Gdayllon Cavalcante Meneses

Syndecan-1 in Acute Decompensated Heart Failure – Association With Renal Function and Mortality –

BACKGROUND Heart failure (HF) is a leading cause of hospitalization throughout the world, and the mortality rate remains elevated. HF is frequently complicated by acute kidney injury (AKI), worsening the patients prognosis. There have been no studies evaluating the role that endothelial glycocalyx damage plays in HF patients and its association with AKI and mortality. METHODS AND RESULTS We measured several endothelial biomarkers in 201 consecutive patients with acute decompensated HF (ADHF) during emergency department (ED) admission. In-hospital mortality, AKI development and 6-month mortality rates were assessed. ADHF patients with worsening renal function had higher levels of syndecan-1 but not those patients with stable chronic kidney disease. Syndecan-1 levels during ED admission were predictive for AKI during the hospital stay (AUC 0.741, P<0.001) and had an even better discriminatory capacity in more severe AKI (AUC 0.812, P<0.001). Additionally, after adjusting for several confounding factors, including biomarkers of endothelial function and endothelial cell activation, syndecan-1 remained associated with in-hospital mortality rates. On a Cox multivariate analysis regression, syndecan-1 was associated with 6-month mortality rates. CONCLUSIONS The concentration of syndecan-1, a marker of glycocalyx damage measured during ED admission, is valuable in assessing the risk of developing AKI and in-hospital mortality. Its association with mortality is strong after 6-month follow-up.

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P < 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P < 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage.

Red propolis ameliorates ischemic-reperfusion acute kidney injury

INTRODUCTION Acute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated. METHODS Male Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis. RESULTS I/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue. CONCLUSION Red propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation.

Inhibitory effects of sertraline in rat isolated perfused kidneys and in isolated ring preparations of rat arteries.

Objectives  Sertraline is often prescribed to patients suffering with end stage renal disease, but its action on kidney has not been investigated. We aimed to investigate the pharmacological action of sertraline on rat kidney with emphasis on the underlying mechanisms involved in the vascular actions of the drug.

Nephroprotective effects of (−)-α-bisabolol against ischemic-reperfusion acute kidney injury

BACKGROUND Ischemia/reperfusion (I/R) in kidney is commonly related to acute kidney injury (AKI), essentially through oxidative stress. (-)-α-Bisabolol is a sesquiterpene isolated from the essential oil of a variety of plants, including chamomile, which has important antioxidant activity. STUDY DESIGN This study intends to evaluate the nephroprotective activity of (-)-α-bisabolol (Bis) in both in vivo and in vitro models of kidney I/R. METHODS Male Wistar rats were submitted to right nephrectomy, followed by ischemia by clamping of the renal artery in the left kidney for 60min. and 48h of reperfusion. The animals were treated orally with Bis (100mg/kg) or vehicle for 24h after reperfusion, and placed in metabolic cages, to evaluate water consumption, diuresis, urinary osmolality, classic biochemical markers and urinary KIM-1 (kidney injury molecule-1). Additionally, the left kidney was collected for histological evaluation and determination of glutathione (GSH) and Thiobarbituric Acid Reactive Substances (TBARS) levels. Tubular epithelial cells LLC-MK2 were used to assess Bis effect on in vitro I/R, by MTT assay. It was performed the cellular respiration tests by flow cytometry: evaluation of the production of cytoplasmic reactive oxygen species by DCFH-DA assay and mitochondrial transmembrane potential analysis with the dye rhodamine 123. RESULTS I/R caused alterations in diuresis, water intake, urinary osmolality, plasmatic creatinine, urea and uric acid, creatinine clearance, proteinuria and microalbuminuria. Treatment with Bis ameliorated all of these parameters. Also, KIM-1 level enhanced by I/R was also diminished in groups treated with Bis. The histological examination showed that Bis attenuated the morphological changes caused by I/R, markedly vascular congestion and intratubular deposits of proteinaceous material. Additionally, Bis was able to reduce the changes observed in TBARS and GSH levels in kidney tissue. In in vitro assay, Bis was capable to partially protect the cell lineage against cell damage induced by I/R. CONCLUSION (-)-α-Bisabolol has a nephroprotective effect in kidney I/R, with antioxidant effect. Moreover, this result seems to be associated to a direct protective effect on tubular epithelia.

