Cytomegalovirus infection in the first year after pediatric kidney transplantation

Cytomegalovirus is common in adult recipients (prevalence of 40–90%). Children are typically seronegative but immunosuppression may prone to primary-infection or viral reactivation, with potentially severe consequences. CMV infection incidence in pediatric kidney transplant recipients has seldom been investigated. The aim of our study was to evaluate the incidence and timing of CMV infection during the first year after renal transplantation. We assembled a retrospective cohort of 136 children who had received a kidney transplant between 2003 and 2014 with a year follow-up. The patients were classified regarding CMV infection as high risk (D+/R?), intermediate risk (R+) or low risk (D?/R?). CMV infection was defined by the viral replication remaining asymptomatic whereas CMV disease concerned viral replication with clinical and/or biological symptoms. Oral valganciclovir was used as prophylaxis for high-risk recipients. A total of 38 patients (27.9%) developed CMV infection, 13 (40.6%) of the 32 D+/R?, 24 (45.3%) of the 53 R+ and 1 (2.0%) of the 51 D?/R?. Of these 38 infected patients, 10 developed tissue-invasive disease. During the first year after kidney transplantation, 27.9% of recipients developed CMV infection. This study confirms the influence of donor and recipient CMV status on infection propensity and highlights the importance of adequate follow-up for intermediate risk patients.     

Limited utility of endomyocardial biopsy in the first year after heart transplantation

BACKGROUND: Surveillance endomyocardial biopsies (EMBs) are used for the early diagnosis of acute cardiac allograft rejection. Protocols became standardized in an earlier era and their utility with contemporary immunosuppression has not been investigated. METHODS: We studied 258 patients after orthotopic heart transplantation comparing 135 patients immunosuppressed by mycophenolate mofetil (MMF) with 123 patients treated by azathioprine (AZA); both with cyclosporine and corticosteroids after induction therapy with rabbit antithymocyte globulin. Fifteen EMBs were scheduled in the first year. Additional EMBs were performed for suspected rejection, after treatment, or for inadequate samples. The MMF group had 1875 EMBs vs. 1854 in the AZA group. RESULTS: The yield of International Society for Heart and Lung Transplantation (ISHLT) grade> or =3A biopsy-proven acute rejection (BPAR) was 1.87% per biopsy (35 of 1875) with MMF vs. 3.13% (58 of 1854) with AZA P=0.024. The number of clinically silent BPAR ISHLT grade > or =3A (the true yield of surveillance EMBs) was 1.39% (26 of 1875) of biopsies MMF vs. 2.1% (39 of 1854) AZA, P=0.48. There were five serious complications requiring intervention or causing long-term sequelae; 0.13% (5 of 3729) per biopsy and 1.94% (5 of 258) per patient. The incidence of all definite and potential complications was 1.42% (53 of 3729) per biopsy and 20.5% (53 of 258) per patient. There was no biopsy-related mortality. CONCLUSION: The yield of BPAR was low in the AZA group and very low in the MMF group. The incidence of complications was also low, but repeated biopsies led to a higher rate per patient. Routine surveillance EMBs and the frequency of such biopsies should be reevaluated in the light of their low yield with current immunosuppression.     

Evolution of right cardiac pressures during the first year after heart transplantation

INTRODUCTION: Preoperative pulmonary hypertension is an adverse prognostic factor for early morbidity-mortality after heart transplantation (HT). The persistence of hypertension is likewise associated with a poorer patient prognosis. The present study investigated the evolution of right cardiac pressures in the first year after HT with respect to the background cardiac disease. METHODS: This study of 60 consecutive patients subjected to HT analyzed the baseline clinical characteristics and mean right atrial and right ventricle systolic and diastolic pressures in a pre-HT study and during biopsies performed in the first 2 weeks as well as at 1, 3, 6, 9, and 12 months after transplantation. The study excluded retransplantations, heart and lung transplantations, and pediatric patients, as well as patients not subjected to biopsy because of early mortality. RESULTS: The mean patient age was 50 years (83% males); 31.7% were diabetics, and 33% showed hypertension. The background heart disease was of ischemic origin in 35% of cases, and consisted of dilated myocardiopathy in 33%, with a mean left ventricle ejection fraction (LVEF) of 23% and a mean pulmonary artery systolic pressure of 50.1 mm Hg. During the postoperative course, an important decrease versus baseline was observed in right heart pressures as soon as 2 weeks post-HT, with a drop in right ventricle (RV) systolic pressure from 50.3 +/- 13.7 to 42.5 +/- 10.4 mm Hg (P = .013), and a drop in RV diastolic pressure from 17.4 +/- 5.8 to 14.2 +/- 4.1 mm Hg (P = .007). This decreased tendency continued to a more moderate extent to the third month, after which the pressures stabilized. The same behavior was observed in patients with diseases of ischemic origin and in those with dilated myocardiopathy. CONCLUSIONS: In our series, right cardiac pressures showed an important decrease in the first days after HT, with stabilization by the third month--though without returning to normal values and without modifications in the first year after transplantation. No differences in this evolutive trend were seen according to the type of background heart disease.     

Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study

BACKGROUND: Transplant coronary artery disease (TxCAD) is a major cause of long-term mortality after heart transplantation. Although vascular remodeling has been implicated in the pathophysiology of TxCAD, its determinants remain unknown. METHODS: Twenty-nine consecutive heart-transplant recipients prospectively received intravascular ultrasound (IVUS) of the left-anterior descending artery 1 and 12 months after transplant, with volumetric reconstruction of the proximal 30 mm. RESULTS: Overall, patients exhibited intimal volume increase (+83%, P<0.001), wheras vessel volume remained largely unchanged (+4%, P=0.270); consequently, overall lumen volume decreased (-6%, P=0.058). Among the clinical and laboratory variables, cytomegalovirus (CMV) infection requiring treatment (occurring in 12 patients), as assessed by pp65 antigenemia, was independently associated with the impaired ability of the vessel wall to enlarge in response to intimal volume increase, ultimately resulting in lumen loss (OR [95% CI]=0.098 [0.010-0.920]; P=0.042). However, adequate vessel response to intimal hyperplasia with consequent lumen preservation was observed in the remaining 17 patients who did not present CMV infection requiring treatment. CONCLUSIONS: The present study demonstrates that either adequate or inadequate coronary remodeling may occur during the first year after transplantation. Moreover, for the first time, it strongly suggests that remodeling modalities may be negatively influenced by the occurrence of clinically relevant CMV infection. Randomized prospective trials are warranted to investigate whether aggressive treatment of CMV infection may help prevent TxCAD.     

How many endomyocardial biopsies are necessary in the first year after heart transplantation?

Since 1989, the immunosuppressive regimen used in all heart transplant (HTx) patients at our center has consisted of a combination of cyclosporin, azathioprine, and prednisone. No prophylactic cytolytic agents have been given. One hundred consecutive patients were followed for periods of 4–56 months (mean 27 months). The incidence of rejection was so low in the initial 18 patients that we felt confident about reducing the number of routine endomyocardial biopsies (EMBs) that were performed. The mean number of EMBs in this subgroup was 10 (median 11). In the next 20 patients, EMB was performed routinely on only three occasions during the 1st post-transplant year (at 2, 4, and 8 weeks). In the subsequent 62 patients, EMB was performed on post-transplant days 10, 20, 30, and 60. Further EMBs were performed after acute rejection episodes had been treated. No noninvasive methods of diagnosing rejection were employed. In 82 consecutive patients, therefore, the mean number of EMBs within the 1st year was five per patient (median four), with 58% undergoing fewer than five EMBs and 25% requiring more than five EMBs. In the entire group of 100 patients, the mean number of EMBs was 5.9. The incidence of acute rejection requiring increased therapy was 24%. Only 7% required i.v. steroids, two of whom (2%) also required ALG and/or OKT3, with 17% requiring increased oral immunosuppression alone. Actuarial survival was 98% at 30 days, 94% at 1 year, and 92% at 2 years. It is possible that we may have missed acute rejection episodes that resolved spontaneously. However, the excellent mediumterm results would suggest that any such rejection episode did not progress to become hemodynamically significant. It may be, therefore, that when an effective immunosuppressive regimen is utilized, the number of EMBs performed at many centers is excessive.     

