Academic literature on the topic 'Kidney replacement therapy (KRT)'

Background and objectivesMore men than women undergo kidney replacement therapy (KRT) despite a larger number of women being affected by CKD. The aim of this multinational European study was to explore whether there might be historic and geographic trends in sex-specific incidence and prevalence of various KRT modalities.Design, setting, participants, & measurementsWe assessed sex-specific differences in KRT incidence and prevalence using data from nine countries reporting to the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) Registry for at least 40 years, during the period 1965–2015. Sex distribution data were compared with the European general population (Eurostat). Statistical methodology included basic descriptive statistics, incidence and prevalence calculations per million population (pmp), as well as their male-to-female ratios. Analyses were stratified by age group and diabetic status.ResultsWe analyzed data from 230,378 patients receiving KRT (38% women). For all KRT modalities, the incidence and prevalence rates were consistently higher in men than women. For example, the KRT incidence increased from 8 pmp in 1965–1974 to 98 pmp in 2005–2015 in women, whereas it rose from 12 to 173 pmp in men during the same period. Male-to-female ratios, calculated for incident and prevalent KRT patients, increased with age (range 1.2–2.4), showing consistency over decades and for individual countries, despite marked changes in primary kidney disease (diabetes more prevalent than glomerulonephritis in recent decades). The proportion of kidney transplants decreased less with age in incident and prevalent men compared with women on KRT. Stratified analysis of patients who were diabetic versus nondiabetic revealed that the male-to-female ratio was markedly higher for kidney transplantation in patients with diabetes.ConclusionsSince the beginning of KRT programs reporting to the ERA-EDTA Registry since the 1960s, fewer women than men have received KRT. The relative difference between men and women initiating and undergoing KRT has remained consistent over the last five decades and in all studied countries.

<b><i>Background:</i></b> The global epidemiology of end-stage kidney disease (ESKD) reflects each nation’s unique genetic, environmental, lifestyle, and sociodemographic characteristics. The response to ESKD, particularly regarding kidney replacement therapy (KRT), depends on local disease burden, culture, and socioeconomics. Here, we explore geographic variation and global trends in ESKD incidence and prevalence and examine variations in KRT modality, practice patterns, and mortality. We conclude with a discussion on disparities in access to KRT and strategies to reduce ESKD global burden and to improve access to treatment in low- and middle-income countries (LMICs). <b><i>Summary:</i></b> From 2003 to 2016, incidence rates of treated ESKD were relatively stable in many higher income countries but rose substantially predominantly in East and Southeast Asia. The prevalence of treated ESKD has increased worldwide, likely due to improving ESKD survival, population demographic shifts, higher prevalence of ESKD risk factors, and increasing KRT access in countries with growing economies. Unadjusted 5-year survival of ESKD patients on KRT was 41% in the USA, 48% in Europe, and 60% in Japan. Dialysis is the predominant KRT in most countries, with hemodialysis being the most common modality. Variations in dialysis practice patterns account for some of the differences in survival outcomes globally. Worldwide, there is a greater prevalence of KRT at higher income levels, and the number of people who die prematurely because of lack of KRT access is estimated at up to 3 times higher than the number who receive treatment. <b><i>Key Messages:</i></b> Many people worldwide in need of KRT as a life-sustaining treatment do not receive it, mostly in LMICs where health care resources are severely limited. This large treatment gap demands a focus on population-based prevention strategies and development of affordable and cost-effective KRT. Achieving global equity in KRT access will require concerted efforts in advocating effective public policy, health care delivery, workforce capacity, education, research, and support from the government, private sector, nongovernmental, and professional organizations.

