京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21263号 / 医博第4381号 / 新制||医||1029(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 柳田 素子, 教授 福田 和彦, 教授 木村 剛 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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INTRODUCTION: In patients who receive treatment for cancer, acute kidney injury (AKI) is arguably one of the most dangerous toxicities that results from cisplatin (CP), a chemotherapeutic agent. While AKI is a common occurrence amongst people who receive cisplatin (CP-AKI), the current risk assessment, intervention methods and understanding the role of magnesium in AKI, are either limited or understudied. OBJECTIVES: We aimed to build on previous CP-AKI risk prediction models, and establish a relationship between serum magnesium levels and AKI. Additionally, we used a feasibility study to test if intravenous magnesium sulfate in patients receiving intraoperative chemotherapy with cisplatin (HIOCC) for malignant mesothelioma can attenuate CP-AKI. This feasibility study was also used to determine a proper dosing regimen to achieve serum magnesium levels of 3 - 4.8 mg/dl. METHODS: We defined acute kidney injury as a 1.5-fold increase in serum creatine, or use of renal replacement therapy (RRT). Using clinical and demographic information from Memorial Sloan Kettering’s database, we conducted multivariable and univariable regression was used to identify the most significant demographic and clinical lab values. Using the information from the statistical analysis we built on previous risk prediction models for cisplatin associated kidney injury. Using the same statistical analysis, we further explored the relationship between serum magnesium values and AKI. In the feasibility study, we recruited patients from Brigham and Woman’s hospital who were receiving HIOCC treatment for mesothelioma. They received an infusion of intravenous magnesium sulfate during surgery. Serum magnesium levels were measured pre-operatively and post-operatively along with serum creatinine values. These were used to obtain pharmacokinetic information to further adjust the infusion rate in patients, lab values were also used to identify any AKI. CONCLUSION: A score-based model created using patient’s age, serum magnesium, albumin, hemoglobin, platelets, cisplatin dose and hypertension is predictive of cisplatin associated acute kidney injury. The feasibility study allowed us to inform phase 2 of an upcoming feasibility study that will include a bolus of 6g Mg/hr and an infusion of 2 g/hr after the bolus. This will work to increase the serum magnesium levels to the therapeutic range.

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The purpose of the dissertation Continuous Elimination Methods in Intensive Care in Prospective of Hospital Nurse is to inform about acute kidney injury and chronic kidney disease. These are major reason to use elimination methods at intensive care units and anesthesiological resuscitation departments. We further determine elimination issues. Continuous elimination methods in intensive care medicine are important medical treatment at acute kidney injury and chronic kidney disease. Particularly, acute kidney injury belongs to frequent complications at critically diseased patients, therefore will be properly discussed. It is afraid, because decreased renal function leads to incapability to excrete waste products of metabolism and sustain homeostasis. Mortality at acute kidney injury is higher than at chronic kidney disease so support or renal replacement therapy, in order to save life, is the only accepted method of choice at present time. The techniques of renal support or replacement therapy are integral part of instensive care medicine. The aim of this thesis is to elaborate latest accessible findings and specialized nursing care at continuous elimination methods. Ve have tried to create integrated, comprehensible summary of knowledge of this topic. We expect these findings are fundamental to high-quality nursing at patients with this disorder. The dissertation was conducted as a method of review and synthesis. As long as this part is purely theoretical-based, it gathers informations from czech and also foreign sources. The data was acquired from scientific publications, technical papers, monographs and web. The outcome of this work can be used for further research of this topic or contribute to resource information for paramedical staff. In the thesis we analyze acute kidney injury, briefly chronic kidney disease, then we proceed through the history of dialysis and its specifications. These are closely explained. We focus on technical aspect of various elimination methods, the division, indication to initation, advantage and disadvantage, vascular access will also be described. The possibilities of anticoagulation have been defined, the types of membrane hemofiltrates and dialysators, substitutional and dialysing solutions have been characterized, the need of dietary measures has been emphasized. The complications that can happen during the use of elimination method have not been left out of consideration. We describe the intensive care units, nurse competencies, their work, monitoration, patients' and elimination unit preparation and vascular access care.

