Urinary Tract Infection In Renal Transplant Recipients: Incidence, Risk Factors, And Impact On Graft Function.

Urinary tract infection (UTI) is the most common infection posttransplant. However, the risk factors for and the impact of UTIs remain controversial. The aim of this study was to identify the incidence of posttransplant UTIs in a series of renal transplant recipients from deceased donors. Secondary objectives were to identify: (1) the most frequent infectious agents; (2) risk factors related to donor; (3) risk factors related to recipients; and (4) impact of UTI on graft function. This was a retrospective analysis of medical records from renal transplant patients from January to December 2010. Local ethics committee approved the protocol. The incidence of UTI in this series was 34.2%. Risk factors for UTI were older age, (independent of gender), biopsy-proven acute rejection episodes, and kidneys from deceased donors (United Network for Organ Sharing criteria). For female patients, the number of pretransplant pregnancies was an additional risk factor. Recurrent UTI was observed in 44% of patients from the UTI group. The most common infectious agents were Escherichia coli and Klebsiella pneumoniae, for both isolated and recurrent UTI. No difference in renal graft function or immunosuppressive therapy was observed between groups after the 1-year follow-up. In this series, older age, previous pregnancy, kidneys from expanded criteria donors, and biopsy-proven acute rejection episodes were risk factors for posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative impact on graft function or survival.

Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results

PURPOSE: Evaluate the bone tissue recovery following transplantation of ovine mesenchymal stem cells (MSC) from bone marrow and human immature dental-pulp stem cells (hIDPSC) in ovine model of induced osteonecrosis of femoral head (ONFH). METHODS: Eight sheep were divided in three experimental groups. First group was composed by four animals with ONFH induced by ethanol through central decompression (CD), for control group without any treatment. The second and third group were compose by two animals, six weeks after ONFH induction received transplantation of heterologous ovine MSC (CD + oMSC), and hIDPSC (CD + hIDPSC), respectively. In both experiments the cells were transplanted without application of any type of immunosupression protocol. RESULTS: Our data indicate that both cell types used in experiments were able to proliferate within injured site providing bone tissue recovery. The histological results obtained from CD+hIDPSC suggested that the bone regeneration in such animals was better than that observed in CD animals. CONCLUSION: Mesenchymal stem cell transplant in induced ovine osteonecrosis of femoral head by central decompression technique is safe, and apparently favors bone regeneration of damaged tissues.

Evaluation of an immunoassay (EMIT) for mycophenolic acid in plasma from renal transplant recipients compared with a high-performance liquid chromatography assay

Mycophenolic acid is an immunosuppressant administered as a bioavailable ester, mycophenolate mofetil. The pharmacokinetics of mycophenolic acid have been reported to be variable. Accurate measurement of concentrations of this drug could be important to adjust doses. The aim of this study was to compare the enzyme-multiplied immunoassay technique (EMIT [Dade Behring; San Jose, CA, U.S.A.]) for mycophenolic acid with a high-performance liquid chromatographic (HPLC) assay using samples collected from renal transplant recipients. The HPLC assay used solid phase extraction and a C18 stationary phase with ultraviolet (UV) detection (254 nm). The immunoassay required no manual sample preparation. Plasma samples (n = 102) from seven patients, collected at various times after a dose, were analyzed using both methods. Both assays fulfilled quality-control criteria. Higher concentrations were consistently measured in patient samples when using EMIT. The mean (+/- standard deviation [SD]) bias (EMIT-HPLC) was 1.88 +/- 0.86 mg/L. The differences in concentrations were higher in the middle of a dosage interval, suggesting that a metabolite might have been responsible for overestimation. Measurement of glucuronide concentrations by HPLC demonstrated only a weak correlation between assay differences and glucuronide concentrations. If the crossreacting substance is active, EMIT could provide a superior measure of immunosuppression; if inactive, further work is needed to improve antibody specificity. In conclusion, it was found that EMIT overestimates the concentration of mycophenolic acid in plasma samples from renal transplant recipients compared with HPLC analysis.

Myocardial scintigraphy and clinical stratification as predictors of events in renal transplant candidates

Background: We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors. Methods: RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death. Results: Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High-risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82). Conclusion: SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing.

