Orientador: André Luis Balbi / Resumo: Introdução: A Doença Renal Crônica (DRC) é uma condição clínica com elevada e crescente prevalência, com repercussão sistêmica, podendo cursar com hipervolemia e consequente congestão de órgãos como os pulmões. O tratamento dialítico também gera uma série de alterações nos sistemas muscular, ósseo, cardiovascular, metabólico e também respiratório. Existem muitos estudos avaliando o sistema respiratório na fase dialítica e poucos avaliam na fase pré-diaítica. Objetivo: Avaliar a função pulmonar e a força muscular respiratória de pacientes com DRC na fase pré-dialítica. Metodologia: Foram assistidos 132 pacientes e 43 avaliados no Ambulatório de Pré-Diálise do Hospital das Clínicas da Faculdade de Medicina de Botucatu, SP (HCFMB), com retornos mensais, em tratamento clínico e programação de diálise. Todos os pacientes estudados foram submetidos inicialmente à avaliação da função pulmonar através da espirometria e logo em seguida avaliação da força muscular respiratória através da manovacuometria, realizadas no laboratório de função pulmonar do HCFMB, pelo mesmo pesquisador em único dia para o mesmo paciente. Resultados: Foram incluídos no estudo 40 pacientes com média de idade de 61 ± 14 anos, sendo 60% do sexo masculino. Com relação à causa, 22 pacientes apresentaram nefropatia diabética (n=13; 32,5%) e nefropatia hipertensiva (n=9; 22,5%).Todos os resultados da espirometria (CVF, VEF1 e VEF1/CVF) foram abaixo do valor predito, com diferença estatística. A maioria dos paciente... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Chronic Kidney Disease (CKD) is a clinical condition with high and increasing prevalence, with systemic repercussions, which can develop with hypervolemia and consequent congestion of organs such as the lungs. The dialysis treatment also generates a series of changes in the muscular, bone, cardiovascular, metabolic and also respiratory systems. There are many studies evaluating the respiratory system in the dialysis phase and few assess it in the pre-dialysis phase. Objective: To evaluate pulmonary function and respiratory muscle strength in patients with pre-dialysis CKD. Methodology: 132 patients were assisted and 43 were evaluated at the Pre-Dialysis Outpatient Clinic of the Hospital das Clínicas, Faculty of Medicine of Botucatu, SP (HCFMB), with monthly returns, in clinical treatment and dialysis schedule. All patients studied were initially submitted to pulmonary function assessment using spirometry and then respiratory muscle strength was assessed using manovacuometry, performed at the HCFMB pulmonary function laboratory, by the same researcher on a single day for the same patient. Results: The study included 40 patients with a mean age of 61 ± 14 years, 60% of whom were male. Regarding the cause, 22 patients had diabetic nephropathy (n = 13; 32.5%) and hypertensive nephropathy (n = 9; 22.5%). All spirometry results (FVC, FEV1 and FEV1 / FVC) were below predicted value, with statistical difference. Most patients (37.5%) had a restrictive ventilatory disord... (Complete abstract click electronic access below) / Mestre

Patients with end-stage renal disease frequently suffer from cardiovascular complications. Many factors contribute to their development: hyperkinetic circulation caused by anaemia, fluid retention and by presence of dialysis arteriovenous access; metabolic changes leading to acceleration of atherosclerosis and increase of vascular stiffness and also fluctuation of blood pressure and organ perfusion during haemodialysis, that cause repeated tissue hypoxia. We performed our research on patients in chronic haemodialysis programme. The project studying long-term patency of dialysis access showed that dialysis graft patency is negatively influenced by presence of coronary artery disease and low serum concentrations of cholesterol. In our studies about tissue hypoxia we proved that haemodialysis patients suffer from hypoxia of cerebral tissue and muscle tissue of the dialysis access arm, and that the hypoxia worsens during dialysis. Factors associated with brain hypoxia are presence of heart failure, higher BNP levels and higher erythrocyte distribution width. One of the serious consequences of brain hypoxia is development of cognitive deficit. Among the negative impact of haemodialysis on the heart, we observed left atrial dysfunction, which is a consequence of long-term remodelling and cannot be...