Background Comorbidities are associated with increased mortality among patients receiving long-term kidney replacement therapy (KRT). However, it is not known whether primary kidney disease modifies the effect of comorbidities on KRT patients’ survival. Methods An incident cohort of all patients (n = 8696) entering chronic KRT in Finland in 2000–2017 was followed until death or end of 2017. All data were obtained from the Finnish Registry for Kidney Diseases. Information on comorbidities (coronary artery disease, peripheral vascular disease, left ventricular hypertrophy, heart failure, cerebrovascular disease, malignancy, obesity, underweight, and hypertension) was collected at the start of KRT. The main outcome measure was relative risk of death according to comorbidities analyzed in six groups of primary kidney disease: type 2 diabetes, type 1 diabetes, glomerulonephritis (GN), polycystic kidney disease (PKD), nephrosclerosis, and other or unknown diagnoses. Kaplan-Meier estimates and Cox regression were used for survival analyses. Results In the multivariable model, heart failure increased the risk of death threefold among PKD and GN patients, whereas in patients with other kidney diagnoses the increased risk was less than twofold. Obesity was associated with worse survival only among GN patients. Presence of three or more comorbidities increased the age- and sex-adjusted relative risk of death 4.5-fold in GN and PKD patients, but the increase was only 2.5-fold in patients in other diagnosis groups. Conclusions Primary kidney disease should be considered when assessing the effect of comorbidities on survival of KRT patients as it varies significantly according to type of primary kidney disease.

The number of patients dialyzed for ESKD exceeds 500,000 in the United States and more than 2.6 million people worldwide, with the expectation that the worldwide number will double by 2030. The human cost of health and societal financial cost of ESKD is substantial. Dialytic therapy is associated with an unacceptably high morbidity and mortality rate and poor quality of life. Although innovation in many areas of science has been transformative, there has been little innovation in dialysis or alternatives for kidney replacement therapy (KRT) since its introduction approximately 70 years ago. Advances in kidney biology, stem cells and kidney cell differentiation protocols, biomaterials, sensors, nano/microtechnology, sorbents and engineering, and interdisciplinary approaches and collaborations can lead to disruptive innovation. The Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and the US Food and Drug Administration, has convened a multidisciplinary group to create a technology roadmap for innovative approaches to KRT to address patients’ needs. The Roadmap is a living document. It identifies the design criteria that must be considered to replace the myriad functions of the kidney, as well as scientific, technical, regulatory, and payor milestones required to commercialize and provide patient access to KRT alternatives. Various embodiments of potential solutions are discussed, but the Roadmap is agnostic to any particular solution set. System enablers are identified, including vascular access, biomaterial development, biologic and immunologic modulation, function, and safety monitoring. Important Roadmap supporting activities include regulatory alignment and innovative financial incentives and payment pathways. The Roadmap provides estimated timelines for replacement of specific kidney functions so that approaches can be conceptualized in ways that are actionable and attract talented innovators from multiple disciplines. The Roadmap has been used to guide the selection of KidneyX prizes for innovation in KRT.

Abstract Background Acute kidney injury (AKI) can affect hospitalized patients with coronavirus disease 2019 (COVID-19), with estimates ranging between 0.5% and 40%. We performed a systematic review and meta-analysis of studies reporting incidence, mortality and risk factors for AKI in hospitalized COVID-19 patients. Methods We systematically searched 11 electronic databases until 29 May 2020 for studies in English reporting original data on AKI and kidney replacement therapy (KRT) in hospitalized COVID-19 patients. Incidences of AKI and KRT and risk ratios for mortality associated with AKI were pooled using generalized linear mixed and random-effects models. Potential risk factors for AKI were assessed using meta-regression. Incidences were stratified by geographic location and disease severity. Results A total of 3042 articles were identified, of which 142 studies were included, with 49 048 hospitalized COVID-19 patients including 5152 AKI events. The risk of bias of included studies was generally low. The pooled incidence of AKI was 28.6% [95% confidence interval (CI) 19.8–39.5] among hospitalized COVID-19 patients from the USA and Europe (20 studies) and 5.5% (95% CI 4.1–7.4) among patients from China (62 studies), whereas the pooled incidence of KRT was 7.7% (95% CI 5.1–11.4; 18 studies) and 2.2% (95% CI 1.5–3.3; 52 studies), respectively. Among patients admitted to the intensive care unit, the incidence of KRT was 20.6% (95% CI 15.7–26.7; 38 studies). Meta-regression analyses showed that age, male sex, cardiovascular disease, diabetes mellitus, hypertension and chronic kidney disease were associated with the occurrence of AKI; in itself, AKI was associated with an increased risk of mortality, with a pooled risk ratio of 4.6 (95% CI 3.3–6.5). Conclusions AKI and KRT are common events in hospitalized COVID-19 patients, with estimates varying across geographic locations. Additional studies are needed to better understand the underlying mechanisms and optimal treatment of AKI in these patients.

