Comparison of Neoral and Sandimmun for induction and maintenance immunosuppression after kidney transplantation

We compared the mean trough level/dose (L/D) ratio, mean coefficient of variation (CV) of individual patients, and graft, patient, and rejection-free survival rates of 40 renal transplant recipients receiving Neoral (CyE) with 103 consecutive renal transplant recipients receiving Sandimmun (CyA). The mean L/D ratio on the 3rd post-transplant day (16.2 vs 11.8, P < 0.04), in the 1st week (24.6 vs 16.1; P < 0.03), and 1st month (39.1 vs 28.7; P < 0.05) were higher in the CyE group. In both groups the L/D ratio improved in proportion to the duration of time post-transplant and reached a maximum in the 3rd post-transplant month. In the early post-transplant period in particular, the number of patients achieving target levels was significantly higher, and the mean dose needed to achieve target levels lower, in the CyE group. The variation in trough levels, demonstrated by the CV, was lower in the CyE group (0.41 ± 0.14) than in the CyA group (0.62 ± 0.21; P < 0.005). Actuarial 1-year patient and graft survival rates in the CyE group were 100 % and 96 %, respectively; these were similar to the 100 % and 95 % in the CyA group. The 1-year rejection-free survival rate in the CyE group was 61 % compared to 43 % in the CyA group (P < 0.02). We conclude that it is possible to obtain higher blood trough levels at lower doses by administering CyE, particularly in the early post-transplant period. The lower variability of trough levels and the higher L/D ratio in the CyE group, which are related to improved bioavailability of CyE, may explain the lower rejection rate among these patients. In this study, the microemulsion formulation of cyclosporin (CyE) was found to be more beneficial and cost-effective as induction and maintenance immunosuppression than the conventional formulation (CyA). Received: 28 January 1997 Received after revision: 13 May 1997 Accepted: 15 May 1997     

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups. Received: 14 April 1998 Received after revision: 24 September 1998 Accepted: 18 December 1998     

Rescue allocation and recipient oriented extended allocation in kidney transplantation—influence of the EUROTRANSPLANT allocation system on recipient selection and graft survival for initially nonaccepted organs

Nonaccepted kidneys grafts enter the rescue allocation (RA) process to avoid discards. In December 2013, recipient oriented extended allocation (REAL) was introduced to improve transparency. The aim of this study was to evaluate the influence of REAL on recipients′ selection and graft function compared to the formerly existing RA as well as to identify factors that influence graft outcome. Therefore, a multicenter study of 10 transplant centers in the same region in Germany was performed. All transplantations after RA or REAL from December 1, 2012, until December 31, 2014, with a follow‐up time until December 31, 2015 were analyzed. 113 of 941 kidney transplantations were performed after RA or REAL (12%). With REAL, the number of refusals before transplantation had increased (12 ± 7.1 vs. 8.6 ± 8.6, P = 0.036), and cold ischemia time has decreased (13.6 ± 3.6 vs. 17.2 ± 4.8 h, P = 0.019). Recipients after REAL needed significantly more allocation points compared to RA to receive a kidney. One‐year graft survival was comparable. If kidneys from the same donor were transplanted to two recipients at one center, the greater the difference in recipient age, the greater the difference in serum creatinine after 12 months (‐0.019 mg/dl per year, P = 0.011) was, that is older recipients showed lower creatinine. REAL influences selection of the recipients compared to the former RA era for successful organ receipt. Graft function is comparable and seems to be influenced by recipient age.     

Immediate and long-term results of ATG induction therapy for delayed graft function compared to conventional therapy for immediate graft function

The use of polyclonal antibodies for delayed graft function (DGF) was tested in 83 renal allograft recipients. Conventional immunosuppression (CI) was given to 52 patients with immediate graft function (IGF) while 31 patients with DGF received the polyclonal antibody ATG. Administration of OKT3 was restricted to steroid-resistant acute rejections in both groups. The incidence and severity of acute rejections, graft survival rate, CMV infections, and lymphocyte subsets were examined. ATG patients experienced a total of 0.6 acute rejections per patient, whereas CI patients had 0.9 on the average (P < 0.05). Second and third acute rejections occurred less frequently and later in the ATG group than in the CI group (P < 0.01). Steroid-resistant acute rejections occurred in 20 of the CI patients (38 %) but in only 7 of ATG patients (23 %). One-year graft survival in the CI and ATG groups was 98.1 % and 93.2 %, respectively. A decreased CD4 + to CD8 + T-lymphocyte ratio of about 0.5 was still detectable 5 years after the initial ATG administration. Hence, patients with DGF appear to benefit from induction therapy with ATG. Received: 3 March 1998 Received after revision: 20 July 1998 Accepted: 23 September 1998     

Comparison of blood group versus HLA-dependent transplantation and its influence on donor kidney survival.

