José Hermógenes Rocco Suassuna

ExoU-induced vascular hyperpermeability and platelet activation in the course of experimental Pseudomonas aeruginosa pneumosepsis.

To address the question whether ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, can induce hemostatic abnormalities during the course of pneumosepsis, mice were instilled i.t. with the ExoU-producing PA103 P. aeruginosa or with a mutant obtained by deletion of the exoU gene. Control animals were instilled with sterile vehicle. To assess the role of ExoU in animal survival, mice were evaluated for 72 h. In all the other experiments, animals were studied at 24 h after infection. PA103-infected mice showed significantly higher mortality rate, lower blood leukocyte concentration, and higher platelet concentration and hematocrit than animals infected with the bacterial mutant, as well as evidences of increased vascular permeability and plasma leakage, which were confirmed by our finding of higher protein concentration in bronchoalveolar lavage fluids and by the Evans blue dye assay. Platelets from PA103-infected mice demonstrated features of activation, assessed by the flow cytometric detection of higher percentage of P-selectin expression and of platelet-derived microparticles as well as by the enzyme immunoassay detection of increased thromboxane A2 concentration in animal plasma. Histopathology of lung and kidney sections from PA103-infected mice exhibited evidences of thrombus formation that were not detected in sections of animals from the other groups. Our results demonstrate the ability of ExoU to induce vascular hyperpermeability, platelet activation, and thrombus formation during P. aeruginosa pneumosepsis, and we speculate that this ability may contribute to the reported poor outcome of patients with severe infection by ExoU-producing P. aeruginosa.

Dividing stage 3 of chronic kidney disease (CKD): 3A and 3B

To the Editor: Changing the chronic kidney disease (CKD) staging system, as proposed by Winearls and Glassock,1 could have a negative impact on prevention. One of the hardest tasks faced by a nephrologist is breaking the news about imminent dialysis to an unsuspecting patient. This gets ever more painful if early signs of kidney disease, such as a mildly depressed glomerular filtration rate (eGFR), were somehow uncovered in the past but the patient was reassured without further testing and sent home only to learn otherwise at a later date. Bad as it seems, this is a recurrent experience for any nephrologist. Therefore, we were concerned with this proposition to revise the Kidney Disease Outcomes Quality Initiative (KDOQI) staging system of CKD and eliminate the current early stages of the system. Although we recognize that a proportion of healthy individuals may be transitorily mislabeled as CKD patients, we believe that it is better to raise the possibility of incipient CKD and discard it afterward than to miss diagnosis by not looking for it. The current staging system of CKD has been very successful in bringing worldwide uniformity to the nomenclature and has met the goal of raising awareness within the renal and nonrenal medical communities to new levels. Rather than a matter of opinion, this is a ripe area for scientific inquiry. We challenge the renal community, as would be the case with any new classification system, to use tools of diagnostic statistics and to determine the predictive values of KDOQI staging within the different categories so that we can act and inform our patients appropriately.

Screening for Decreased Glomerular Filtration Rate and Associated Risk Factors in a Cohort of HIV-Infected Patients in a Middle-Income Country

With the introduction of combined active antiretroviral therapy and the improved survival of HIV-infected patients, degenerative diseases and drug toxicity have emerged as long-term concerns. We studied the prevalence of decreased glomerular filtration rate (GFR) and associated risk factors in a cohort of HIV-infected patients from a middle-income country. Our cross-sectional study included all adult patients who attended an urban outpatient clinic in 2008. GFR was estimated using the CKD-EPI equation. The prevalence ratio (PR) of decreased GFR (defined as <60 mL/min/1.73 m2) was estimated using generalizing linear models assuming a Poisson distribution. We analyzed data from 1,970 patients, of which 82.9% had been exposed to ART. A total of 249 patients (12.6%) had a GFR between 60 and 89 mL/min/1.73 m2, 3.1% had a GFR between 30 and 59, 0.3% had a GFR between 15 and 29, and 0.4% had a GFR <15. Decreased GFR was found in only 74 patients (3.8%). In the multivariate regression model, the factors that were independently associated with a GFR below 60 mL/min/1.73 m2 were as follows: age ≥50 years (PR = 3.4; 95% CI: 1.7–6.8), diabetes (PR = 2.0; 95% CI: 1.2–3.4), hypertension (PR = 2.0; 95% CI: 1.3–3.2), current CD4+ cell count <350 cells/mm3 (PR = 2.1; 95% CI: 1.3–3.3), past exposure to tenofovir (PR = 4.7; 95% CI: 2.3–9.4) and past exposure to indinavir (PR = 1.7; 95% CI: 1.0–2.8). As in high-income countries, CKD was the predominant form of kidney involvement among HIV-infected individuals in our setting. The risk factors associated with decreased glomerular filtration were broad and included virus-related factors as well as degenerative and nephrotoxic factors. Despite the potential for nephrotoxicity associated with some antiretroviral drugs, in the short-term, advanced chronic renal disease remains very rare.

