Evaluation of Frozen and Paraffin Sections Using the Maryland Aggregate Pathology Index Score in Donor Kidney Biopsy Specimens of a Brazilian Cohort.

The Maryland aggregate pathology index (MAPI) score is an important tool developed to help pathologists in evaluating potential organs for transplantation. It is based on analysis of five variables (present or absent): arteriolar hyalinosis (4 points), periglomerular fibrosis (2 points), arterial wall-lumen ratio superior to 0.5 (2 points), global glomerulosclerosis in more than 15% of glomeruli (2 points), and interstitial scar (3 points). Kidneys with a MAPI score >7 points are considered inadequate for donation. This study aimed to evaluate pathology agreement between frozen sections (FS) and paraffin sections (PS) using the MAPI score in a cohort of 262 biopsy specimens obtained at the General Hospital of Fortaleza, Brazil. We performed a retrospective review of pathological reports of FS (signed out by an on-call pathologist) and their corresponding PS (authorized by a specialist in renal pathology). Agreement was calculated using the Kappa test. Kappa values ranging from 0.29 to 0.51 were obtained when MAPI parameters were separately evaluated. When the score was used, the coefficient was 0.59. Fourteen of 262 kidneys were classified as inadequate for donation using PS and 8 cases were diagnosed using FS. There were no differences between wedge-shaped and filiform samples, apart from the mean number of glomeruli. Discordant cases had no statistical difference from concordant ones when clinical and macroscopic pathological parameters were analyzed. The MAPI score can be useful to minimize disagreements between FS and PS, but more effort should be made to standardize criteria and enable pathologists to recognize chronic lesions in FS samples.

Pre-emptive Therapy for Cytomegalovirus in Post-transplantation Liver Patients With Donor-Positive/Recipient-Negative Serostatus.

INTODUCTION: Infection by cytomegalovirus (CMV) is a major cause of morbidity among immunosuppressed patients, especially after solid organ transplantation. The risk of CMV after organ transplantation is strongly related to the serology of the donor and the recipient. The objective of this study was to analyze the outcomes and costs of pre-emptive therapy in patients after liver transplantation with donor-positive/recipient-negative (D+/R-) serostatus. METHODS: This retrospective study analyzed all patients who underwent liver transplantation with CMV serostatus D+/R- between January 2012 and December 2015. The service protocol adopts pre-emptive therapy. The outcomes and costs of this therapy are described. RESULTS: Of the 119 patients undergoing liver transplantation, 19 were D+/R- and entered the main analysis. Of these, 7 had positive polymerase chain reaction (PCR) results, and 1 developed CMV disease. Of the 6 patients who received no treatment, none developed CMV disease. Analyzing costs, pre-emptive therapy for these patients generated service savings of R$32,346.00. CONCLUSIONS: Although outcomes of universal prophylaxis and pre-emptive therapy are similar, pre-emptive therapy save on costs and have to be considered in patients with high-risk CMV disease after liver transplantation.

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

BACKGROUND: 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. METHODS: HIV-infected kidney transplant recipients and matched controls were evaluated for the incidence of delayed graft function (DGF), acute rejection (AR), infections, graft function, and survival of patients and renal grafts. RESULTS: Fifty-three HIV-infected recipients and 106 controls were enrolled. Baseline characteristics were similar, but a higher frequency of pre-transplant positivity for hepatitis C virus and cytomegalovirus infections was found in the HIV group. Immunosuppressive regimens did not differ, but a trend was observed toward lower use of anti-thymocyte globulin in the group of HIV-infected recipients (P = 0.079). The HIV-positive recipient group presented a higher incidence of treated AR (P = 0.036) and DGF (P = 0.044). Chronic Kidney Disease Epidemiology Collaboration estimated that glomerular filtration rate was similar at 6 months (P = 0.374) and at 12 months (P = 0.957). The median number of infections per patient was higher in the HIV-infected group (P = 0.018). The 1-year patient survival (P < 0.001) and graft survival (P = 0.004) were lower, but acceptable, in the group of HIV-infected patients. CONCLUSIONS: In the Brazilian experience, despite somewhat inferior outcomes, kidney transplantation is an adequate therapy for selected HIV-infected recipients.

