<p>Reduced kidney function around the time of surgery is an important risk factor for postoperative mortality. Despite this there is limited information on how reduced kidney function prior to surgery alters prognosis, what causes sudden decrements in kidney function after surgery (known as acute kidney injury), or how they might be avoided. The studies in this thesis inform these knowledge gaps. Chapter 2 describes the results of a post hoc analysis of the interaction between preoperative estimated glomerular filtration rate, a marker of kidney function, and postoperative cardiac troponin T, a marker of heart damage, for predicting 30-day mortality in a prospective cohort study of patients undergoing noncardiac surgery. Chapter 3 uses administrative and clinical data from a single centre to inform the risk of acute kidney injury after noncardiac surgery by concentrations of preoperative hemoglobin and change in postoperative hemoglobin. Chapter 4 uses the same data to determine a definition of intraoperative hypotension that is prognostic of acute kidney injury, myocardial injury and death. Chapter 5 describes a randomized controlled trial that compares a novel therapeutic procedure called remote ischemic preconditioning to a sham procedure in patients undergoing cardiac surgery.</p> / Doctor of Philosophy (PhD)

Chronic kidney disease is an urgent public health problem in the U.S., affecting 15% of all adults, and more than 740,000 have progressed to end-stage renal disease (ESRD), requiring life-sustaining renal replacement therapy (RRT). ESRD has devastating health, quality-of-life, and economic consequences, rendering most patients unable to maintain employment and costing Medicare $36 billion in 2017. Arguably, the most disadvantaged subgroup is the subset of patients that received no or minimal pre-ESRD nephrology care, which currently accounts for one third of the total ESRD population. This subgroup suffers increased morbidity and mortality, and has limited access to kidney transplantation, the optimal RRT. Despite this subgroup representing a large minority of the ESRD patient population, there has been no U.S.-based examination of their ESRD diagnosis experiences, coping styles and strategies, and RRT decision-making preferences. Therefore, we conducted a study that compared the ESRD diagnosis experiences, coping styles and strategies, and RRT decision-making preferences among patients with varying amounts of pre-ESRD nephrology care. We also assessed nephrologists’ current practices and perspectives on the manner and timing of RRT education for patients with varying amounts of pre-ESRD care. This mixed methods study provides a comprehensive understanding of the diagnosis experiences, coping styles and strategies, and RRT decision-making preferences of patients facing sudden and unexpected ESRD diagnosis. The study contributes important knowledge about this subgroup of patients that can influence and improve health care delivery. The results of this research will inform future intervention-based investigations to improve care for patients with minimal or no pre-ESRD nephrology care. / Public Health

La revisión crítica titulada “Cuidados de enfermería en la hipotensión intradialítica a pacientes en hemodiálisis” es un estudio secundario que utiliza la metodología de Enfermería Basada en Evidencia (EBE). Su objetivo es describir los cuidados de enfermería para pacientes con hipotensión intradialítica durante la hemodiálisis. La investigación se basó en la pregunta clínica del esquema PIS: ¿Cuáles son los cuidados de enfermería en la hipotensión intradialítica a pacientes en hemodiálisis? La metodología utilizada incluyó una estrategia de búsqueda de información a través de literatura nacional e internacional en español, inglés y portugués, utilizando bases de datos como BVS, PubMed, Epistemonikos y Google Académico. Se seleccionaron palabras clave (DECS) y se usaron fichas para la recolección bibliográfica. De los 5742 artículos recopilados, se seleccionaron 14 artículos científicos basándose en su antigüedad y validados con la guía de Validez Gálvez Toro, quedando finalmente 2 artículos, seleccionados por tener en común filtros como los últimos 5 años de antigüedad y texto completo, además se seleccionó un artículo que fue analizado utilizando el programa de lectura crítica TREND. Este análisis respondió a la pregunta planteada, describiendo que las intervenciones de enfermería durante las sesiones de hemodiálisis incluyeron el uso de dializado frío, la posición de Trendelenburg, ajustes en la medicación antihipertensiva, la administración intravenosa de cloruro de sodio, la monitorización continua de la presión arterial y la restricción de alimentos durante la hemodiálisis. / The critical review titled “Nursing care in intradialytic hypotension in patients on hemodialysis” is a secondary study that uses the Evidence-Based Nursing (EBE) methodology. Its objective is to describe nursing care for patients with intradialytic hypotension during hemodialysis. The research was based on the clinical question of the PIS scheme: What are the nursing care for intradialytic hypotension in patients on hemodialysis? The methodology used included an information search strategy through national and international literature in Spanish, English and Portuguese, using databases such as BVS, PubMed, Epistemonikos and Google Scholar. Keywords were selected (DECS) and cards were used for bibliographic collection. Of the 5742 articles collected, 14 scientific articles were selected based on their age and validated with the Gálvez Toro Validity guide, leaving finally 2 articles, selected for having in common filters such as the last 5 years of age and full text, in addition, they were selected an article that was analyzed using the TREND critical reading program. This analysis answered the question posed, describing that nursing interventions during hemodialysis sessions included the use of cold dialysate, the Trendelenburg position, adjustments in antihypertensive medication, intravenous administration of sodium chloride, continuous monitoring of blood pressure and food restriction during hemodialysis.