Glycocalyx injury in adults with nephrotic syndrome: Association with endothelial function.

BACKGROUND Glomerulopathy is a group of diseases that affect mainly young adults. Endothelial dysfunction, atherosclerosis, and increased cardiac mortality can complicate the evolution of such patients. However, there is no study evaluating endothelial glycocalyx in this pathology. METHODS This cross-sectional study included 49 patients with untreated primary nephrotic syndrome that were otherwise healthy. In addition to routine laboratory measurements, syndecan-1, intercellular adhesion molecule-1 (ICAM-1), and e-selectin were measured. Moreover, flow-mediated dilation (FMD) was used as the main endothelial function surrogate. RESULTS Of the 49 patients with nephrotic syndrome, 25 (51.0%) were females. The mean age of patients was 39.0±12.1y. FMD was reduced in nephrotic patients in comparison with controls (3.7±1.7 vs. 6.6±1.1%, p<0.001). Nephrotic patients had higher levels of ICAM-1 (616.6±219.7 vs. 356.9±102.0ng/ml, p<0.001) and syndecan-1 (180.3±64.1 vs. 28.2±9.8ng/ml, p<0.001). No significant difference was observed regarding e-selectin (129.9±54.2 vs. 120.2±61.5ng/ml, p=0.489). After adjusting for age and glomerular filtration rate, syndecan-1 was significantly associated with 24-h urinary protein excretion, LDL-cholesterol, HDL-cholesterol, and triglycerides. While age, LDL-cholesterol, and 24-h urinary protein excretion were associated with FMD in the multivariate analysis, when syndecan-1, ICAM-1, and e-selectin were added to the model, only syndecan-1 was independently associated with FMD. CONCLUSIONS We demonstrated that syndecan-1, a marker of endothelial glycocalyx damage, is increased in patients with nephrotic syndrome and near-normal renal function. Moreover, we determined its association with nephrotic syndrome features and suggest it can have a role in the endothelial dysfunction of these patients.

Leprosy nephropathy: a review of clinical and histopathological features.

Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes.

Preliminary Study on Tubuloglomerular Dysfunction and Evidence of Renal Inflammation in Patients with Visceral Leishmaniasis

Visceral leishmaniasis (VL) is a re-emerging zoonosis of worldwide distribution. Monocyte chemotactic protein-1 (MCP-1) and malondialdehyde (MDA) are inflammation biomarkers that have never been investigated in VL. The aim of this study is to investigate the association between renal abnormalities and inflammation biomarkers in VL. This study is a preliminary prospective study with 16 VL adult patients evaluated before treatment compared with a group of 13 healthy volunteers and 5 VL patients evaluated after treatment. Urinary concentration and acidification tests were performed. MCP-1 and MDA were quantified in urine. Urinary concentration deficit was found in all VL patients before (100%) and four VL patients after (80%) treatment. Urinary acidification deficit was found in nine cases before (56.2%) and two cases after (40%) treatment. Urinary MCP-1 (374 ± 359 versus 42 ± 29 pg/mg creatinine, P = 0.002) as well as urinary MDA (5.4 ± 2.6 versus 2.0 ± 0.8 μmol/mL) showed significant differences between VL patients and controls. These data show that VL patients present urinary concentration and acidification deficit, which can persist even after specific treatment. Urinary MCP-1 and MDA are elevated in patients with VL, which suggests renal inflammation and incipient renal damage.

CLINICAL CHARACTERISTICS, OUTCOMES AND RISK FACTORS FOR DEATH AMONG CRITICALLY ILL PATIENTS WITH HIV-RELATED ACUTE KIDNEY INJURY

SUMMARY Background: The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU). Methods: A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated. Results: Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 ± 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 ± 19 vs. 38.6 ± 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0-153.0, p < 0.001). Conclusion: Non-survivor HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death.

Visceral leishmaniasis-associated nephropathy in hospitalised Brazilian patients: new insights based on kidney injury biomarkers

To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis.