Elizete Keitel

Clinical evaluation of a dried blood spot method for determination of mycophenolic acid in renal transplant patients.

OBJECTIVES The aim of this study is to evaluate the clinical application of dried blood spots (DBS) sampling in renal transplant patients under mycophenolic acid (MPA) immunosuppression, comparing measurements performed in paired plasma and DBS samples. DESIGN AND METHODS 77 paired DBS and plasma samples were obtained from 19 renal transplant patients. MPA was measured in both matrices by HPLC-DAD. Estimated plasma concentrations (EPC) were calculated from DBS concentrations (DC) using the formula EPC=DC/[1-(Hct/100)], using either individual or mean hematocrit (Hct). Agreement between methods was evaluated using Passing-Bablok regression and Bland-Altman difference plots. RESULTS MPA concentrations in DBS were in mean 60.7% of those measured in plasma. EPC calculated from DBS and patients individual Hct presented a high correlation with blood plasma (r=0.9862), and comparable absolute values (slope 1.0563 and intercept -0.0739), being in mean 102.2% of the measured plasma concentrations. EPC can also be calculated with the mean Hct of the group of patients, with similar results. CONCLUSIONS DBS sampling can be used for TDM of MPA in a clinical setting, employing conventional HPLC equipment, presenting similar results to plasma samples after a proper mathematical treatment. Moreover, due to its intrinsic stability and handling safety, DBS sampling can be considered a useful alternative especially in developing countries where sample logistics could be a major difficulty.

Kidney transplantation in children weighing less than 15 kg: Extraperitoneal surgical access–experience with 62 cases

Small children are a challenging group in whom to perform KT. This retrospective study analyzed the results of 62 KTs in children weighing <15 kg, performed between 1998 and 2010, using extraperitoneal access and anastomosis of the renal vessels of donors to the aorta and IVC or iliac vessels of the recipients. Thirty‐two (51.6%) grafts were LRDTs and 30 (48.4%) were DDRTs—28 of them pediatric. The mean age at KT was 3.7 ± 2.2 yr (1–12), and the mean weight was 12.3 ± 2.1 kg (5.6–14.9). Ten children weighed <10 kg, and five (8.1%) children presented previous thrombosis of the venous system. At one and five yr, patient survival was 93.2% and 84.2%, and graft survival was 85.2% and 72.7%. There were no differences between the rates for LRDT and DDRT. There were six vascular complications (four vascular thromboses, one laceration, and one renal artery stenosis) and two perirenal collections. Extraperitoneal access is a valid KT technique in children weighing <15 kg.

Use of tacrolimus and the development of posttransplant diabetes mellitus: a Brazilian single-center, observational study.

INTRODUCTION Posttransplant diabetes mellitus (PTDM) is considered to be a serious complication of kidney transplantation that may reduce patient and graft survival. The immunosuppressant tacrolimus (TAC) increases the risk of developing PTDM. PURPOSE We sought to estimate the risk of PTDM among renal transplant recipients treated with TAC, to identify other risk factors for PTDM, and to describe its consequences. METHODS We retrospectively analyzed 413 recipients of ages >or=18 years who were free of diabetes before kidney transplantation. They were treated with TAC, cyclosporine (CyA), or sirolimus (SIR) plus steroid therapy with a minimum follow-up posttransplant of 6 months. PTDM was diagnosed according to American Diabetes Association guidelines. RESULTS The mean age was 42.3 years and 230 (55.7%) were male. The initial immunosuppression for 171 (41.4%) patients was TAC; 221 (53.5%), CyA; and 21 (5.1%), SIR. PTDM occurred in 85/413 (20.6%) of patients. The median time to PTDM development was 54 days posttransplant. The cumulative incidence of PTDM was 24.6% and 17.2% for TAC and CyA treatment groups, respectively. In the intention-to-treat analysis, the proportion of patients receiving TAC who developed PTDM was significantly higher than that of CyA (HR = 1.6 [1.01-2.42]; P = .04). The Kaplan-Meier method showed that 78.5% patients taking TAC were free of PTDM at 6 months compared with 88.8% taking CyA (P = .003). The other independent risk factors were body mass index (BMI; P < .0001); recipient age (P < .0001) and acute rejection episodes (AE; P = .01). Three-year actuarial graft survivals were 85.5% for PTDM patients compared with 93.3% for those without diabetes (P = .021); patient survivals, 88.9% and 96.7%, respectively (P = .017). CONCLUSION The incidence of PTDM is associated with TAC use, recipient age, BMI, and ARE. Therefore, PTDM is an important risk factor for graft loss and mortality.

