Renal Transplantation in HIV-Infected Patients: The First Portuguese Review

INTRODUCTION: With the introduction of combination antiretroviral therapy (cART), prognosis of human immunodeficiency virus (HIV) infection has been improved and kidney transplantation (KT) in HIV-positive patients became possible. METHODS: We reviewed the demographic, clinical, laboratory, and therapeutic data of all the HIV-infected patients who underwent KT between 2009 (first KT in Portugal in a HIV-infected patient) and May 2014. Case accrual was through all Portuguese KT centers where a KT in an HIV-infected patient was performed. Patients were transplanted following the American and Spanish guideline recommendations that included maintenance on cART, undetectable plasma HIV RNA copies, and absolute CD4 counts of ≥ 200 cells/μL in the last 6 months. RESULTS: Fourteen KT were performed on men and 3 on women. The mean age of patients at the time of transplantation was 49.9 ± 11.7 years. HIV status was known for 12 ± 5 years. Eight patients had AIDS in the past and all patients received grafts from deceased donors. Twelve patients (64.7%) underwent induction therapy with basiliximab and 2 patients experienced early graft loss. In 2 patients, humoral rejection was diagnosed and in 3 patients, cellular rejection. Two patients died and an additional patient had early graft loss. CONCLUSION: KT is a possible, but challenging, renal replacement therapy in selected HIV-positive patients. Even in those with AIDS criteria in the past, when the disease is controlled, and after the reconstitution of the immune system with cART, KT can be performed. Nevertheless, the risk-benefit ratio for each patient needs to be taken in consideration.

Tetanus as a cause of acute renal failure: possible role of rhabdomyolysis

To study the frequency and examine the role of rhabdomyolysis in the acute renalfailure in tetanus 18 patients with the diagnosis of generalized tetanus consecutively admitted to the infectious disease hospital were evaluated. Ofthese 14 were male and 4female with mean age of 31.8± 2.0 years. Except for mild proteinuria recorded in 9 patients, the urinalysis were unremarkable. Serum creatinine higher than 1.4mg/dl was recorded in 39% of the patients, abnormal levels of CPK in 87,5% and serum myoglobin greater than 120µg/l in 39% of the patients. Oliguria was documented in one patient and none required diafysis therapy. No correlation wasfound between renal failure and myoglobin and/or CPK serum levels. Acute renalfailure in tetanus was not infrequent; usualfy it was non-oliguric, mild and transient and not related to the severity of the disease or to serum levels of myoglobin and/or CPK.

Prevalence of latent tuberculosis and treatment adherence among patients with chronic kidney disease in Campo Grande, State of Mato Grosso do Sul

Introduction The primary strategy for tuberculosis control involves identifying individuals with latent tuberculosis. This study aimed to estimate the prevalence of latent tuberculosis in chronic kidney disease (CKD) patients who were undergoing hemodialysis in Campo Grande, State of Mato Grosso do Sul, Brazil, to characterize the sociodemographic and clinical profiles of patients with latent tuberculosis, to verify the association between sociodemographic and clinical characteristics and the occurrence of latent tuberculosis, and to monitor patient adherence to latent tuberculosis treatment. Methods This epidemiological study involved 418 CKD patients who were undergoing hemodialysis and who underwent a tuberculin skin test. Results The prevalence of latent tuberculosis was 10.3%. The mean patient age was 53.43±14.97 years, and the patients were predominantly men (63.9%). The population was primarily Caucasian (58.6%); half (50%) were married, and 49.8% had incomplete primary educations. Previous contact with tuberculosis patients was reported by 80% of the participants. Treatment adherence was 97.7%. Conclusions We conclude that the prevalence of latent tuberculosis in our study population was low. Previous contact with patients with active tuberculosis increased the occurrence of latent infection. Although treatment adherence was high in this study, it is crucial to monitor tuberculosis treatment administered to patients in health services to maintain this high rate.

A qualidade de vida da pessoa com doença renal crónica em programa regular de hemodiálise

Dissertação de mestrado em Enfermagem

Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Outcome of acute renal failure associated with cardiac surgery in infants

OBJECTIVE: To analyze the impact of acute renal failure (ARF) on the evolution of infants undergoing cardiac surgery. METHODS: We assessed 15 infants undergoing cardiac surgery who developed (ARF). Their demographic, clinical and surgical data, and evolution were analyzed. RESULTS: Their mean age was 4.4±4.0 months (8 days to 24 months). Twelve infants were males, and 4 patients already had ARF at surgery. The primary cause of ARF was immediate acute cardiac dysfunction in 10 infants, cardiac dysfunction associated with sepsis in 2 infants, and isolated sepsis in 3 infants. All children depended on mechanical ventilation during their postoperative period, 14 infants used vasoactive drugs, and 11 had an infectious process associated with ARF. Thirteen infants required dialytic treatment. Eleven infants developed oluguric ARF, and all had to undergo peritoneal dialysis; of the 4 patients with non-oliguric, 2 required dialysis, the main indication being hypervolemia. Of these 13 dialyzed infants, 4 died in the first 24 hours because of the severity of the underlying cardiac disease (mean urea level of 49±20 mg/dl). The mortality rate for the entire group was 60% , and it was higher among the patients with oliguria ARF (73% vs 25%, p<0.001). The cause of death was acute cardiac dysfunction in 6 infants (early type-1ARF) and sepsis in the 3 remaining infants (late type-2 ARF). CONCLUSION: The mortality rate of ARF associated with cardiac surgery in infants was hight, being higher among children with oliguria; peritoneal dialysis was indicated due to clinically uncontrolled hypervolemia and not to the uremic hypercatabolic state.

