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Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

BACKGROUND: In combination with everolimus (EVL), cyclosporine A (CsA) may be used at low exposure, so reducing the risk of renal dysfunction in renal transplant recipients (RTR). We evaluated whether higher exposure of EVL could allow a further reduction of CsA. METHODS: De novo RTR were randomized to standard exposure EVL (C0 3-8 ng/mL) with low-concentration CsA (C2 maintenance levels 350-500 ng/mL, group A) or higher EVL exposure (C0 8-12 ng/mL) with very low-concentration CsA (C2 maintenance levels 150-300 ng/mL, group B). The primary endpoints were 6-month creatinine clearance (CrCl) and biopsy-proven acute rejection (BPAR) rate. After 6 months, patients were followed up (observational extension) to 12 months. RESULTS: Two hundred eighty-five RTR (97% from deceased donors) were enrolled. Two patients per group died (1.4%). The 6-month death-censored graft survival was 90.2% in group A and 97.9% in group B and was unchanged at 12 months (P=0.007). There was no significant difference between groups at 6 months in CrCl (59.9 vs. 57.8 mL/min) and BPAR rates (14.7% vs. 11.9%) and also at 12 months (CrCl 62.5+/-20.7 vs. 61.3+/-22.0 mL/min, BPAR 14.7% vs. 14.1%). No significant differences were seen in treated acute rejections, steroid-resistant acute rejections, treatment failures, or delayed graft function, although there was a trend to better results in group B. CONCLUSIONS: EVL given at higher exposure for 6 months plus very low CsA concentration may obtain low acute rejection rate and good graft survival in De novo renal transplantation. However, there was no difference between groups in CrCl.

BACKGROUND: Relative survival, a methodology previously used in epidemiologic studies of cancer, compares the observed survival of a patient cohort with expected survival derived from general population life tables. We examined relative survival in patients treated by long-term dialysis in the Italian Dialysis and Transplantation Registry in order to determine the prognosis of dialysis patients. STUDY DESIGN: Cohort study drawn from a registry. SETTING & PARTICIPANTS: Patients enrolled in the Italian Dialysis and Transplantation Registry. FACTORS: Sex, age, primary kidney disease, renal replacement therapy modality, and main comorbid conditions. OUTCOMES: Death from any cause. MEASUREMENTS: Relative survival ratio (the ratio of observed survival in the population of interest to the survival expected given the age- and period-specific mortality of the general population) and excess mortality rate (difference between observed and expected mortality rates). RESULTS: In January 2000 to December 2008, a total of 27,642 patients were included. The 5-year relative survival estimate was 55.6% (95% CI, 54.7%-56.5%). The excess mortality rate showed a peak at 3 months (21 deaths/100 patient-years), then decreased, becoming constant from the end of year 1 to year 8, with leveling off at about 10 deaths/100 patient-years. Older age, systemic diseases, and diabetes showed the strongest association with excess mortality. Peritoneal dialysis was associated with a lower relative excess risk in only the first year of treatment. LIMITATIONS: The patient cohort comprises about half the Italian patients beginning dialysis therapy in the period. CONCLUSIONS: This study highlights the applicability of relative survival methods in dialysis patients. This measure allows estimation of disease prognosis and severity comparisons among chronic diseases. The excess mortality rate appears to be a more sensitive and informative measure than the simple proportion of survivors.

BACKGROUND: Patients with chronic renal failure (CRF) suffer from a series of complications linked to the atherosclerotic process in which the endothelial dysfunction mediated by the activation of some adhesion molecules plays an important role. This study aims to evaluate circulating levels of intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) in patients with predialysis CRF, on maintenance hemodialysis (HD) and after kidney transplantation (KTx) and to correlate them with some inflammation and nutritional indexes. METHODS: Thirty two patients with predialysis CRF, 30 on maintenance HD, 36 after KTx and 28 subjects as a control group (C) were included in this study. Circulating levels of ICAM-1 and VCAM-1 were assayed using a specific sandwich ELISA kit. As inflammation indexes, TNFalpha and C-reactive protein (CRP) and, as nutritional indexes, body mass index (BMI), serum albumin, cholesterol, triglycerides, and fibrinogen (F) were evaluated. RESULTS: Serum levels of ICAM-1 and VCAM-1 were progressively higher from C to KTx patients, to those with CRF and those on HD (ANOVA for both; p

