No description available.

No description available.

No description available.

No description available.

Acute kidney injury (AKI) may result from perioperative renal medullary hypoxia. Despite high oxygen delivery to the kidney, the medullary thick ascending limb (mTAL) in the outer renal medulla is susceptible to hypoxia because of its high oxygen consumption and relatively low rate of blood flow. The objective of this study was to evaluate the effect of a low pO2 (8% FiO2 for 5 h) on the major function of the mTAL and to develop a strategy to protect the mTAL in this setting. Evidence of hypoxia-induced reduction in mTAL function included low interstitial and urine osmolality but only a minimal rise in Na+ excretion; this was prevented by pre-treatment with desmopressin acetate (dDAVP), a vasopressin analogue which may increase tissue pO2. A decrease in urine osmolality may be of diagnostic value for hypoxic renal damage and dDAVP may prevent acute kidney injury in the perioperative setting.

Acute kidney injury (AKI) may result from perioperative renal medullary hypoxia. Despite high oxygen delivery to the kidney, the medullary thick ascending limb (mTAL) in the outer renal medulla is susceptible to hypoxia because of its high oxygen consumption and relatively low rate of blood flow. The objective of this study was to evaluate the effect of a low pO2 (8% FiO2 for 5 h) on the major function of the mTAL and to develop a strategy to protect the mTAL in this setting. Evidence of hypoxia-induced reduction in mTAL function included low interstitial and urine osmolality but only a minimal rise in Na+ excretion; this was prevented by pre-treatment with desmopressin acetate (dDAVP), a vasopressin analogue which may increase tissue pO2. A decrease in urine osmolality may be of diagnostic value for hypoxic renal damage and dDAVP may prevent acute kidney injury in the perioperative setting.

Currently, the only treatment for end stage renal disease is dialysis or kidney transplantation. These methods contain obvious limitations such as the palliative nature of dialysis treatment and the lack of available organs for transplantation. As a result, there is a dire unmet need for alternative options. Regenerative therapies that focus on stimulating the regrowth of injured tissue can be a promising alternative. A critical step in the development of such therapeutic remedies is obtaining robust models that mimic the complex nature of the human kidney. The proximal tubules are a particular region of interest due to their important role in reabsorption and secretion of the glomerular filtrate and the blood, making them particularly susceptible to nephrotoxicity and renal pathologies. For this reason, the goal of this thesis was to engineer a 3D model of human proximal tubulogenesis that would allow for both developmental and regenerative studies. The ideal assay would mimic the human 3D structure and function of proximal tubules in a tunable, robust matrix that can be easily analyzed in throughput screenings for regenerative medicine and toxicity applications. In this thesis, we show the development, characterization, and application of an in vitro human renal tubulogenesis model using a modular and tunable biohybrid starPEG-heparin hydrogel platform. A range of hydrogel mechanics and compositions were systematically tested to determine the optimal conditions for renal tubulogenesis. The results revealed that only soft hydrogels based on heparin and matrix metalloproteinase (MMP) enzymatically cleavable crosslinkers led to the generation of polarized tubule structures. The generated tubules display polarization markers, extracellular matrix components, and organic anion transport functions which mimic the human renal proximal tubule. To the best of our knowledge, this is the first system where human renal tubulogenesis can be monitored ex vivo from single cells to physiologically sized tubule structures in a 3D tunable matrix. Moreover, it was found that heparin played a role in the polarization of proximal tubule cells in the hydrogel culture. The established starPEG-MMP-heparin based hydrogel model was then tested for its application as a renal tubulogenesis model by the addition of pro and anti-tubulogenic factors. It was found that the addition of growth factors and MMP inhibitors could promote and inhibit tubulogenesis, respectively. This model can be used to modulate tubulogenesis by adjusting the mechanical properties of the hydrogel, growth factor signaling, and the presence of insoluble cues (such as adhesion peptides), potentially providing new insights for regenerative therapy. To examine if the established hydrogel-based renal tubulogenesis model could be applied as a drug toxicity platform, the nephrotoxic, chemotherapeutic drug, cisplatin was incubated with the renal tubule model. The tubular structures showed a dose-dependent drug response resembling the human clinical renal pathology. The injured tubular structures also expressed the early in vivo proximal tubule injury biomarker, kidney injury molecule-1 (KIM-1). In conclusion, a hydrogel-based renal tubulogenesis model was successfully developed, characterized, and applied as a nephrotoxicity assay. Our findings suggest that the established hydrogel-based model can additionally be used for personalized medicine, where a patient’s predisposition to drug-induced renal injury or specific renal regenerative medicine treatments could be examined. This platform provides a novel approach to study human nephrotoxicity and renal regenerative medicine ex vivo, limiting the need for animal models, and potentially paving the way for more reliable preclinical trials.

