Características de los tratamientos biológicos en enfermedades reumáticas en Argentina: quinto informe del registro BIOBADASAR / Features of rheumatic diseases biological treatments in Argentina: BIOBADASAR fifth report

Introducción: El proyecto BIOBADASAR (Registro argentino deeventos adversos con tratamientos biológicos en reumatología)comenzó en agosto de 2010, para recabar información a largo plazosobre los eventos adversos en tratamientos biológicos en pacientescon enfermedades reumáticas en la práctica clínica cotidiana enArgentina.Pacientes y método: Se registraron datos de cada paciente,tratamientos y acontecimientos adversos relevantes o importantes.Los pacientes debían tener enfermedad diagnosticada y tratadacon un agente biológico. Cada caso se comparó con un control:un paciente con tratamiento no biológico con característicasdemográficas similares. Se analizaron los datos con análisis de lavarianza, con test de t de Student, Mann Whitney, test chi2, o testexacto de Fisher. El análisis de supervivencia de los tratamientoshasta su discontinuación o interrupción se realizó con el método deKaplan-Meier y test log-rank...

Background: BIOBADASAR (Argentine Registry of Adverse Eventsin Biological Treatments in Rheumatology) was started in August2010 to obtain long-term information of patients with rheumatic diseases,treatments and adverse events in everyday clinical practice.Patients and methods: Data on patients’ demographics,treatments and adverse events were collected. Patients had a diagnosisof a rheumatic disease and were treated with biological agent.To compare information, a control group was included, consisting ofpatients treated with similar demographic characteristics but treatedwith a non-biological agent. Data were analysed with Anova,Student´s t, Mann Whitney, chi2, Fisher´s exact tests, as appropriate.Survival analysis of treatments was performed with Kaplan-Meiercurves and log-rank test...

Variances in the Use of Everolimus in Kidney Transplantation: A 2-Year Registry of Everyday Practice.

BACKGROUND: Everolimus (EVL)-based immunosuppressive strategies may permit the reduction of calcineurin inhibitors (CNI) and their side effects, while offering a safe and efficient treatment. Our aim was to describe our experience with EVL in everyday practice and provide information for its optimal utilization. METHODS: Prospective, multicenter study of 181 kidney transplant recipients treated with EVL as part of their immunosuppressive regimen, with a follow-up of 24 months. We studied demographic data, transplant characteristics, clinical information, drugs used, serum creatinine, estimated glomerular filtration rate (eGFR), rejection episodes, and adverse events. RESULTS: In total, 181 renal transplant recipients were included. Of these, 30 (16.6%) received EVL de novo and 151 (83.4%) were converted; median time from transplantation to conversion was 10 (range, 1-312) months. Main reasons for conversion were prevention of interstitial fibrosis and tubular atrophy (23.9%), intolerance to immunosuppressants (11.1%), neoplasia (13.9%), nephrotoxicity (8.9%), and cytomegalovirus infections (8.3%). The eGFR values at baseline, months 12, and 24 were 46.4 ± 27.4 mL/min, 54.8 ± 22.9 mL/min, and 55.9 ± 26.5 ml/min, respectively. Two of 181 (1.1%) patients died, 5 of 181 (2.8%) lost their grafts, 12 of 181 (6.6%) had an episode of acute rejection, 13 of 181 (7.2%) had ≥1 serious event and infection, and 85 of 181 (49.9%) had ≥1 nonserious adverse event or infection. Multivariate analysis showed that increased eGFR at month 24 was associated with lower donor age, shorter time from transplant to EVL introduction, and a baseline eGFR ≥40 mL/min. CONCLUSION: Through different strategies among centers, the inclusion of EVL improved renal function during the first 12 months.

Cryptococcosis Presenting as a Colonic Ulcer in a Kidney Transplant Recipient: A Case Report.