Changes in weight during the first year after kidney transplantation

CONTEXT: Obesity frequently occurs following kidney transplantation and is of concern because of the associated risk for cardiovascular complications. OBJECTIVE: To examine weight gain over the first year after kidney transplantation to determine associations with gender, ethnicity, and cardiovascular risk factors. DESIGN: A retrospective analysis was completed on patients who had received transplants between January 1998 and January 2002 and who had matching baseline and 1-year follow-up data and a functional graft. PARTICIPANTS: The sample consisted of 171 recipients (33% women, 58% African Americans, and 39% whites) with a mean age of 44 +/- 12.2 years. MAIN OUTCOME MEASURES: Outcome measures included fasting blood sugar, triglycerides, creatinine levels, and body mass index categorized as normal, overweight, or obese. RESULTS: The total group showed a significant increase in mean weight (6.2 +/- 10.7 kg) and body mass index (2.1 +/- 3.8). Although equivalent at baseline, by 1 year after transplantation there were significantly more obese than normal-weight recipients, regardless of gender or ethnicity, with African Americans increasing more than whites and women more than men. At baseline, those characterized as obese versus normal weight were older (47 vs. 41 years; P < .05), with a higher fasting blood sugar. At 1 year, differences in age and fasting blood sugar disappeared; however, the obese group had higher triglycerides (235 vs. 165, P = .01). CONCLUSIONS: Weight gain after transplantation was not explained by demographic and clinical factors. We speculate additional variables such as genetic factors influence weight gain and warrant study.     

Timing of heart transplantation after a recent pulmonary embolism.

In patients with heart failure, the complication of pulmonary embolism often delays listing for heart transplantation by several weeks. We report a patient, previously palliated with a Fontan operation for a complex single ventricle, who underwent heart transplantation soon after successful thrombolytic therapy due to a large pulmonary embolus.     

Non-Hodgkin's lymphoma after kidney or heart transplantation: frequency of occurrence during the first posttransplant year

Abstract The incidence of non-Hodgkin's lymphoma was analysed in over 70000 kidney transplant recipients and over 10000 heart, heart-lung or lung transplant recipients. An increased incidence of lymphomas during the first posttransplant year was observed in cadaver kidney recipients as compared to related kidney recipients, in thoracic organ recipients as compared to kidney recipients, in heart-lung recipients as compared to heart or lung recipients, in patients transplanted in North America as compared to patients transplanted in Europe, in patients receiving cyclosporine in combination with azathioprine as compared to patients with other immunosuppressive regimens, and in patients receiving ATG/ALG or monoclonal OKT3 for rejection prophylaxis.     

Twenty-four year single-center experience of hepatitis B virus infection in heart transplantation

Objective

Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. We have reported the outcome of (1) recipients with hepatitis B surface antigen (HBsAg)-positive; HBsAg-negative recipients who receive donor hearts from HBsAg-positive donors; and treatment with lamivudine of hepatitis B flare-ups after heart transplantation, using case numbers that range from 100 to 200.

Methods

From July 1987 to May 2011, all 412 orthotopic heart transplant recipients and donors underwent routine preoperative screening for hepatitis B virus markers and liver function parameters. Lamivudine was prescribed prophylactically for recipients with elevated serum enzyme levels or an HBV DNA virus load before transplantation, or when there was evidence of hepatitis B flare-up after transplantation. Postoperative HBV markers and liver function parameters were collected over a mean follow-up time of 7.8 years.

Results

Thirty-four recipients were HBsAg-positive before heart transplantation, and 23 experiencing HBV reactivation upon follow-up requiring lamivudine treatment. Clinical responses were achieved in all of them: 15 were complete and two, slow partial responses. Twenty-six recipients with an HBV naïve status at the time of heart transplantation, and three patients received donor hearts from an HBsAg-positive donor under perioperative hepatitis B immunoglobulin prophylaxis. HBV infection was successfully prevented in two patients, but the other one contracted HBV hepatitis, which was successfully treated with lamivudine.

Conclusions

HBV reactivation after the heart transplantation was common but usually well controlled with lamivudine treatment. Although posttransplantation liver function deteriorated for a period, there was no HBV infection-related morbidity or mortality. Perioperative hepatitis B immunoglobulin prophylaxis can successfully prevent HBV naïve recipients from infection in some cases, but HBsAg-positive donors should only be considered in high risk situations.     

Causes of renal allotransplant loss during first year after renal transplantation

The causes of the renal allotransplant (RAT) removal during first year after the kidney transplantation performance were studied. Of 270 renal allotransplantations performed in 56 (20.5%) of recipients the transplant was removed during first year after the operation. In 36 (64.3%) of patients transplantnephrectomy was performed for immune conflict presented, in 12 (21.4%) of observations purulent-septic complications have become the cause of RAT removal and in 8 (14.3%)--the vascular causes (thrombosis of RAT artery, vein).     