BACKGROUND: The advantages of organ allocation based on human leukocyte antigen (HLA) typing are controversial. This evaluation compares the results of HLA-dependent and non-HLA-dependent allocation in the transplantation of donor kidneys. METHODS: Seventy-seven donor kidney pairs explanted locally between 1984 and 1994 were examined. One half of each pair was transplanted locally in Bonn on the basis of criteria including blood group, waiting time and currently negative cross-match. The other half of these pairs was allocated in accordance with the Eurotransplant (ET) criteria. RESULTS: Cold ischaemia time was an average of 14.02 h in Bonn vs. 24.18 h in the ET group (P<0.0001). The number of HLA mismatches was calculated and, for example, for locus A it was 1.13 in Bonn vs. 0.73 in the ET group (P=0.0003). One-year graft survival for the locally transplanted kidneys was 92.2% and, for the ET kidneys, 90.9%. Five-year survival was 79.5% vs. 81.7%, respectively. Patient survival after 1 year was 100% vs. 97.4%, and after 5 years, 93.4% vs. 93.1%. CONCLUSION: The results show that it is possible to provide patients with a locally allocated kidney graft that enables good function after a short waiting period. This procedure avoids long cold ischaemia time and long waiting periods.     

A randomized trial comparing losartan with amlodipine as initial therapy for hypertension in the early post-transplant period.

BACKGROUND: Blockade of the renin-angiotensin-aldosterone system in the early post-transplant period remains controversial. Angiotensin II-receptor blockers (ARB) have many benefits to the patient with chronic kidney disease and these benefits may also apply to the renal transplant recipient (RTR). Additionally, there are theoretical benefits of ARB use in RTR. This study was designed to investigate the safety of early ARB use after renal transplantation. METHODS: RTR with serum creatinine levels <3.0 mg/dl were randomized to receive either ARB (n = 29) or calcium-channel blocker (CCB; n = 27) as initial therapy for post-transplant hypertension. Differences in potassium, creatinine and haemoglobin concentrations were compared at baseline, 3, 6 and 12 months after transplantation. RESULTS: Withdrawal from the assigned treatment was high: 12 in the ARB group (due to hyperkalaemia in six) and 17 in the CCB group (due to intractable oedema in seven and post-transplant erythrocytosis requiring an angiotensin-converting enzyme inhibitor in seven). There were no differences in blood pressure, haemoglobin or creatinine concentration at any time-points. Mean potassium concentrations were only slightly higher in the ARB vs CCB group (range: 4.2-4.3 vs 3.7-3.8 mEq/l, respectively, but clinically significant) and the number of patients with potassium values >6.0 mEq/l was higher in ARB (n = 7) vs CCB (n = 1). CONCLUSIONS: These data suggest that hyperkalaemia is the major complication that occurs with the use of ARB in the immediate post-transplant period. ARB use does not affect renal function or complicate the post-transplant management of RTR. Other than reducing the incidence of post-transplant erythrocytosis, ARB use does not cause an excess incidence of anaemia. Strategies to reduce the risk of hyperkalaemia may allow increased use of ARB immediately after kidney transplantation.     