We present a case of a 59-year-old woman with Chagas disease who received a kidney transplant. At month 44 post-transplantation, the patient presented with diarrhea that had persisted for 2 months. Colonoscopy showed a colon ulcer and differential diagnoses included cytomegalovirus, bacteria, or parasite infection; drug-related diarrhea; Crohn's disease; celiac disease; and malignancy. The ulcer tissue was positive for Cryptococcus neoformans. Successful treatment consisted of amphotericin B for 8 days and oral fluconazole (800 mg daily) for 3 months. This case illustrates that a colonic ulcer, although rare, could be cryptococcosis.

A rare case of Cryptococcus gattii pneumonia in a renal transplant patient.

Cryptococcus neoformans and Cryptococcus gattii are environmental fungi that can cause fever, cough, pneumonia, meningoencephalitis, dissemination, and death. C. gattii causes cryptococcomas more frequently than does C. neoformans and may require prolonged antifungal treatment. We present a rare case of C. gattii pneumonia in a renal transplant patient. A 44-year-old man, living in a rural area endemic for C. gattii and who had received a kidney transplant, was admitted to the hospital with fever, vomiting, weight loss, and diarrhea. A chest computed tomography revealed 2 alveolar, nodular, subpleural infiltrates in the periphery of the lungs. Differential diagnoses included infectious infiltrates, granulomatosis, embolization, and hemorrhage. C. gattii, molecular type VGI, was confirmed on day 28. Treatment consisted of amphotericin B at 1 mg/kg/day or fluconazole at 800 mg/day for first 6 weeks, followed by fluconazole at 400 mg/day for the subsequent 12 months. Response to the therapy has been slow. Because of the occurrence of outbreaks and its high morbidity and mortality rates, physicians must be aware of this complication in transplant recipients to avoid delays in diagnosis and to provide prompt management.

Renal transplantation in obese patients: experience in an Argentine center.

Possible complications of renal transplants in obese patients have raised concerns among nephrologists. We describe the outcomes of 110 renal transplant patients according to body mass index (BMI). Recipient BMI was calculated by using height and weight at time of transplantation and categorized according to World Health Organization guidelines. The patients' BMI values were as follows: underweight, n = 8 (7.27%); normal weight, n = 55 (50%); overweight, n = 30 (27.27%); and obese, n = 17 (15.45%). Mean age was significantly different among groups: underweight, 27.62 ± 7.57 years; normal weight, 44.98 ± 15.55 years; overweight, 50.53 ± 13.90 years; and obese, 52.11 ± 10.41 years (P < .05). Donor age and mean time of dialysis treatment were comparable in all groups. Underweight patients had a significantly larger proportion of living donors than those with higher BMIs. Calculated glomerular filtration rate (using the Modification of Diet in Renal Disease equation) were significantly different among the groups at 30, 60, and 90 days' posttransplantation. At 180 days, however, it was comparable: underweight, 62.96 ± 40.77 mL/min/1.73 m(2); normal weight, 53.55 ± 26.23 mL/min/1.73 m(2); overweight, 47.52 ± 16.37 mL/min/1.73 m(2); and obese, 46.19 ± 17.56 mL/min/1.73 m(2) (P = .34). Incidence of delayed graft function was as follows: underweight, 0%; normal weight, 30.4%; overweight, 53.3%; and obese, 64.1% (P < .05). The incidence of surgical complications, incidence of rejection within the first 6 months' posttransplantation, and graft and patient survival rates over 6 months did not differ among the groups. Because transplantation in obese patients may be associated with higher risks and costs, the evaluation of each center experience is imperative. Longer term assessments are warranted, but our short-term results show that outcomes in overweight or obese renal transplant patients are comparable to those in patients with lower BMI.

Conversion to belatacept-based immunosuppression therapy in renal transplant patients.