肾移植术后院内尿路感染的细菌学分析

目的：探讨肾移植术后院内发生尿路感染(UTI)的细菌学分布。方法：将148例肾移植患者分早期组和近期组,分析其UTI的细菌学分布情况。结果：早期组76例中发生UTI30例。分离出真菌16株,肠杆菌科菌14株,粪肠球菌4株,其他菌11株,其中多重耐药菌9株;并发严重毒血症4例。近期组72例中发生UTI16例,分离出真菌4株。肠杆菌科菌9株,粪肠球菌5株,其他菌4株;其中多重耐药菌株共同10株;并发严重毒血症7例。结论：大肠杆菌、粪肠球菌是肾移植术后院内发生UTI的主要病原菌;多重耐药菌株感染、严重毒血症及支原体感染。增加了肾移植的近期风险。     

Impact of cytomegalovirus infection,year of transplantation,and donor age on outcomes after liver transplantation for hepatitis C

Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is almost universal. However, variables that hasten the progression of allograft injury have not been fully defined. Cytomegalovirus (CMV) is a common infection post-LT, and its impact on the course of post-LT HCV infection remains unclear. We investigated the impact of CMV infection on patient and graft outcomes in 93 consecutive HCV-infected liver transplant recipients. Data were collected prospectively, with surveillance cultures for CMV and protocol liver biopsies. CMV infection (defined as isolation of CMV from blood and treatment with ganciclovir) occurred in 25 patients (26.9%). Graft failure (defined as cirrhosis, relisting for LT, re-LT, or death) was significantly more common in CMV-positive compared with CMV-negative patients (52% v 19.1%; P = .002). Fibrosis stage 2 or greater on the 4-month liver biopsy specimen was more common in CMV-infected patients (45% v 16.4%; P = .01). Patients who underwent LT in more recent years had an increased risk for graft failure. Donor and recipient age, CMV infection, and mycophenolate mofetil use were significantly associated with graft failure in a stepwise multivariate analysis. CMV infection occurs in approximately one quarter of HCV-infected liver transplant recipients and is an independent risk factor for graft failure in these patients. Whether CMV mediates this by inducing increased immunosuppression or directly enhancing HCV replication requires further study. (Liver Transpl 2002;8:362-369.)     

Short- and long-term impact of neutropenia within the first year after kidney transplantation

The aim of this retrospective single-center study was to investigate the short- and long-term impact of neutropenia occurring within the first year after kidney transplantation, with a special emphasis on different neutropenia grades. In this unselected cohort, 225/721 patients (31%) developed 357 neutropenic episodes within the first year post-transplant. Based on the nadir neutrophil count, patients were grouped as neutropenia grade 2 (<1.5–1.0*10⁹/l; n = 105), grade 3 (<1.0–0.5*10⁹/l; n = 65), and grade 4 (<0.5*10⁹/l; n = 55). Most neutropenia episodes were presumably drug-related (71%) and managed by reduction/discontinuation of potentially responsible drugs (mycophenolic acid [MPA] 51%, valganciclovir 25%, trimethoprim/sulfamethoxazole 19%). Steroids were added/increased as replacement for reduced/discontinued MPA. Granulocyte colony-stimulating factor was only used in 2/357 neutropenia episodes (0.6%). One-year incidence of (sub)clinical rejection, one-year mortality, and long-term patient and graft survival were not different among patients without neutropenia and neutropenia grade 2/3/4. However, the incidence of infections was about 3-times higher during neutropenia grade 3 and 4, but not increased during grade 2. In conclusion, neutropenia within the first year after kidney transplantation represents no increased risk for rejection and has no negative impact on long-term patient and graft survival. Adding/increasing steroids as replacement for reduced/discontinued MPA might supplement management of neutropenia.     

一例原位心脏移植术后一年随访报告

１例终末期扩张型心产现患者施行原位心脏移植手术，至今存活已逾１年，其生活质量十分良好。本文详细介绍与讨论患者术后一年期间的免疫抑制治疗及排以应的监测。术后第２、１６周增出现过２次急性排斥反应，均用甲基泼尼松龙冲击治疗告愈。