No / Aims: An increasing dialysis population and insufficient supply of transplant organs necessitate that patients are carefully evaluated prior to registration on the national waiting list to ensure effective utilization of a scarce resource. We have assessed listing practice in two renal units within the North of England Transplant Alliance. Methods: Demographic, ethnic and clinical data were recorded at initiation of dialysis for patients from two northern English cities, Bradford (n = 209) and Hull (n = 202) between 1994 ¿ 2000. Patients were stratified by two co-morbidity scoring systems. Multivariate and survival analyses were undertaken by registration status. Results: Overall, 159 patients were registered onto the waiting list. Stratification by co-morbidity predicted listing at high and low risk, but with overlap at medium scores. There was no difference in overall co-morbid burden between the two centers (p = 0.161 and 0.316, respectively, for two scoring systems). Logistic regression analysis demonstrated a center effect, Hull having an odds ratio for listing of 0.48 compared to Bradford (p = 0.041). Short- and medium-term survival in the listed group was high regardless of co-morbid score (22 vs 174 deaths in the non-listed group). In this cohort, five patients died with grafts, another three died whilst active on the waiting list. The remaining 14 patients had been removed from the list prior to death. Summary: Co-morbidity scoring schemes are unlikely to be sophisticated enough to accurately identify those who would most benefit from transplantation, and the value of clinical judgment is well-shown in this study. Standardization of registration will result in more equitable allocation of organs. However, this study has demonstrated that there are differences in listing practices even within a single alliance. Continuous assessment will allow judicious removal from the waiting list of patients who have developed an unacceptable co-morbid burden.

Wood products are subject to deterioration by numerous processes, as a biological material. Today, a significant area of preservative development is the utilization of existing plant residues that have water-repelling, antibacterial, antifungal, and insecticidal properties as components of wood protectants. Parthenium argentatum, known as guayule (wy-oo-lee), is a promising wood protectant due to its resin. However, the resin's complicated chemical, physical, and solvent-resistant properties make it difficult to use. The primary goal of this study was to eliminate the use of any solvent and rely on thermal modification only to fractionate usable compounds from guayule resin. Utilizing heated dialysis and steam distillation methods, small volume fractions of resin were recovered as water-borne components. These fractions were subjected to both Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography with Mass Spectrometry (GC-MS) to determine their chemical composition. Both recovery and analysis approaches detected, sorted, and compared hundreds of chemicals. These findings were compared to earlier research to identify termiticidal and wood-protectant possibilities. The compounds that were identified of the highest interest were diethyl phthalate (DEP), β-caryophyllene (BEP), cumanin, β-guaiene, ingenol, 10-epi-γ-eudesmol, and various naphthalene derivatives. The difficulty arises in the volume of resin that needs to be converted to steam-distilled fractions to recover a fraction volume substantial enough to treat large quantities of wood products. This study also compared oil and resin blends to untreated control samples for termite protection to 50-70% cross-sectional area deterioration, control samples lost 40.59% to 47.37% weight. However, Hemp Seed Oil/Guayule Resin Blend treated wood had no termite damage and minor weight loss (2.87% to 4.76%), indicating good protection. Soybean Oil/Guayule Resin Blend worked well with even better weight loss (7.28% to 9.30%). The Petroleum Diesel/Guayule Resin Blend offered moderate protection with a 19.81% to 26.01% weight decrease. Hemp seed oil is more termite-resistant than petroleum-based treatments, making it an eco-friendly wood preservation option, according to this study. This study details the processes and analyses applied to guayule resin to recover a quantifiable thermally modified fraction for component determination.

