First epidemiologic study in Argentina of the prevalence of BK viruria in kidney transplant patients.

BACKGROUND: The worldwide seroprevalence of human BK polyomavirus (BKV) in adults is 80%. About 10%-60% of renal transplant recipients experience BKV infection, nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation. METHODS: An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10(7) copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included. RESULTS: Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10(7) copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3-7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed. CONCLUSIONS: This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.

Grand rounds to provide feedback on procurement activities.

INTRODUCTION: The Argentine Society of Transplants has set in motion an activity called Grand Rounds to Provide Feedback on Procurement Activities with the purpose of informing, training, and creating awareness by providing information about the evolution of transplanted patients. OBJECTIVE: To measure, describe and analyze the impact that the transplant results presented at the rounds had on participants. RESULTS: One hundred and fifty-eight surveys were conducted. The respondents' average age was 40.06 years (95% confidence interval [CI 95%] 38.39-41.73) including 52.08% women (CI 95%: 43.92%-60.24%); 77.14% physicians (CI 95%: 84.09%-70.18%); 7.85% nurses (CI 95%: 3.4%-12.31%;) and 4.28% surgical nurses and other professional (CI 95%: 0.93%-7.64). When asked how comforted they felt when they learnt about a transplantation, the score prior to the round was 4 (CI 95%: 3.79-4.20) and after it, 4.8 (CI 95%: 4.69-4.90; P < .05). When asked about the transparency of the donation process, the average score before the round was 4.16 (CI 95%: 3.96-4.36) and after it, 4.76 (CI 95%: 4.67-4.86; P < .05). When asked how proactive they considered themselves before, before the average score was 3.54 (CI 95% 3.30-3.78) and post-round, 4.53 (CI 95%: 4.38-4.67; P < .05). When asked if they thought that this activity might be useful for them to manage future donors, 97.41% (CI 95%: 89%-96.98%) of respondents answered affirmatively. The answers to the question whether they thought this activity might increase donation were affirmative in 92.99% of cases; "Don't know", 6.36%; and negative in less than 1%. When consulted about their feelings, the preferred one was "happiness" for 46.82% of respondents; followed by "satisfaction" for 29.36% and "emotion" for 23.80%. The analysis of the open-ended questions revealed that the rounds were perceived as closure of the procurement-transplantation process. CONCLUSIONS: This widely accepted tool was viewed as a vehicle to interconnect links in the work process from organ procurement to transplantation.

Results of the conversion to everolimus in renal transplant recipients with posttransplantation malignancies.

Management of posttransplantation malignancies should include control of the neoplasia and preservation of renal function. Conversion to everolimus (EVL) would potentially have both effects. Twenty-one patients were converted to EVL due to posttransplantation neoplasms. We have presented herein descriptive data and postconversion (PC) outcomes among subjects of mean age 53.6 +/- 10.1 years (range, 36-69), 57.1% were males, undergoing conversion at 108.2 +/- 74.7 (range, 5-316) months after transplantation. All patients received standard immunosuppressive therapy and 9.5% had been induced with thymoglobulin. Malignant neoplasms were as follows: skin (n = 7), gynecological (n = 3), gastrointestinal (n = 3), PTLD (n = 2), renal (n = 2), CNS (n = 1), seminoma (n = 1), Kaposi's sarcoma (n = 1), and prostate cancer (n = 1). PC to EVL, calcineurin inhibitors (CNIs) were discontinued in 18 of 19 patients, mycophenolate in 9/12, and azathioprine in 5/7; all patients continued to receive steroids. In 16 patients (79%) tumors were removed. Chemotherapy was performed in 2 patients with PTLD and radiotherapy was performed in 1 patient with prostate cancer. Mean follow-up was 505 days (range, 59-1151); baseline glomerular filtration rate (GFR) was 53.5 +/- 21.6 mL/min versus 48.5 +/- 25.7 mL/min (P = not significant [NS]) at the last control. One patient experienced graft loss at day 744 after conversion due to chronic rejection. Adverse events were observed in 57% of patients and 28% displayed infections; no patient discontinued EVL. There were 2 deaths: 1 due to an infection and the other due to postsurgical complication. No deaths due to cancer progression were observed. The results observed in this series suggested that conversion to EVL for a posttransplantation neoplasm is a valid therapeutic alternative to preserve graft function and control disease progression.

National survey of anemia prevalence after kidney transplantation in Argentina.