Impact of early cyclosporin average blood concentration on early kidney transplant failure

This retrospective study served to examine the correlation between the degree of cyclosporin (CyA) exposure, as estimated by a single pharmacokinetic (PK) profile performed at 1 week post-transplant, and the outcome of 290 consecutive renal transplants performed over a 6-year period. For this retrospective analysis patients were stratified into four historical groups based on 12- versus 24-h PK studies and on the use of radioimmunoassay versus fluorescence polarization immunoassay methods for estimates of CyA concentrations. Four PK measures – trough concentration (C₀), average concentration values (C_av; i. e., the dosing interval-corrected area under the concentration-time curve), maximum concentration (C_max), and time to maximum concentration (t_max) – were examined as predictors of patient, graft, and rejection-free survival rates for each of the four groups individually and for all groups combined. Patients with an initial C_av≥ 550 ng/ml had higher 1-year (88 %) and 6-year (66 %) graft survival rates than patients with C_av < 550 ng/ml, who had 1- and 6-year graft survival rates of 80 % and 59 %, respectively (P = NS). Statistically significant differences were observed in graft survival rates between patients with C_av < 550 versus C_av≥ 550 ng/ml at 30 (88 % vs 96 %; P < 0.02), 60 (85 % vs 94 %; P < 0.007), 90 (85 % vs 94 %; P < 0.02), and 180 (83 % vs 92 %; P < 0.05) days. Moreover, patients with C_av < 550 ng/ml displayed more severe rejection episodes, as judged by Banff classification, than patients who displayed C_av≥ 550 ng/ml (grades II and III; 71 % vs 50 %; P = 0.036). In contrast, the C₀, C_max, and t_max values did not correlate with patient, graft, or rejection-free survival rates. The pharmacokinetic parameter of C_av correlated strongly with early graft survival and may, therefore, be a useful predictor of those renal transplant patients who may require more intensive post-transplant monitoring of CyA concentrations by serial PK studies to improve graft survival. Received: 27 May 1997 Received after revision: 8 August 1997 Accepted: 21 August 1997     

Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early graft function in liver transplantation

Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks coagulating activity. The aim of this study was to determine if the presence of DCP in the donor could be used as a marker of post-transplant graft function. We collected data and serum samples on 90 organ donors. DCP level was correlated with donor-specific factors and with graft function intraoperatively and in the early post-transplant period. Twenty-seven donors (30.0 %) had positive DCP levels before harvesting. Although recipients were similar in demographics, preoperative liver function, and primary disease distribution, patients transplanted with livers from DCP-positive donors needed significantly more intraoperative transfusion. Furthermore, donor DCP positivity was identified as a preoperative risk factor for poor early graft function based on multivariate analysis (odds ratio = 6.58, P = 0.0032). Our findings suggest that DCP is another valuable marker for evaluating the quality of donor livers. Received: 30 June 1997 Received after revision: 14 October 1997 Accepted: 19 November 1997     

Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation

A nested polymerase chain reaction (nPCR) for Epstein-Barr virus (EBV) DNA, RNA in situ hybridization (EBER-ISH), and immunostaining against the ZEBRA EBV protein for diagnosis of EBV hepatitis were performed on 43 liver biopsy specimens obtained from 18 patients in the 1st year after liver transplantation (LTX). The findings were related to liver histology and results of EBV-nPCR on concomitantly obtained serum samples. EBV DNA was detected in 30 % and RNA in 34 % of the liver biopsy specimens using nPCR and EBER-ISH, respectively, giving a significant correlation between the two methods (P = 0.003). All but one patient had detectable EBV DNA in serum samples obtained within 1 month of the biopsy. More than 90 % of the nPCR and EBER-ISH-positive biopsy specimens were obtained 3 months or less post-LTX. There was no significant difference in EBV genome findings in biopsy specimens with or without lymphocytic-immunoblastic infiltrates, either in nPCR (P = 0.73) or in ISH (P = 0.73). Two of three biopsy specimens with these histological changes suggesting a viral genesis were positive in EBV-nPCR but negative in ISH. Histopathological changes in EBV hepatitis may be nonspecific and masked by other complications. The use of EBV-nPCR and EBER-ISH in liver graft biopsy specimens of heavily immunosuppressed patients may give an early indication of EBV-related disease and can be used to guide therapeutic intervention. Received: 5 January 1998 Received after revision: 21 April 1998 Accepted: 20 May 1998     

Cytomegalovirus pneumonitis after kidney transplantation is not caused by plugging of cytomegalic endothelial cells only

