Natália A. Rocha

Acute kidney injury after trauma: Prevalence, clinical characteristics and RIFLE classification.

Background: Acute kidney injury (AKI) is an uncommon but serious complication after trauma. The objective of this study was to evaluate the prevalence, clinical characteristics and outcome of AKI after trauma. Patients and Methods: This was a retrospective study performed from January 2006 to January 2008 in an emergency specialized hospital in Fortaleza city, northeast of Brazil. All patients with AKI admitted in the study period were included. Prevalence of AKI, clinical characteristics and outcome were investigated. Results: Of the 129 patients admitted to the intensive care unit (ICU), 52 had AKI. The mean age was 30.1 ± 19.2 years, and 79.8% were males. The main causes of AKI were sepsis in 27 cases (52%) and hypotension in 18 (34%). Oliguria was observed in 33 cases (63%). Dialysis was required for 19 patients (36.5%). Independent risk factors associated with AKI were abdominal trauma [odds ratio (OR) = 3.66, P = 0.027] and use of furosemide (OR = 4.10, P = 0.026). Patients were classified according to RIFLE criteria as Risk in 12 cases (23%), Injury in 13 (25%), Failure in 24 (46%), Loss in 1 (2%) and End-stage in 2 (4%). Overall in-hospital mortality was 95.3%. The main cause of death was sepsis (24%). Mortality was 100% among patients with AKI. Conclusions: AKI is a fatal complication after trauma, which presented with a high mortality in the studied population. A better comprehension of factors associated with death in trauma-associated AKI is important, and more effective measures of prevention and treatment of AKI in this population are urgently needed.

Risk factors for acute kidney injury in visceral leishmaniasis (Kala-Azar).

The aim of this study was to investigate the factors associated with acute kidney injury (AKI) in patients with visceral leishmaniasis (VL). The study patients had a diagnosis of VL and were admitted to a tertiary hospital. A multivariate analysis was performed to analyze the risk factors for AKI. A total of 224 patients were included. The mean age was 36 +/- 15 years. AKI was observed in 33.9% of cases. Risk factors associated with AKI were male gender (odds ratio [OR] = 2.2; P = 0.03), advanced age (OR = 1.05; P < 0.001), and jaundice (OR = 2.9; P = 0.002). There was an association between amphotericin B use and AKI (OR = 18.4; P < 0.0001), whereas glucantime use was associated with lower incidence of AKI compared with amphotericin B use (OR = 0.05; P < 0.0001). Mortality was 13.3%, and it was higher in AKI patients (30.2%). Therefore, factors associated with AKI were male gender, advanced age, and jaundice. Amphotericin B was an important cause of AKI in VL.

Acute kidney injury in children with visceral leishmaniasis.

Background: There is no comprehensive study about renal function in children with visceral leishmaniasis (VL). The aim of this study was to investigate the incidence of acute kidney injury (AKI) in children with VL using pRIFLE classification and to determine the risk factors for AKI. Methods: A retrospective cohort study was conducted with 146 patients younger than 14 years of age with VL diagnosis in one center located at the northeast of Brazil from December 2003 to 2010. AKI was evaluated by pediatric Risk, Injury, Failure, Loss, End-stage kidney disease (pRIFLE) criteria. Results: The mean age was 5 ± 4.0 years (range, 5 months to 14 years), and 53.4% were males. AKI was observed in 67 patients (45.9%). The distribution according to the pRIFLE criteria was as follows: risk 45 (67.2%), injury 21 (31.3%), and failure 1 (1.5%). Patients in the AKI group were significantly younger (P < 0.001) and had jaundice (P = 0.028) and secondary infections (P = 0.001) more often than non-AKI patients. The AKI group had a significantly lower serum sodium (P = 0.03), potassium (P = 0.009), serum albumin (P = 0.001), and elevated serum globulins (P = 0.04), and a more prolonged prothrombin time (P = 0.001) at admission. Independent risk factors for AKI were: secondary infections (OR: 3.65, 95% CI: 1.426–9.358, P = 0.007), serum albumin decrement (OR: 1.672, 95% CI: 1.065–2.114, P = 0.019 per each 1 mg dL–1 serum albumin decrement), and high serum globulin (OR: 1.35, 95% CI: 1.031–1.779, P = 0.029 per each 1 mg dL–1 serum globulin increment). Conclusions: AKI is a frequent complication in children with VL. The risk factors for AKI were secondary infections, high serum globulin and low serum albumin.