Introducción: La insuficiencia renal crónica (IRC), enfermedad que causa daño irreversible a la función renal, de evolución lenta y progresiva, causando sufrimiento al enfermo y familia. Objetivo: Determinar la influencia de una educación para la salud en el bienestar y autocuidado del paciente con terapia de diálisis peritoneal para prevenir complicaciones. Metodología: Estudio de tipo cuantitativo, diseño preexperimental, cuya población estuvo conformada por todos los pacientes asistentes al programa de diálisis peritoneal del HNGAI. La muestra fue de 30 pacientes según criterios de inclusión y exclusión. Para la recolección de datos se utilizó un cuestionario y dos guías de observación mediante entrevista en el pre y postest. La intervención incluyó 4 sesiones abordándose: conocimientos sobre IRC, diálisis peritoneal, complicaciones, protección del catéter y bolsa dializadora, prácticas de higiene y nutrición. Todas las sesiones incluyeron técnicas de exposición, diálogo, demostración y redemostracion. Los datos fueron tabulados y procesados en el paquete estadístico SPSS versión 20; mediante uso de la estadística descriptiva. Resultados: En la evaluación inicial se alcanzó un nivel de bienestar medio (63%) y autocuidado adecuado(70%). Mientras que, después de la intervención educativa se logró un nivel de bienestar alto (93%) y autocuidado adecuado (100%). Conclusión: La intervención educativa mejoró significativamente el bienestar y autocuidado de los pacientes en diálisis peritoneal. Resaltando que la enfermera debe integrar a su labor una actividad continua de educación y acompañamiento al paciente y familia según sus necesidades.

No description available.

MicroRNAs (miRNAs) are short, non-coding RNA sequences which regulate gene expression. Regulation is mediated primarily through binding to complementary sites in their un-translated regions which leads to mRNA degradation or translational repression. Hypoxia is a known feature of many tumours, and increased hypoxia is associated with poor prognosis. Hypoxia leads to the up-regulation of many genes involved in a variety of functions including angiogenesis, a shift to glycolytic metabolism, and cell proliferation. This is mediated by the heterodimeric transcription factor HIF (hypoxia inducible factor), which is stabilised in hypoxia. In normoxia, the von-Hippel Lindau protein (VHL) targets HIF for degradation. Mutation in the VHL gene, as is frequently seen in clear cell renal cell cancer (CCRCC), results in constitutive over-expression of HIF and its gene targets, leading to a pro-angiogenic and pro-tumourigenic state. This thesis examined the expression of hypoxia-regulated miRNAs in cancer. The principal aims were to determine gene targets of miR-210, and to explore the effects of its over-expression and knock-down, both in vitro and in vivo. The expression of hypoxia-regulated miRNAs was examined in clinical renal tumour samples with matched normal tissue controls, and correlated with VHL mutation status. It was found that miR-210 targeted the iron sulphur cluster homologue (ISCU) gene, and was responsible for much of its down-regulation in hypoxia. Knock-down of ISCU had consequences on cell metabolism, in particular involving mitochondrial function and iron metabolism. miR-210 was found to be highly over-expressed in clear cell renal tumours (CCRCC), with greater expression seen in tumours with VHL mutations. miR-210 over-expression was also observed in papillary renal tumours, but to a lesser extent than in CCRCCs. miR-210 expression appeared to be correlated with reduced stage and grade, and improved survival. ISCU protein expression in CCRCCs was determined by immunohistochemistry, which showed that its expression correlated negatively with miR-210 expression, suggesting a functional role of miR-210 in vivo.