Long-term impact of renal transplantation on liver fibrosis during hepatitis C virus infection

BACKGROUND & AIMS: During hepatitis C virus (HCV) infection, liver fibrosis progression after renal transplantation remains controversial. The aim of this cohort study with controls was to compare liver histopathologic features during HCV infection between renal transplant recipients and matched groups of hemodialyzed patients or controls without renal disease and untreated for HCV. METHODS: Each renal transplant recipient (group 1, n = 30) was matched at first liver biopsy (LB) using the main factors known to influence progression of fibrosis with one HCV hemodialyzed patient (group 2, n = 30) and one HCV-infected patient (nonhemodialyzed, nontransplanted; group 3, n = 30). Patients from group 1 were also matched with those of group 3 on the time between 2 consecutive LBs performed 37 months apart. LBs were evaluated according to the Knodell index, METAVIR score, and rate of fibrosis progression per year (fibrosis unit). RESULTS: The rate of fibrosis progression per year between the first and second LBs was significantly lower (P = 0.03) in group 1 (0.067; 95% confidence interval: -0.05, 0.18) than group 3 (0.20; 95% confidence interval: 0.13, 0.26). At the second LB, the Knodell index and activity or fibrosis in METAVIR were lower in group 1 than group 3 (4.2 +/- 0.4 vs. 7.5 +/- 0.6, 0.5 +/- 0.1 vs. 1.3 +/- 0.2, and 1.4 +/- 0.2 vs. 2.3 +/- 0.2 respectively, P < 0.01). CONCLUSIONS: Our study suggests that liver fibrosis progression is low in most HCV-infected renal transplant recipients with moderate liver disease at baseline.     

肾移植术后高脂血症患者碱性成纤维细胞生长因子和受体mRNA表达及辛伐他汀降脂治疗对其影响

目的研究肾脏移植术后高脂血症患者外周血单个核细胞中碱性成纤维细胞生长因子(bFGF)及其受体FGFR2 mRNA表达水平及降脂治疗后的改变。方法肾移植术血脂正常组、血脂增高组及正常对照组各30例,血脂增高组应用辛伐他汀20mg／a进行降脂治疗,于服药后1．5、3个月复查血脂,同时应用逆转录-多聚合酶链反应方法检测外周血单个核细胞碱性成纤维细胞生长因子及其受体mRNA表达。结果伴高脂血症的肾移植受者辛伐他汀降脂治疗1,5个月血脂水及外周血单个核细胞中bFGF及其受体FGFR2 mRNA显著高于血脂正常组及对照组,辛伐他汀治疗1．5个月后血脂水平及bFGF、FGFR2 mRNA表达水平显著下降,治疗3个月时进一步下降。结论伴高脂血症的肾移植受者bFGF及其受体FGFR2 mRNA表达水平上调,可能是高脂血症引起动脉硬化、慢性移植肾病的机制之一。辛伐他汀降脂治疗可使碱性成纤维细胞生长因子及其受体的表达下调。     

Stenting for superior vena cava obstruction in pediatric heart transplant recipients.

BACKGROUND: Superior vena cava (SVC) obstruction can be a complication in heart transplant recipients. We reviewed our experience with relief of SVC obstruction using endovascular stents in pediatric heart transplant recipients. METHODS: Study cohort included pediatric heart transplant recipients, followed at our institution, who required endovascular stent placement for SVC obstruction. Data retrieved retrospectively included cardiac diagnosis, age, and weight at transplant, surgical technique of transplant (bicaval vs. biatrial anastomosis), previous cardiovascular surgeries, presenting symptoms, date of SVC stent placement, and need for reintervention. RESULTS: From March 1990 to June 2006, 5.1% (7/138) pediatric heart transplant recipients who were followed at our institution had SVC obstruction requiring stent placement. Median age and weight at transplant was 9 months and 8.7 kg, respectively. Four patients previously had a cavopulmonary anastomosis. Transplant surgery involved bicaval anastomosis in 6 and biatrial in 1. Of the 7 patients included in the study, 2 were asymptomatic, 2 were symptomatic (1 with chylothorax, 1 with headache), and 3 were identified at the time of transplant surgery. Median time from transplant surgery to SVC stent placement was 2 months (0-14 months). Three patients required reintervention as redilation of SVC stent (n = 1) or additional SVC stent (n = 2). In one patient the stent migrated to the pulmonary artery but was retrieved. CONCLUSION: SVC obstruction can be an important complication following heart transplantation, especially in infants with previous cavopulmonary anastomosis, undergoing heart transplant using bicaval technique. SVC obstruction can be safely and effectively treated using endovascular stents.     