In addition to life-threatening pneumonia, cytomegalovirus (CMV) may also cause subclinical pulmonary dysfunction after kidney transplantation. To investigate the role of plugging of cytomegalic endothelial cells in the pulmonary capillary bed, we prospectively determined specific carbon monoxide diffusion capacity (KCOc) and its components: the pulmonary diffusing membrane factor (Dm) and pulmonary capillary blood volume (Vcap) before and during CMV infection in 13 kidney transplant recipients and 13 controls. During CMV infection, mean KCOc decreased significantly by 28 % of the initial value (mean KCOc 79 vs 109; P < 0.005 ) due to a decrease in both Vcap and Dm. The KCOc in controls showed a significantly smaller decrease due to a slightly lower Vcap. We conclude that kidney transplant recipients with CMV infection have significant pulmonary diffusion disturbances due to a combination of lower Vcap and lower Dm. The most likely explanation for this phenomenon is a local inflammatory process due to CMV and not plugging of cytomegalic endothelial cells only. Received: 25 February 1998 Received after revision: 26 June 1998 Accepted: 22 September 1998     

Primary liver disease as a determinant for acute rejection after liver transplantation

Background: Graft rejection and infection remain major problems following liver transplantation; both are heavily influenced by the immunosuppressive regimen. Despite the disparity in the primary disease leading to transplantation, all patients receive the same post-transplant immunosuppressive treatment in a given center. The aim of this study is to detect a possible effect of the underlying disease on the incidence of early acute rejection episodes after orthotopic liver transplantation (OLT). Patients and Methods: Retrospective analysis on all 101 consecutive liver transplants performed in 95 patients between 1983 and March 1998; five of these patients, surviving less than 30 days, were not included. The immunosuppressive regimen was based on conventional triple therapy during the whole study period. The diagnosis and treatment of acute rejection within the first 30 days post-OLT was uniform throughout the whole study period. Results: Though there were no differences with respect to patients' characteristics [age, child classification, number of HLA-mismatches or cytomegalovirus (CMV)-serocompatibility], patients with primary biliary cirrhosis (PBC) showed a significant increase of acute rejection after OLT compared with the other patients transplanted for other liver diseases (P = 0.024). The incidence of infection was not elevated in patients transplanted for PBC when compared with other diagnoses. Conclusion: Our results indicate that primary liver disease may be a determinant for acute graft rejection in PBC. Furthermore, these results suggest that immunosuppressive regimens based on the underlying disease should be considered. Received: 19 October 1998 Accepted: 28 January 1999     

HLA Points Assigned in Cadaveric Kidney Allocation Should Be Revisited: An Analysis of HLA Class II Molecularly Typed Patients and Donors

The points now assigned for the quality of HLA match have received significant scrutiny to be modified in an effort to help reduce disparity in access to kidneys of minority groups, and since differences in graft survival between groups of patients in each of the HLA matched groups is less now than in the past. We analyzed long-term (5-year) graft survival in 746 DR DNA typed recipients of cadaveric kidneys transplanted from 1994-2001 whose donors were also DR DNA typed, with allocation based on those DNA-based typings. Five-year graft survival was not significantly different for recipient groups irrespective of if they had zero (84%), one (92%), two (89%), or three to four B, DR mismatches (79%) (log-rank = 0.15; died with a functioning graft [DWFG] censored). Mismatching of three and four DR and DQ antigens in black but not white patients was associated with significantly worse survival (Relative Risk = 2.9) (p = 0.002). The incidence of minority transplants in the well-matched group (zero and one B, DR mismatch), 12.8% (20/156) was over half that of the less well-matched group, 27.1% (160/590) (p < 0.001). Our data indicate that the current HLA-B, DR-based point system used to allocate kidneys warrants re-evaluation. Our data, taken in the context of the UNOS data, which has recently been re-evaluated, suggest that the only HLA-DR remain as a component of the national kidney allocation algorithm so as to increase access of kidneys to minorities and minimize graft loss.     