Belatacept, a fusion protein that prevents stimulation of the CD28 receptor, does not have the adverse renal, cardiovascular, and metabolic adverse effects associated with calcineurin inhibitors (CNIs). We present data on 8 renal transplant patients with graft dysfunction who were switched from CNI-based immunosuppressive therapy to belatacept in response to patients' specific needs. In patients 1 through 5, the belatacept regimen comprised 5-mg/kg doses on days 1, 15, 28, 43, and 57, then every 28 days with a decrease in the CNI dose. The CNI dose was tapered: 100% on day 1, 60% on day 15, 30% on day 23, and discontinued on day 29. In patients 6, 7, and 8, belatacept was administered at 10 mg/kg on days 1, 5, 15, 28, 60, and 90, and then at 5 mg/kg every 28 days. CNIs were withdrawn completely on day 1. Reasons for switching were intolerance to CNI, CNI toxicity, vascular lesions, interstitial fibrosis/tubular atrophy, or arterial hypertension. Renal function improved in all cases. Belatacept is approved to be used de novo; the uniqueness of our cases is that it was used in conversion and in patients with renal dysfunction. In the short term, patients did not present with any serious adverse events related to belatacept or cellular or humoral acute rejection episodes.

Use of everolimus in renal transplant recipients: data from a national registry.

Proliferation signal inhibitors, such as everolimus, offer immunosuppression without the toxicity of calcineurin inhibitors. This descriptive and prospective study reports outcomes at 1 year and predictors of improved estimated glomerular filtration rate (eGFR) in 174 renal transplant recipients from a national registry of the use of everolimus. At 1 year after conversion, 48.85% of patients had improved eGFR compared with baseline. The mean time from transplantation to initiation of treatment with everolimus was 47.97 months, the median 22 (range, 0-312) months. The kidneys were from deceased donors in 120 patients (68.79%) and from living donors in 54 (31.21%); 35 (20.83%) were expanded-criteria donors. When comparing the baseline versus 12-month values of laboratory results, total cholesterol levels and platelet counts differed significantly-191.55 ± 43.92 mg/dL versus 204.52 ± 41.29 mg/dL (P < .05) and 213,411 ± 63,231/mm(3) vs 255,571 ± 59,153/mm(3), respectively (P < .05)-but remained within clinically controllable ranges. Glycemia, triglycerides, hematocrit, hemoglobin, and leukocytes remained stable. Logistic regression analysis of baseline variables showed that the only independent prognostic factor for improved eGFR at 1 year was the conversion of patients to everolimus within the first 12 months after transplantation (odds ratio, 2.17; 95% confidence interval, 1.15-4.10). In conclusion, regarding the effectiveness of everolimus in our subjects, the only predictor of improved eGFR identified at 1 year was conversion within 12 months after transplantation.

Cerebral trypanosomiasis in a renal transplant recipient.

Chagas disease is a lifelong, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi. The main form of disease transmission is vector borne, but vertical transmission, such as by organ transplantation from a chronically infected donor, is also possible. The brain tumor-like form can occur years after infection and has been described in patients with acquired immunodeficiency syndrome, and in a very few cases in transplant recipients. We describe the case of a kidney transplant patient who was human immunodeficiency virus negative and infected with T. cruzi, and developed cerebral trypanosomiasis that was successfully treated with benznidazole at 7 mg/kg/day for 60 days. The risk of Chagas disease transmission should not be underestimated in renal transplant patients, even in non-endemic areas. Chagas disease can present as a tumor-like brain lesion, very difficult to differentiate from other opportunistic infectious or neoplastic processes. Frequent monitoring for T. cruzi infection is essential to promptly implement treatment, which, in our patient, proved to be effective and safe.

Infections with blaKPC-2-producing Klebsiella pneumoniae in renal transplant patients: a retrospective study.

In renal transplant recipients, the urinary tract is the most common site of infections that might be caused by pathogens while on immunosuppressive therapy. The spread of enterobacteria resistant to carbapenem is worrying, as it is generally used as this agent is the first-line therapy for infections caused by Enterobacteriaceae producing extended spectrum ß-lactamases. The most frequently encountered class A carbapenemases are the Klebsiella pneumoniae carbapenemase (KPC) enzymes. We describe the treatment and outcomes of 6 renal transplant patients who had urinary tract infections (UTIs) with blaKPC-2-producing K pneumoniae, confirmed by polymerase chain reaction amplification, namely 13.33% of renal transplant patients in the study period. Four patients survived, including 1 with reinfections and relapse, and 2 patients died. The antibiotics used for treatment, alone or combined, were colistin (n = 6, 42.8%), tigecycline (n = 5, 35.7%), doxycycline (n = 3, 21.4%), meropenem (n = 3, 21.4%), and fosfomycyn (n = 1, 7%). UTIs caused by carbapenemase-producing K pneumoniae are life-threatening. In the cases presented, favorable results were achieved with monotherapies using colistin, doxycycline, or meropenem.

