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.

De novo use of everolimus with elimination or minimization of cyclosporine in renal transplant recipients.

BACKGROUND: The purpose of two similarly designed multicenter, prospective, parallel-group, open-label studies was to evaluate early cyclosporine (CsA) elimination versus minimization from an everolimus-CsA-steroid regimen in de novo renal transplant patients. METHODS: Within 24 hours after transplantation, 170 renal transplant patients received everolimus (trough levels 3-8 ng/mL), CsA, and steroids. Those eligible (n = 114) were randomized (1:1) at 3 months to have CsA elimination by month 4 to 6 (±1 week) with everolimus trough levels maintained at 6 to 12 ng/mL or CsA minimization, until 12 months. The randomized population excluded those who discontinued the study prior to randomization due to adverse events, acute rejection episodes of Banff grade IIb/III, or worsening renal function during the month prior to randomization. RESULTS: At 12 months, the estimated glomerular filtration rate (Nankivell) with CsA elimination was noninferior versus CsA minimization (P < .0001, α-level 0.05; 90% confidence interval 0.6-8.5) by 7 mL/min/1.73 m(2) (noninferiority margin). Composite efficacy failure was comparable with CsA elimination and CsA minimization (18.9% and 17.5%, respectively, P = 1.000) and no graft loss or death was reported after randomization. Cytomegalovirus infections were rare under everolimus treatment, and no pneumonitis episode was reported. CONCLUSION: In our selected randomized study population, immediate initiation of everolimus allowed CsA elimination. Renal function was stable on everolimus-based, CsA-free maintenance regimen without compromising efficacy.

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.

[Efficacy, tolerability and safety of cyclosporine for microemulsion in the treatment of active rheumatoid arthritis. Open study]. / Eficacia, tolerabilidad y seguridad de la ciclosporina para microemulsión en el tratamiento de la artritis reumatoidea activa. Estudio abierto.

Cyclosporine for microemulsion has been widely used in the treatment of rheumatoid arthritis (RA) with remarkably good results over progression of joint damage, as reported by the GRISAR Study. A local group in Argentina, performed a prospective, open label study (Neo-Ra-02), consisting of 12 centres which recruited 50 RA patients, who were followed during 6 months in order to assess efficacy, tolerability and safety of cyclosporine microemulsion in the treatment of RA. Efficacy parameters were: morning stiffness, functional evaluation (HAQ, Lee and Ritchie index) and laboratory and radiological (Larsen score) assessments. Safety parameters were: blood pressure and renal, liver and hematological laboratory data. Patients criteria for participation were: presence of active RA (as defined by the ACR), Steinbrocker anatomic and functional grade I to III, disease evolution no longer than 5 years, no previous history of hypertension, renal or liver disease and absence of DMARDs use during the previous 2 months. There was a statistically significant decrease in morning stiffness and in pain evolution. Improvement became evident after 4 weeks of treatment. Reduction of Ritchie index was significant also at 4 weeks and the same observation was made with tenderness and swollen joint scores. Regarding evolution of CRP and RF, a statistically significant reduction was observed only in positive RF. Safety parameters showed no significant increase in serum creatinine or uric acid: 6/50 patients developed mild hypertension with only a significant increase in systolic blood pressure in comparison with baseline. Cyclosporine microemulsion demonstrated efficacy with minimal adverse events (12% mild hypertension) when appropriately monitored and administered in low doses (3 mg/kg/day).