Effects of high glucose concentrations on the endothelial function of the renal microcirculation of rabbits

OBJECTIVE: To assess the acute effects of high glucose concentrations on vascular reactivity in the isolated non diabetic rabbit kidney. METHODS: Rabbits were anaesthetized for isolation of the kidneys. Renal arteries and veins were cannulated for perfusion with Krebs-Henselleit solution and measurement of perfusion pressure. After 3 hours of perfusion with glucose 5,5 mM (control ) and 15 mM, the circulation was submitted to sub maximal precontraction (80% of maximal response) trough continuous infusion of noradrenaline 10 mM. Vascular reactivity was then assessed trough dose-responses curves with endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators. The influence of hyperosmolarity was analyzed with perfusion with mannitol 15mM. RESULTS: A significant reduction in the endothelium-dependent vasodilation in glucose 15mM group was observed compared to that in control, but there was no difference in endothelium-independent vasodilation. After perfusion with mannitol 15 mM, a less expressive reduction in endothelium-dependent vasodilation was observed, only reaching significance in regard to the greatest dose of acetylcholine. CONCLUSION: High levels of glucose similar to those found in diabetic patients in the postprandial period can cause significant acute changes in renal vascular reactivity rabbits. In diabetic patients these effects may also occur and contribute to diabetes vascular disease.

Lesão renal aguda após revascularização do miocárdio com circulação extracorpórea

FUNDAMENTO: A lesão renal aguda (LRA) é uma doença complexa para a qual, atualmente, não há uma definição padrão aceita. A AKIN (Acute Kidney Injury Network) representa uma tentativa de padronização dos critérios para diagnóstico e estadiamento da LRA, baseando-se nos critérios RIFLE (risk, injury, failure, loss, e end-stage kidney disease), publicados recentemente. OBJETIVOS: Avaliar a incidência e mortalidade associada à LRA em pacientes submetidos à revascularização do miocárdio (RM) com circulação extracorpórea (CEC). MÉTODOS: O total de 817 pacientes foi dividido em dois grupos: LRA negativa (-), com 421 pacientes (51,5%), e LRA positiva (+), com 396 pacientes (48,5%). Foi considerado LRA a elevação da creatinina em 0,3 mg/dl ou aumento em 50% da creatinina em relação a seu valor basal. RESULTADOS: A mortalidade em 30 dias dos pacientes com e sem LRA foi de 12,6 % e 1,4%, respectivamente (p < 0,0001). Em um modelo de regressão logística multivariada, LRA após RM com CEC foi preditora independente de óbito em 30 dias (OR 6,7 - p = 0,0002). Esse grupo de pacientes teve maior tempo de permanência em UTI [mediana 2 dias (2 a 3) vs. 3 dias (2 a 5) - p < 0,0001)] e uma maior proporção de pacientes com permanência prolongada na terapia intensiva (> 14 dias) - 14% vs. 2%; p < 0,0001. CONCLUSÃO: Na população estudada, mesmo uma discreta alteração da função renal baseada nos critérios do "Acute Kidney Injury Network - AKIN" foi preditora independente de óbito em 30 dias após RM com CEC.

Biomarkers in Cardiology - Part 2: In Coronary Heart Disease, Valve Disease and Special Situations

Cardiovascular diseases are the main causes of mortality and morbidity in Brazil. Their primary and secondary preventions are a priority for the health system and require multiple approaches for increased effectiveness. Biomarkers are tools used to identify with greater accuracy high-risk individuals, establish a faster diagnosis, guide treatment, and determine prognosis. This review aims to highlight the importance of biomarkers in clinical cardiology practice and raise relevant points regarding their application and perspectives for the next few years. This document was divided into two parts. This second part addresses the application of biomarkers in coronary heart disease, valvular diseases, cardio-oncology, pulmonary embolism, and cardiorenal syndrome.