Orientador: Jacqueline Teixeira [UNESP Caramori / Resumo: Introdução: Glomerulopatias cursam em diferentes formas de apresentação clínica e laboratorial, podendo ser classificadas como primárias ou secundárias e são a terceira causa de doença renal crônica (DRC) com necessidade de diálise no Brasil. Distúrbio mineral e ósseo (DMO) é uma das complicações da DRC e está presente já nos estágios iniciais, quando as concentrações séricas de fosfato e de hormônio da paratireoide (PTH) podem ainda estar normais, porém já há aumento da concentração sérica do fator de crescimento de fibroblasto (FGF) 23. Essa instalação precoce do DMO contribui para aumento do risco cardiovascular. O processo de aterosclerose é uma resposta inflamatória a uma série de agressores, conhecidos como fatores de risco, classificados em tradicionais e não tradicionais. Os pacientes com glomerulopatias primárias estão expostos a uma série desses fatores, formando um grupo bastante heterogêneo. A avaliação da espessura médio-intimal de carótidas (EMIC) e da vasodilatação fluxo-mediada (VFM) são maneiras não invasivas de avaliação do risco cardiovascular. Hipótese: Pacientes com glomerulopatias primárias apresentam alta prevalência de aterosclerose e disfunção endotelial, não explicada totalmente pelos fatores de risco tradicionais, mas provavelmente influenciada pela instalação precoce do DMO. Objetivo geral: Avaliar os principais marcadores de aterosclerose em pacientes portadores de glomerulopatias primárias, incluindo os fatores de risco não tradicionais. Método: ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Glomerulonephritis can present in different clinical and laboratory ways, can be classified as primary or secondary and are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the CKD complications and is already present in the early stages of the disease. At these stages, serum phosphate and parathyroid hormone (PTH) concentrations may still be normal, but there is an increase in serum concentration of fibroblast growth factor (FGF) 23. This early onset of MBD contributes to increase cardiovascular risk. Atherosclerosis is an inflammatory response of the endothelium to a number of aggressors, known as risk factors, classified into traditional and nontraditional. Patients with primary glomerulonephritis are exposed to a number of these factors, composing a heterogeneous group. Evaluation of carotid intima-media thickness (CIMT) and flow-mediated vasodilation (FMV) are noninvasive ways of assessing cardiovascular risk. Hypothesis: There is a high prevalence of atherosclerosis and endothelial dysfunction in patients with primary glomerulonephritis not totally explained by traditional risk factors, but probably influenced by early onset of MBD. Objective: Evaluate the markers of atherosclerosis in patients with primary glomerulonephritis, including nontraditional risk factors. Method: Clinical, observational, cross-sectional and controlled study that included patients with primary glomerulonephriti... (Complete abstract click electronic access below) / Doutor