Diagnostic yield of bronchoalveolar lavage following renal transplantation

Abstract: Organ transplant recipients are at high risk of infectious pulmonary complications. In this retrospective study, the diagnostic yield of bronchoalveolar lavage (BAL) was evaluated in renal transplant recipients. The results were analysed in special regard to the clinical presentation of pulmonary infections and the possible impact of new immunosuppressive agents. Over a 5‐year period 91 BAL were performed in 71 renal transplant recipients. Microorganisms were isolated from 69% of BAL (63/91): bacteria 32%; cytomegalovirus (CMV) 27%; Pneumocystis carinii (PC) 22%; other viruses 9% (HSV; EBV, RSV, adenovirus, HHV8); Aspergillus fumigatus 1%. Total cell counts and neutrophil counts in BAL were significantly elevated in bacterial infection, whereas BAL positive for PC showed eosinophilia (P<0.05). There was no association between clinical symptoms and the radiological pattern of infiltrates and the type of infection. Immunosuppression containing tacrolimus or mycophenolate mofetil was associated with a significantly higher percentage of PC and CMV infections compared to cyclosporin‐based immunosuppression (65% vs. 30%, P<0.005). A considerable number of PC and CMV infections occurred beyond 6 months after transplantation. In conclusion, BAL has a high diagnostic yield in renal transplant recipients. Infection with CMV and PC should also be considered beyond 6 months after transplantation, and prophylaxis for opportunistic infections should be given if the immunosuppression is intensified.     

Time course of resolution of pulmonary hypertension and right ventricular remodeling after orthotopic cardiac transplantation

Most patients with severe congestive heart failure have secondary pulmonary hypertension (PHT). Elevation of pulmonary vascular resistance (PVR) to greater than 480 dynes.sec.cm-5 (6 Wood units) is currently the principle hemodynamic contraindication to orthotopic cardiac transplantation. We performed serial two-dimensional Doppler echocardiographic examinations and right heart catheterizations in 24 recipients (21 men, 14-58 years old) of orthotopic cardiac transplants to determine the time course of resolution of PHT and the concomitant remodeling of the donor right ventricle. Right and left heart filling pressures declined in parallel and reached the upper normal range at 2 weeks after the transplant procedure and remained unchanged at 1 year follow-up. Mean pulmonary arterial pressure (mm Hg) decreased from 38 +/- 9 preoperatively to 22 +/- 5 at 2 weeks and was 19 +/- 5 at 1 year after the transplantation procedure. At 1 year after surgery, PVR had decreased from 202 +/- 89 dynes.sec.cm-5 preoperatively to 99 +/- 36 dynes.sec.cm-5 (p less than .001), while cardiac output increased from 3.7 +/- 1.2 to 6.3 +/- 1.5 liters/min (p less than .001). Echocardiographic analysis showed that transplant recipients had an enlarged right ventricle on day 1 after surgery, and a volume overload contraction pattern and tricuspid regurgitation was present in the majority. This increase in right ventricular size was maintained at 1 year follow-up while the incidence of tricuspid regurgitation decreased. We conclude that there is rapid resolution of moderately elevated pulmonary arterial pressures after cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.     

Low incidence of transplant coronary artery disease in Chinese heart recipients.

OBJECTIVES: This study sought to assess the incidence of transplant coronary artery disease (CAD) in Chinese heart recipients. BACKGROUND: The prevalence of transplant CAD detected by angiography at 1, 2 and 4 years after heart transplantation was 11%, 22% and 45%, respectively. The incidence of transplant CAD in Chinese heart recipients has not been reported. METHODS: For those recipients surviving for more than 1 year after transplantation, coronary angiography was performed annually for surveillance of transplant CAD. The recipient characteristics, donor characteristics, rejection episodes, medication and human leukocyte antigen (HLA) mismatches were recorded. RESULTS: Fifty patients were included in this study. Thirteen (26%) recipients had ischemic heart disease. Two patients (4%) had active cytomegalovirus (CMV) infection after transplantation. The mean number of rejection episodes in the 1st year after transplantation was 1.15. Among 47 patients with complete data of donor and recipient histocompatibility antigens, there were seven patients (14.9%) with two or fewer HLA mismatches. Among 74 angiograms of 50 patients reviewed, only one patient had discrete stenosis less than 50% in the middle portion of the left anterior descending artery at 1 year after transplantation. The cumulative incidence of transplant CAD was 2% at 1 year and 2% at 2 and 4 years after transplantation. CONCLUSIONS: The incidence of transplant CAD was low in Chinese heart transplant recipients. Low percentage of ischemic heart disease in recipients, low occurrence of active CMV infection and rejection episodes after transplantation, less racial disparity, and lower HLA mismatches may be the important factors.     