Transfer of Cholesterol and Other Lipids From a Lipid Nanoemulsion to High-density Lipoprotein in Heart Transplant Patients

Background: Beyond the first year after a heart transplant (HT) procedure, patients often develop dyslipidemias, which may be implicated in the genesis of transplant coronary heart disease. High-density lipoprotein (HDL) has a several anti-atherogenic properties, but the status of HDL in HT patients is still controversial. Nonetheless, determination of HDL cholesterol concentration is not sufficient for evaluation of the overall HDL protective role. In this study, a fundamental functional property of HDL, the ability to simultaneously receive the major lipid classes, was tested in HT patients. Methods: Twenty HT patients and 20 healthy normolipidemic subjects paired for gender, age and body mass index were studied. Blood samples were collected after 12-hour fasting for determination of plasma lipids, glucose, paraxonase I (PON 1) activity, HDL diameter and transfer of labeled lipids from an artificial nanoemulsion to HDL. Results: Plasma triglycerides (159 +/- 63 vs 94 +/- 35 mg/dl) and glucose (104 +/- 20 vs 86 +/- 10 mg/dl) were greater in HT patients than in control subjects. HDL cholesterol was lower and HDL diameter was smaller in the HT group (HDL cholesterol: 44 +/- 11 vs 55 +/- 15 mg/dl; HDL diameter: 8.8 +/- 0.6 vs 9.0 +/- 1.2 nm). PON 1 activity did not differ (87 +/- 47 vs 75 +/- 37 nmol/min/ml). The transfer rates of free cholesterol and cholesteryl esters were diminished in HT patients (HT: 8.4 +/- 1.2% and 3.8 +/- 0.6%; controls: 9.7 +/- 1.9% and 4.7 +/- 1.2%, respectively). Conclusions: The transfer of free cholesterol and cholesteryl esters to HDL is diminished in HT patients; disturbance in the ability of HDL to receive lipids may affect the anti-atherogenic properties of the lipoprotein. J Heart Lung Transplant 2009;28:1075-80. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.

Transurethral injection therapy with carbon-coated beads (Durasphere (R)) for treatment of recurrent pyelonephritis in kidney transplant patients with vesico-ureteral reflux to the allograft

Introduction and objectives: Recurrent transplant pyelonephritis (RTP) secondary to vesico-ureteral reflux (VUR) to the transplant kidney (KTx) remains a significant cause of infectious complications with impact on patient and graft outcomes. Our objective was to verify the safety and efficacy of transurethral injection of Durasphere (R) to relieve RTP secondary to VUR after renal transplantation. Patients and methods: Between June 2004 and July 2008, eight patients with RTP (defined as two or more episodes of pyelonephritis after transplantation) and VUR to the KTx were treated with subureteral injections of Durasphere (R). The mean age at surgery was 38.8 +/- 13.8 yr (23-65). The patients were followed regularly every six months. The mean interval between the KTx and the treatment was 76 +/- 74.1 (10-238 months). The mean follow-up was 22.3 +/- 16.1 months (8-57 months). Results: Six patients (75%) were free of pyelonephritis during a mean period of follow-up of 23.2 +/- 17.1 months (8-57 months). Two of them had no VUR and four cases presented with G II VUR (pre-operative G IV three cases and one case G III). In one case, symptomatic recurrent cystitis made a second treatment necessary. This patient remained free of infections for three yr after the first treatment and for 18 months after the second treatment. Of the remaining two patients, one had six episodes of RTP before treatment in a period of three yr and only two episodes after treatment in two yr of follow-up. The last case had a new episode of pyelonephritis five months after treatment. Conclusions: Transurethral injection therapy with Durasphere (R) is a safe and effective minimally invasive treatment option for KTx patients with recurrent RTP. A second treatment seems to be necessary in some cases.

Cutaneous Mycobacterium haemophilum infection in a kidney transplant recipient after acupuncture treatment

P>Mycobacterium haemophilum is a slow-growing nontuberculous mycobacterium that can cause disease in both immunocompetent and immunocompromised patients. The most common clinical presentations of infection are the appearance of suppurative and ulcerated skin nodules. For the diagnosis, samples collected from suspected cases must be processed under the appropriate conditions, because M. haemophilum requires lower incubation temperatures and iron supplementation in order to grow in culture. In this case report, we describe the occurrence of skin lesions in a kidney transplant recipient, caused by M. haemophilum, associated with acupuncture treatment. The diagnosis was established by direct smear and culture of material aspirated from cutaneous lesions. Species identification was achieved by characterization of the growth requirements and by partial sequencing of the hsp65 gene. The patient was successfully treated with clarithromycin and ciprofloxacin for 12 months. Considering that the number of patients receiving acupuncture treatment is widely increasing, the implications of this potential complication should be recognized, particularly in immunosuppressed patients.