Epidemiology of tuberculosis after kidney transplantation in a developing country

Tuberculosis (TB) is a great challenge in kidney transplantation, and is often associated with high morbidity and mortality. The aim of this study was to evaluate the epidemiology, clinical manifestations, and impact of TB in kidney transplant (KT) recipients.

Diffuse parenchymal form of malakoplakia in renal transplant recipient: a case report.

Malakoplakia is an unusual chronic inflammatory disease related to prior urinary tract infection. It is characterized by the presence of macrophages with foamy cytoplasm exhibiting larger PAS positive inclusions that stain for calcium and iron. Malakoplakia affects renal allograft and is associated with severe morbidity. Herein, the authors report a new case of renal graft malakoplakia in a 23-year-old female patient. The patient received a living-related donor renal transplantation with a high immunological risk. Plasmapheresis and intravenous immunoglobulin (i.v. Ig) treatment, pre- and post-transplant, and induction with rabbit anti-thymocyte globulins were used due to presence of donor specific antibodies and positive B cross match by flow cytometry. The patient had an early urinary tract infection with a good outcome. On Day 36 post-transplant (PO), the patient returned to the clinic with fever, graft pain and acute renal dysfunction leading to hemodialysis. Escherichia coli (E. coli) was present in the blood and urine culture. At the time, the renal biopsy revealed numerous sheets of macrophages with foamy, eosinophilic cytoplasm showing several PAS positive granules and large inclusions that stained strongly with hematoxylin, calcium (von Kossa method) and iron (Prussian blue). The patient was diagnosed with malakoplakia related to a kidney transplant. Despite prolonged treatment with antibiotics, determined by a susceptibility test, the patient did not recover renal function and remained on dialysis.

Freqüência de dermatoses infecciosas em 208 pacientes transplantados renais

BACKGROUND: Chronic immunosuppressive therapy predisposes renal transplant recipients to a heightened susceptibility to infectious dermatoses. OBJECTIVES: evaluate the frequency of infectious dermatoses in 208 renal transplant recipients over a 12-month period and verify the relation between the onset of dermatoses and the time elapsed since transplantation. METHOD: 208 renal transplant recipients, taken from a population of 720 transplant recipients, received a dermatological examination for a year. Dermatopathological examination, mycological examination, bacteriologic examination, and cultures were taken from suspected lesions. RESULTS: the prevalence of infectious dermatosis was 89.4% in this population. The more frequent fungal, viral and bacterial infections were respectively pitiyriasis versicolor (17.8%), warts (32.2%), and folliculitis (4.3%). CONCLUSION: infectious dermatoses are common in renal transplant recipients. Their occurrence is progressively higher as time passes after the transplantation, therefore making the frequent dermatological examination of these recipients very important.

Histopathological analysis of pre-implantation donor kidney biopsies: association with graft survival and function in one year post-transplantation

INTRODUCTION Pre-implantation kidney biopsy is a decision-making tool when considering the use of grafts from deceased donors with expanded criteria, implanting one or two kidneys and comparing this to post-transplantation biopsies. The role of histopathological alterations in kidney compartments as a prognostic factor in graft survival and function has had conflicting results. OBJECTIVE This study evaluated the prevalence of chronic alterations in pre-implant biopsies of kidney grafts and the association of findings with graft function and survival in one year post-transplant. METHODS 110 biopsies were analyzed between 2006 and 2009 at Santa Casa de Porto Alegre, including live donors, ideal deceased donors and those with expanded criteria. The score was computed according to criteria suggested by Remuzzi. The glomerular filtration rate (GFR) was calculated using the abbreviated MDRD formula. RESULTS No statistical difference was found in the survival of donors stratified according to Remuzzi criteria. The GFR was significantly associated with the total scores in the groups with mild and moderate alterations, and in the kidney compartments alone, by univariate analysis. The multivariate model found an association with the presence of arteriosclerosis, glomerulosclerosis, acute rejection and delayed graft function. CONCLUSION Pre-transplant chronic kidney alterations did not influence the post-transplantation one-year graft survival, but arteriosclerosis and glomerulosclerosis is predictive of a worse GFR. Delayed graft function and acute rejection are independent prognostic factors.

