Publications by authors named "Irene L Noronha"

The term adsorption is defined as the process in which molecules accumulate in the interfacial surface layer of a solid. The solid material is the sorbent, and the substance in the adsorbed state is called adsorbate. The basic principles and mechanisms involved in hemoadsorption include flow dynamics, chemical characteristics of synthetic materials, adsorption isotherms, mass transfer zone, and the Vroman effect.

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There is a paucity of literature addressing the epidemiology of metabolic disorder-associated kidney disease in developing countries, but extrapolating from the high prevalence of metabolic syndrome in low- and middle-income countries, and the known high prevalence of diabetic kidney disease in the same, the health and economic impact of metabolic disorder-associated kidney disease and diabetic kidney disease is substantial. Resource constraints in developing countries amplify the challenges in preventing, detecting, and treating metabolic disorder-associated kidney disease and diabetic kidney disease. There is diminished capacity for kidney care and hence poorer clinical outcomes including disproportionately higher rates of death and disability when compared with high-income countries.

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Lipoprotein glomerulopathy (LPG) is an ultrarare kidney disorder caused by pathogenic variants in the APOE gene. Although kidney biopsy presents typical findings, such as dilated capillary loops containing lipoprotein thrombi, definitive diagnosis requires molecular genetic analysis of APOE. There is no specific treatment for the disease, and, in the scenario of a disorder with glomerular lipoprotein deposition, it may recur after kidney transplantation.

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Cell therapy utilizing mesenchymal stromal cells (MSCs) through paracrine mechanisms holds promise for regenerative purposes. Peritoneal fibrosis (PF) is a significant complication of peritoneal dialysis. Various strategies have been proposed to protect the peritoneal membrane (PM).

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Chronic kidney disease (CKD) is considered an important health issue worldwide. The renin-angiotensin-aldosterone system (RAAS) blockade through the administration of angiotensin II receptor blockers, such as Losartan (LOS), has been considered the best strategy for CKD treatment for decades. However, this approach promotes only partial detention of CKD progression and cannot reverse renal damage.

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Background: Kidney biopsy registries are valuable tools for guiding clinical practice and developing health policies. In 2021, the Brazilian Society of Nephrology (SBN) created the Brazilian Kidney Biopsy Registry (BKBR). This is the first BKBR report, presenting patient data from 2021.

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Endothelin-1 is a potent vasoconstrictor that has diverse physiological functions in the kidney, including in the regulation of blood flow and glomerular filtration, electrolyte homeostasis and endothelial function. Overexpression of endothelin-1 contributes to the pathophysiology of both diabetic and non-diabetic chronic kidney disease (CKD). Selective endothelin receptor antagonists (ERAs) that target the endothelin A (ET) receptor have demonstrated benefits in animal models of kidney disease and in clinical trials.

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Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for type 2 diabetes (T2D) treatment, have demonstrated significant cardiovascular and renal benefits in heart failure (HF) and chronic kidney disease (CKD), irrespective of T2D. This review provides an analysis of the multifaceted mechanisms underlying the cardiorenal benefits of SGLT2i in HF and CKD outside of the T2D context. Eight major aspects of the protective effects of SGLT2i beyond glycemic control are explored: ) the impact on renal hemodynamics and tubuloglomerular feedback; ) the natriuretic effects via proximal tubule Na/H exchanger NHE3 inhibition; ) the modulation of neurohumoral pathways with evidence of attenuated sympathetic activity; ) the impact on erythropoiesis, not only in the context of local hypoxia but also systemic inflammation and iron regulation; ) the uricosuria and mitigation of the hyperuricemic environment in cardiorenal syndromes; ) the multiorgan metabolic reprogramming including the potential induction of a fasting-like state, improvement in glucose and insulin tolerance, and stimulation of lipolysis and ketogenesis; ) the vascular endothelial growth factor A (VEGF-A) upregulation and angiogenesis, and ) the direct cardiac effects.

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Article Synopsis
  • The phase 3 DUPLEX trial is testing sparsentan, a new medication for patients with focal segmental glomerulosclerosis (FSGS), focusing on its safety and effectiveness.
  • This global study involves 371 patients aged 8 to 75, comparing sparsentan 800 mg to irbesartan 300 mg, while analyzing their baseline characteristics related to FSGS severity.
  • As the largest interventional study of its kind, DUPLEX aims to provide valuable insights into sparsentan's treatment effects across a diverse, worldwide patient population.
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Collapsing glomerulopathy (CG) is most often associated with fast progression to kidney failure with an incidence apparently higher in Brazil than in other countries. However, the reason for this occurrence is unknown. To better understand this, we performed an integrated analysis of clinical, histological, therapeutic, causative genetic and genetic ancestry data in a highly genetically admixed cohort of 70 children and adult patients with idiopathic CG (ICG).

