Chronic kidney disease (CKD) remains a global public health problem. The initial damage after ischemia/reperfusion (I/R) injury plays an important role in the pathogenesis of acute kidney injury (AKI) and predisposition to CKD. Several studies have been showing that nontraditional risk factors such as AKI and hypovitaminosis D could also be involved in CKD progression. Vitamin D deficiency (VDD) is associated with hemodynamic changes, activation of inflammatory pathways and renal disease progression (RDP) following I/R-AKI. Strategies for prevention and/or slowing RDP have been determined and the sufficiency of vitamin D has been emerging as a renoprotective factor in many diseases. Therefore, we investigated the effect of the restoration of vitamin D levels in the progression of I/R injury (IRI) in rats previously deficient in vitamin D. On day 30, male Wistar rats were submitted to bilateral 45 min IRI and divided into three groups: IRI, standard diet for 120 days; VDD+IRI, vitamin D-free diet for 120 days; and VDD+IRI+R, vitamin D-free diet in the first 30 days and just after I/R, we reintroduced the standard diet in the last 90 days. After the 120-day protocol, VDD+IRI+R rats presented an improvement in the renal function and renal protein handling followed by a smaller fractional interstitial area. Furthermore, those animals exhibited a reestablishment regarding the hemodynamic parameters and plasma levels of aldosterone, urea and PTH. In addition, the restoration of vitamin D levels reestablished the amount of MCP1 and the renal expressions of CD68+ and CD3+ cells in the VDD+IRI+R rats. Also, VDD+IRI+R rats showed a restoration regarding the amount of collagen type III and renal expressions of fibronectin, vimentin and α-SMA. Such changes were also accompanied by a reestablishment on the renal expression of VDR, Klotho, JG12, and TGF-β1. Our findings indicate that the restoration of vitamin D levels not only improved the renal function and hemodynamics but also reduced the inflammation and fibrosis lesions observed in I/R-AKI associated with VDD. Thus, monitoring of vitamin D status as well as its replacement in the early stages of kidney injury may be a therapeutic alternative in the mitigation of renal disease progression.

BackgroundTenofovir disoproxil fumarate (TDF), a widely prescribed component in antiretroviral regimens, has been associated with nephrotoxicity. Nebivolol is a third generation selective β-1 adrenergic receptor blocker and may protect renal structure and function through the suppression of oxidative stress and enhancement of nitric oxide (NO) synthesis. We aimed to investigate whether nebivolol could be an effective therapeutic strategy to mitigate tenofovir-induced nephrotoxicity.MethodsWe allocated Wistar rats to four groups: control (C), received a standard diet for 30 days; NBV, received a standard diet for 30 days added with nebivolol (100 mg/kg food) in the last 15 days; TDF, received a standard diet added with tenofovir (300 mg/kg food) for 30 days; and TDF+NBV, received a standard diet added with tenofovir for 30 days and nebivolol in the last 15 days.ResultsLong-term exposure to tenofovir led to impaired renal function, induced hypertension, endothelial dysfunction and oxidative stress. Nebivolol treatment partially recovered glomerular filtration rate, improved renal injury, normalized blood pressure and attenuated renal vasoconstriction. Administration of nebivolol contributed to reductions in asymmetric dimethylarginine (ADMA) levels as well as increases in endothelial nitric oxide sintase (eNOS) accompanied by renin-angiotensin-aldosterone system downregulation and decreases in macrophage and T-cells infiltrate. Furthermore, nebivolol was responsible for the maintenance of the adequate balance of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels and it was associated with reductions in NADPH oxidase (NOX) subunits.ConclusionNebivolol holds multifaceted actions that promote an advantageous option to slow the progression of kidney injury in tenofovir-induced nephrotoxicity.

Objetivo: Revisar evidências cientí­ficas atuais referentes í  alimentação vegetariana para a elaboração de um guia prático para profissionais nutricionistas. Metodologia: Revisão narrativa da literatura atual, compreendendo publicações de 1998 a 2016, nos idiomas português, espanhol e inglês. Resultados: O vegetarianismo, anteriormente criticado pelas consequências provindas de um possí­vel desequilí­brio nutricional, hoje tem se tornado uma alternativa para a melhora da saúde, apresentando um aumento crescente em adeptos a esta dieta e de interesses tanto da indústria quanto da ciência. Evidências apontam que vegetarianos apresentam menor prevalência de excesso de peso e de doenças crônicas não transmissí­veis. Conclusão: A prática da dieta vegetariana, assim como outros padrões alimentares, pode ser segura e adequada oferta nutrientes necessários para um estilo de vida saudável, sob orientação de um profissional Nutricionista.Palavras-chave: dieta vegetariana, deficiências nutricionais, ciclos da vida, doenças crônicas não transmissí­veis.

Acute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor β and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.