Collaborative Brazilian Pediatric Renal Transplant Registry (CoBrazPed-RTx): A Report From 2004 to 2013.

BACKGROUND: The Collaborative Brazilian Pediatric Renal Transplant Registry started in 2004 as a multicenter initiative aiming to analyze, report, and share the results of pediatric kidney transplantation in Brazil. Data from all pediatric kidney transplants performed between January 2004 and December 2013 were recorded electronically and periodically updated. All patients under 18 years old from the participating centers were enrolled. Demographic data, etiology of chronic kidney disease, and patient and graft survival were analyzed. From a total of 2443 pediatric kidney transplants performed in Brazil during the study period, we report data from 1751 pediatric renal transplants performed in 13 centers enrolled in the collaborative study. Median age at transplantation was 12.4 years, and most of recipients were male (56%). The most common underlying renal etiologies were obstructive uropathy (31%) and glomerulopathy (26%). METHODS: According to donor source, 1155 (66%) of transplants were performed with deceased donors (DD). Initial immunosuppression consisted mainly of tacrolimus, mycophenolate, steroids, and induction therapy with anti-IL-2R antibodies. RESULTS: One-year graft survival (death-censored) was 93% and 90% (log rank test, P < .01), respectively, for living donor (LD) and DD. Graft losses (15%) were most frequently caused by vascular thrombosis, chronic allograft nephropathy, death with functioning kidney, acute rejection, and recurrent renal disease. Recipients of DD had 2.02 (95% confidence interval: 1.14-3.59) times the hazard of graft loss compared with those of LD (P = .015). Patient survival rates at 1 and 5 years were 98% and 97% for LD and 97% and 93% for DD, respectively. The mortality rate was 3.8%, mainly as the result of infection and cardiovascular disease. CONCLUSIONS: The results of this collaborative pediatric transplant study are comparable to international registries. Our effort has been able to maintain an exchange of information, both among the participating centers and with other international registries.

Historical cohort with diabetes mellitus after kidney transplantation and associated factors of its development in adult patients of a transplantation reference center in the State of Ceará, Brazil.

Post-transplantation diabetes mellitus (PTDM) is an important complication related to kidney transplantation (KT), and its occurrence is associated with increased morbidity and mortality. Nevertheless, KT is considered to be the most effective treatment option that offers better quality of life for patients with end-stage kidney disease. This study aimed to describe the occurrence of PTDM and the risk factors associated with its development in kidney transplant patients of a transplantation reference center in the State of Ceará (Brazil). This historical cohort study, based on medical records data, included adult patients undergoing KT from January 2006 to December 2010 in a public tertiary hospital. Multivariate analysis was performed with the use of a logistic regression model, with PTDM presence as dependent variable and the possible risk factors under study as independent variables. Throughout the evaluated period, 430 KTs were performed; 92 patients were excluded. Diabetes mellitus was already present in 9.2% of patients before KT. Hyperglycemia during the 1st month after transplantation occurred in 34.5% of recipients, and the occurrence of PTDM to the end of study was 19.9%. Factors associated with PTDM development were: fasting plasma glucose 1 month after KT (P < .001; odds ratio [OR] 1.05), deceased-donor KT (P = .015; OR 3.53), impaired fasting glucose before transplantation (P = .014; OR 4.10), and acute rejection occurrence (P = .003; OR 6.43). High PTDM occurrence was found, in accordance with the literature. Identification of factors associated with PTDM development, as well as its early diagnosis, could result in long-term improvement in patient and graft survivals.

Post-transplantation weight gain: prevalence and the impact of steroid-free therapy.