Renal transplantation in human immunodeficiency virus-infected recipients: a case-control study from the Brazilian experience

Highly active antiretroviral therapy has turned human immunodeficiency virus (HIV)‐infected patients with end‐stage renal disease into suitable candidates for renal transplantation. We present the Brazilian experience with kidney transplantation in HIV‐infected recipients observed in a multicenter study.

Simultaneous Pancreas-Kidney Transplantation: Evaluation of Graft Function, Cholesterol, Triglycerides, and Immunosuppressive Regimens

AIMS To evaluate pancreas graft function, use of insulin, cholesterol, triglyceride levels, prescription of lipid-lowering drugs, and immunosuppressive regimens among recipients of simultaneous pancreas-kidney transplants (SPKT), who had initial immunosuppression with tacrolimus, sirolimus, and corticosteroids. METHODS From 2000 to 2007, we performed 73 SKPT, among which we conducted a retrospective data analysis on 51 medical records of patients who had been followed for at least 6 to 72 months. We excluded from the analysis eight recipients who died before 6 months: eight with early pancreas graft losses and six for continued follow-up in other centers. RESULTS There were four pancreas graft losses after 6 months due in two diabetes mellitus recurrence, one posttuberculosis treatment, and one after use of nonsteroidal inflammatory medication. Mean plasma glucose levels ranged from 84 to 103 mg/dL, while glycosylated hemoglobin (HbA1) levels ranged from 5.7% to 6.2%. At 6, 12, 36, and 60 months, 80%, 91%, 86%, and 75% of recipients, respectively, had HbA1 lower than 6.5%. In the same period, 10%, 8%, 10%, and 11% of recipients became insulin-dependent. Mean cholesterol levels (mg/dL) at 6, 12, 36, and 60 month were 190, 180, 196 and 193, while triglyceride levels (mg/dL) were 162, 129, 106, and 113 respectively. Recipients rate of lipid-lowering drug use was 18%, 21%, 20%, and 22% at 6, 12, 36, and 60 months. Mean serum creatinine levels (mg/dL) with standard deviations were 1.3 +/- 0.4, 1.5 +/- 0.4, 1.6 +/- 0.5, 1.8 +/- 0.9, at 6, 12, 36 and 60 months respectively. Nineteen recipients had sirolimus suspended and 14 recipients, tacrolimus suspended as well for various reasons. CONCLUSION Mean plasma glucose levels were normal during the period. About 10% of recipients became insulin-dependent and 20% required lipid-lowering drugs. The immunosuppressive regimen protocol had to be changed in 60% of patients.

A safety evaluation of belatacept for the treatment of kidney transplant.

ABSTRACT Introduction: Improving long-term survival in kidney transplantation is one of the main goals in modern immunosuppressive research. Current standard immunosuppression based in a combination of calcineurin inhibitors (CNI) and antiproliferatives, with or without steroids, has improved short-term graft survival. In the last decade, belatacept has been evaluated as a CNI free option regimen addressing better kidney transplant outcomes. Areas covered: This paper reviewed the indications, mechanisms of action, pharmacology and published trials using belatacept in different clinical situations. The main objective was to evaluate the safety of this immunosuppressive drug. Expert opinion: Kidney transplant patients receiving belatacept demonstrated improvement in renal function, less chronic allograft nephropathy, a more favorable metabolic profile and lower donor-specific antibody formation compared with cyclosporine. Based on the published data and on our personal experience, we have good expectations on belatacept use in the future. If these characteristics will translate in sustained better renal function, less chronic kidney disease-related complications and lower cardiovascular risk, improving patient and graft survival and quality of life, is still to be assessed with longer term follow-up and a larger number of exposed patients.