Acute kidney injury (AKI) is a major complication in hospitalized patients and is associated with elevated mortality rates. Numerous recent studies indicate that AKI also significantly increases the risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), hypertension, cardiovascular disease, and mortality in those patients who survive AKI. Moreover, the risk of ESRD and mortality after AKI is substantially higher in patients with preexisting CKD. However, the underlying mechanisms by which AKI and CKD interact to promote ESRD remain poorly understood. The recently developed models that superimpose AKI on rodents with preexisting CKD have provided new insights into the pathogenic mechanisms mediating the deleterious interactions between AKI and CKD. These studies show that preexisting CKD impairs recovery from AKI and promotes the development of mechanisms of CKD progression. Specifically, preexisting CKD exacerbates microvascular rarefaction, failed tubular redifferentiation, disruption of cell cycle regulation, hypertension, and proteinuria after AKI. The purpose of this review is to discuss the potential mechanisms by which microvascular rarefaction and hypertension contribute to impaired recovery from AKI and the subsequent progression of renal disease in preexisting CKD states.

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Introduction: Renal transplantation is the treatment of choice for patients with end stage renal disease [ESRD]. An increased risk of ESRD has been demonstrated when comparing donors to age matched healthy non-donors. There are no outcome data in Africa on long term donor renal function or mortality. Therefore, this study aimed to assess long term health complications in the living donor population and evaluate risk factors associated with poor health outcomes of the donors. Methods: This was a retrospective review with prospective follow up of persons undergoing living related donor nephrectomy for renal transplantation, at Groote Schuur Hospital (GSH) from January 2005 to November 2017. We retrospectively analysed baseline demographics, clinical information including blood pressure and renal function (creatinine, eGFR and proteinuria) and compared them with follow up blood pressure and renal function. Results: The majority of the donors were of mixed ancestry 94/154(61%) and 1st degree relatives 111/154 (72%) of which 63/111 (56.8%) donors were siblings. Hypertension developed in 16/31 (51.6%) donors at follow-up. Those developing hypertension had a higher mean baseline blood pressure (systolic blood pressure 139±11.3 mmHg and diastolic blood pressure 85.5±7.3 mmHg). 21/49(42.9%) developed chronic kidney disease [CKD], of which, 16 donors had an eGFR < 60 ml/min/1.73m2 . In those that developed CKD there was a higher percentage of males (p=0.018) and they were older (p=0.048) at baseline. Baseline systolic and diastolic blood pressures was not statistically different in those that developed CKD. 3/31(9.6%) donors developed diabetes. Conclusions: In South Africa, CKD is on the rise and the need for kidney donors for patients with ESRD is therefore also increasing. This study demonstrates that our living donors are at increased risk of CKD and hypertension and therefore need to be followed up more rigorously.

Fifteen percent of adults in the United States have been diagnosed with chronic kidney disease (CKD). CKD is the slow, progressive, and irreversible loss of kidney function. The most effective means of controlling CKD is by managing dietary phosphorus intake. It is important that staff nurses be educated about effective patient education tools to improve dietary phosphorus management. The purpose of this project was to educate primary care nurses about phosphorus management in CKD patients through the introduction of the phosphorus pyramid as a visual tool. The project sought to understand if an educational intervention regarding phosphorus management in CKD patients could increase the primary care nurse's knowledge. The John Hopkins evidence-based practice model informed the development of this project. Ten primary care nurses participated in a 45-minute education program which focused on the use of the Phosphorus Pyramid. A pre and post-test of knowledge was completed via a Likert scale questionnaire that measured knowledge related to the educational objectives of the program. The posttest scores showed an increase of 15% overall in staff's knowledge regarding dietary phosphorus management, the participants were more likely to correctly answer questions related to the phosphorus content of food and drink. The phosphorus pyramid will serve as a user-friendly tool to assist patients in identifying high phosphorus foods that need to be avoided and low phosphorus foods that are recommended to incorporate in their renal diet. This project supports social change by improving the healthcare team's knowledge regarding dietary recommendations for CKD patients thereby contributing to improved patient outcomes and reduced healthcare costs.

Background: Deaths in the world caused by kidney disease are increasing and in Sweden1,100 new patients start dialysis treatment every year. The diagnosis entails a major lifechange for the affected person. As a nurse, it is therefore important to have goodknowledge of affected people’s own experiences to be able to perform good nursing. Aim: The purpose of the study is to illuminate adult’s experiences of living with chronickidney failure. Methods: A literature review based on nine qualitative studies. Database searches wereconducted in Cinahl, PubMed and Scopus. The analysis was conducted using Friberg's fivestep model. Results: The analysis revealed four main categories: “a body that limits life”, “living withlife-threatening illness and an uncertain future”, “dependency on healthcare” and“experiencing support”. Conclusion: Chronic kidney failure leads to limitations in life such as physical, mental,social and financial. People's experiences of the disease are improved with the supportfrom fellow patients, healthcare personnel and the family's involvement in the diseaseprocess. More research is needed on the afflicted patient experiences of nursing in chronic renal failure.