Serial assessment of left ventricular function and mass after orthotopic heart transplantation: a 4-year longitudinal study.

Long-term changes in left ventricular performance and geometry in the transplanted human heart have been incompletely described. Therefore, two-dimensional echocardiograms were performed on 22 recipients of an orthotopic heart transplant at 1 month (32 +/- 20 days), 1 year (11 +/- 3 months) and 4 years (54 +/- 9 months) after transplantation. All studies were performed at a time when the patient had no pathologic evidence of rejection. Ten healthy men served as a normal control group. Over 4 years of follow-up, mean systolic blood pressure in the study patients increased from 121 +/- 12 (p = NS vs. values in the control group) to 139 +/- 11 mm Hg (p less than 0.05 vs. both control values and values at 1 month); mean diastolic blood pressure increased from 72 +/- 7 (p = NS vs. normal values in the control group) to 93 +/- 8 mm Hg (p less than 0.05 vs. both control values and values at 1 month). Left ventricular end-systolic volume increased from 42 +/- 10 (p = NS vs. control values) to 51 +/- 14 ml (p less than 0.05 vs. both control values and values at 1 month) and end-diastolic volume increased from 103 +/- 28 (p = NS vs. control values) to 112 +/- 27 ml (p less than 0.05 vs. control values) over 4 years. Left ventricular mass and ejection fraction did not change significantly within the patient cohort and remained similar to that found in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative assessment of valvular function after cardiac transplantation by pulsed doppler echocardiography

In 31 patients who had undergone cardiac orthotopic transplantation, valvular regurgitation was studied by echocardiographic and pulsed Doppler over 2 years. The first week after cardiac transplantation, transplant recipients had an increase in the severity of tricuspid, mitral (group II), and aortic regurgitation, as well as a greater number of simultaneously regurgitating valves when compared with those in a group of 60 normal subjects of similar age to heart donors: transplant recipients, trivalvular regurgitation 48% (95% confidence interval [CI] 30 to 66) vs control group, 5% (CI 1 to 13; p <0.001). Moderate-severe tricuspid regurgitation (TR) was the most frequent occurrence (55%, CI 36 to 73) followed by pulmonary (PR) (42%, CI 25 to 61), moderate mitral (MR) (32%, CI 15 to 51), and mild aortic (AR) (23%, CI 10 to 43) regurgitation. These regurgitations were asymptomatic at rest except for TR. TR was associated with right-sided heart failure in 76% of patients in the early postoperative period and controlled with diuretic drugs. This regurgitation correlated with persistence of post-transplant pulmonary hypertension (r = 0.6) and was not related to pulmonary hypertension before cardiac transplant. There was also no relation found between donor ischemia time or episodes of cardiac rejection. The follow-up of these regurgitations decreased significantly during the first months: TR from 55% (CI 36 to 73) to 21% (CI 8 to 40) at 2 months (p <0.05); PR from 42% (CI 26 to 61) to 18% (CI 6 to 36) at 2 months (p <0.01); MR from 29% (CI 14 to 48) to 3% (CI 0 to 18) at 3 months (p = 0.01); and AR from 23% (CI 10 to 43) to 0% (CI 10 to 43) at 3 months (p = 0.01); they did not reappear during the follow-up period.     

Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients.