The soluble urokinase-type plasminogen activator receptor (suPAR) is involved in the pathogenesis of acute kidney injury (AKI). Our goal was to establish the optimal suPAR cut-off point for predicting the need for kidney replacement therapy (KRT) use in sepsis patients and to analyze survival rates based on the suPAR level, AKI diagnosis, and the requirement for KRT. In total, 51 septic patients were included (82% septic shock; 96% mechanically ventilated, 35% KRT). Patients were stratified according to the AKI diagnosis and the need for KRT into three groups: AKI(+)/KRT(+), AKI(+)/KRT(−), and AKI(−)/KRT(−). A control group (N = 20) without sepsis and kidney failure was included. Sepsis patients had higher levels of the suPAR than control (13.01 vs. 4.05 ng/mL, p < 0.001). On ICU admission, the suPAR level was significantly higher in the AKI(+)/KRT(+) group than in the AKI(+)/KRT(−) and AKI(−)/KRT(−) groups (18.5 vs. 10.6 and 9.5 ng/mL, respectively; p = 0.001). The optimal suPAR cut-off point for predicting the need for KRT was established at 10.422 ng/mL (area under the curve 0.801, sensitivity 0.889, specificity 0.636). Moreover, patients AKI(+)/KRT(+) had the lowest probability of survival compared to patients AKI(+)/KRT(−) and AKI(−)/KRT(−) (p = 0.0003). The results indicate that the suPAR measurements may constitute an important element in the diagnosis of a patient with sepsis.

Background and objectivesAKI requiring KRT is associated with high mortality and utilization. We evaluated the use of an AKI Standardized Clinical Assessment and Management Plan (SCAMP) on patient outcomes, including mortality, hospital length of stay, and intensive care unit length of stay.Design, setting, participants, & measurementsWe conducted a 12-month controlled study in the intensive care units of a large academic tertiary medical center. We alternated use of the AKI-SCAMP with use of a “sham” control form in 4- to 6-week blocks. The primary outcome was risk of inpatient mortality. Prespecified secondary outcomes included 30- and 60-day mortality, hospital length of stay, and intensive care unit length of stay. Generalized estimating equations were used to estimate the effect of the AKI-SCAMP on mortality and length of stay.ResultsThere were 122 patients in the AKI-SCAMP group and 102 patients in the control group. There was no significant difference in inpatient mortality associated with AKI-SCAMP use (41% versus 47% control). AKI-SCAMP use was associated with significantly reduced intensive care unit length of stay (mean, 8; 95% confidence interval, 8 to 9 days versus mean, 12; 95% confidence interval, 10 to 13 days; P<0.001) and hospital length of stay (mean, 25; 95% confidence interval, 22 to 29 days versus mean, 30; 95% confidence interval, 27 to 34 days; P=0.02). Patients in the AKI-SCAMP group were less likely to receive KRT in the context of physician-perceived treatment futility than those in the control group (2% versus 7%; P=0.003).ConclusionsUse of the AKI-SCAMP tool for AKI KRT was not significantly associated with inpatient mortality, but was associated with reduced intensive care unit length of stay, hospital length of stay, and use of KRT in cases of physician-perceived treatment futility.Clinical Trial registry name and registration numberAcute Kidney Injury Standardized Clinical Assessment and Management Plan for Renal Replacement Initiation, NCT03368183.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN02060221.mp3