Validation of a strategy to diagnose coronary artery disease and predict cardiac events in high-risk renal transplant candidates

Background We validated a strategy for diagnosis of coronary artery disease ( CAD) and prediction of cardiac events in high-risk renal transplant candidates ( at least one of the following: age >= 50 years, diabetes, cardiovascular disease). Methods A diagnosis and risk assessment strategy was used in 228 renal transplant candidates to validate an algorithm. Patients underwent dipyridamole myocardial stress testing and coronary angiography and were followed up until death, renal transplantation, or cardiac events. Results The prevalence of CAD was 47%. Stress testing did not detect significant CAD in 1/3 of patients. The sensitivity, specificity, and positive and negative predictive values of the stress test for detecting CAD were 70, 74, 69, and 71%, respectively. CAD, defined by angiography, was associated with increased probability of cardiac events [log-rank: 0.001; hazard ratio: 1.90, 95% confidence interval (CI): 1.29-2.92]. Diabetes (P=0.03; hazard ratio: 1.58, 95% CI: 1.06-2.45) and angiographically defined CAD (P=0.03; hazard ratio: 1.69, 95% CI: 1.08-2.78) were the independent predictors of events. Conclusion The results validate our observations in a smaller number of high-risk transplant candidates and indicate that stress testing is not appropriate for the diagnosis of CAD or prediction of cardiac events in this group of patients. Coronary angiography was correlated with events but, because less than 50% of patients had significant disease, it seems premature to recommend the test to all high-risk renal transplant candidates. The results suggest that angiography is necessary in many high-risk renal transplant candidates and that better noninvasive methods are still lacking to identify with precision patients who will benefit from invasive procedures. Coron Artery Dis 21: 164-167 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Treatment of Coronary Artery Disease in Hemodialysis Patients Evaluated for Transplant-A Registry Study

Background. We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD). Methods. We analyzed 519 patients with CKD (56+/-9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography. Results. In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction >= 70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft-intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48-15.10; death: hazard ratio=3.39; % confidence interval 1.41-8.45). Conclusions. In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

Mini-microabscess syndrome in liver transplant recipients

Cytomegalovirus (CMV) is a significant cause of morbidity in immunosuppressed patients. It is characterized in the liver by parenchymal microabscesses, usually containing CMV-infected cells. However, not all hepatic microabscesses are due to CMV infection. In 1992, we described ''mini'' microabscess (MMA) syndrome, a distinct clinical syndrome that occurs in transplanted livers. This report analyzes the clinical and laboratory features of 57 cases of MMA syndrome occurring in 52 patients and compares these with 19 biopsy-proven cases of CMV infection. The diagnosis of MMA syndrome can only be made histologically. The microabscesses are smaller and more numerous than in CMV infection, and there are no viral inclusions present. CMV DNA could not be detected in liver biopsy specimens with MMAs by using ''nested'' polymerase chain reaction (PCR), indicating that MMA syndrome is not caused by CMV infection. The pattern of liver enzyme and bilirubin elevation is predominantly hepatocellular, with transaminase levels elevated, on average, six to eight times the upper limit of normal. The clinical features of MMA syndrome are that it predominantly affects female (40 of 52 patients) orthotopic liver transplant (OLT) recipients of all ages (range, 11 months to 66.9 years). MMA syndrome is unrelated to the indication for initial OLT and tends to occur later after transplantation than CMV infection (median, 91 days post-OLT vs. 32 days for CMV hepatitis). Although the etiology of MMA syndrome is not clear, it does not appear to adversely affect graft or patient survival.

Validation of plasma clearance of (51)Cr-EDTA in adult renal transplant recipients: comparison with inulin renal clearance

Plasma clearance of (51)Cr-EDTA ((51)Cr-EDTA-Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between (51)Cr-EDTA-Cl and renal inulin clearance (In-Cl) in renal transplant recipients as well to determine the repeatability of (51)Cr-EDTA-Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of (51)Cr-EDTA-Cl and In-Cl were performed. A single dose of 3.7MBq of (51)Cr-EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In-Cl and (51)Cr-EDTA-Cl and to determine the better concordance between all possibilities of measure for the (51)Cr-EDTA-Cl. The mean of In-Cl was 44.5 +/- 17.9 ml/min/1.73 m(2). There was a positive correlation between In-Cl and all possible measurements of (51)Cr-EDTA-Cl. (51)Cr-EDTA-Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for (51)Cr-EDTA-Cl was a reliable method to measure GFR compared with In-Cl and comprises a suitable method to be used in kidney transplanted patients.

Sonographic Diagnosis of a Ureteral Inguinal Hernia in a Renal Transplant

Complications related to renal transplants have been widely reported in the literature. The most common complications include acute tubular necrosis, rejection, perirenal fluid collections, vascular complications, and urinary tract obstruction, which are promptly identified by imaging studies. Here we report a case of a patient with a rare cause of obstruction: a ureteral inguinal hernia. This is the sixth report of this condition, and, to our knowledge, no previous case has been reported in which sonography played an important role in promptly identifying the underlying condition and allowing additional less hazardous studies, therefore aiding case management.

Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature

P>Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient`s triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.