Orientador: Flávia Heloísa dos Santos / Resumo: Introdução: A doença renal crônica (DRC) atinge um percentual significativo de idosos, além de estar relacionada a uma série de comorbidades, em especial, o transtorno neurocognitivo leve (TNL). A diminuição da taxa de filtração glomerular está significativamente associada a déficits globais na cognição, função executiva, linguagem e memória. Em virtude disso, a triagem cognitiva é fundamental para a população com DRC. Objetivo geral: Estimar a prevalência de TNL em doentes renais crônicos em tratamento dialítico, comparando com um grupo controle (GC) pareado por sexo e idade, e contrastar o uso de diferentes instrumentos de screening para esta finalidade. Material e método: Estudo transversal, caso-controle, no qual foram avaliados 54 pacientes em HD (GHD) e 54 controles saudáveis (GC), pareados por sexo e idade. Os pacientes foram submetidos a avaliação neuropsicológica, compreendida por testes de triagem (Mini-Exame do Estado Mental – MEEM; Avaliação Cognitiva de Montreal – MoCA; Mini-Cog), teste de inteligência (Escala Wechsler Abreviada de Inteligência – WASI), avaliação de qualidade de vida (QV) (The Medical Outcomes Study 36 item Short-Form Health Survey- SF-36), sintomas de ansiedade e depressão (Inventário de Ansiedade de Beck – BAI; Inventário de Depressão de Beck), complementados por dados sociodemográficos, clínicos e laboratoriais. Resultados: O GHD tinha medianas de 60 anos (50-67; intervalo interquartil) de idade, tempo de tratamento de 23 meses (10-51) e 40,74... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Chronic kidney disease (CKD) affects a significant percentage of the elderly, and is also related to a series of comorbidities, especially mild neurocognitive disorder (mNCD). The decrease in the glomerular filtration rate is significantly associated with global deficits in cognition, executive function, language and memory. As a result, cognitive screening is essential for the population with CKD. General objective: To estimate the prevalence of mNCD in patients with CKD undergoing dialysis, comparing to a control group (CG) matched by sex and age, and to contrast the use of different screening instruments for this purpose. Material and methods: Cross-sectional, case-control study, in which 54 patients on HD (HDG) and 54 healthy controls (CG), matched by sex and age, were evaluated. Patients underwent neuropsychological assessment, comprising screening tests (Mini-Mental State Examination - MMSE; Montreal Cognitive Assessment - MoCA; Mini-Cog), intelligence test (Wechsler Abbreviated Intelligence Scale - WASI), assessment of quality of life (QOL) (The Medical Outcomes Study 36 item Short-Form Health Survey- SF-36), symptoms of anxiety and depression (Beck Anxiety Inventory - BAI; Beck Depression Inventory - BDI), complemented by sociodemographic, clinical and laboratory data. Results: The HDG had medians of 60 years-old (50-67; interquartile range), treatment time of 23 months (10-51) and 40.74% had DM as the underlying disease. The groups did not differ in age... (Complete abstract click electronic access below) / Doutor

Purpose of Review: This article reviews the evidence on optimal medical therapy (OMT) versus coronary revascularization in patients with stable ischemic heart disease (SIHD) and advanced chronic kidney disease (CKD). Recent Findings: A post hoc analysis of the COURAGE trial in patients with SIHD and CKD showed no difference in freedom from angina, death, and nonfatal myocardial infarction (MI) between OMT and percutaneous intervention plus OMT compared with patients without CKD. The ISCHEMIA-CKD trial of 777 patients with advanced CKD revealed no difference in cumulative incidence of death or nonfatal MI at 3 years between OMT and revascularization but the composite of death or new dialysis was higher in the invasive arm. Additionally, there were no significant or sustained benefits in related to angina-related health status in invasive versus conservative strategy. Summary: An initial revascularization strategy does not reduce mortality or MI or relieve angina symptoms in patients with SIHD and advanced CKD.