ABSTRACT The European Renal Association (ERA) Registry Annual Report 2019 will be its last pre-pandemic report. From 2020 on, registry data will incorporate any potential impact of coronavirus disease 2019 (COVID-19) on kidney replacement therapy (KRT) practices in Europe. The 2019 report focussed on age comparisons and found substantial differences in the distribution of primary renal disease, treatment modality, kidney donor type and the survival probabilities for different age categories. The report presents data that support a correlation (R2 = 0.43, P &lt; 0.00001) between the incidence of KRT per million population (pmp) and the median age at the start of KRT in the different regions and countries, suggesting that initiating KRT at an older median age may be a determinant of KRT incidence. The causes of the lower age at KRT in some countries should be explored. These may include, but are not limited to, KRT not being offered to the elderly or the elderly refusing KRT. In this regard, there was a correlation between the median age at the start of KRT and per capita gross domestic product (GDP) (R2 = 0.26, P &lt; 0.0046), suggesting that the availability of resources may be a factor that limits the offer of KRT to the elderly. The UK may represent a case to study these issues. Both age at initiation of KRT and KRT incidence are below the European median and lower than that expected for GDP. Furthermore, there are differences between the various countries within the UK, as well as documented racial differences, the latter being a piece of information missing for most European countries.

Background and objectivesDuring the coronavirus disease 2019 outbreak, the treatment of families with children on long-term KRT is challenging. This study was conducted to identify the current difficulties, worries regarding the next 2 months, and mental distress experienced by families with children on long-term KRT during the coronavirus disease 2019 outbreak and to deliver possible management approaches to ensure uninterrupted treatment for children on long-term KRT.Design, setting, participants, & measurementsA multicenter online survey was conducted between February 10 and 15, 2020, among the families with children on long-term KRT from five major pediatric dialysis centers in mainland China. The primary caregivers of children currently on long-term KRT were eligible and included. Demographic information, severe acute respiratory syndrome coronavirus 2 infection status, current difficulties, and worries regarding the next 2 months were surveyed using a self-developed questionnaire. The Patient Health Questionnaire-9 and the General Anxiety Disorder Scale-7 were used to screen for depressive symptoms and anxiety, respectively.ResultsAmong the children in the 220 families included in data analysis, 113 (51%) children were on dialysis, and the other 107 (49%) had kidney transplants. No families reported confirmed or suspected cases of coronavirus disease 2019. Overall, 135 (61%) and 173 (79%) caregivers reported having difficulties now and having worries regarding the next 2 months, respectively. Dialysis supply shortage (dialysis group) and hard to have blood tests (kidney transplantation group) were most commonly reported. A total of 29 (13%) caregivers had depressive symptoms, and 24 (11%) had anxiety. After the survey, we offered online and offline interventions to address their problems. At the time of the submission of this paper, no treatment interruption had been reported.ConclusionsThe coronavirus disease 2019 outbreak has had physical, mental, logistical, and financial effects on families with children on long-term KRT.

Purpose: Severe acute kidney injury (AKI) is a potential complication of COVID-19-associated critical illness. This has implications for the management of COVID-19-associated AKI and the resulting increased need for kidney replacement therapy (KRT) in the intensive care unit (ICU) and elsewhere in the hospital. The Canadian Society of Nephrology COVID-19 Rapid Review Team has sought to collate and synthesize currently available resources to inform ethically justifiable decisions. The goal is the provision of the best possible care for the largest number of patients with kidney disease while considering how best to ensure the safety of the health care team. Information sources: Local, provincial, national, and international guidance and planning documents related to the COVID-19 pandemic; guidance documents available from nephrology and critical care-related professional organizations; recent journal articles and preprints related to the COVID-19 pandemic; expert opinion from nephrologists from across Canada. Methods: A working group of kidney specialist physicians was established with representation from across Canada. Kidney physician specialists met via teleconference and exchanged e-mails to refine and agree on the proposed suggestions in this document. Key findings: (1) Nephrology programs should work with ICU programs to plan for the possibility that up to 30% or more of critically ill patients with COVID-19 admitted to ICU will require kidney replacement therapy (KRT). (2) Specific suggestions pertinent to the optimal management of AKI and KRT in patients with COVID-19. These suggestions include, but are not limited to, aspects of fluid management, KRT vascular access, and KRT modality choice. (3) We describe considerations related to ensuring adequate provision of KRT, should resources become scarce during the COVID-19 pandemic. Limitations: A systematic review or meta-analysis was not conducted. Our suggestions have not been specifically evaluated in the clinical environment. The local context, including how the provision of acute KRT is organized, may impede the implementation of many suggestions. Knowledge is advancing rapidly in the area of COVID-19 and suggestions may become outdated quickly. Implications: Given that most acute KRT related to COVID-19 is likely to be required initially in the ICU setting, close collaboration and planning between critical care and nephrology programs is required. Suggestions may be updated as newer evidence becomes available.