Impact of empagliflozin in patients with diabetes and heart failure

Heart failure (HF) is a common disease with increased risk for mortality and morbidity among patients with type 2 diabetes mellitus (T2DM). Optimal glycemic control in this patient population is challenging as many available therapies can potentially exacerbate symptoms of HF. Empagliflozin is one in a novel class of agents, the sodium glucose co-transporter 2 (SGLT2) inhibitors, that lowers blood glucose by increasing urinary glucose excretion and improves glycemic control and lowers body weight and blood pressure. In the recent EMPA-REG OUTCOME trial, empagliflozin was shown to improve cardiovascular outcomes in patients with T2DM and established cardiovascular risk where it reduced HF hospitalizations and cardiovascular death, with a consistent benefit among patients both with and without baseline HF. Here, we review the empagliflozin data on HF outcomes and discuss potential mechanisms for its benefits in HF with a focus on the potentially significant impact that empagliflozin may have on the care of patients with T2DM and HF in the future.

Renal Function Improvement with Pentavalent Antimonial Agents in Patients with Visceral Leishmaniasis

Background: The aim of this study is to investigate tubular and glomerular function after visceral leishmaniasis (VL) treatment with pentavalent antimonials. Methods: This is a prospective study including 14 patients with VL diagnosis treated with pentavalent antimonials. Urine acidification and concentration tests were performed. Estimated glomerular filtration rate (eGFR), fractional excretion of sodium (FENa) and potassium (FEK) and free water clearance (CH2O) were measured to assess glomerular and tubular function. Results: The VL group had a significantly lower FEK, serum sodium and plasma osmolality (Posm). No significant differences were found regarding proteinuria, eGFR, FENa or CH2O. Patients in the VL group had lower urinary osmolality (Uosm) before DDAVP use when compared to the control group, as well as a lower U/Posm. The urinary pH before and after CaCl2 load was higher in the VL group. Conclusion: This study shows evidence of reversal of some tubular dysfunction in VL, but other dysfunctions may persist, especially urinary acidification capacity.

ApoCIII as a Cardiovascular Risk Factor and Modulation by the Novel Lipid-Lowering Agent Volanesorsen

Purpose of ReviewApolipoprotein CIII (ApoCIII) is now recognized as a key regulator in severe hypertriglyceridemia, chylomicronemia, and conditions of triglyceride-rich lipoprotein (TRL) remnant excess due to its inhibition of lipoprotein lipase (LPL) and hepatic lipase, leading to decreased hepatic reuptake of TRLs, as well as enhanced synthesis and secretion of VLDL from the liver. ApoCIII gain-of-function mutations are associated with atherosclerosis and coronary heart disease (CHD), and contribute to the development of cardiometabolic syndrome, hypertriglyceridemia, and type 2 diabetes mellitus. Conversely, loss-of-function mutations in ApoCIII are associated with lower levels of plasma triglycerides (TG), attenuation of vascular inflammatory processes such as monocyte adhesion and endothelial dysfunction, and potentially, a reduction in the incidence and progression of atherosclerosis and cardioprotection.Recent FindingsEvidence is now emerging that volanesorsen, a second-generation antisense oligonucleotide drug targeting ApoCIII messenger RNA resulting in decreases in TG in patients with familial chylomicronemia syndrome, severe hypertriglyceridemia, and metabolic dyslipidemia with type 2 diabetes giving support to the hypothesis that ApoCIII is a powerful inhibitor of LPL, and when reduced, endogenous clearance of TRLs can result in substantial reductions in TG levels.SummaryDiscovery of the ApoCIII inhibitor volanesorsen opens a new era of lipid-lowering drugs for reduction in TG and potentially for reduction in LDL-C. Herein, this review will provide an update on the pathophysiology of ApoCIII-linked atherosclerosis and the development of the first drug to target ApoCIII, volanesorsen, as a promising lipid-lowering agent.

Comparative analysis of pediatric and adult visceral leishmaniasis in Brazil.