Bakgrund: Kronisk njursjukdom klassas som en folksjukdom och orsakar samhället stora kostnader samt lidande för de drabbade. Globalt beror nästan var tjugonde dödsfall på njursjukdom. En behandlingsform för njursjukdom är hemodialys. Kronisk njursvikt är en allvarlig sjukdom, patienterna spenderar mycket tid på sjukhus och kan behöva omfattande vård vilket ställer krav på vårdpersonal.  Syfte: Att belysa patienters erfarenheter av att behandlas med hemodialys vid kronisk njursvikt. Metod: Litteraturstudien baserades på tio kvalitativa vetenskapliga studier som återfanns i databaserna PubMed och CINAHL. Studierna kvalitetsgranskades och analyserades med hjälp av Fribergs fyrstegsmetod. Resultat: Analysen resulterade i fyra kategorier och tio subkategorier. Kategorierna var: Omfattande begränsningar, Hantering av en ny verklighet, Framtidsperspektiv och Omgivningens betydelse. Kategorierna och subkategorierna beskriver hur de upplever samt påverkas av hemodialys vid kronisk njursvikt. Konklusion: Patienter som genomgår hemodialysbehandling påverkas fysiskt, psykiskt, socialt och ekonomiskt. Det är av vikt att vårdpersonal får grundläggande kunskap om hur patienterna påverkas i det vardagliga livet för att kunna ge fullgod vård. / Background: Chronic kidney disease is a disease that has high prevalence in the population and causes large costs to the society and suffering for those affected. Globally, almost every twentieth death is caused by kidney disease. Hemodialysis is one of the treatment options. Chronic kidney disease is a serious illness, the patients spend a lot of time at hospitals and may need comprehensive care which put requirements on the healthcare professionals.  Aim: To highlight the experiences of patients with chronic kidney disease undergoing hemodialysis. Methods: A literature study based on ten qualitative studies. Database searches were conducted in PubMed and CINAHL. After the quality review the analysis was conducted using Friberg’s four-stage model.  Results: The analysis resulted in four categories and ten subcategories. The categories were: Extensive restrictions, Dealing with a new reality, Perspectives on the future, The importance of the social surroundings. The categories and subcategories describe the experiences and impact of the hemodialysis treatment the patients must live through. Conclusion: Patients undergoing hemodialysis are affected physically, mentally, socially and economically. It is important for healthcare professionals to understand how and to what extent hemodialysis affect the patients and their relatives to provide good care.

Nutritional therapy is very significant for dialysis patients. The basis of the diet in hemodialysis treatment is a sufficient energy intake, increased protein intake, which corresponds to the needs of the dialysis patient. It can be difficult for patients to grasp a change in their diet compared to the period of pre-dialysis treatment, constant monitoring of all dietary restrictions due to insufficient filtration capacity of the kidneys, and at the same time compiling a still varied and balanced diet. For this reason, it is more than desirable for patients to be provided with the possibility of regular nutritional education and consultation. This individual care is essential for improving the quality of the patient's life and adequate support for hemodialysis treatment. This work aims to evaluate the change in the composition of the diet of hemodialysis patients after regular nutritional education. In addition to the adjustment of eating habits, other anthropometric and laboratory parameters related to the nutritional status of dialysis patients were also monitored. Patients were divided into two groups, according to their preferences. The first monitored group recorded their meals by hand or electronically. Patients from the second control group did not record their diet, instead they tried to...