The treatment of end-stage renal disease (ESRD) by dialysis and transplantation (renal replacement therapy - RRT) imposes major social and economic burdens on the patient, the family and society. Data obtained from 2 Scottish and 4 European renal units indicate that non-renal comorbid illness significantly increased patient mortality. Furthermore, application of a simple risk stratification method based on age and comorbidity divided patients into groups which carried different survival rates. Multivariate analysis showed that even after adjustment for comorbidity and age, an apparent "centre effect" persisted which ranked the centres. A further study examined factors influencing early mortality on RRT. The method of risk stratification described can be used for comparative survival studies by national and international registries. The generic health status questionnaire (the SF-36) which has been validated in the UK was administered to patients receiving all 3 modalities of RRT and their health status compared with a large sample of the general population. Patients' quality of life was influenced by mode of treatment and like survival was also shown to relate to comorbidity. Further studies of the incidence and prevalence of chronic renal failure in Grampian showed that advancing age and comorbidity significantly influenced the decision by non-nephrologists to refer a patient to the renal service. The results of this study have manifest resource implications for the provision of renal services. A protocol for the use of erythroprotein in the Aberdeen renal unit was developed and implemented. Its efficacy was monitored by studying defined outcome measures. This study showed that formal implementation of the protocol led to an increase in the proportion of patients with haemoglobin concentrations in the acceptable range and a fall in the number of blood transfusions.

Malnutrition is common in acute kidney injury (AKI) patients, particularly on the ICU, where they often receive renal replacement therapy (RRT). RRT may exacerbate loss of water-soluble micronutrients (e.g. trace elements, amino acids and B-vitamins). No clinical study has quantified these losses and contrasted between types of RRT that use different methods to remove solutes i.e. by diffusion (intermittent haemodialysis, IHD) by convection (continuous veno-venous haemofiltration, CVVH) or by a combination of both (sustained low-efficiency diafiltration, SLEDf). Using a prospective, observational design patients (n=24 per modality) were consented before their first treatment session. Blood and RRT effluent (dialysate or filtrate) were sampled at baseline (pre-RRT), mid and end-RRT. Amino acids were measured by HPLC, trace elements by ICP-MS and B-vitamins (B1, B3, B6, B9, B12) by LC-MS. Plasma concentrations were corrected for dialysis dose using the urea reduction ratio (for IHD & SLEDf, but not CVVH). Micronutrient losses (mass-corrected) were calculated as concentration × RRT effluent volume, corrected for plasma concentration and RRT dose (i.e. solute removal index). Data were analysed by restricted maximum likelihood estimating equations (Genstat v16, VSNi Ltd, UK). Patients receiving CVVH had significantly higher plasma amino acids, but not plasma trace elements, at baseline (amino acids: CVVH, 3762 ± 357; IHD, 2039 ± 337; SLEDf, 2505 ± 423 µmol/L; trace elements: IHD, 4156 ± 465; SLEDf 3732 ± 521; CVVH 3982 ± 465 µg/L). At RRT end, plasma amino acids and trace elements had significantly reduced (429 ± 223 µmol/L; 600 ± 400 µg/L, respectively). No trace element was lost to a greater extent between types of RRT, but many ( > 10) individual amino acids declined to a much greater extent with SLEDf vs. HD or CVVH (e.g. effect size for lysine was -64 ± 23 µmol/L). Two significant sources of micronutrient loss were noted: to effluent and through dialyser adsorption. The latter contributed < 1g amino acids but in effluent recorded losses of up to 25g were noted with CVVH (5-10g for IHD and SLEDf, respectively). Effluent losses of trace elements varied significantly, but in all cases were greater for CVVH (e.g. effect size for copper was +850 ± 475 µg vs. HD or SLED-F). B-vitamins were not detectable in effluent. Significant loss of micronutrients during RRT, particularly for patients in ICU, is a possible aggravating factor for patients known to be at high risk of malnutrition. The type of RRT used influences the pattern of loss but not consistently for all nutrients. Adsorption of amino acids to dialysers adds a small, but cumulative loss that may become important if further treatment sessions are indicated.

Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2018.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 39-40).
According to the Centers for Disease Control and Prevention, there are approximately 1.5 million cases of sepsis and over 250,000 resultant deaths each year [1]. One of the major effects of sepsis is organ failure, notably in the kidneys, lungs, liver, and brain. In the case where the kidneys fail, renal replacement therapy (RRT) may be performed in order to sustain the functionality of the kidneys and overall ameliorate patients' outcomes. The goal of this work is to determine the relationship between undergoing RRT and patient outcome. The Philips-MIT eICU Collaborative Research Database was used to identify patients with sepsis and acute kidney injury, and split the cohort into those who had undergone RRT and those who did not. Multivariate logistic regression and propensity score analysis were utilized to evaluate the treatment effect on mortality. The patients who underwent RRT had a significantly better outcome than those who did not (odds ratio = 0.260465, 95% confidence interval = 0.211568 to 0.320664, p<0.001). From the filtered patients, the percentage of men to women increased with those who underwent RRT (55.08% vs. 53.78%) as well as the percentage of African Americans (25% vs. 15.63%) and Other (5.86% vs. 4.04%) ethnicities. In addition to gender and ethnicity, other covariates such as Sequential Organ Failure Assessment score, cirrhosis, and metastatic cancer had a great impact on patient outcomes. This work concludes that RRT does in fact benefit the patient outcome and dialysis is a statistically significant feature within the dataset.
by Peniel N. Argaw.
M. Eng.

Philosophiae Doctor - PhD
End stage renal disease (ESRD), a more severe form of kidney disease, is considered to be a complex trait that may involve multiple processes which work together on a background of a significant genetic susceptibility. Black Africans have been shown to bear an unequal burden of this disease compared to white Europeans, Americans and Caucasians. Despite this, most of the genetic and epidemiological advances made in understanding the aetiology of kidney diseases have been done in other populations outside of sub-Saharan Africa (SSA). Very little research has been undertaken to investigate key genetic factors that drive ESRD in Africans compared to patients from rest of world populations. Therefore, the primary aim of this Bioinformatics thesis was twofold: firstly, to develop and apply a whole exome sequencing (WES) analysis pipeline and use it to understand a genetic mechanism underlying ESRD in a South African population of mixed ancestry. As I hypothesized that the pipeline would enable the discovery of highly penetrate rare variants with large effect size, which are expected to explain an important fraction of the genetic aetiology and pathogenesis of ESRD in these African patients. Secondly, the aim was to develop and set up a multicenter clinical database that would capture a plethora of clinical data for patients with Lupus, one of the risk factors of ESRD. From WES of six family members (five cases and one control); a total of 23 196 SNVs, 1445 insertions and 1340 deletions, overlapped amongst all affected family members. The variants were consistent with an autosomal dominant inheritance pattern inferred in this family. Of these, only 1550 SNVs, 67 insertions and 112 deletions were present in all affected family members but absent in the unaffected family member. Following detailed evaluation of evidence for variant implication and pathogenicity, only 3 very rare heterozygous missense variants in 3 genes COL4A1 [p.R476W], ICAM1 [p.P352L], COL16A1 [p.T116M] were considered potentially disease causing. Computational relatedness analysis revealed approximate amount of DNA shared by family members and confirmed reported relatedness. Genotyping for the Y chromosome was additionally performed to assist in sample identity. The clinical database has been designed and is being piloted at Groote Schuur medical Hospital at the University of Cape Town. Currently, about 290 patients have already been entered in the registry. The resources and methodologies developed in this thesis have the potential to contribute not only to the understanding of ESRD and its risk factors, but to the successful application of WES in clinical practice. Importantly, it contributes significant information on the genetics of ESRD based on an African family and will also improve scientific infrastructure on the African continent. Clinical databasing will go a long way to enable clinicians to collect and store standardised clinical data for their patients.

