Prospective cohort study of Torque Teno Virus (TTV) viral load kinetics and the association with graft rejection in renal transplant patients.

INTRODUCTION: Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. MATERIALS AND METHODS: Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. RESULTS: Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p < 0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p < 0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). CONCLUSIONS: Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.

Surveillance Registry of Sirolimus Use in Recipients of Kidney Allografts From Expanded Criteria Donors.

BACKGROUND: The use of expanded criteria donor (ECD) kidneys has increased the overall availability of renal transplants. This study assessed the use of sirolimus in patients receiving Argentina-ECD kidneys. METHODS: This observational, open-label, 1-arm, prospective, longitudinal pilot study was conducted at 8 transplant centers in Argentina. Adults receiving kidney transplants (without pancreas) from ECDs were eligible if they were converted to sirolimus 1 to 36 months' posttransplantation, with sirolimus becoming base therapy within 1 month after conversion. Patients were followed up for 1 year. Outcomes included reasons for conversion, acute rejection, patient and graft survival, graft status, and safety. RESULTS: The intention-to-treat population included 52 patients (mean age, 48.7 years). Calcineurin inhibitor nephropathy (40%) and chronic allograft nephropathy (25%) were the most frequent reasons for conversion. Two acute rejections occurred during follow-up, but no patients experienced graft loss. One patient died during follow-up, and 3 patients died within 1 month of the last sirolimus dose. Levels of serum creatinine and creatinine clearance remained stable from baseline to week 52/53. Mean proteinuria measured in a subset of patients was 0.2 ± 0.2 g/24 hours before conversion and increased to 0.6 ± 1.2 g/24 hours at week 24/25 and 0.5 ± 0.6 g/24 hours at week 52/53. Adverse events were consistent with those in previous conversion trials; the most common were infections and infestations (54%). CONCLUSIONS: This pilot study illustrates the potential benefits of sirolimus in recipients of ECD kidneys in Argentina. Larger, randomized controlled trials are needed to confirm these findings and to clarify the long-term benefits of sirolimus in this patient population.

Conversion to sirolimus allows preservation of renal function in kidney and kidney-pancreas allograft recipients.

The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney-pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr(baseline) 51.4 vs CCr(6m) 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0-453) versus 0 mg/24 hours (range, 0-309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 +/- 37 vs. 186.6 +/- 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.

[Acute peripheral demyelinating polyneuropathy and acute renal failure after administration of FK506]. / Polineuropatía desmielinizante periférica aguda e insuficiencia renal aguda secundaria a la administración de FK 506.

FK 506 is a potent immunosuppressive agent in clinical use in solid organ transplantation since 1989. Approximately 5% of patients receiving FK 506 develop major central nervous system toxicity but peripheral nervous system involvement is very uncommon, and there are only 4 reported cases of demyelinating polyneuropathy in patients who received a liver transplant. We report a case of demyelinating polyneuropathy associated with the use of FK 506 in a renal transplant recipient.

Polineuropatía desmielinizante periférica aguda e insuficiencia renal aguda secundaria a la administración de FK 506. / [Acute peripheral demyelinating polyneuropathy and acute renal failure after administration of FK506]

FK 506 is a potent immunosuppressive agent in clinical use in solid organ transplantation since 1989. Approximately 5

of patients receiving FK 506 develop major central nervous system toxicity but peripheral nervous system involvement is very uncommon, and there are only 4 reported cases of demyelinating polyneuropathy in patients who received a liver transplant. We report a case of demyelinating polyneuropathy associated with the use of FK 506 in a renal transplant recipient.

Short term effects of air pollution on mortality in the city of Lyon, France, 1985-90.

OBJECTIVE: The short term association between daily mortality and ambient air pollution in the city of Lyon, France (population, 410,000) between 1985 and 1990 was assessed using time series analysis. DESIGN: This study followed the standardised design and statistical analysis (Poisson regression) that characterise the APHEA project. METHODS: Four categories of cause of death were studied: total (minus external causes), respiratory, cardiovascular, and digestive causes (as a control condition). RESULTS: No association was found with any cause of death for nitrogen dioxide (NO2) and ozone (O3), nor, for any pollutant, for digestive conditions. Sulphur dioxide (SO2) and, to a much lesser degree, suspended particles (PM13), were significantly related to mortality from respiratory and cardiovascular conditions. The relative risk (RR) of respiratory deaths associated with a 50 micrograms/m3 increment of mean daily SO2 over the whole period was 1.22 (95% CI 1.05, 1.40); the RR for cardiovascular deaths was 1.54 (1.22, 1.96). The corresponding RRs for PM13 were 1.04 (1.00, 1.09) for respiratory mortality and 1.04 (0.99, 1.10) for cardiovascular deaths. CONCLUSIONS: The effects of particulates were slightly increased during the cold season. When particulates concentrations were greater than 60 micrograms/m3, the joint SO2 effect was increased, suggesting some interaction between the two pollution indicators. These results agree with other studies showing an association between particulate pollution and daily mortality; however, they also suggest the noxious effect of SO2.

[A network of epidemiological information in community medicine practice: methodological principles of the VENUS Program]. / Un réseau d'information épidémiologique en pratique médicale de ville: principes méthodologiques du programme VENUS.

Implementation of epidemiological studies involving the participation of large networks of ambulatory care physicians requires prior resolution of the methodological dilemma between a "volunteer sentinel doctors" approach and one based on sampling techniques. A study of the VENUS program (concerning Sexually Transmitted Diseases) illustrates this latter approach for which formulae are proposed for estimating the rate of incidence in the population. Methodological implications of this technique are commented upon, and the complementary indications for the two techniques for gathering information on ambulatory morbidity are discussed.