Multiple correspondence analysis in predictive logistic modelling: Application to a living-donor kidney transplantation data

This work deals with the use of multiple correspondence analysis (MCA) and a weighted Euclidean distance (the tolerance distance) as an exploratory tool in developing predictive logistic models. The method was applied to a living-donor kidney transplant data set with 109 cases and 13 predictors. This approach, followed by backward and forward selection procedures, yielded two models, one with four and another with two predictors. These models were compared to two other models, ordinarily built by backward and forward stepwise selection, which yielded, respectively, five and two predictors. After internal validation, the models performance statistics showed similar results. Likelihood ratio tests suggested that backward approach achieved a better fit than the forward modelling in both methods and the Vuongs non-nested test between backward-built models suggested that these were undistinguishable. We conclude that the tolerance distance, in combination with MCA, could be a feasible method for variable selection in logistic modelling, when there are several categorical predictors.

Hemodynamic assessment in the critically ill patient

A growing fraction of the clinical duties of Nephrologists is undertaken inside intensive care units. While assessing patients with acute renal failure in the context of circulatory collapse, which are also edematous and/or with impaired gas exchanges, the Nephrologist must decide between two opposing therapies: 1) remove volume with the aid of dialysis or diuretics to improve the edematous state; 2) volume expand to improve hemodynamics. To minimize the odds of making incorrect choices, the Nephrologist must be familiar with the tools available for determining the adequacy of volume status and for invasive hemodynamic monitoring in the critically ill patient. In this manuscript, we will briefly review the physiology of extra cellular fluid volume regulation and then tackle the issue of volume status assessment, based on clinical and hemodynamic criteria.

Predialysis hypernatremia is a prognostic marker in acute kidney injury in need of renal replacement therapy

BACKGROUND AND OBJECTIVES The present study aimed to evaluate the prognostic impact of predialysis dysnatremia in patients with acute kidney injury requiring renal replacement therapy (RRT). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS A secondary analysis of a prospective multicenter cohort study was performed. Serum sodium (Na) concentrations were categorized immediately before the first RRT as normonatremia (135≤Na ≤145mEq/L), hyponatremia (mild [130≤Na ≤134mEq/L] or severe [Na ≤129mEq/L]), and hypernatremia (mild [146≤Na ≤155mEq/L] or severe [Na ≥156mEq/L]). Multivariable logistic regression was used to estimate the impact of sodium levels categories on hospital mortality. RESULTS Dysnatremia occurred in 47.3% of 772 included patients. Hypernatremia was more frequent than hyponatremia (33.7% vs 13.6%, P=.001). Intensive care unit (ICU) and hospital mortality rates were 64.6% and 69%, respectively. Hospital mortality was higher in severe hypernatremia (89.1% [95% confidence interval {CI}, 78.7%-95.8%] vs 64.6% [CI, 59.8%-69.2%], P<.001, in normonatremia). Older patients, clinical admission, number of comorbidities, length of ICU stay before the beginning of RRT, and the number of organ dysfunctions were associated with higher hospital mortality. In multivariate analysis, severe hypernatremia (odds ratio, 2.87; 95% CI, 1.2-6.9), poor chronic heath status, severity of illness, sepsis, and lactate were independently associated with outcome. CONCLUSION Almost 50% of patients with acute kidney injury in need of RRT in the ICU had mild or severe dysnatremia before dialysis initiation. Hypernatremia was the main sodium disturbance and independently associated with poor outcome in the study population.