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Article Synopsis
  • The PROTECT trial, a phase 3 study, evaluated the effectiveness of sparsentan, a dual receptor antagonist, in reducing proteinuria compared to irbesartan in patients with immunoglobulin A nephropathy over 110 weeks.* -
  • A total of 406 patients were randomly assigned to either sparsentan or irbesartan, with the primary goal being the change in proteinuria at 36 weeks and secondary goals related to kidney function and safety over the trial duration.* -
  • The findings from the trial, which included a significant reduction in proteinuria with sparsentan, provide important insights into potential treatment strategies for patients with kidney conditions.*
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Article Synopsis
  • - A phase 3 trial investigated the long-term effects of sparsentan versus irbesartan in treating focal segmental glomerulosclerosis (FSGS) over 108 weeks, enrolling 371 patients aged 8 to 75.
  • - At 36 weeks, sparsentan showed a significantly higher rate of partial remission of proteinuria (42%) compared to irbesartan (26%), and this positive response continued up to 108 weeks.
  • - However, there were no significant differences in the estimated glomerular filtration rate (eGFR) slopes between the two groups at the final analysis, indicating that while proteinuria improved, kidney function as measured by eGFR remained similar with both treatments. *
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CKD progression depends on the activation of an intricate set of hemodynamic and inflammatory mechanisms, promoting renal leukocyte infiltration, inflammation and fibrosis, leading to renal function loss. There are currently no specific drugs to detain renal fibrogenesis, which is a common end-point for different nephropathies. Clinical therapy for CKD is mostly based on the management of hypertension and proteinuria, partially achieved with renin-angiotensin-aldosterone system (RAAS) blockers, and the control of inflammation by immunosuppressive drugs.

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Article Synopsis
  • Sparsentan is a new type of medication being tested in the ongoing PROTECT trial for adults with IgA nephropathy (IgAN), with potential benefits in reducing inflammation and improving blood flow, without suppressing the immune system.
  • The PROTECT trial is a large, international study comparing the effectiveness and safety of sparsentan against the active drug irbesartan in patients with significant proteinuria who have not found success with previous treatments.
  • Results from 404 enrolled patients showed a mix of demographics and health statuses, which will help understand how sparsentan works across different populations and stages of chronic kidney disease (CKD).
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Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety.

Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries.

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In the last decades, improvements in the average life expectancy in the world population have been associated with a significant increase in the proportion of elderly people, in parallel with a higher prevalence of non-communicable diseases, such as hypertension and diabetes. As the kidney is a common target organ of a variety of diseases, an adequate evaluation of renal function in the approach of this population is of special relevance. It is also known that the kidneys undergo aging-related changes expressed by a decline in the glomerular filtration rate (GFR), reflecting the loss of kidney function, either by a natural senescence process associated with healthy aging or by the length of exposure to diseases with potential kidney damage.

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The ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment.

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The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious.

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Background: Progressive fibrous thickening of peritoneal membrane (PM) is a major complication of long-term peritoneal dialysis. TGF-β/SMAD pathway activation, inflammation and neoangiogenesis have an important role in PM changes induced by peritoneal dialysis. Here, we investigated the effects of paclitaxel (PTX) carried in lipid core nanoparticles (LDE) on the development of peritoneal fibrosis (PF) in rats.

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Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors.

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Global prevalence of chronic kidney disease (CKD) has increased considerably in the recent decades. Overactivity of the renin-angiotensin-aldosterone system (RAAS), associated to renal inflammation and fibrosis, contributes to its evolution. The treatments currently employed to control CKD progression are limited and mainly based on the pharmacological inhibition of RAAS, associated with diuretics and immunosuppressive drugs.

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Neutrophils are the first leukocytes recruited to the site of infection and are thought to be responsible for fungal elimination from the skin such as dermatophytes. Neutrophils are able to secrete reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) that can kill different fungi, including , spp., , and .

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This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort.

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Objectives: The aim of this study was to test whether lipid core nanoparticles loaded with paclitaxel (LDE-PTX) protect rat aortic allograft from immunological damage.

Methods: Fisher and Lewis rats were used differing in minor histocompatibility loci. Sixteen Lewis rats were allocated to four-animal groups: SYNG (syngeneic), Lewis rats receiving aorta grafts from Lewis rats; ALLO (allogeneic), Lewis rats receiving aortas from Fisher rats; ALLO+LDE (allogeneic transplant treated with LDE), Lewis rats receiving aortas from Fisher rats, treated with LDE (weekly injection for 3 weeks); ALLO+LDE-PTX (allogeneic transplant treated with LDE-PTX), Lewis rats receiving aortas from Fisher rats treated with LDE-PTX (4 mg/kg weekly for 3 weeks).

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Sepsis is the leading cause of acute kidney injury (AKI) and lung injury worldwide. Despite therapeutic advances, sepsis continues to be associated with high mortality. Because Brazilian green propolis (GP) has promising anti-inflammatory, antioxidant, and immunomodulatory properties, we hypothesized that it would protect kidneys and lungs in rats induced to sepsis by cecal ligation and puncture (CLP).

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