Late onset cytomegalovirus disease in liver transplant recipients: de novo reactivation in recurrent hepatitis C virus hepatitis

Late onset cytomegalovirus (CMV) disease (occurring more than 1 year post-transplant] was documented in two liver transplant recipients with recurrent hepatitis C virus hepatitis in the absence of factors known to precipitate CMV disease, i. e., primary acquisition of CMV, allograft rejection, augmented immunosuppression, concomitant infections, or blood transfusions. Both patients had CMV enteritis (with CMV adrenalitis in one case]; however, other symptoms and signs of overt CMV infection, i. e., fever, leukopenia, or atypical lymphocytes, were lacking. Hepatitis C virus is an immunomodulatory virus; impaired CMV-specific T-cell responses may have accounted for the predisposition of our patients to unprovoked, late onset CMV disease. Given the high incidence of hepatitis C virus recurrence after liver transplantation, awareness of the occurrence and recognition of the unusual presentation of CMV disease in this setting is both clinically relevant and significant, particularly since CMV is treatable if recognized promptly. Received: 25 September 1997 Received after revision: 27 January 1998 Accepted: 2 March 1998     

The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation

BACKGROUND: Mycophenolate mofetil (MMF) has proven to be a very effective drug for the prevention of acute rejection following renal transplantation when dosed as prescribed at 2 or 3 g/d. However, circumstances arise in clinical transplantation where the dose must be lowered, either to avoid drug toxicity or because of concurrent infection. The impact on the incidence of acute rejection and graft survival when the MMF dose must be lowered has not previously been investigated. METHODS: In this study, a cohort of 721 kidney transplant recipients who received immunosuppression using MMF in conjunction with cyclosporine and prednisone and OKT3 (n = 425) or Simulect (n = 296) induction were evaluated. Clinical outcomes were compared and contrasted between patients with and without MMF dose changes within the first year post-transplantation. RESULTS: The majority of patients (70.3%, n = 507) had at least one dose change within the first post-transplant year. Compared with the 214 patients who did not have a dose change, these patients had a much higher incidence of acute rejection within the first post-transplant year (23.3% vs. 3.7%, p < 0.001). This resulted in a significantly decreased 3-yr death-censored graft survival (76.3% vs. 88.3%, p = 0.003). The incidence of acute rejection for patients who had a dose change was highest if the dose change occurred within the first post-transplant month (34.4%). The incidence of acute rejection for the dose change patients was influenced by recipient ethnicity (African-American vs. Caucasian) and the type of induction agent used (OKT3 vs. Simulect). CONCLUSION: Altering the dose of MMF within the first post-transplant year correlated with a significantly worse clinical outcome in this cohort of renal transplant recipients. These data suggest that avoidance of MMF dose changes within the first year after renal transplantation would result in improved graft survival.     

Long-term results of living kidney transplantation from HLA-identical sibling donors under calcineurin inhibitor immunosuppression

BACKGROUND: Recently, it has been revealed that alloantigen-independent causes are important factors for late graft loss in kidney transplantation. We compared the results of living kidney transplantation from HLA-identical siblings with those from HLA-non-identical siblings to analyse the impact of alloantigen-independent factors on long-term graft survival. METHODS: Two hundred and sixty-six recipients who were grafted from their siblings between 1983 and 2002 were subdivided into those transplanted from HLA-identical donors (n=86) and those from HLA-non-identical donors (n=180). RESULTS: The incidence of acute rejection was significantly lower in the HLA-identical group than in the HLA-non-identical group (9.3% vs 53.9%, respectively; P<0.0001). Graft survival was significantly higher in the HLA-identical group than in the HLA-non-identical group (91.3% vs 79.2% at 5 years, 80.3% vs 66.8% at 10 years and 59.1% vs 51.7% at 15 years, respectively; P=0.0372). Although acute rejection was not seen as a cause of graft loss in the HLA-identical group, death with functioning graft, recurrence of the original disease or chronic allograft nephropathy were observed as the major causes of graft loss in the late period of the HLA-identical group. CONCLUSION: We concluded that alloantigen-independent causes constitute a crucial factor for graft loss in the late period of HLA-identical kidney transplantation.     

Amino acids in rinse effluents as a predictor of graft function after transplantation of fatty livers in rats