Thesis (M. A. (PHARM.) -- University of Limpopo, 2019 / Introduction Multidisciplinary team (MDT) approach has emerged as one solution to improving chronic kidney disease (CKD) care. The MDT may include a nephrologist, physicians, nurses, dietitians, pharmacists, and social workers, all working together to deliver effective care to patients with CKD. Participation of pharmacists within the renal MDT at Polokwane hospital seems to be limited. The perceived barriers to pharmacists providing renal care services to CKD patients at Polokwane hospital could inform future strategy development, to enhance their participation. The aim of this study was to explore the role of pharmacists in renal care and develop strategies to maximise their participation in the renal multidisciplinary health care team, based on their participation at Polokwane hospital, Limpopo province. Method A qualitative study using semi-structured interviews was conducted with a purposeful sample of 8 members of the renal MDT and 9 pharmacists. The audiotaped interviews were transcribed exactly as said and analysed using thematic content analysis. Results Four themes emerged from the analysis: ‘pharmacist’s current scope of practice within the renal MDT’, ‘potential future roles of pharmacists’, ‘perceived barriers to participation of pharmacists within the renal MDT’ and ‘recommendation/Strategies to incorporate pharmacists into the MDT’. Results have shown that pharmacists have an absent role within the renal MDT. Their role is limited to just dispensing and managing stock, with no role in direct patient care. Both pharmacists and MDT members showed preference to working together during renal care. Pharmacy services suggested include medication reviews, provision of patient education and counselling, patient adherence improvement, dosage workouts, patient monitoring and education on contraindicated drugs and drug interactions. Shortage of staff, pharmacists lack of clinical skills, lack of communication and attitude of pharmacists were perceived as the major barriers to participation of pharmacists within the renal xii MDT. To overcome these barriers, it was recommended that the department of health (DoH) provide more pharmacy staff and educational opportunities in the form of workshops, to equip pharmacists clinically and broaden competency and knowledge on effective communication and coordination. In addition, it was recommended that the clinical curriculum at Universities be revised, to build solid foundation on MDT care and pharmacology and that the MDT programme be standardized through standard treatment guidelines (SOP’s), policies and drawing of job descriptions. Conclusion The role of pharmacists at Polokwane hospital is confined to just stock management and dispensing. There are promising avenues for future development of their role during patient care, which can be achieved by addressing the barriers highlighted Recommendations The expansion of the role of pharmacists within the renal MDT will require improved partnership between health care professionals, resources, legislations and guidance from formal SOPs. Having a national framework for pharmacy practice from Ministry of Health, supported by educational opportunities and a pro-active professional association would be key to incorporating pharmacists within the renal MDT.

No description available.

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease worldwide and occurs in up to 40% of patients with diabetes. The standard of care for DKD treatment has not kept up with the current health epidemic, which has led to a heavy economic toll and substantial health burden. Targeting either cell surface (cs)GRP78, activated α2-macroglobulin (α2M*) or preventing their interaction may provide a novel anti-fibrotic therapeutic target for the treatment of DKD and potentially non-diabetic chronic kidney disease (CKD) as well. Previously our lab has shown that HG-induced csGRP78 is a mediator of PI3k/Akt signaling and downstream extracellular matrix (ECM) protein production in glomerular mesangial cells (MC). However, the ligand responsible for activating high glucose (HG)-induced csGRP78 had not yet been determined. We have shown thus far that α2M is endogenously produced, secreted, and activated (denoted α2M*) in HG by MC, which leads to its binding to and activation thereof csGRP78. Further, α2M knockdown or α2M* neutralization attenuated Akt activation, the production of the profibrotic cytokine connective growth tissue factor (CTGF) and ECM proteins fibronectin and collagen IV. We have also shown that integrin β1 (Intβ1), a transmembrane receptor, associated with csGRP78 under HG conditions and likely acts as a tether to present csGRP78 completely extracellularly on MC. Interestingly, Intβ1 activation, even in the absence of HG, was sufficient to induce csGRP78 translocation. Further, inhibition of either csGRP78 or Intβ1 prevented synthesis, secretion and signaling of TGFβ1. This data implicates a role for Intβ1 as a required signaling partner for csGRP78-mediated profibrotic signaling. To further our understanding of csGRP78/ α2M*’s role in DKD, we investigated their ability to mediate TGFβ1 signaling through its non-proteolytic activator thrombospondin-1 (TSP1). Here, HG-induced TSP1 expression, ECM deposition, and activation of TGFβ1 was regulated by the PI3k/Akt pathway via csGRP78/α2M* in MC. Furthermore, we assessed whether this csGRP78/ α2M* axis is relevant to promoting profibrotic signaling in other renal cell types, including proximal tubule epithelial cells (PTEC) and renal fibroblasts (RF), that contribute to the pathogenesis of both later stage DKD and non-diabetic CKD. We show evidence here that HG and direct treatment with TGFβ1, a key pathologic regulator of kidney fibrosis, induce GRP78 surface translocation as well as the endogenous production and activation of α2M in both PTEC and RF. Inhibition of either csGRP78 or α2M* prevented TGFβ1 signaling measured as Smad3 activation as well as downstream ECM production. Interestingly, inhibition of this pathway under direct TGFβ1 treatment did not prevent Smad3 activation, implicating a role for Smad-independent TGFβ1 signaling through this axis. We identified the known noncanonical TGFβ1 signaling partners, yes associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ), are mediated by csGRP78 and α2M*. Lastly, we evaluated the potential therapeutic benefit of inhibiting csGRP78/α2M* interaction in the kidney fibrosis model, unilateral ureteral obstruction (UUO). Here, we show evidence that inhibition of this signaling axis using an inhibitory peptide can prevent renal fibrosis. Whether this peptide also prevents fibrosis in DKD is currently being assessed. Together, these studies strongly implicate targeting csGRP78/α2M* interaction as a novel anti-fibrotic therapeutic intervention for early and late stage DKD, as well as a potential role in non-diabetic CKD. / Thesis / Doctor of Philosophy (Medical Science) / Diabetic kidney disease is the leading cause of kidney failure in developed nations. This progressive disease leads to the loss of kidney function due to an accumulation of scar proteins in the kidney over time. High glucose is a major factor that causes this to occur. Our lab studies specific kidney cells called mesangial cells, proximal tubule epithelial cells, and fibroblasts that produce scar proteins in the presence of high glucose. We have shown that when these cells are treated with high glucose, this causes the movement of a protein called GRP78 that normally resides inside the cell to move to the cell’s surface where it can interact with other proteins. My research has established that the proteins alpha 2-macroglobulin (ɑ2M), integrin β1 (Intβ1), and thrombospondin-1 (TSP1) can bind to GRP78 on the cell surface and cause cells to make scar proteins. Preventing ɑ2M or Intβ1 from binding to GRP78 or preventing TSP1 production prevents mesangial cells from making scar proteins when exposed to high glucose. In a mouse model that overproduces these scar proteins, we showed that preventing cell surface GRP78 and α2M interaction prevents scar protein production and is thus a novel potential treatment option for kidney disease.