BACKGROUND: Hypertension and cyclosporine-induced nephrotoxicity are common complications in heart transplant recipients. Omega-3 fatty acids may prevent blood pressure rise early, but have not been studied long-term after heart transplantation. METHODS AND RESULTS: Forty-five clinically stable hypertensive heart transplant recipients were studied 1-12 years after transplantation and randomized in a double-blind fashion to receive either 3.4 g of omega-3 fatty acids daily or placebo for 1 year. Ambulatory 24 h blood pressure monitoring and haemodynamic studies were performed before randomization and at the end of the study. Systolic blood pressure increased by 8+/-3 mmHg (P<0.01) in the placebo group, with a non-significant increase in diastolic blood pressure of 3+/-2 mmHg (P=0.10), accompanied by a 14% increase in systemic vascular resistance (P<0.05). In contrast, no change in blood pressure or systemic vascular resistance was recorded in the omega-3 group. Plasma creatinine increased (P<0.01) and glomerular filtration rate decreased (P<0.05) in the placebo group, while no changes were observed in the omega-3 group. The antihypertensive effect was related to an increase in serum eicosapentaenoic and docosahexaenoic acid. CONCLUSION: Treatment with omega-3 fatty acids may reduce the long-term continuous rise in blood pressure after heart transplantation and may offer a direct or indirect renoprotective effect, making these fatty acids a potentially attractive treatment for post-transplant hypertension.     

N末端B型利钠肽原和高敏C反应蛋白在心脏移植术后排斥反应中的意义

目的 分析原位心脏移植术后心内膜心肌活检(EMB)结果 与血N末端B型利钠肽原(NT-proBNP)和高敏C反应蛋白(hs-CRP)水平的关系,评价NT-proBNP和hs-CBP在诊断心脏移植术后排斥反应中的作用.方法 回顾分析阜外心血管病医院自2004年6月至2007年1月61例原位心脏移植患者术后3周、3～4个月、5～6个月、12个月的EMB及每次EMB前的血NT-proBNP和hs-CRP检查结果 ,分析NT-proBNP和hs-CRP与排斥反应之间的相关性.结果 NT-proBNP浓度于术后随时间推移呈下降趋势(r=-0.520,P=0.000),术后半年内NT-proBNP水平明显高于半年以后(P=0.002).排斥反应阳性组(病理分级≥2级)的NT-proBNP浓度高于阴性组(P=0.073);在排除时间影响之后,两组NT-proBNP浓度差异有统计学意义(P=0.025).NT-proBNP测定值的受试者工作特征(ROC)曲线显示,曲线下面积(AUC)为0.566(P=0.344).界值(cutoff值)为6.00×10-16mol/L时,其敏感性、特异性分别为57.1%、44.8%;cutoff值为8.00×10-16mot/L时,其敏感性、特异性分别为38.1%、61.0%.术后半年内hs-CRP水平高于半年以后(P=0.069).排斥反应阳性组的hs-CRP浓度高于阴性组(P=0.138);在排除时间影响之后,两组hs-CRP浓度差异仍无统计学意义(P=0.073).分别以NT-proBNP 4.00×10-16mol/ L和hs-CRP 3 ms/ L为分界点,NT-proBNP和hs-CRP同时高于分界点的有20例次(病理分级≥2级有5例次),而NT-proBNP和hs-CRP同时低于分界点的有26例次(病理分级≥2级有3例次),两者差异无统计学意义(P=0.232).结论 NT-proBNP浓度于心脏移植术后呈下降趋势,术后NT-proBNP浓度升高与排斥反应有相关性,但其诊断排斥反应的价值较低.心脏移植术后hs-CRP浓度升高与排斥反应无明显相关性,其与NT-proBNP一起不能提高诊断排斥反应的准确性.     

Primary bronchogenic carcinoma after heart or lung transplantation: radiologic and clinical findings

Chronic immunosuppression in organ transplant recipients predisposes to the development of malignant disease. The authors describe their 29-year institutional experience of bronchogenic carcinoma developing after heart and lung transplantation. Seven cases of bronchogenic carcinoma were diagnosed in 1,119 heart and lung transplant recipients. Computed tomography scans and radiographs at time of diagnosis, as well as prior radiographs available in six patients were retrospectively analyzed by two radiologists in consensus. The seven cases involved six heart and one lung transplant recipients. Six patients were smokers with a mean smoking history of 66 pack-years. Mean time interval from transplantation to cancer detection was 25 months. Radiologic findings consisted of a solitary pulmonary nodule (n = 3), mass with satellite nodules (n = 1), and obstructive pneumonitis (n = 1). In the sixth patient, the cancer was not radiographically visible because of obscuration by adjacent fibrosis. On review, radiographic abnormalities were present a mean of 12 months prior to diagnosis in 66% of patients. In the heart or lung transplant population, bronchogenic carcinoma develops in recipients with extensive smoking histories. It presents radiographically as a nodule, mass, or obstructive pneumonitis, and is usually visible on radiographs before the time of diagnosis.     