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2016-09-09T12:48:51Z No. of bitstreams: 4 Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 1.pdf: 3581171 bytes, checksum: 0e5521af5f633f8415423063cda690f3 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 2.pdf: 902776 bytes, checksum: 16eddca9ca127b94fc6c55ed6a691300 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 3.pdf: 128655 bytes, checksum: 236893a1942f321bbe3d36424a293450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-09T15:24:50Z (GMT) No. of bitstreams: 4 Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 1.pdf: 3581171 bytes, checksum: 0e5521af5f633f8415423063cda690f3 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 2.pdf: 902776 bytes, checksum: 16eddca9ca127b94fc6c55ed6a691300 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 3.pdf: 128655 bytes, checksum: 236893a1942f321bbe3d36424a293450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-09T15:24:50Z (GMT). No. of bitstreams: 4 Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 1.pdf: 3581171 bytes, checksum: 0e5521af5f633f8415423063cda690f3 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 2.pdf: 902776 bytes, checksum: 16eddca9ca127b94fc6c55ed6a691300 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 3.pdf: 128655 bytes, checksum: 236893a1942f321bbe3d36424a293450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-03-02 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Surgeries and anesthesia performed on dogs could cause kidney injury or worsen their renal functions if they are already sick. There is a literature gap in studies discussing post-surgery monitoring and its effects. This study aimed to evaluate dogs who undergone surgeries, in animals considered healthy and in those who had any renal alterations before surgery to evaluate if they developed any renal impairment due to surgery and anesthesia. Dogs were monitored and evaluated before and after surgeries in order to detect if they had any renal injury due to surgery or post-operative procedures. Evaluation took place right after the surgery and after certain time range from the surgery (Two, Seven, 28 and 90 days). Blood and Urine samples were drawn from the dogs to better classify them as healthy or having kidney injury. Consequently, hematological, urinary and blood gases profiles were proceeded. Few dogs with normal renal function that were submitted to surgery had transitory renal injury (23%). Nephropatic dogs that received specific therapy for renal protection did not presented tubular lesion due to surgery. Hypotension occurred in nephropatic dogs despite the use of non-hypotensive drug therapy but in a low frequency and had brief renal impairment. Anesthesia induced hypotension in non nephropatic dogs (54%) for the usage of hypotensive drug therapy. / Procedimentos anestésicos podem contribuir para a disfunção renal no paciente hígido ou mesmo agravar a injúria do nefropata. Na medicina veterinária, há um déficit de literatura sobre a temática relacionando lesão renal decorrente da anestesia e monitorização destes animais, uma vez que o acompanhamento no pós-operatório, na maioria das vezes, não é realizado. O estudo objetivou avaliar a morfofuncionalidade do rim em 23 cães submetidos a cirurgia atendidos no Hospital Veterinário da Escola de Veterinária e Zootecnia da Universidade Federal de Goiás. Exames clínicos e laboratoriais foram feitos para determinação do perfil renal dos pacientes e, posteriormente, determinar se os mesmos seriam incluídos no grupo nefropata ou no grupo não nefropata. Exames de bioquímica sérica e urinária, exame de urina, razão PU/CU, hemogasometria, hemograma e excreção fracionada de sódio e potássio foram procedidos. Os pacientes foram monitorizados com mensurações dos parâmetros clínicos e laboratoriais anterior ao procedimento, ao final da cirurgia, com dois dias, sete, 28 e 90 dias. Constatou-se que cães sem evidência clínica e laboratorial de nefropatia e submetidos a condições adequadas de pré, trans e pós-operatório houve lesão tubular secundária a anestesia foi transitória e em poucos pacientes (23%). Cães nefropatas estabilizados e submetidos protocolos diferenciados no pré, trans e pósoperatório, não apresentaram indicativo de lesão tubular secundária a anestesia. Na cirurgia, os cães nefropatas (30%) submetidos a protocolos anestésicos sem acepromazina, apresentam menor ocorrência de hipotensão que os não nefropatas (54%), submetidos a protocolos anestésicos com acepromazina. Hipotensão anestésica afeta a integridade renal de forma transitória.

Empiric antimicrobial therapy often consists of the combination of Gram-positive coverage with vancomycin (VAN) and Gram-negative coverage, specifically an anti-pseudomonal beta-lactam, such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports demonstrate increasing nephrotoxicity rates among patients treated with the combination of VAN and PTZ. This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI), as defined by the RIFLE criteria, compared to VAN and PTZ monotherapies. Overall, 11,650 patients were analyzed, with 1,647 (14.1%) AKI cases occurring. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, p<0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (aOR=2.03; 95% CI 1.74-2.39; aOR=2.31; 95% CI 1.97-2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs were independently associated with increased AKI rates, as were increased duration of therapy, length of hospital stay, increasing severity of illness, and increasing baseline renal function. VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy.

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