Anemia is prevalent in kidney transplant recipients and likely contributes to morbidity and mortality. The definition of anemia as established by the World Health Organization and subsequently adopted by the American Society of Transplantation is a hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men. Using this definition, the prevalence of anemia is nearly 30%. The National Survey of Post Transplant Anemia (PTA) in kidney transplant recipients in Argentina was conducted to evaluate the incidence of PTA at 1 year and its relationship to variables that influence transplantation outcome. At 1 year posttransplantation, mean (SD) hemoglobin concentration was 12.43 (1.77) g/dL (n = 379), hematocrit concentration was 38.26% (5.59%) (n = 379), serum creatinine concentration was 1.51 (0.72) mg/dL (n = 380), and creatinine clearance was 60.8 (22.47) mL/min (n = 334). The prevalence of PTA in Argentina at 1 year posttransplantation was 42.25%. At univariate analysis, female sex, immunosuppression regimen (mycophenolate mofetil plus mammalian target of rapamycin), and pediatric age group were associated with anemia. At multivariate analysis, only renal function and pediatric age group were associated with anemia. The mean hemoglobin level at year of transplant was 12.43 g/dL +/-1.77 and the prevalence of PTA in Argentina at year of transplant is 42.25%. Results of our survey show a correlation between Hb levels and graft function and pediatric recipient.

Use of enteric-coated mycophenolate sodium in de novo renal transplant recipients with high incidence of delayed graft function.

Patients with delayed graft function (DGF) are at risk of increased incidence for acute rejection episodes (ARE). Mycophenolate mofetil or induction therapy has produced a reduction in ARE incidence. An open, prospective, 3-month trial was performed in a group of Argentinian renal transplant recipients. We recruited 46 patients, 71.7% men, aged 41.7 +/- 13.8 years; including 36 (78.3%) recipients of cadaveric donors (CD) who were aged 43.4 +/- 15.5 years with a cold ischemia time of 19.4 hours +/- 5.4 minutes, and 10 (27.7%) recipients of living donors (LD) aged 37.8 +/- 12.9 years. HLA mismatches >or= 3 were observed in 58.4% of CD and in 7% of LD. All patients received two doses of basiliximab (20 mg each, days 0 and 4), cyclosporine microemulsion (CsA-ME) monitored by the second-hour concentrations (C2), enteric-coated mycophenolate sodium (EC-MPS; 720 mg twice a day, and steroids. A 58% incidence of DGF was observed. At the end of the third month the incidence of biopsy-proven ARE was 15%, with a median serum creatinine of was 1.54 +/- 0.42 mg/dL, including three grafts lost. Two patients died. No patient required EC-MPS dose discontinuation but 20% of patients required dose adjustments. The absence of discontinuations and the low incidence of dose adjustments of EC-MPS in this high-risk de novo population provided support of a suitable tolerability profile for this EC-MPS, and the possibility to impact efficacy results.

Evaluation of cortical bone by peripheral quantitative computed tomography in renal transplant recipients.

BACKGROUND: The absolute risk of fractures in renal transplant patients is 3 times that of matched controls. Most of the symptomatic fractures are peripheral, suggesting a greater compromise of cortical bone. Peripheral quantitative computed tomography (pQCT) is a new imaging technique that allows separate noninvasive evaluations of cortical and trabecular bones. We investigated cortical bone by pQCT in 12 renal transplant patients (seven men and five women) for comparison with 27 normal controls. METHODS: pQCT (XCT 960, Stratec, Pforheim, Germany) was performed upon the distal radius of the nondominant forearm (15% the length of the ulna, proximal from the radius end plate). We evaluated total and cortical bone mineral density (TBMD, cBMD), total (cross-sectional) and cortical area (TA, cA), cortical thickness (cThk), endosteal and periosteal circumferences, and the buckling ratio (r/cThK). RESULTS: Compared with normal controls transplant patients as a whole showed a significant increase in TA, in endosteal circumference (P < .001), and in the buckling ratio (P < .001) with a significant reduction in cThK (P < .001). Female patients had a marked decrease in cA (51.4 vs 69.3 [pixel n]; P < .0001) and cThK (2.08 vs 2.78 mm; P < .0001). Male patients also had a decrease in cThK (2.54 vs 3.30 mm; P = .0001) and an increase in endosteal perimeter (31.2 vs 26.4 mm; P < .0001). Total time on dialysis prior to renal graft correlated negatively with cortical thickness (r = .62; P < .01). CONCLUSIONS: Our results suggest that a marked thinning of cortical bone may explain the increased incidence of peripheral fractures among renal transplant patients.

[Antiviral sensitivity of herpes simplex virus in immunocompromised patients]. / Estudio de sensibilidad antiviral de virus herpes simplex en pacientes trasplantados.

The Herpes simplex Virus (HSV) resistance to acyclovir (ACV) occurs in a 5% of the inmunocompromised patients, approximately. The treatment with analogs of nucleosides, causes the appearance of resistent HSV-ACV stocks (ACVr) which can be produced by alteration in genes coding for the TK or the DNA-polymerase. A previous large-scale clinical study on ACVr HSV strains isolated from patients infected with human immunodeficiency virus indicated that 96% of ACVr HSV mutants were low producers of, or deficient in, TK activity (TK-), with 4% being TK mutants with an altered substrate specificity. No DNA Pol mutants were isolated. The pirophosphate analogs generate resistance in the gene of DNA-polymerase by mutation. In this paper we show the methodology used for the determination of sensibilite profiles to ACV and Phoscarnet (PFA) in a population of inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of transplanted patients. All samples, were inoculated in human fibroblasts and the HSV isolates were identified by inmunofluorescence whith monoclonal antibodies. These strains were amplified and the profile of susceptibility determinated in Vero cells, using 100 tissue culture inhibition dosis 50 (TCID50) of each Viral stock and the specific antiviral drugs in different concentrations. The cytopathic effect (CPE) was evaluated after 72hs. post infection. The 50% inhibitory concentration (CI50) was calculated from the percentage of inhibition of the ECP based on the concentration of the drug. From 46 isolations, 26 were HSV-1 and 20 were HSV-2. Two of them, one HSV-1 and one HSV-2, were resistant to ACV and none of the isolates were resistant to PFA.