A falência de ultrafiltração (UFF) é uma causa importante de interrupção da diálise peritoneal (DP) enquanto terapia renal substitutiva. Além da inflamação crônica e aguda causadas à membrana peritoneal (MP) pelos produtos de degradação da glicose, produtos avançados da glicosilação, pH ácido das soluções e infecções, -bloqueadores (BB) também foram implicados na gênese da UFF. A vasoconstrição arteriolar esplâncnica é considerada a causa provável da UFF por BB. O nebivolol (NV), um bloqueador 1-adrenérgico altamente seletivo que, diferente de outros BB, possui efeito vasodilatador por aumento de óxido nítrico (NO) por ativar a via L-arginina-NO, foi testado em pacientes idosos com ICC e levou à redução na mortalidade. O objetivo desse estudo é analisar os efeitos do NV sobre a ultrafiltração (UF), MP e características do efluente em um modelo animal de DP, através do estudo de fenômenos envolvidos na degeneração da MP e UFF, como transição epitélio mesenquimal (EMT) e fibrose, além de parâmetros humorais e celulares de inflamação. 21 camundongos C57BL/6 fêmeas, não urêmicos, com 12 a 14 semanas, foram submetidos à colocação de cateter peritoneal. Após uma semana, foram divididos em 3 grupos de 7 animais: grupo controle (observação 30 dias), grupo SDP (2 mL/ dia de solução glicosada de diálise peritoneal a 4,25% através do cateter, por 30 dias) e grupo NV (além da infusão, receberam 8 mg/kg/dia de NV por gavagem, por 30 dias). Após 30 dias, comparou-se espessura submesotelial, volume de UF, velocidades de transporte de pequenos solutos, marcação submesotelial de pan-citoqueratina, para quantificar EMT, contagem de vasos, linfangiogênese diafragmática e concentração de IL-6 e IL-10 no efluente. A espessura da MP foi de 23,14 m no grupo controle, no grupo SDP foi de 102,4 m e no grupo NV, 29,04 m, com p<0,05. O volume de UF foi 1,94mL para o grupo controle, para o grupo SDP, 1,56 mL e, para o grupo NV, 2,05 mL, também com p<0,05. Houve menor EMT, menor angiogênese e tendência a transporte mais lento de solutos no grupo tratado, assim como menor concentração de IL-6 e proporções de populações de linfócitos semelhantes às do grupo controle. Concluímos que a droga impediu o desenvolvimento de UFF, através do bloqueio de fenômenos como EMT, espessamento da MP e neoangiogênese, além de preservar características de imunidade celular e humoral locais, merecendo ser estudada em pacientes submetidos à DP / Ultrafiltration failure (UFF) is a major cause of peritoneal dialysis (PD) discontinuation. Besides peritoneal membrane (PM) acute and chronic inflammation caused by glucose degradation products, advanced glycation end-products, acidic pH of the solutions and peritoneal infections, also -blockers (BBs) have been implicated in UFF genesis. Splanchnic arteriolar vasoconstriction has been considered the probable cause of UFF induced by BBs. Nebivolol (NV), a highly selective 1-adrenergic blocker, unlike other BBs, has a vasodilatory effect caused by its ability to increase nitric oxide (NO) through L-arginine-NO pathway activation. NV has been tested in elderly patients with congestive heart failure and led to mortality reduction. The aim of this work is to analyze the effects of NV over ultrafiltration (UF), PM and effluent characteristics in an animal model of PD. For that end, phenomena known to be involved in PM degeneration and UFF, such as epithelial-to-mesenchymal transition (EMT), fibrosis, as well as cellular and humoral parameters of inflammation have been studied. 21 C57BL/ 6 female non uremic mice, ageing 12 to 14 weeks, underwent peritoneal catheter placement. One week later, they were divided into 3 groups of 7 animals: control group (observation for 30 day), PDF group (2 mL/ day of 4.25% dextrose peritoneal dialysis fluid injected through the catheter for 30 days) and NV group (besides the PDF infusion, this group received 8 mg/ kg/ day of NV by gavage, for 30 days). After 30 days, submesotelial thickness, UF volume, small solute transport speed, submesotelial pan-cytokeratin staining (EMT quantification), vessel count, diaphragmatic lymphangiogenesis and IL-6 and IL-10 concentrations in the effluent were compared. PM thickness was 23.14 m in the control group, 102.4 m in the PDF group and 29.04 m in the NV group, p <0.05. UF volume was 1.94 mL in the control group, 1.56 mL in the SDP group, and in the NV group, 2.05 mL, p <0.05. There was less EMT, less angiogenesis and a tendency to a slower solute transport in the treated group. Lower levels of IL-6 and similar lymphocyte populations proportions to the control group were also found. We conclude that the drug can prevent UFF development, through blockade of phenomena such as EMT, PM thickening and neoangiogenesis, while characteristics of local cellular and humoral immunity were preserved. These results warrant a clinical study of the drug in PD patients