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21008号 / 医博第4354号 / 新制||医||1028(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 小川 修, 教授 横出 正之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Renal phase-contrast magnetic resonance imaging (PC-MRI) is an MRI modality where the phase component of the MR signal is made sensitive to the velocity of water molecules in the kidneys. PC-MRI is able to assess the Renal Blood Flow (RBF), which is an important biomarker in the development of kidney disease. RBF is analyzed with the manual or semi-automatic delineation by experts of the renal arteries in PC-MRI. This is a time-consuming and operator-dependent process. We have therefore trained, validated and tested a fully-automated deep learning model for faster and more objective renal artery segmentation. The PC-MRI data used in model training, validation and testing come from four studies (N=131 subjects). Images were acquired from three manufacturers with different imaging parameters. The best deep learning model found consists of a deeply-supervised 2D attention U-Net with residual skip connections. The output of this model was re-introduced as an extra channel in a second iteration to refine the segmentation result. The flow values in the segmented regions were integrated to provide a quantification of the mean arterial flow in the segmented renal arteries. The automated segmentation was evaluated in all the images that had manual segmentation ground-truths that come from a single operator. The evaluation was completed in terms of a segmentation accuracy metric called Dice Coefficient. The mean arterial flow values that were quantified from the auto-mated segmentation were also evaluated against ground-truth flow values from semi-automatic software. The deep learning model was trained and validated on images with segmentation ground-truths with 4-fold cross-validation. A Dice segmentation accuracy of 0.71±0.21 was achieved (N=73 subjects). Although segmentation results were accurate for most arteries, the algorithm failed in ten out of 144arteries. The flow quantification from the segmentation was highly correlated without significant bias in comparison to the ground-truth flow measurements. This method shows promise for supporting RBF measurements from PC-MRI and can likely be used to save analysis time in future studies. More training data has to be used for further improvement, both in terms of accuracy and generalizability.

Chronic kidney disease (CKD) affects 13.4% of adults in America; and 38% in people aged 65 years or older[1]. In addition, cardiovascular disease (CVD) is the leading cause of death in CKD patients with end-stage kidney disease. CKD is associated with chronic inflammation, which contributes to the progression of CVD[2]. Furthermore, CKD alter apolipoprotein profile and elevate plasma lipid levels. It has been reported that 68.8% of CKD patients are associated with hyperlipidemia[3]. Therefore, hyperlipidemia is the critical risk factor for cardiovascular morbidity and mortality in CKD patients [4, 5]. In addition, trained immunity has been shown to play a critical role in chronic inflammatory diseases[6]. However, whether trained immunity promotes the inflammation in hyperlipidemia-CKD remains unclear. Circulating lipopolysaccharide (LPS) is significantly increased in atherosclerotic and CKD patients[7]. Clinical data indicates that circulating LPS is positively associated with the progression of CKD, and its levels even higher in patients with hemodialysis or dialysis[8]. Studies found that circulating LPS is delivered into cytosol for caspase-4/11 activation[9]. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) involving 10,061 patients found that targeting interleukin-1β (IL-1β) innate immunity pathway is significantly lowered the rate of recurrent cardiovascular events independent of lipid-level lowering[10]. Therefore, inhibiting the secretion of proinflammatory cytokine IL-1β has high potential to future development of novel therapeutics for hyperlipidemia-CKD accelerated CVD. Gasdermin D (GSDMD) is cleaved by inflammatory caspase-1 and caspase-4. N-terminal GSDMD binds to plasma membrane forming protein channel [11] and mediates the secretion of IL-1β[12, 13]. We found that caspase-1 activation was significantly decreased in caspase-4/11 deficient high-fat diet (HFD)-CKD mice, indicating that caspase-4 could regulate caspase-1 activation in HFD-CKD. Whether increased cytosolic LPS contribute to the increased vascular inflammation via caspase-4/11-GSDMD-IL-1β pathway remains unknown. In this study, we used HFD fed 5/6 nephrectomy CKD mice in vivo and cytosolic LPS stimulation in human aortic endothelial cell (HAECs) in vitro. We made the following results: 1) Inflammatory pathways are significantly increased in the aorta of HFD-CKD compared to HFD-Sham, normal diet (ND)-CKD, and ND-Sham. 2) Expression levels of endothelial cell activation markers (ICAM1 and VCAM1) are significantly increased in the aorta of HFD-CKD mice compared to HFD-Sham, ND-CKD, and ND-Sham. 3) Caspase-4 activation and N-GSDMD cleavage are significantly increased in the aorta of HFD-CKD mice compared to HFD-Sham, ND-CKD, and ND-Sham and in cytosolic LPS stimulated HAECs. 4) The increased inflammatory pathways and increased expression of adhesion molecules are decreased in the deficiency of caspase-4 in vivo and in the presence of caspase-4 inhibitor and N-terminal GSDMD cleavage inhibitor in vitro. 5) The increased mitochondrial ROS promote endothelial cell activation via caspase-4-GSDMD axis. Taken together, the caspase-4/11-GSDMD axis mediates endothelial cell activation and vascular inflammation in the aorta of HFD-CKD mice compared to controls. Furthermore, the increased endothelial cell activation and vascular inflammation are restored by caspase-4/11 deficiency in the aorta of HFD-CKD mice. These evidence indicate that inhibiting caspase-4/11-GSDMD axis could be a potential therapeutic target for inhibiting vascular inflammation associated with hyperlipidemia-CKD. / Biomedical Sciences