Eficacia, tolerabilidad y seguridad de la ciclosporina para microemulsión en el tratamiento de la artritis reumatoidea activa. Estudio abierto. / [Efficacy, tolerability and safety of cyclosporine for microemulsion in the treatment of active rheumatoid arthritis. Open study]

Cyclosporine for microemulsion has been widely used in the treatment of rheumatoid arthritis (RA) with remarkably good results over progression of joint damage, as reported by the GRISAR Study. A local group in Argentina, performed a prospective, open label study (Neo-Ra-02), consisting of 12 centres which recruited 50 RA patients, who were followed during 6 months in order to assess efficacy, tolerability and safety of cyclosporine microemulsion in the treatment of RA. Efficacy parameters were: morning stiffness, functional evaluation (HAQ, Lee and Ritchie index) and laboratory and radiological (Larsen score) assessments. Safety parameters were: blood pressure and renal, liver and hematological laboratory data. Patients criteria for participation were: presence of active RA (as defined by the ACR), Steinbrocker anatomic and functional grade I to III, disease evolution no longer than 5 years, no previous history of hypertension, renal or liver disease and absence of DMARDs use during the previous 2 months. There was a statistically significant decrease in morning stiffness and in pain evolution. Improvement became evident after 4 weeks of treatment. Reduction of Ritchie index was significant also at 4 weeks and the same observation was made with tenderness and swollen joint scores. Regarding evolution of CRP and RF, a statistically significant reduction was observed only in positive RF. Safety parameters showed no significant increase in serum creatinine or uric acid: 6/50 patients developed mild hypertension with only a significant increase in systolic blood pressure in comparison with baseline. Cyclosporine microemulsion demonstrated efficacy with minimal adverse events (12

mild hypertension) when appropriately monitored and administered in low doses (3 mg/kg/day).

[New spine and non-spine fractures in 871 women/year treated with oral pamidronate plus calcium and vitamin D supplements]. / Nuevas fracturas vertebrales y no vertebrales en 871 mujeres/año tratadas con pamidronato oral y suplementos de calcio y vitamina D.

A sample of 871.3 patients/year was conformed by 205 postmenopausal women, aged 64.8 +/- 18.2 years (mean +/- SD), followed up during 51 +/- 12 months. All have osteoporosis, diagnosis assessed through radiological findings of at least one atraumatic fracture or vertebral crush ("severe osteoporosis" according to the new WHO classification). Each woman received 100 mg/day oral pamidronate (enteric coated soft gelatin capsules), half an hour before breakfast. Additional calcium and vitamin D were supplemented as follows: Total daily calcium = 1 g provided by diet and/or calcium carbonate. Vitamin D equivalent to 400-1200 IU/day. All patients were recommended to improve their physical activity, at least by walking exercise. Clinical examination radiological, bone mineral density (BMD) and biochemical studies were periodically performed. But, fracture indicence was the end-point of the study. Same was related to the 1,673 fall episodes recorded in the sample. In addition, height loss, lumbar BMD, proximal femur BMD, are also reported. Data has been cross-sectional collected in March 1995. All patients improved the symptomatology, specifically pain. This, and the good tolerability of the treatments proved to be considerably favorable for their compliance. Within the observation period, only 12 patients decreased their height (5.85%; mean = 0.85 cm; range = 0.5-2.0 cm). Lumbar spine BMD increased in 90% of 48 women. Mean gain after 2 years was 5.3 +/- 1.0% (p < 0.001). Proximal femur increased in 78% of other 32 women. Mean gain 6.3 +/- 0.7% (p < 0.001) after 2 years. A total of 78 new fractures were recorded, 47 vertebral crush, 29 forearm fractures and 2 hip fractures. Its incidence related to the fall episodes was of 2.8; 1.7 and 0.12% respectively. When compared with a historical estimated data, from an untreated population (Cummings SR et al, 1994), both, the total number of new fractures and the new hip fractures were significantly lower (p < 0.01) in our treated population than the reference data. Pamidronate, in oral doses of 100 mg/day, adequately supplemented with calcium and vitamin D, proved to be effective and a well tolerated therapy. The low rate of height's loss, BMD significant increases in subgroups of patients and the low rate of new fractures, strongly support the use of the compound to treat severe osteoporotic women. To our knowledge, this is the first time, that the new fracture incidence is related to the fall frequency reported in a bisphosphonate treated sample.