There are too few reliable markers by which one can predict future function of a liver before implantation. Consequently, the purpose of this study was to test the hypothesis that amino acids in rinse–effluents could predict transplant outcome in marginal fatty livers from rats. Amino acids were measured in the rinse effluent from the livers immediately after harvest and graft preparation or cold storage. Amino acids in the effluent were twice as high in ethanol-treated animals compared to those in nonfatty controls. Ethanol-treated fatty livers survived for no longer than 7 days after transplantation while 83 % of nonfatty controls survived (P < 0.05). In subsequent studies, the cold-storage time was decreased to 6 h to determine whether failing fatty livers released more amino acid than grafts that would function normally. There was a significant increase in amino acids in the effluent of fatty grafts compared to controls. Moreover, the sum of the four selected amino acids (alanine, valine, histidine, leucine) was lower than 23 nmol/g liver in functional livers, whereas failing grafts had totals significantly higher than 25 nmol/g liver. The sum of the four amino acids correlated well with 24 h post-transplant serum AST levels (r = 0.78, P < 0.0001). So we can conclude that amino acid release can serve as a useful marker of graft viability and reliably predicts survival. Received: 14 August 1998 Received after revision: 10 December 1998 Accepted: 3 March 1999     

Effect of peritransplant FTY720 alone or in combination with post-transplant tacrolimus in a rat model of cardiac allotransplantation

FTY720 is a recently discovered compound that is derived from the fungus Isaria sinclairii. Using a DA donor-to-LEW recipient rat combination, we assessed the efficacy of peritransplant FTY720 alone or in combination with post-transplant tacrolimus on the survival of cardiac allografts. Peritransplant FTY720 given orally at a dose of 5 mg/kg on days –1 and 0 prolonged graft survival from 5 to 13 days (P < 0.05). Combining peritransplant FTY720 with post-transplant tacrolimus resulted in a further prolongation of allograft survival. The lymphocyte count in transplanted rats decreased within 24 h to 46.6 %. Analysis of lymphocyte subsets by FACS revealed that FTY720 affected the total population of CD3-bearing T cells while the ratio of CD4 to CD8 cells remained unchanged. Kidney and liver biochemistry remained elevated for 2 weeks. In conclusion, FTY720 is a powerful immunosuppressive agent when used as induction therapy and may have an additive effect – perhaps a synergistic one – with post-transplant tacrolimus. Received: 27 October 1997 Received after revision: 23 March 1998 Accepted: 15 April 1998     

Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: −7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m²). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.     

Urological complications following renal transplantation

A total of 1016 consecutive renal transplants performed between 1976 and 1990 were analysed retrospectively to determine the incidence of urological complìcations and possible predisposing factors. Some 189 episodes of ureteric obstruction and/or urinary leak occurred in 143 patients (overall incidence 14.1 %). The median annual rate of urinary leak was 5.1%; that of ureteric obstruction was 4.5% pre-1986 and 16.1% post-1986. Sixty-three episodes of urinary leak occurred in 54 patients from 1 day to 3 months post-transplant and 60% involved the distal ureter. Thirty were treated primarily by reconstructive surgery, ten required nephrectomy and three died of associated sepsis. A total of 126 episodes of ureteric obstruction occurred in 104 patients from 1 day to 12 years post-transplant and 86% involved the distal ureter. Prior to 1986, 10/11 patients with ureteric obstruction were treated by reconstructive surgery, but since then 88 (95%) have been treated by percutaneous nephrostomy, with or without stenting, with only one graft lost and no deaths. Children had a significantly increased incidence of ureteric obstruction (P<0.001) whilst male recipients had an increased incidence of urinary leak (P=0.04). More patients with ureteric obstruction than those without had two or more episodes of rejection (P=0.03). No single cause for the increased incidence of ureteric obstruction since 1986 has been identified. Continued attention to technical detail and further study of this trend is warranted.     

Donor left ventricular hypertrophy increases risk for early graft failure

A review of factors contributing to early mortality after cardiac transplantation revealed that up to 25 % of deaths were due to primary graft dysfunction unrelated to rejection or infection. In light of this finding, evaluation of a donor heart with regard to its suitability for transplantation takes on added importance. In an effort to screen the suitability of donor hearts in the region covered by the Northwest Organ Procurement Agency (USA), all donors are evaluated by two-dimensional transthoracic echocardiography as part of the initial evaluation. A total of 110 donor echocardiograms were reviewed and an attempt was made to correlate the 30-day outcome with the parameters measured. An unexpected finding was that the presence of left ventricular hypertrophy in the donor heart was associated with an increase in the incidence of donor heart dysfunction compared with donors with normal echocardiographic profiles (33 % vs 3 %, P = 0.007). Received: 12 February 1996 Received after resision: 27 June 1997 Accepted: 14 July 1997