitus, higher number of pre-CABG myocardial infarctions, renal transplantation before 1984, older age, and unstable angina before CABG. CONCLUSIONS: Myocardial revascularization can be performed with acceptable short- and long-term results in patients with renal disease who have renal transplantation either before or after the revascularization procedure. Diabetes mellitus was a highly prevalent condition among these patients, and cardiac disease was their most common mode of death. PTCA and CABG, as performed at this institution, posed little risk for renal allograft loss. Modification of risk factors for coronary atherosclerosis, rigorous cardiac evaluation of patients at risk for coronary artery disease before renal transplantation, and aggressive use of revascularization procedures to decrease the incidence of myocardial infarction are proposed as ways to prolong the survival of renal transplant patients with ischemic heart disease.     

Analysis of Donor Risk in Living-Donor Hepatectomy: The Impact of Resection Type on Clinical Outcome

The progressive shortage of liver donors has mandated investigation of living-donor transplantation (LDT). Concerns about increasing risk to the donor are evident, but the impact of the degree of parenchymal loss has not been quantified. We analyzed clinical and biological variables in 45 LDT performed by our team over 2years to assess risks faced in adult LDT. All donors are alive and well with complete follow-up through to February 2001. When the three operations were compared, right hepatectomy (RH) was significantly longer in terms of anesthesia time and blood loss compared with left hepatectomy (LH) and left lobectomy (LL). Donor remnant liver was significantly reduced after RH compared with LH and LL. There were significant functional differences as a consequence of the remnant size, measured by an increase in peak prothrombin time after RH. RH for adults represents a markedly different insult from pediatric donations in terms of parenchymal loss and early functional impairment. Left hepatectomy donation offers modest advantage over right lobes but seems to confer substantial technical risk for a small gain in graft size. Unless novel strategies are developed to enhance liver function of the LH graft in the adult recipient, right lobe donation will be necessary for adult LDT.