Successful Live Kidney Transplantation After Chikungunya Disease in the Donor

José Andrade Moura-Neto, Ana Flávia de Souza Moura, Edison Souza, Jorge Luiz de Carvalho Henriques Jr, Mônica Barcellos Arruda, Luciana Santos Pessoa, Lídia Theodoro Boullosa, Orlando da Costa Ferreira Junior and José Hermógenes Rocco Suassuna Clinical and Academic Unit of Nephrology, Hospital Universitário Pedro Ernesto, Rio de Janeiro State University, Rio de Janeiro, Brazil; CSB Group of Nephrology, Salvador, Brazil; and Molecular Virology Laboratory, Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Renouncement of renal replacement therapy: withdrawal andrefusal

Renouncement of renal replacement therapy (RRT) is a medical dilemma. This review covers the concept, the magnitude, the prognosis, and discusses strategies and management approaches about this subject in patients with CKD and AKI. Evidence suggests that refusal is more frequent and carries a more guarded prognosis than withdrawal of RRT. When RRT is not expected to be beneficial in terms of survival or quality of life, conservative treatment and palliative care are alternatives. We review the historical evolution of guidelines about renouncement of RRT and palliative care, and highlight the absence of specific recommendations in Brazil. However renouncement of RRT may be ethically and legally accepted in Brazil, as the right to a dignified death. Longer life expectancy, economic pressures, and greater awareness will require a more detailed discussion about indications and sustainable use of RRT, and possibly the elaboration of national guidelines.

Oncocitoma renal em paciente transplantado: achados de imagem naultrassonografia com contraste

Abstract Renal oncocytoma is an infrequently reported renal neoplasm, often asymptomatic, which usually behaves as a benign entity and is identified accidentally on radiological imaging. Transplant patients under long-term immunosuppressive drugs have a high prevalence of cancers, such as skin cancers, lymphoproliferative disorders, and renal carcinomas. We present a case report of an asymptomatic renal oncocytoma in a kidney transplant recipient presenting persistent hematuria. The features of computed tomography and contrast-enhanced ultrasound (CEUS) are presented. This was the first time we used CEUS in a transplant kidney recipient presenting a renal mass, allowing the real-time visualization of contrast-enhancement patterns during all vascular phases for the differential diagnosis of renal tumors. Although the pattern of intense vascularization could mislead to an early judgment as a malignant lesion, it could help to exclude other renal lesions without inducing nephrotoxicity.Renal oncocytoma is an infrequently reported renal neoplasm, often asymptomatic, which usually behaves as a benign entity and is identified accidentally on radiological imaging. Transplant patients under long-term immunosuppressive drugs have a high prevalence of cancers, such as skin cancers, lymphoproliferative disorders, and renal carcinomas. We present a case report of an asymptomatic renal oncocytoma in a kidney transplant recipient presenting persistent hematuria. The features of computed tomography and contrast-enhanced ultrasound (CEUS) are presented. This was the first time we used CEUS in a transplant kidney recipient presenting a renal mass, allowing the real-time visualization of contrast-enhancement patterns during all vascular phases for the differential diagnosis of renal tumors. Although the pattern of intense vascularization could mislead to an early judgment as a malignant lesion, it could help to exclude other renal lesions without inducing nephrotoxicity.

The Potential for CEUS to Detect Segmental Renal Allograft Infarction Case Report

This case study provides a report on a patient who had a segmental renal allograft infarction. The cause of this infarction within the segmental vessels was theorized to be due to prolonged warm ischemia within the organ donor. The area of infarction was visualized by the use of contrast-enhanced ultrasound (CEUS). This report raises the question as to whether routine sonographic imaging can demonstrated the sequence of infarction within a fresh renal allograft, as is routinely noted in native kidneys. This report highlights the importance of taking the segmental infarction into consideration when approaching the renal allograft recipient. CEUS could provide an important clinical application for the diagnosis of renal allograft infarctions and avoid more invasive procedures. Knowledge of the lack of sequence of sonographic changes in renal allograft infarction helps in assessing the function and outcomes of renal allograft recipients.