This thesis assessed cognitive impairment in people with end stage kidney disease. It found that over a third were cognitively impaired. More than half of those who had not yet started kidney replacement treatment and those already receiving haemodialysis were more likely than other groups to be cognitively impaired. The implications from these findings will influence people being able to make informed decisions about their healthcare, and that changes for patient education ought to occur due to altered levels of understanding.

This thesis explored the dimensions of decision-making of nurses managing continuous renal replacement therapy in the intensive care unit. Variations in the levels of decision-making were largely the result of contextual factors including workforce characteristics, management practices, socialisation and organisational constraints. The concepts also constitute an explanation of the ways in which the interplay of social, organisational and technological boundaries constructed the process of nursing clinical decision-making and performance with advanced technology. These finding suggest that there is an urgent need for organisational and social change in the nursing profession in Saudi Arabia.

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As doenças crônicas na atualidade têm recebido atenção especial das organizações que tratam da saúde. Essas doenças repercutem de diversas maneiras no cotidiano do indivíduo, envolvendo seus aspectos físico, psicológico e social. Uma das doenças crônicas que está incidindo de forma negativa na vida do sujeito é a Doença Renal Crônica (DRC), a qual se refere à alteração na função do rim, de modo que, quando avançada leva o paciente a iniciar a Terapia Renal Substitutiva (TRS). Os dois métodos de TRS são a hemodiálise (HD) e a diálise peritoneal (DP), o primeiro é realizado em ambiente ambulatorial e o segundo em domicílio. Nesse sentido, o objetivo deste estudo foi relacionar a presença de estresse e depressão considerando a percepção de suporte familiar em pacientes em diálise peritoneal e hemodiálise, associada a dados demográficos. Participaram da pesquisa 77 sujeitos que realizam TRS, esses foram divididos em dois grupos, 47 pacientes que realizam HD ambulatorial e 30 pacientes em DP domiciliar de dois centros de diálise. Os instrumentos foram Questionário Sociodemográfico, Inventário de Sintomas de Stress para Adultos de Lipp (ISSL), Inventário de Percepção de Suporte Familiar (IPSF) e Escala Baptista de Depressão (EBADEP-Hosp-Amb). A análise dos dados foi realizada pelos testes Mann Whitney e Kruskal Wallis. Os resultados desse estudo apontaram que os pacientes em DP apresentam maior sintomatologia de estresse do que os que realizam HD, no que se refere à sintomatologia de depressão, os dois grupos apresentaram baixa sintomatologia, e em relação a percepção do suporte familiar, os pacientes em DP mantiveram a classificação Alta e os em HD Médio-Alto. No que tange aos cruzamentos dos dados com os sociodemográficos, houve ocorrência de significância estatística para o grupo de HD em relação ao gênero, estado civil, satisfação com a religião, suporte religioso e tempo de tratamento. Os achados referentes ao grupo de DP contrariaram a hipótese, apresentando maior frequência de estresse comparado aos pacientes que realizam HD. Este trabalho apresentou algumas limitações como o número de pacientes e possibilidade de comparação com outros estudos com a mesma amostra e instrumentos utilizados. No entanto, sua relevância na área da Psicologia e interface com outras áreas da saúde pode ser a semente para outros projetos a fim de minimizarem a dor pela qual tantos pacientes estão expostos diante da doença e tratamento.
Chronic diseases nowadays are receiving special attention from the health organizations. These diseases reverberate in different ways in the daily life of the individual, involving its physical, psychological and social aspects. One of the chronic diseases that is incurring in a negative way on the person’s life is the Chronic Kidney Disease (DRC), which refers to the kidney’s function alteration, in such way that, when advanced, it takes the patient to start Kidney Replacement Therapy (TRS). The two TRS methods are hemodialysis (HD) and peritoneal dialysis (DP); the first is done in an ambulatory ambient and the second at home. In these terms, the purpose of this study was to relate the presence of stress and depression considering the perception of family support in patients in peritoneal dialysis and hemodialysis, associated to demographic data. 77 people who passed through TRS were part of this research, those were divided in two groups, 47 patients who did ambulatory HD and 30 patients who did DP at home from two dialysis center. The instruments were the Sociodemographic Questionnaire, Lipp's Inventory of Symptoms of Stress for Adults (ISSL), Perception of Family Support Inventory (IPSF) and Baptista's Depression Scale (EBADEP-Hosp-Amb). This study’s results pointed the patients in DP presented bigger symptomatology of stress than the ones in HD. In the matter of depression’s symptomatology, both groups presented low symptomatology, and in relation to the family’s support perception, the patients in DP maintained a High classification and the ones in HD, Medium-High. Concerning the crossing of the data with the Sociodemographics, there was an occurrence of statistical significance for the group in HD in regarding the genre, marital status, fulfillment with religion, religious support and time of treatment. What was found in relation to the group in DP contradicted the hypothesis, presenting more frequency of stress compared to the patients in HD. This study presented some limitations such as the number of patients and possibility of comparison to other studies with the same sample and instruments used. However, its importance on the Psychology field and interface with other health areas can be a seed for other projects in order to minimize the pain to which so many patients are exposed before the disease and treatment.