Numerous formulas have been developed to estimate renal function from biochemical, demographic and anthropometric data. Here we compared renal function derived from 12 published prediction equations with glomerular filtration rate (GFR) measurement by plasma iohexol clearance as reference method in a group of 81 renal transplant recipients enrolled in the Mycophenolate Mofetil Steroid Sparing (MY.S.S.) trial. Iohexol clearances and prediction equations were carried out in all patients at months 6, 9 and 21 after surgery. All equations showed a tendency toward GFR over-estimation: Walser and MDRD equations gave the best performance, however not more than 45% of estimated values were within +/-10% error. These formulas showed also the lowest bias and the highest precision: 0.5 and 9.2 mL/min/1.73 m2 (Walser), 2.7 and 10.4 mL/min/1.73 m2 (MDRD) in predicting GFR. A significantly higher rate of GFR decline ranging from -5.0 mL/min/1.73 m2/year (Walser) to -7.4 mL/min/1.73 m2/year (Davis-Chandler) was estimated by all the equations as compared with iohexol clearance (-3.0 mL/min/1.73 m2/year). The 12 prediction equations do not allow a rigorous assessment of renal function in kidney transplant recipients. In clinical trials of kidney transplantation, graft function should be preferably monitored using a reference method of GFR measurement, such as iohexol plasma clearance.

We evaluated total and ionized plasma magnesium levels, and erythrocyte and platelet magnesium concentrations from two groups of renal transplant recipients treated either with cyclosporine, azathioprine and prednisolone (group CAP, n = 8) or with azathioprine and prednisolone (group AP, n = 13), and in a group of age- and sex-matched healthy subjects (n = 10). Reduced plasma (total and ionized), erythrocyte and platelet magnesium concentrations were found in both CAP and AP groups with respect to controls (CAP: total plasma Mg median 0.61 vs 0.86 mmol/L, p0.01, ionized plasma Mg median 0.43 vs 0.58 mmol/L, p0.001, erythrocyte Mg median 2.18 vs 2.56 mmol/L, p0.05, platelet Mg median 1.75 vs 2.84 mmol/10(8) cells, p0.001; AP: total plasma Mg median 0.62 vs 0.86 mmol/L, p0.01, ionized plasma Mg median 0.48 vs 0.58 mmol/L, p0.001, erythrocyte Mg median 2.30 vs 2.56 mmol/L, p0.05, platelet Mg median 1.75 vs 2.84 mumol/10(8) cells, p0.001), while no difference was found between the two groups of transplant recipients as regards plasma and intracellular magnesium levels. Magnesium fractional excretion was higher in transplant recipients than in the control group (Mg fractional excretion median AP 18.6 per cent and CAP 12.8 per cent vs controls 3.5 per cent), whereas no difference was found between patients and control subjects for urinary magnesium 24h excretion. Moreover, in the whole group of transplant recipients (n = 21), urinary magnesium showed an inverse correlation with platelet (rs = -0.54, p0.05) and ionized plasma magnesium (rs = -0.48, p0.05), and time after transplantation showed a negative correlation with platelet magnesium concentrations (rs = -0.73, p0.001), and a direct correlation with fractional magnesium excretion (rs = 0.53, p0.05). Finally, a direct relationship between platelet magnesium and ionized plasma magnesium was also detected in the whole group of transplant recipients (rs = 0.47, p0.05). Both intraplatelet magnesium depletion and ionized plasma magnesium reduction induced by immunosuppressive therapy could be involved in the increased risk from atherosclerotic disease in renal transplant recipients.

Since the high rate of cardiovascular disease in renal transplant recipients, alterations of lipoprotein profile in such patients were extensively evaluated, but the HDL subclass profile was not completely clarified. Renal transplant recipients usually show normal to high plasma levels of HDL cholesterol, even if some investigations suggested a persistence of low HDL2 levels: this was not useful in terms of cardiovascular protection. We designed this study in order to evaluate HDL subfractions distribution in renal transplant recipients. We studied 55 renal transplant recipients, treated with prednisone, azathioprine and/or cyclosporine, and 34 healthy normolipidemics as controls. In all subjects cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, apolipoproteins A-I and B levels and HDL subfractions, as determined by nondenaturing polyacrylamide gradient gel electrophoresis, were assayed. Renal transplant recipients had cholesterol, triglycerides, LDL cholesterol and apolipoproteins A-I and B levels significantly higher than controls; HDL cholesterol levels were slightly, but not significantly, increased in comparison with controls (respectively 51.1 ± 15.5 and 46.1 ± 10.8 mg/dl). Multivariate analysis showed that only the time since transplantation was significantly associated with HDL cholesterol levels. When HDL subfractions were analyzed, renal transplant recipients presented significantly lower levels of HDL(3a), and HDL(3b) and, in males, higher levels of HDL(2b) than controls. HDL cholesterol levels were positively correlated with HDL(2b) levels in both renal transplant recipients and controls, and negatively correlated with HDL(3b) in controls. In conclusion, in renal transplant recipients, we failed to demonstrate any decrease of HDL2 particles. On the basis of a nonatherogenic HDL profile, we suggest that the increased cardiovascular risk in renal transplant recipients might be accounted for by other risk factors.