Laila Viana

Wound healing complications in kidney transplant recipients receiving everolimus.

Background De novo use of mammalian target of rapamycin inhibitors after kidney transplantation is associated with a concentration-dependent incidence of wound healing adverse events (WHAE). The objective of this analysis was to compare the incidence of WHAE in patients receiving everolimus (EVR) or mycophenolate sodium (MPS). Methods This was a predefined subanalysis of a single-center prospective randomized study in which 288 kidney transplant recipients receiving tacrolimus and prednisone were randomized for 3 different regimens: rabbit antithymocyte globulin (r-ATG)/EVR (N = 85); basiliximab (BAS)/EVR (N = 102); BAS/MPS (N = 101). Clinical WHAE were prospectively collected using a prespecified case report form in all study visits. Abdominal ultrasound was performed at 30 days posttransplant to capture subclinical abnormalities. Surgeons were blinded to randomized treatment and no specific surgical procedures were implemented. Results A higher proportion of patients in BAS/EVR showed at least 1 clinical WHAE (22.3% vs 35.3% vs 22.0%, P = 0.03) and total clinical and subclinical WHAE (35% vs 42% vs 26%, P = 0.014) compared with BAS/MPS, respectively. A higher proportion of patients in r-ATG/EVR showed subclinical WHAE (13% vs 7% vs 4%, P = 0.025) compared with BAS/MPS, respectively. Patients receiving EVR showed a higher risk of developing clinical or subclinical WHAE (r-ATG/EVR vs BAS/MPS hazard ratio 1.30; BAS/EVR vs BAS/MPS hazard ratio 1.73, P = 0.028). Conclusions In this cohort of de novo kidney transplant recipients receiving tacrolimus and prednisone, the use of EVR was associated with higher incidence of combined clinical and subclinical WHAE compared with MPS.

Cost-Effectiveness Analysis of Everolimus versus Mycophenolate in Kidney Transplant Recipients Receiving No Pharmacological Prophylaxis for Cytomegalovirus Infection: A Short-Term Pharmacoeconomic Evaluation (12 Months)

BACKGROUND Modern immunosuppressive regimens, although associated with improved 1-year graft survival, are associated with adverse effects, including opportunistic infections, diabetes mellitus after transplantation, cardiovascular complications, and de novo malignancies. OBJECTIVES To determine the short-term (12 months) cost-effectiveness of everolimus (EVR) versus mycophenolate sodium (MPS) in kidney transplant recipients receiving induction therapy, tacrolimus, prednisone, and no prophylaxis for cytomegalovirus infection. METHODS A Markov state transition model was designed. Data from a single-center prospective trial were used along with data from the centers medical bills database. The target population comprised adults with low immunological risk submitted to first ABO-compatible transplantation with kidneys recovered from living or deceased donors. The time horizon was 12 months. The interventions included tacrolimus and prednisone plus a single 3-mg/kg dose of rabbit antithymocyte globulin (ATG) and EVR or basiliximab (BAS) and EVR or BAS and MPS. The clinical outcomes considered for this analysis were cytomegalovirus infection/disease, acute rejection, graft dysfunction, surgical complications, graft loss, and life-years gained. RESULTS ATG/EVR was cost-saving compared with BAS/MPS on all evaluated outcomes; BAS/EVR outperformed BAS/MPS on most of the evaluated outcomes. Results were confirmed by sensitivity analysis. CONCLUSIONS Compared with MPS, EVR is an alternative immunosuppressive agent that is able to provide resource-saving to the health care provider with effectiveness gains for the patient.

Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and Everolimus

Background: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). Methods: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. Results: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m2, p = 0.207). Conclusion: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.

Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation.

BACKGROUND The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation. METHODS 144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R-), use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months. RESULTS The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R-, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG), 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC=0.849±0.042, p<0.001). Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation. CONCLUSION Targeted preemptive therapy in patients with perceived higher risk for cytomegalovirus infection/disease was effective in preventing severe clinical presentation, including tissue invasive and late cytomegalovirus infection. This strategy is associated with direct and indirect cost-savings.

The influence of mTOR inhibitors on the incidence of CMV infection in high-risk donor positive-recipient negative (D+/R−) kidney transplant recipients

Several studies and meta‐analysis suggest the mTOR inhibitors are associated with reduced incidence of CMV infection after kidney transplantation, although their effects on the high‐risk population have not been investigated thoroughly.