Background: The aim of this study was to compare clinical manifestations, laboratory data, morbidity and mortality between adults and children with visceral leishmaniasis, with a focus on kidney function. Methods: This was a retrospective cohort study with 432 patients with visceral leishmaniasis diagnosed at 1 center in the northeast of Brazil. Patients were divided into 2 groups according to age (>21 years and ⩽21 years old). Results: The time between onset of symptoms and beginning of treatment was longer in adults (89.5 versus 48.5 days, P < 0.001); signs and symptoms were similar in both groups. Failure of treatment with glucantime was more common in adults (17.6% versus 8.8%, P = 0.008). Acute kidney injury was observed in 160 patients (37.0%), and it was more severe in adults. Risk factors for acute kidney injury in adults were hypokalemia, leukopenia, chills and amphotericin B use. In children, secondary infections were found to increase the risk for acute kidney injury. Overall mortality was 8.8%, and it was significantly higher in adults (12.6% versus 4.1%, P = 0.002). Conclusions: The adult population had more severe laboratory abnormalities and a worse prognosis, possibly due to delay in diagnosis. Acute kidney injury is prevalent in both groups, and it is usually more severe in adults.

Usefulness of alirocumab and evolocumab for the treatment of patients with diabetic dyslipidemia

ABSTRACT In 2015, the US Food and Drug Administration (FDA) approved the anti-proprotein convertase subtilsin/kexin type 9 (PCSK9) monoclonal antibodies, alirocumab and evolocumab, to treat patients with hypercholesterolemia and mixed dyslipidemia. Since then, considerable attention has been paid to the use of these monoclonal antibodies for the treatment of diabetic dyslipidemia with a goal of reducing the risk for cardiovascular disease. Recently, consensus statements on the clinical use of PCSK9 inhibitors in patients with type 2 diabetes mellitus, who are unable to achieve the goal of low-density lipoprotein cholesterol (<70 mg/dL or <1.8 mmol/L), have been published by panels of experts in Greece, Europe (European Society of Cardiology and European Atherosclerosis Society Task Force), and the United States (American College of Cardiology Consensus Committee). On December 1, 2017, the FDA approved evolocumab to prevent heart attack, stroke, and coronary revascularization. In this article, we review recent advances concerning the pathophysiology of diabetic dyslipidemia, the physiology of PCSK9, the mechanisms of action of PCSK9 inhibitors, clinical trials examining PCSK9 inhibitors in type 2 diabetes, and perspectives of nonstatin therapy in the treatment of diabetic dyslipidemia.

SGLT2 inhibition and heart failure—current concepts

Type 2 diabetes mellitus (T2DM) is a major risk factor for several cardiovascular (CV) conditions, including heart failure (HF). However, until recently, no therapy to treat patients with diabetes could also reduce CV risks related to HF. The EMPA-REG OUTCOME trial with empagliflozin was the first to demonstrate significant cardioprotective benefits in this population. Its impressive 35% reduction in hospitalizations for HF drew the attention of the scientific community to the possibility that pharmacologic sodium-glucose cotransporter 2 (SGLT2) inhibition could be part of the armamentarium for treating patients with HF, with and without diabetes. The recently published CANVAS Program (with canagliflozin) and real-life data from the CVD-Real Study (using dapagliflozin, empagliflozin, and canagliflozin) further strengthened this hypothesis, suggesting that the observed benefit is not restricted to a particular drug, but is rather a class effect. This review explores the effects of pharmacologic SGLT2 inhibitors’ use in cardiac function and discusses the potential role of this class of medication as a treatment for HF.

Cardiovascular outcomes in diabetic kidney disease: insights from recent clinical trials

The prevalence of type 2 diabetes is catalyzing a pandemic in kidney disease, with ensuing cardiovascular complications. The effort to identify antidiabetic agents capable of promoting benefits that go beyond the bounds of glucose control has produced remarkable outcomes in recent cardiovascular outcomes trials in patients with type 2 diabetes mellitus, many of whom have diabetic kidney disease. Two novel antidiabetic drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), improve cardiovascular outcomes in different ways, with SGLT2is reducing the risk of heart failure and cardiovascular death and GLP-1 RAs being associated with reduced risk of myocardial infarction and cardiovascular death. Further mechanistic studies and additional cardiovascular outcome trials are ongoing and are expected to determine whether these benefits are a result of class effect, as well as to delineate optimum timing for intervention and population target.