<p>Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients. </p><p>In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization. </p><p>On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.</p>

Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients. In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization. On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.

A falência de ultrafiltração (UFF) é uma causa importante de interrupção da diálise peritoneal (DP) enquanto terapia renal substitutiva. Além da inflamação crônica e aguda causadas à membrana peritoneal (MP) pelos produtos de degradação da glicose, produtos avançados da glicosilação, pH ácido das soluções e infecções, -bloqueadores (BB) também foram implicados na gênese da UFF. A vasoconstrição arteriolar esplâncnica é considerada a causa provável da UFF por BB. O nebivolol (NV), um bloqueador 1-adrenérgico altamente seletivo que, diferente de outros BB, possui efeito vasodilatador por aumento de óxido nítrico (NO) por ativar a via L-arginina-NO, foi testado em pacientes idosos com ICC e levou à redução na mortalidade. O objetivo desse estudo é analisar os efeitos do NV sobre a ultrafiltração (UF), MP e características do efluente em um modelo animal de DP, através do estudo de fenômenos envolvidos na degeneração da MP e UFF, como transição epitélio mesenquimal (EMT) e fibrose, além de parâmetros humorais e celulares de inflamação. 21 camundongos C57BL/6 fêmeas, não urêmicos, com 12 a 14 semanas, foram submetidos à colocação de cateter peritoneal. Após uma semana, foram divididos em 3 grupos de 7 animais: grupo controle (observação 30 dias), grupo SDP (2 mL/ dia de solução glicosada de diálise peritoneal a 4,25% através do cateter, por 30 dias) e grupo NV (além da infusão, receberam 8 mg/kg/dia de NV por gavagem, por 30 dias). Após 30 dias, comparou-se espessura submesotelial, volume de UF, velocidades de transporte de pequenos solutos, marcação submesotelial de pan-citoqueratina, para quantificar EMT, contagem de vasos, linfangiogênese diafragmática e concentração de IL-6 e IL-10 no efluente. A espessura da MP foi de 23,14 m no grupo controle, no grupo SDP foi de 102,4 m e no grupo NV, 29,04 m, com p<0,05. O volume de UF foi 1,94mL para o grupo controle, para o grupo SDP, 1,56 mL e, para o grupo NV, 2,05 mL, também com p<0,05. Houve menor EMT, menor angiogênese e tendência a transporte mais lento de solutos no grupo tratado, assim como menor concentração de IL-6 e proporções de populações de linfócitos semelhantes às do grupo controle. Concluímos que a droga impediu o desenvolvimento de UFF, através do bloqueio de fenômenos como EMT, espessamento da MP e neoangiogênese, além de preservar características de imunidade celular e humoral locais, merecendo ser estudada em pacientes submetidos à DP / Ultrafiltration failure (UFF) is a major cause of peritoneal dialysis (PD) discontinuation. Besides peritoneal membrane (PM) acute and chronic inflammation caused by glucose degradation products, advanced glycation end-products, acidic pH of the solutions and peritoneal infections, also -blockers (BBs) have been implicated in UFF genesis. Splanchnic arteriolar vasoconstriction has been considered the probable cause of UFF induced by BBs. Nebivolol (NV), a highly selective 1-adrenergic blocker, unlike other BBs, has a vasodilatory effect caused by its ability to increase nitric oxide (NO) through L-arginine-NO pathway activation. NV has been tested in elderly patients with congestive heart failure and led to mortality reduction. The aim of this work is to analyze the effects of NV over ultrafiltration (UF), PM and effluent characteristics in an animal model of PD. For that end, phenomena known to be involved in PM degeneration and UFF, such as epithelial-to-mesenchymal transition (EMT), fibrosis, as well as cellular and humoral parameters of inflammation have been studied. 21 C57BL/ 6 female non uremic mice, ageing 12 to 14 weeks, underwent peritoneal catheter placement. One week later, they were divided into 3 groups of 7 animals: control group (observation for 30 day), PDF group (2 mL/ day of 4.25% dextrose peritoneal dialysis fluid injected through the catheter for 30 days) and NV group (besides the PDF infusion, this group received 8 mg/ kg/ day of NV by gavage, for 30 days). After 30 days, submesotelial thickness, UF volume, small solute transport speed, submesotelial pan-cytokeratin staining (EMT quantification), vessel count, diaphragmatic lymphangiogenesis and IL-6 and IL-10 concentrations in the effluent were compared. PM thickness was 23.14 m in the control group, 102.4 m in the PDF group and 29.04 m in the NV group, p <0.05. UF volume was 1.94 mL in the control group, 1.56 mL in the SDP group, and in the NV group, 2.05 mL, p <0.05. There was less EMT, less angiogenesis and a tendency to a slower solute transport in the treated group. Lower levels of IL-6 and similar lymphocyte populations proportions to the control group were also found. We conclude that the drug can prevent UFF development, through blockade of phenomena such as EMT, PM thickening and neoangiogenesis, while characteristics of local cellular and humoral immunity were preserved. These results warrant a clinical study of the drug in PD patients