The diagnostic yield and complications of open lung biopsies in kidney transplant patients with pulmonary disease

BACKGROUND The purpose of this study was to assess the efficacy of open lung biopsy (OLB) in determining the specific diagnosis and the related complications in patients with undiagnosed diffuse pulmonary infiltrates. METHODS This single center, retrospective study included adult kidney transplant patients who underwent OLB. The patients had diffuse pulmonary infiltrates without definitive diagnoses and failed to respond to empiric antibiotic treatment. We analyzed the number of specific diagnoses, changes in treatment and the occurrence of complications in these patients. A logistic regression was used to determine which variables were predictors of hospital mortality. RESULTS From April 2010 to April 2014, 87 patients consecutively underwent OLB. A specific diagnosis was reached in 74 (85.1%) patients. In 46 patients (53%), their therapeutic management was changed after the OLB results. Twenty-five (28.7%) patients had complications related to the OLB. The hospital mortality rate was 25.2%. Age, SAPS3 score and complications related to the procedure were independent predictors of all-cause mortality. CONCLUSIONS OLB is a high-risk procedure with a high diagnostic yield in kidney transplant patients with diffuse pulmonary infiltrates who did not have a definitive diagnosis and who failed to respond to empiric antibiotic treatment. Complications related to OLB were common and were independently associated with intra-hospital mortality.

The current burden of cytomegalovirus infection in kidney transplantrecipients receiving no pharmacological prophylaxis

Cytomegalovirus (CMV) infection in kidney transplantation has changed its clinical spectrum, mostly due to the current and more effective immunosuppression. In the absence of preventive strategies it is associated with significant morbi-mortality. OBJECTIVE This study evaluated the incidence of CMV events and its effect on outcomes of kidney transplantation in recipients without pharmacological prophylaxis or targeted preemptive treatment. RESULTS The study cohort comprised 802 recipients of kidney transplants between 04/30/2014 and 04/30/2015. The majority received induction with anti-thymocyte globulin (81.5%), tacrolimus and prednisone in combination with either mycophenolate (46.3%) or azathioprine (53.7%). The overall incidence of CMV events was 42% (58.6% infection and 41.4% disease). Patients with CMV showed higher incidence of first treated acute rejection (19 vs. 11%, p = 0,001) compared with those without CMV but no differences in graft loss, death or loss to follow-up. The incidence of delayed graft function was higher (56% vs. 37%, p = 0.000) and the eGFR at 1 (41 ± 21 vs. 54 ± 28 ml/min, p = 0.000) and 12 months (50 ± 19 vs. 61 ± 29 ml/min, p = 0.000) were lower in patients with CMV. Recipients age (OR = 1.03), negative CMV serology (OR = 5.21) and use of mycophenolate (OR = 1.67) were associated with increased risk of CMV. Changes in immunosuppression was more often in patients with CMV (63% vs. 31%, p = 0.000). CONCLUSION the incidence of CMV events was high and associated with higher incidence of acute rejection and changes in immunosuppression. Besides traditional risk factors, renal function at 1 month was independently associated with CMV infection.

The effect of anti-thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis

The use of mTOR inhibitors is associated with lower incidence of CMV infections but its effect on viral load has not been investigated.

Clinical Features of Kidney Transplant Recipients Admitted to the Intensive Care Unit

Introduction: There is a paucity of data regarding the complications in kidney transplant patients who may require intensive care unit (ICU) management, despite being the most common solid organ transplant worldwide. Objective: To identify the main reasons for ICU admission and to determine the factors associated with hospital mortality in kidney transplant recipients. Design: This single-center retrospective cohort study was conducted between September 2013 and June 2014, including all consecutive kidney transplant patients requiring ICU admission. We collected data on patient demographics, transplant characteristics, clinical data, and prognostic scores. The independent determinants of hospital mortality were identified by multiple logistic regression analysis. We also assessed the performance of Simplified Acute Physiology Score 3 (SAPS 3) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Results: We analyzed data from 413 patients, the majority of whom were admitted late after renal transplantation (1169 days; 63-3003 days). The main reason for admission was sepsis (33.2%), followed by cardiovascular disease (16%). Age (odds ratio [OR] 1.05, confidence interval [CI], 1.01-1.09), SAPS 3 score (OR 1.04, CI, 1.01-1.08), the need for mechanical ventilation (OR 26.47, CI, 10.30-68.08), and vasopressor use (OR 3.34, CI, 1.37-8.13) were independently associated with hospital mortality. The performance of SAPS 3 and APACHE II scores was poor in this population and overestimated the mortality rates. Conclusion: Sepsis was the main reason for ICU admission in kidney transplant recipients, followed by cardiovascular disease. Age and disease severity were associated with hospital mortality.

Histoplasmose disseminada em uma paciente transplantada renal

Histoplasmosis is a fungus infection that mainly affects immunosuppressed patients. The authors present a case of a kidney transplant recipient who developed sepsis-like histoplasmosis, na atypical but severe manifestation of the disease. The fungus was found in blood and in a skin biopsy, and the treatment with liposomal amphotericin resulted in hepatotoxicity.