Human Tissue Kallikrein Activity in Angiographically Documented Chronic Stable Coronary Artery Disease

AbstractBackground:Human tissue kallikrein (hK1) is a key enzyme in the kallikrein–kinin system (KKS). hK1-specific amidase activity is reduced in urine samples from hypertensive and heart failure (HF) patients. The pathophysiologic role of hK1 in coronary artery disease (CAD) remains unclear.Objective:To evaluate hK1-specific amidase activity in the urine of CAD patientsMethods:Sixty-five individuals (18–75 years) who underwent cardiac catheterism (CATH) were included. Random midstream urine samples were collected immediately before CATH. Patients were classified in two groups according to the presence of coronary lesions: CAD (43 patients) and non-CAD (22 patients). hK1 amidase activity was estimated using the chromogenic substrate D-Val-Leu-Arg-Nan. Creatinine was determined using Jaffé’s method. Urinary hK1-specific amidase activity was expressed as µM/(min · mg creatinine) to correct for differences in urine flow rates.Results:Urinary hK1-specific amidase activity levels were similar between CAD [0.146 µM/(min ·mg creatinine)] and non-CAD [0.189 µM/(min . mg creatinine)] patients (p = 0.803) and remained similar to values previously reported for hypertensive patients [0.210 µM/(min . mg creatinine)] and HF patients [0.104 µM/(min . mg creatinine)]. CAD severity and hypertension were not observed to significantly affect urinary hK1-specific amidase activity.Conclusion:CAD patients had low levels of urinary hK1-specific amidase activity, suggesting that renal KKS activity may be reduced in patients with this disease.

Atendimento no Ambulatório de Nutrição Renal da Faculdade de Nutrição da Universidade Federal Fluminense e Hospital Universitário Antônio Pedro : efeitos de um programa de treino de força intradialítica em pacientes renais crónicos

Relatório de estágio de mestrado, Nutrição Clínica, Universidade de Lisboa, Faculdade de Medicina, 2015

Schistosomal glomerular disease (a review)

In this review paper schistosomal glomerulopathy is defined as an immune-complex disease. The disease appears in 12-15 per cent of the individuals with hepatosplenic schistosomiasis. Portal hypertension with collateral circulation helps the by pass of the hepatic clearance process and the parasite antigens can bind to antibodies in the circulation and be trapped in the renal glomerulus. Chronic membranousproliferative glomerulonephritis is the most commom lesion present and the nephrotic syndrome is the usual form of clinical presentation. The disease can be experimentally produced, and schistosomal antigens and antibodies, as well as complement, can be demonstrated in the glomerular lesions. Specific treatment of schistosomiasis does not seem to alter the clinical course of schistosomal nephropathy.

New measurements of energy expenditure and physical activity in chronic kidney disease.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

Effect on renal function of tenofovir co-administered with either efavirenz or boosted lopinavir or boosted atazanavir: the Swiss HIV Cohort Study

Reduced re'nal function has been reported with tenofovir disoproxil fumarate (TDF). It is not clear whether TDF co-administered with a boosted protease inhibitor (PI) leads to a greater decline in renal function than TDF co-administered with a non-nucleoside reverse transcriptase inhibitor (NNRTI).Methods: We selected ail antiretroviral therapy-naive patients in the Swiss HIV Cohort Study (SHCS) with calibrated or corrected serum creatinine measurements starting antiretroviral therapy with TDF and either efavirenz (EFV) or the ritonavir-boosted PIs, lopinavir (LPV/r) or atazanavir (ATV/r). As a measure of renal function, we used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate the glomerular filtration rate (eGFR). We calculated the difference in eGFR over time between two therapies using a marginal model for repeated measures. In weighted analyses, observations were weighted by the product of their point of treatment and censoring weights to adjust for differences both in the sort of patients starting each therapy and in the sort of patients remaining on each therapy over time.Results: By March 2011, 940 patients with at least one creatinine measurement on a first therapy with either TDF and EFV (n=484), TDF and LPVlr (n=269) or TDF and ATV/r (n=187) had been followed for a median of 1. 7, 1.2 and 1.3 years, respectively. Table 1 shows the difference in average estimated GFR (eGFR) over time since starting cART for two marginal models. The first model was not adjusted for potential confounders; the second mode! used weights to adjust for confounders. The results suggest a greater decline in renal function during the first 6 months if TDF is used with a PI rather than with an NNRTI, but no further difference between these therapies after the first 6 months. TDF and ATV/r may lead to a greater decline in the first 6 months than TDF and LPVlr.Conclusions: TDF co-administered with a boosted PI leads to a greater de cline in renal function over the first 6 months of therapy than TDF co-administered with an NNRTI; this decline may be worse with ATV/r than with LPV/r.

Renal sodium handling and nighttime blood pressure.

Blood pressure follows a circadian rhythm with a physiologic 10% to 20% decrease during the night. There is now increasing evidence that a blunted decrease or an increase in nighttime blood pressure is associated with a greater prevalence of target organ damage and a faster disease progression in patients with chronic kidney diseases. Several factors contribute to the changes in nighttime blood pressure including changes in hormonal profiles such as variations in the activity of the renin-angiotensin and the sympathetic nervous systems. Recently, it was hypothesized that the absence of a blood pressure decrease during the nighttime (nondipping) is in fact a pressure-natriuresis mechanism enabling subjects with an impaired capacity to excrete sodium to remain in sodium balance. In this article, we review the clinical and epidemiologic data that tend to support this hypothesis. Moreover, we show that most, if not all, clinical conditions associated with an impaired dipping profile are diseases associated either with a low glomerular filtration rate and/or an impaired ability to excrete sodium. These observations would suggest that renal function, and most importantly the ability to eliminate sodium during the day, is indeed a key determinant of the circadian rhythm of blood pressure.