(1) Background: Patients with severe chronic kidney disease (CKD G4–G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute coronary syndrome (NSTE-ACS) requiring revascularization remain undefined. (2) Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included, and 300 matched patients with normal renal function were selected as a control cohort. (3) Results: In the CKD cohort, 222 patients (76%) had NSTE-ACS with indication for coronary revascularization. Diagnostic performance was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75–0.87 versus 0.85, 0.80–0.89, p = 0.68), and the ROC-derived cutoff value was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3 h changes, sensitivity increased to 98%, and PPV and NPV improved up to 93% and 86%, respectively. (4) Conclusions: In patients with severe CKD and suspected ACS, the diagnostic accuracy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay-specific cutoff levels combined with early absolute changes.

Feline morbilliviruses (FeMV) are fairly newly discovered paramyxoviruses found in cats. The first description indicated an association with widely distributed chronic kidney disease (CKD) in the host species. In various studies, a global prevalence and a further genotype, designated FeMV-2, and the involvement of other organ systems in infected individuals were shown. Using an immunofluorescence assay, we detected an overall seroprevalence of FeMV in almost half of the cats investigated (n = 380), with a significantly increased proportion in younger animals. In comparison to European Shorthair cats, the rate of seropositivity is higher in pedigree cats. Regardless of the breed, FeMV infection was associated with increased blood creatinine concentrations, suggesting an association with CKD. Further analysis indicated that this association was the strongest in animals having high IFA titers against FeMV-2. In addition, a significant association between FeMV-positive status and the prevalence of feline lower urinary tract disease (FLUTD, or idiopathic cystitis) was detected. This association was dominated by cats having antibodies against FeMV-1 only. To further evaluate the positive correlation between FeMV seroprevalence and CKD as well as FLUTD, consideration of additional clinical characteristics and laboratory parameters is warranted, and controlled infection studies with both FeMV genotypes are necessary. Clinicians should, however, be aware of a possible link between renal and lower urinary tract disease and FeMV infections.