Amelioration of renal damage by administration of anti-thymocyte globulin to potential donors in a brain death rat model.

Brain death (BD), a non-immunological factor of renal injury, triggers an inflammatory process causing pathological signs of cell death in the kidney, such as necrosis and apoptosis. Kidneys from brain dead donors show lower success rates than kidneys from living donors and one strategy to improve transplantation outcome is to precondition the donors. For the first time, anti-rat thymoglobulin (rATG) was administered in an experimental brain death animal model to evaluate if it could ameliorate histopathological damage and improve organ function. Animals were divided into three groups: V (n=5) ventilated for 2h; BD (n=5) brain death and ventilated for 2h; and BD+rATG (n=5) brain death, ventilated for 2h, rATG was administered during brain death (10mg/kg). We observed lower creatinine levels in treatment groups (means): V, 0·88±0·22 mg/dl; BD, 1·37±0·07 mg/dl; and BD+rATG, 0·64±0·02 mg/dl (BD versus BD+rATG, P<0·001). In the BD group there appeared to be a marked increase of ATN, whereas ATN was decreased significantly in the rATG group (V, 2·25±0·5 versus BD, 4·75±0·5, P<0·01; BD+rATG, 2·75±0·5 versus BD 4·75±0·5 P<0·01). Gene expression was evaluated with reverse transcription-polymerase chain reaction; tumour necrosis factor (TNF)-α, interleukin (IL)-6, C3, CD86 showed no significant difference between groups. Increased IL-10 and decreased CCL2 in BD+rATG compared to BD (both cases P<0·01). Myeloperoxidase was increased significantly after the brain death setting (V: 32±7·5 versus BD: 129±18). Findings suggest that rATG administered to potential donors may ameliorate renal damage caused by BD. These findings could contribute in the search for specific cytoprotective interventions to improve the quality and viability of transplanted organs.

A comparison of the psychometric strengths of the public-domain Zung Self-rating Depression Scale with the proprietary Beck Depression Inventory-II in Barbados.

OBJECTIVE: To compare the psychometric strengths of two venerable measures of depression, the Zung Self-rating Depression Scale (Zung SDS) and the Beck Depression Inventory-II (BDI-II) in a Caribbean university student population and to provide researchers and clinicians interested in measures of depression with psychometric evidence that differentiates the two instruments for a Caribbean sample. METHODS: Undergraduate student volunteers (n = 415; 75% females, 25% males; mean age = 25.2 years) completed the instruments as part of a larger study. Correlational analyses evaluated internal con-sistency reliabilities. Missing value analyses and corrected item-total correlations are also reported for each scale. RESULTS: The BDI-II demonstrated marginally superior internal consistency reliability (alpha = 0.88) than the Zung SDS (alpha = 0.85). Correlation between the Zung SDS and the BDI-II was strong (r = 0.67, p < 0.01). The Zung SDS was less psychometrically adequate, only 53% of respondents (compared to 81% for the BDI-II) completed the entire form, suggesting that the structure or wording of the questions may be problematic. Comparison of corrected item-total correlations and missing value analyses indicates that many Zung SDS items are problematic. A preliminary effort to evaluate the factor structure of the Zung SDS was complicated by the large number of missing values. CONCLUSION: Head-to-head comparison of the Zung SDS and the BDI-II indicates that the BDI-II demonstrates superior psychometric properties. This paper does not evaluate sensitivity and specificity; nonetheless, researchers interested in measures of depressive symptoms and clinicians looking for a tool to assess depression in Barbados can be confident in the strong psychometric properties of the BDI-II demonstrated thus far Modified versions of the Zung SDS merit further research.

Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model.

Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia-reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.