INTRODUCTION: Weight gain after renal transplantation has a multifactorial etiology, which can be associated with complications such as hypertension, dyslipidemia and diabetes, with a probable impact on cardiovascular morbidity and mortality post-transplantation. OBJECTIVE: The objectives of this study were to investigate the prevalence of weight gain and obesity post-transplantation among renal recipients of a hospital and to evaluate the impact of immunosuppressive therapy without steroids. MATERIALS AND METHODS: We have evaluated all patients who had kidney transplantations performed between January 2005 and December 2009 at General Hospital of Fortaleza, who were older than 18 years of age and had at least 12 months of follow-up post-transplantation. Overweight was defined as body mass index (BMI) between 25 and 30 kg/m(2) and obesity >30 kg/m(2). The association between weight gain and the following variables was investigated: age and gender of the recipient and the donor, donor type, steroid use, presence of systemic arterial hypertension (SAH) and diabetes mellitus, creatinine, glucose, cholesterol, and triglycerides. RESULTS: The study population included 203 recipients; 59.5% were males, their mean age systemic arterial hypertension (SAH) was 37 years, and 64.2% had deceased donors. In regard to immunosuppression, 41.3% made use of steroids. After 36 months of follow-up, the average weight gain was 6.6 kg in relation to the first month post-transplantation. Among the variables studied, the recipient's younger age and female gender, the younger donor, and the creatinine level were associated with greater weight gain after 36 months of transplantation. CONCLUSION: The percentage of weight gain was on average 9% after 36 months post-transplantation, although the prevalence of overweight and obesity increased significantly in the same period. The use of steroid therapy had no impact on the percentage of weight gain post-transplantation, and association was observed only between the younger age and the female gender of the recipient, the younger donor age, and the creatinine level with the highest weight gain post-transplantation.

The risk factors for and effects of visceral leishmaniasis in graft and renal transplant recipients.

BACKGROUND: The aim of this study was to identify the risk factors for visceral leishmaniasis (VL) in renal transplant recipients and to analyze the impacts of this disease on graft success and patient health. METHODS: This retrospective, case-control study examined 120 renal transplant patients in a VL endemic area. The treatment group included patients (n=20) who developed VL after transplantation, and the control group (n=100) was composed of renal transplant recipients without VL. This study evaluated socioeconomic, demographic, clinical, and laboratory variables. Bivariate analysis and multiple logistic regressions were performed to identify potential risk factors. RESULTS: The average time between transplantation and Leishmania infection in the treatment group was 29.4 months. Seventeen (85%) patients were cured and 3 (15%) died. In 95% of the cases, a myelogram was used for initial identification of Leishmania forms. The significant risk factors for VL in renal transplant recipients were cytomegalovirus infection after transplantation (odds ratio [OR], 5.29; 95% confidence interval [CI], 1.27-21.97) and living with cats (OR, 5.74; 95% CI, 1.15-28.76). Bacterial infection after transplantation (OR, 3.00; 95% CI, 0.96-9.37) and unpaved streets in the neighborhood (OR, 2.14; 95% CI, 0.71-6.43) tended to increase the risk of VL, whereas a negative Rh factor tended to protect against VL (OR, 0.26; 95% CI, 0.06-1.02). CONCLUSION: Cytomegalovirus infection after transplantation and living with cats increased the risk of VL in renal transplant recipients living in VL endemic areas.

Creatinine-based equations predicting chronic kidney disease after kidney donation.

BACKGROUND: Kidney donation is associated with few adverse outcomes in living donors. The aim of this study was to evaluate the outcomes of living kidney donors and the utility of creatinine-based equations to predict chronic kidney disease. METHODS: The study population was selected among 154 living kidney donors from 2001 to 2009. Seventy-eight patients underwent medical consultation to review demographic data and perform laboratory evaluations. Estimated glomerular filtration rate (GFR) values were obtained by three equations: Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (C-G) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Receiver operating characteristic (ROC) analysis was performed to determine the area under the curve of each equation to predict evolution to chronic kidney disease. RESULTS: The overall median age was 39 years including 64% of women subjects. The mean follow-up after kidney donation was 65 ± 34 months. During follow-up, 20.5% of patients developed hypertension. Serum creatinine values above 1.5 mg/dL were detected in 14.1% of cases. Dyslipidemia was present in 33.3% of donors at the last follow-up. According to measured creatinine clearance and the C-G equation, only four and six donors had renal failure (defined as GFR < 60 mL/min), a number that increased to 23 (29.4%) when considering the MDRD or CKD-EPI equations (P < .05). ROC curves performed to explore the GFR measurements to predict renal failure occurrence after donation showed the CKD-EPI to be the only one with a significant area under the curve (0.7442, P = .003). CONCLUSION: Living kidney donors should receive careful long-term follow-up. Assessment of renal function before donation using CKD-EPI creatinine-based equations must be performed preferentially. A careful approach should be adopted for the detection and treatment of other complications such as hypertension and dyslipidemia.