Systemische Infektionen mit S. aureus (MSSA und MRSA) und Infektionen des Gefäßzugangs bei HD-Patienten sind eine der wichtigsten Ursachen für Morbidität und Mortalität in dieser speziellen Population. Infektionsrisikos stellen die zunehmende Verwendung von Fremdkörpern, wie Katheter und Graft als Gefäßzugänge, sowie die intensivmedizinische Behandlung bei älteren und multimorbiden Patienten dar. Unter den bakteriell bedingten Infektionen bleiben Staphylokokken der am häufigsten nachgewiesene Stamm. Mit dem zunehmenden Gebrauch von Vancomycin zur Behandlung von MSSA-Infektionen hat das Vorkommen von MRSA zugenommen. Dies macht die Entwicklung von alternativen Antibiotikaregimen nötig, die eine Selektion von MRSA-Spezies verhindern. Unter dieser Überlegung wurde auf die Behandlung mit Vancomycin bei Zugangs-bezogenen Infektionen verzichtet. Es wurde im Jahr 2000 durch ein Standardregime bestehend aus Flucloxacillin und Rifampicin ersetzt. Mithilfe eines Screeningprogramms wurde nach MSSA- (n=88) und MRSA- (n=1) Kolonisationen gesucht. Dies gelang mit Hilfe von Querschnitts-Screenings und Indikations-Screeninguntersuchungen bei Aufnahme über den Zeitraum von 2000 bis 2010. Eine Besiedlung mit MRSA wurde bei nur einem Patienten während des 10-Jahres-Screenings registriert. Die gefundenen MSSA-Kolonisationen bei HD-Patienten beeinflussten die Morbidität und Mortalität nicht. Die Anzahl an HD-Patienten mit MSSA-Kolonisation nahm während des Beobachtungszeitraums von zehn Jahren ab Behandlungen mit dem Vancomycin-freien Regime waren generell erfolgreich und resultierten in einem Rückgang der klinischen und laborativen Infektionsmarker und/oder negativen Blutkulturen. Es konnte gezeigt werden, dass mit dem Gebrauch von vancomycinfreien Antibiotikaregimen ein erfolgreiches Management von Staphylokokkus-assoziierten Zugangsinfektionen bei HD-Patienten möglich ist.