T-helper cell responses in liver transplant recipients: correlation with cytomegalovirus and other major infections

Mitogen concanavalin A (ConA) response and cytomegalovirus (CMV)-specific memory response were assessed in 24 liver transplant recipients and compared with healthy subjects. Transplant recipients as compared to healthy subjects had a lower CMV memory response at 2 weeks (P=0.023), and at 1 month (P=0.06), but a comparable response at 3 months. CMV recipient+/donor+(R+/D+) patients had the greatest increase in CMV-specific memory response at 2-3 months as compared to all other groups. Within this R+/D+ group, CMV-specific memory response was significantly more robust in patients who never had CMV infection as compared to those who developed CMV infection (P=0.035). ConA response at 2 weeks was significantly lower in patients with major infections as compared to those without them (SI 5.4 vs. 38.1, P=0.039). Thus, reconstitution of CMV-specific T-helper cell response was distinct for subsets of liver transplant recipients based on the recipient and donor CMV serostatus. Impairment in proliferative response to ConA identified a subgroup of patients with major infections after liver transplantation.     

Late and atypical cytomegalovirus disease in solid-organ transplant recipients.

Posttransplantation cytomegalovirus (CMV) disease typically occurs 1-4 months after solid-organ transplantation. The case definition invariably includes unexplained fever for > or =3 days, often with leukopenia. Late and atypical presentation of CMV disease has been rarely reported. Five cases of late and atypical CMV disease in heart (n = 1), liver (n = 1), and kidney (n = 3) transplant recipients occurred within a 4-month period in early 1999. These patients presented at a median of 25 months after organ transplantation (range, 6 months to 22 years). Atypical findings included absence of fever in 3 patients, elevated white blood cell counts in 4 patients, and normal platelet counts in 4 patients. Four patients were at risk for primary CMV infection, and 3 received ganciclovir prophylaxis for 3 months. One patients was treated for rejection, and 2 patients had induction muromonab-CD3 (Orthclone; Orthobiotech). Two of the patients had pulmonary CMV disease, but neither of these patients had hypoxia. Two patients had enterocolitis, one of whom had chronic colitis for a year. These cases may represent a changing epidemiology and clinical presentation of CMV disease in solid-organ transplant recipients in an era of changing immunosuppression and improved CMV disease prevention in the early posttransplantation period.     

Persistent lack of human herpesvirus-6 specific T-helper cell response in liver transplant recipients

Background. Specific immunologic defects predisposing to human herpesvirus‐6 (HHV‐6), e.g. the role of HHV‐6 specific T‐helper cell memory response in liver transplant recipients, have not been assessed. Methods. T‐helper function (mitogen ConA response) as a marker of overall immunocompetence and T‐helper response (memory response) specific to HHV‐6 and cytomegalovirus (CMV) were assessed in 15 liver transplant recipients and compared with 25 healthy subjects. Samples were tested pretransplant, at 2 weeks, 1 month, 2–3 months, and 1 year posttransplantation. Stimulation index (SI) >3 was considered a positive response. Results. Seven percent (1/15) of the transplant recipients at any time posttransplantation, as compared to 64% (16/25) of the healthy subjects, had a positive HHV‐6 memory response (P = 0.00065). HHV‐6‐specific memory response in transplant recipients at 2 weeks (SI 1.43), 1 month (SI 1.1), and 2–3 months (SI 1.3) was significantly more suppressed than in healthy subjects (SI 17.5, P = 0.0001). Although transplant recipients as compared to healthy subjects also had a lower CMV‐specific memory response posttransplant (P = 0.0439), CMV‐specific memory response recovered significantly at 1 month (P = 0.03) and at 2–3 months (P = 0.027) as compared to that at 2 weeks. However, HHV‐6 memory response was persistently absent up to 2–3 months with partial recovery at 1 year; 7% of the patients at 2–3 months, but 25% at 1 year had a positive HHV‐6 specific memory response. Forty percent (6/15) of the patients developed HHV‐6 viremia a mean of 4 weeks posttransplant. Patients with HHV‐6 viremia had greater suppression of HHV‐6 memory response at 1 month than those without viremia (mean SI, 0.96 vs. 1.3, P = 0.08). All but one of the patients had a positive ConA response. Conclusion. Prolonged suppression of HHV‐6 memory response, but not overall T‐helper cell function was documented and may play a role in the pathogenesis of HHV‐6 infection in liver transplant recipients. Memory response to CMV after liver transplantation was significantly more robust than to HHV‐6.     