Successful organ transplantation from donors poisoned with a carbamate insecticide.

Currently, liver transplantation is the only option for patients with end-stage liver disease. In Brazil, the mortality rate on the waiting list is about 25%. Multiple strategies to expand the donor pool are being pursed, however, grafts from poisoned donors are rarely used. This report documents successful liver, kidney and heart transplantations from four female donors who suffered brain death by hypoxia despite cardiopulmonary resuscitation following Aldicarb exposure ([2-methyl-2-(methylthio)propionaldehyde O-(methylcarbamoyl)-oxime]). The success rate of 12 grafts from four donors poisoned by Aldicarb was 91% 6 months after transplantation. Poisoned patients are another pool of organ donors who at present are probably underused by transplantation services. More studies are necessary to confirm the safety for the recipients.

Visceral leishmaniasis in renal transplant recipients: clinical aspects, diagnostic problems, and response to treatment.

Visceral leishmaniasis (VL) is a parasitic infection that uncommonly affects renal transplantation recipients, even in endemic areas. It may be associated with other infections, or masked by these, and may present subclinically and/or atypically for extended periods. The evolution may be particularly severe and diagnosis is often delayed. If not adequately diagnosed and treated, VL can be fatal and so should be suspected in renal transplantation recipients presenting unexplained fever, splenomegaly, and pancytopenia. The authors report 8 cases of VL out of a total of 800 renal transplant recipients from two transplant hospitals centers in Brazil. The clinical, diagnostic, and therapeutic features are reviewed.

A new cyclosporin derivative, SDZ-IMM-125, prolongs renal allograft survival in dogs.

Previous studies in vitro and in rodent transplantation models have suggested that an analogue of cyclosporin, SDZ-IMM-125, has immunosuppressive properties at least equivalent to that of cyclosporin. As the bioavailability of the drug was considered to be greater than that of cyclosporin, it was hoped that lower doses could be used with the avoidance of nephrotoxicity. Renal allografts were undertaken between beagle dogs from two partially inbred breeding colonies. After transplantation, SDZ-IMM-125 was given orally at a dosage of 5, 7.5, 10 or 20 mg/kg/day, and graft survival compared to that in dogs given cyclosporin 10 mg/kg or in untreated animals. The results showed that SDZ-IMM-125 is immunosuppressive in dogs and prolongs graft survival up to 50 days at a dosage of 20 mg/kg/day. However, at this dose histological changes suggestive of liver toxicity were observed in one dog, and mild anaemia was produced,but there was no evidence of nephrotoxicity. Absorption profiles suggested that the drug is rapidly absorbed and metabolized, and that a more frequent daily dosage may be appropriate. Overall, there appeared to be no significant advantage for the analogue SDZ-IMM-125 over cyclosporin. The transplant model was associated with a high spontaneous renovascular thrombosis rate, particularly after cyclosporin administration, which was prevented by the daily administration of aspirin.

A new method for quantification of islets by measurement of zinc content.

The ability to quantify the yield of pancreatic islet tissue after isolation is important for interlaboratory comparisons and for the assessment of islet yield prior to clinical transplantation. Because pancreatic islets contain a much higher concentration of zinc than other tissues, we investigated the analysis of zinc as a measure of islet tissue yield. Rat islets of standard diameter 250 microns were handpicked into samples containing 10-80 islets. The zinc content was measured by EAAS and showed a linear correlation with islet number. A zinc binding fluorescent dye, TSQ, was investigated as a way of simplifying the zinc measurement for routine use. Samples of 10-80 islets of 250 microns were sonicated in 3 ml zinc-free water, 0.18 mumol TSQ was added, and the TSQ-zinc fluorescence was measured at 480 nm. A linear correlation was observed. Exocrine contamination up to 50% barely affected the results. Islet zinc content also was shown to be correlated linearly with islet number for freshly isolated human islets. Measurement of zinc by TSQ fluorescence is a rapid, cheap, and objective measure of islet tissue content.