Estudio de sensibilidad antiviral de virus herpes simplex en pacientes trasplantados / [Antiviral sensitivity of herpes simplex virus in immunocompromised patients]

The Herpes simplex Virus (HSV) resistance to acyclovir (ACV) occurs in a 5

of the inmunocompromised patients, approximately. The treatment with analogs of nucleosides, causes the appearance of resistent HSV-ACV stocks (ACVr) which can be produced by alteration in genes coding for the TK or the DNA-polymerase. A previous large-scale clinical study on ACVr HSV strains isolated from patients infected with human immunodeficiency virus indicated that 96

of ACVr HSV mutants were low producers of, or deficient in, TK activity (TK-), with 4

being TK mutants with an altered substrate specificity. No DNA Pol mutants were isolated. The pirophosphate analogs generate resistance in the gene of DNA-polymerase by mutation. In this paper we show the methodology used for the determination of sensibilite profiles to ACV and Phoscarnet (PFA) in a population of inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of transplanted patients. All samples, were inoculated in human fibroblasts and the HSV isolates were identified by inmunofluorescence whith monoclonal antibodies. These strains were amplified and the profile of susceptibility determinated in Vero cells, using 100 tissue culture inhibition dosis 50 (TCID50) of each Viral stock and the specific antiviral drugs in different concentrations. The cytopathic effect (CPE) was evaluated after 72hs. post infection. The 50

inhibitory concentration (CI50) was calculated from the percentage of inhibition of the ECP based on the concentration of the drug. From 46 isolations, 26 were HSV-1 and 20 were HSV-2. Two of them, one HSV-1 and one HSV-2, were resistant to ACV and none of the isolates were resistant to PFA.

Estudio de sensibilidad antiviral de virus herpes simplex en pacientes trasplantados. / [Antiviral sensitivity of herpes simplex virus in immunocompromised patients]

The Herpes simplex Virus (HSV) resistance to acyclovir (ACV) occurs in a 5

of the inmunocompromised patients, approximately. The treatment with analogs of nucleosides, causes the appearance of resistent HSV-ACV stocks (ACVr) which can be produced by alteration in genes coding for the TK or the DNA-polymerase. A previous large-scale clinical study on ACVr HSV strains isolated from patients infected with human immunodeficiency virus indicated that 96

of ACVr HSV mutants were low producers of, or deficient in, TK activity (TK-), with 4

being TK mutants with an altered substrate specificity. No DNA Pol mutants were isolated. The pirophosphate analogs generate resistance in the gene of DNA-polymerase by mutation. In this paper we show the methodology used for the determination of sensibilite profiles to ACV and Phoscarnet (PFA) in a population of inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of transplanted patients. All samples, were inoculated in human fibroblasts and the HSV isolates were identified by inmunofluorescence whith monoclonal antibodies. These strains were amplified and the profile of susceptibility determinated in Vero cells, using 100 tissue culture inhibition dosis 50 (TCID50) of each Viral stock and the specific antiviral drugs in different concentrations. The cytopathic effect (CPE) was evaluated after 72hs. post infection. The 50

inhibitory concentration (CI50) was calculated from the percentage of inhibition of the ECP based on the concentration of the drug. From 46 isolations, 26 were HSV-1 and 20 were HSV-2. Two of them, one HSV-1 and one HSV-2, were resistant to ACV and none of the isolates were resistant to PFA.

Chagas' disease in patients with kidney transplants: 7 years of experience 1989-1996.

Chagas' disease was present in 17.22% of persons undergoing kidney transplantation in an Argentine Hospital. The criterion for attributing reactivation of chronic Chagas' disease and transmission of Trypanosoma cruzi to grafts was detection of parasites in blood (patent parasitemia) or tissues. Reactivation was diagnosed in 5 (21.7%) of 23 recipients. Ten (43.4%) of 23 chagasic recipients without reactivation of chronic Chagas' disease had abrogation of serological reactivity. T. cruzi infection was transmitted to 3 (18.7%) of 16 non-chagasic recipients. Reactivation and infection were diagnosed by patent parasitemia or cutaneous panniculitis. For diagnosis, detection of parasites in blood and tissues had more relevance than serology. Sequential monitoring detected early reactivation and infection, permitting application of preemptive or therapeutic therapy with benznidazole, thus inhibiting, in all patients, severe clinical disease produced by a progressive and systemic replication of the parasite.