BACKGROUND AND AIMS Acute kidney injury (AKI) alters renal haemodynamics, leads to tubular injury, activates pathways of inflammation, proliferation and cell death. The initial damage caused by ischaemia/reperfusion injury (IRI) plays an important role in the pathogenesis of the AKI and predisposition to chronic kidney disease (CKD). Vitamin D deficiency has been considered a risk factor for kidney disease and is associated with haemodynamic changes and tubulointerstitial damage. Obesity is directly related to diabetes mellitus (DM) and hypertension, the main metabolic disorders responsible for the progression to end-stage kidney disease. In addition, studies have been showing that adipose tissue expansion can increase the secretion of pro-inflammatory cytokines and its possible influence on the course of CKD. Thus, we evaluated the influence of both obesity and vitamin D deficiency risk factors on renal disease progression in a murine model of renal IRI. METHOD We followed Male wistar rats during a 90-day protocol. On day 45, we submitted all rats to bilateral 45 min IRI surgery. We shared the animals into four groups: i) Standard (S)—fed a standard diet for 90 days; ii) Vitamin D Deficient (VDD)—fed a vitamin D-free diet for 90 days; iii) High-fat (H)—fed a high-fat diet for 90 days; and iv) High-fat vitamin D deficient (H + VDD)—fed a high-fat vitamin D-free diet for 90 days. We evaluated insulin clearance (Cin); mean arterial pressure (MAP); anthropometrical parameters such as body mass index (BMI) and abdominal circumference (AC); plasma levels of 25(OH)D, aldosterone, leptin, glucose, triglycerides and cholesterol as well as renal tissue levels of collagen type 3 (COL-3) and MCP-1 by ELISA. Moreover, we performed qPCR and immunoblotting for vitamin D receptor (VDR) in adipose and renal tissues, respectively. We also analysed α-actin expression by immunohistochemistry and evaluated the fractional interstitial area (FIA). All the results are described in Table 1. RESULTS H + VDD animals presented a lower glomerular filtration rate, higher MAP and increased anthropometrical and metabolic parameters compared to the other groups. In addition, we observed severe morphological damage, characterized by an increase in the fractional interstitial area and renal expression of α-actin, MCP-1 and COL-3. CONCLUSION Our study suggests that the association between vitamin D deficiency and obesity impairs the haemodynamics, renal function and metabolic parameters in the H + VDD rats. In addition, obesity-associated to vitamin D deficiency aggravated the renal inflammation and morphological alterations associated to renal disease progression. FUNDING: CAPES and FAPESP (2019/20840–0, 2018/12297–1, 2018/04930–6).

CIP) (eDOC BRASIL, Belo Horizonte/MG) P964 A produção do conhecimento nas ciências da saúde 2 [recurso eletrônico] / Organizador Benedito Rodrigues da Silva Neto. -Ponta Grossa (PR): Atena Editora, 2019. -(A Produção do Conhecimento nas Ciências da Saúde; v. 2) Formato: PDF 1. Abordagem interdisciplinar do conhecimento. 2. Saúde -Pesquisa -Brasil. I. Silva Neto, Benedito Rodrigues da. II. Série. CDD 610.7 Elaborado por Maurício Amormino Júnior -CRB6/2422 O conteúdo dos artigos e seus dados em sua forma, correção e confiabilidade são de responsabilidade exclusiva dos autores. 2019 Permitido o download da obra e o compartilhamento desde que sejam atribuídos créditos aos autores, mas sem a possibilidade de alterá-la de nenhuma forma ou utilizá-la para fins comerciais.

BACKGROUND AND AIMS Obstructive nephropathy decreases renal blood flow (RBF) and glomerular filtration rate (GFR). Glycogen synthase kinase 3β (GSK3 β), an apoptotic enzyme, is increased in a model of unilateral obstruction. Treatment with a single dose of lithium, a selective inhibitor of GSK3β, accelerated recovery of renal function in models of cisplatin and ischemia-reperfusion induced acute kidney injury (AKI). The aim of this study was to evaluate the efficacy of a single dose of lithium in the treatment of AKI induced by bilateral ureteral obstruction (BUO) METHOD Adult male Wistar rats were divided in four groups: (i) sham (sham operated); (ii) lithium: rats treated with lithium chloride 80 mg/Kg BW Intraperitonially (IP); (iii) BUO during 24 h; (iv) BUO during 24 h and treated with the same dose immediately after ureteral desobstruction. The rats were anesthetized 48 h after desobstruction to measure inulin clearance and renal blood flow. At the end of the clearance experiments, the rats were euthanized and the kidneys were removed to measure GSK3 β renal expression. RESULTS As described in the Table 1, BUO showed markedly reduction of GFR and RBF associated with an increase of GSK3β. A single dose of lithium administration ameliorated all these alterations. CONCLUSION Lithium treatment attenuated renal dysfunction in this model of BUO-associated AKI by improving inulin clearance. These therapeutic effects were due to an inhibition of renal expression of GSK3β. This may be a new therapeutic approach for BUO-induced AKI.

Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3β (GSK3β) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibrosis. Treatment with a single dose of lithium, an inhibitor of GSK3β, accelerated recovery of renal function in cisplatin and ischemic/reperfusion-induced AKI models. We aimed to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI. Male Wistar rats were allocated to four groups: Sham, received saline 0.9% intraperitoneally (IP); lithium (Li), received a single IP injection of lithium chloride (LiCl) 80 mg/kg body weight (BW); glycerol (Gly), received a single dose of glycerol 50% 5 mL/kg BW intramuscular (IM); glycerol plus lithium (Gly+Li), received a single dose of glycerol 50% IM plus LiCl IP injected 2 hours after glycerol administration. After 24 hours, we performed inulin clearance experiments and collected blood / kidney / muscle samples. Gly rats exhibited renal function impairment accompanied by kidney injury, inflammation and alterations in signaling pathways for apoptosis and redox state balance. Gly+Li rats showed a remarkable improvement in renal function as well as kidney injury score, diminished CPK levels and an overstated decrease of renal and muscle GSK3β protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NFκB and caspase renal protein expression and increased the antioxidant component MnSOD. Lithium treatment attenuated renal dysfunction in rhabdomyolysis-associated AKI by improving inulin clearance and reducing CPK levels, inflammation, apoptosis and oxidative stress. These therapeutic effects were due to the inhibition of GSK3β and possibly associated with a decrease in muscle injury.