The diagnosis of pneumonia in renal transplant recipients using invasive and noninvasive procedures

STUDY OBJECTIVES: We used invasive and noninvasive procedures to determine the causes of pneumonia in renal transplant recipients. SUBJECTS AND METHODS: We retrospectively surveyed 565 renal transplant recipients (transplants received March 1984 to August 2001) to find those with pneumonia. Noninvasive diagnostic methods included serologic testing, and blood and sputum cultures with stains. Invasive procedures included fiberoptic bronchoscopy and percutaneous transthoracic procedures. RESULTS: A total of 92 patients were enrolled. Of these, 71 patients had a definite etiologic diagnosis of pneumonia. The major infectious pathogens were bacterial (n = 21) and mixed bacterial infection (n = 10), Mycobacterium tuberculosis (TB) [n = 18], and fungi (n = 8). Noninvasive and invasive procedures led to the diagnosis of pneumonia in 31.5% (n = 29) and 45.6% (n = 42) of patients, respectively. Bronchoscopy was used in 64 patients, with a diagnostic yield of 38 cases (59.3%). Patients were 3.62 times more likely to contract pneumonia within 12 months of renal transplantation than they were > or =12 months thereafter (95% confidence interval, 1.33 to 9.84). Twenty-seven of the 92 patients (29.3%) died. The pneumonia mortality rate has dropped significantly since 1996 (41.8% vs 10.8%, p = 0.002). CONCLUSION: Both invasive and noninvasive procedures are useful in the diagnosis of pneumonia, with declining mortality, in renal transplant recipients. Bacterial and mixed bacterial infection, TB, and fungal infection are the most common pathogens; cases are most likely to occur within 1 year after renal transplantation.     

A prospective cross-sectional study of BK virus infection in non-renal solid organ transplant recipients with chronic renal dysfunction

BACKGROUND: Polyomavirus (primarily BK virus [BKV]) infection is an important cause of chronic renal dysfunction in renal transplant recipients, but its possible contribution to chronic renal dysfunction in non-renal solid organ transplant (NRSOT) recipients has not been fully explored. METHODS: We performed a prospective, cross-sectional study of consecutive NRSOT recipients with unexplained chronic renal dysfunction of at least a 3 months duration. Medical records were reviewed, and polymerase chain reaction was used to amplify BKV-specific sequences from serum and urine samples. The potential associations between various demographic and transplant variables and BKV infection were assessed. RESULTS: Thirty-four consecutive NRSOT recipients (23 lung, 8 liver, 2 heart, 1 heart-lung) with chronic renal dysfunction were enrolled at a median of 3.5 years (range 0.3-12.5 years) post transplantation. Five of the 34 (15%) patients had BKV viruria (range 1040-1.8 x 10(6) copies/mL), but none had BKV viremia. BK viruria was associated with mycophenolate mofetil use (5 of 19 [26%] vs. 0 of 15, P = 0.03) and a history of cytomegalovirus disease (3 of 4 [75%] vs. 2 of 30 [7%], P < 0.01). However, the mean estimated creatinine clearance was similar in patients with or without BKV viruria (49 vs. 47 mL/min). CONCLUSIONS: BKV viruria was present in a proportion of NRSOT patients with otherwise unexplained chronic renal dysfunction. The possibility that BKV infection might contribute to chronic renal dysfunction in this setting warrants further investigation.     

Comparison of higher dose and lower dose ganciclovir for cytomegalovirus prophylaxis in seropositive heart transplant recipients

S.-O. Lee, J.H. Rim, H. Sung, S.-H. Kim, S.-H. Choi, C.W. Lee, T.J. Yun, J.-W. Lee, J.H. Woo, Y.S. Kim, J.-J. Kim. Comparison of higher dose and lower dose ganciclovir for cytomegalovirus prophylaxis in seropositive heart transplant recipients.
Transpl Infect Dis 2010: 12: 31–37. All rights reserved
Background. We performed a retrospective historical cohort study to compare the efficacy of higher dose (HD, 10 mg/kg/day for 2 weeks, followed by 5 mg/kg/day intravenously for 2 weeks) and lower dose (LD, 5 mg/kg/day for 4 weeks) ganciclovir (GCV) for cytomegalovirus (CMV) prophylaxis in seropositive heart transplant recipients.
Methods. All consecutive patients undergoing heart transplantation (HT) between June 1999 and January 2008 at our institution were enrolled. All recipients were seropositive for CMV before HT. Before October 2005, 72 patients received the HD regimen and after October 2005, 36 patients received the LD regimen. We followed up all patients for 1 year.
Results. In the HD group 43 of 72 patients (60%) developed CMV infections vs. 21 of 36 patients (58%) in the LD group ( P =0.89). CMV diseases occurred in 4 patients of the HD group (6%) and 4 patients of the LD group (11%) ( P =0.44). The incidence of acute rejection was not significantly different between the 2 groups (14% vs. 6%; P =0.33). Among patients who completed 4-week courses of prophylaxis, 32 of 58 patients (55%) in the HD group developed CMV infections vs. 18 of 30 patients (60%) in the LD group ( P =0.66). CMV diseases occurred in 3 patients of the HD group (5%) and 4 of the LD group (13%) ( P =0.22). Acute rejection incidence did not differ significantly between the 2 groups (17% vs. 7%; P =0.21).
Conclusions. LD GCV for CMV prophylaxis may not be inferior to the HD regimen in seropositive HT recipients.     

Increased renal and forearm vasoconstriction in response to exercise after heart transplantation.

OBJECTIVE--To test the hypothesis that the loss of the inhibitory effect of the cardiac ventricular afferent fibres on the vasomotor centre would result in increased vasoconstrictor drive to the forearm and renal vascular beds during supine exercise in heart transplant recipients. DESIGN--Comparison of regional haemodynamic response to exercise in heart transplant recipients and two age matched control groups. SETTING--Regional heart transplant unit. PATIENTS AND METHODS--Orthotopic heart transplant recipients (n = 10), patients with NYHA class II heart failure (n = 10), and normal controls (n = 10) underwent short duration maximal supine bicycle exercise. MAIN OUTCOME MEASURES--Simultaneous measurements were made of heart rate, systemic blood pressure, oxygen consumption (VO2), forearm blood flow, and renal blood flow. Forearm blood flow was measured by forearm plethysmography and renal blood flow by continuous renal vein thermodilution. RESULTS--The peak forearm vascular resistance was significantly greater in the transplant group than in the controls (mean (SEM) 75 (18) v 40 (7) resistance units, p < 0.05). The percentage fall in renal blood flow at peak exercise was significantly greater in heart transplant recipients than in the controls (44% (4%) v 32% (4%), p < 0.05) as was the percentage increase in renal vascular resistance (transplants: 116% (19%) v controls: 78% (17%), p < 0.05). Regional haemodynamics during exercise in the heart failure group were not significantly different from those in the controls. CONCLUSIONS--These findings suggest that surgical division of the cardiac ventricular afferent fibres results in increased vasoconstrictor drive to the kidneys and non-exercising muscle during exercise. This mechanism may contribute to persistent exercise limitation and renal impairment after heart transplantation.     

Hyperuricemia and gout among heart transplant recipients receiving cyclosporine.

PURPOSE: To determine the frequency and characteristics of hyperuricemia and gouty arthritis among cyclosporine-treated heart transplant recipients. PATIENTS AND METHODS: One hundred ninety-six surviving adult heart or heart/lung transplant recipients were evaluated. Medical records were reviewed to determine peak serum uric acid levels after transplantation, and to evaluate potential risk factors for hyperuricemia. Patients were surveyed by postal questionnaire for a history of gouty arthritis, with positive responses evaluated by telephone interview and/or examination of the patient. RESULTS: Hyperuricemia occurred in 72% of male and 81% of female patients and was not correlated with cyclosporine level, presence of hypertension, or degree of renal insufficiency. Eleven (6%) patients had gout prior to transplantation; 14 (8%) had onset of definite gout and seven (4%) had probable gout a mean of 17 months after transplantation. Polyarticular arthritis and/or tophi developed in six (43%) of the posttransplant-onset definite gout group within a mean of 31 months. CONCLUSION: Both hyperuricemia and gouty arthritis occur with increased frequency among cyclosporine-treated heart or heart/lung transplant recipients. The clinical course of gout in these patients is often accelerated, with management complicated by the patients' renal insufficiency and interaction with transplant-related medications.