BACKGROUND: Early and appropriate antibiotic administration has been shown to be the most effective intervention for reducing mortality in critically ill patients with septic shock and multiple organ dysfunction syndrome (MODS). However, despite its relevance, antibiotic dosing in those patients with MODS including acute kidney injury (AKI) that require continuous renal replacement therapy (CRRT) still represents a major challenge for clinicians. In our environment, the broad[spectrum beta[lactams meropenem and piperacillin (in combination with tazobactam) are the antibiotics most frequently prescribed to these patients with very high levels of sickness severity. The impact of septic shock, AKI and CRRT on these antibiotics’ dose requirements is vital, as medical interventions and the disease itself are likely to produce significant variations in their pharmacokinetics (PK), which may lead to alterations in drug concentrations over time and hence compromise the achievement of drug concentrations within the therapeutic range. However, it is still very complex to individualize piperacillin and meropenem dosing in patients with septic shock and AKI necessitating CRRT. HYPOTHESIS: Meropenem and piperacillin dosing is not optimal in critically ill patients with septic shock and AKI requiring CRRT due to disease and medical[driven variations in antibiotic PK and, therefore, in dose requirements, which may lead to failure in the achievement of therapeutic concentrations. AIMS: 1. To evaluate the suitability of current meropenem and piperacillin dosing recommendations in critically ill patients with septic shock and AKI necessitating CRRT; 2. To identify the sources of variability that compromise optimal drug dosing in this patient population; and 3. To develop new recommendations that allow dose individualization considering these variability sources. METHODS: Three studies have been developed under the study hypothesis and aims. Study 1: Literature review. A systematic literature review and critical evaluation of the available evidence on meropenem and piperacillin dosing in critically ill patients with septic shock and AKI necessitating CRRT has been performed. Studies 2 and 3: Characterization of the PK of meropenem and piperacillin in critically ill patients with septic shock and AKI necessitating CRRT. Two observational, prospective, multicenter, open[label pharmacokinetic studies have been performed in the Intensive Care Units from three Spanish tertiary hospitals. Thirty patients with septic shock and CRRT receiving meropenem and 19 patients receiving piperacillin have been enrolled. Two population PK models have been developed and subsequently validated with data from these patients, and Monte Carlo simulations have been undertaken using NONMEM v.7.3®. RESULTS: The main finding of study 1 is that present “oneTsizeTfitsTall” dosing recommendations for meropenem and piperacillin in critically ill patients with septic shock and AKI requiring CRRT are based on studies with some drawbacks, such as: 1) different sickness severities and levels of renal function, 2) different admission diagnostics (medical versus surgical versus trauma), 3) different clinical managements mainly CRRT settings, 4) heterogeneous PK methodologies, and 5) different PD targets for dosing recommendations. This scenario limits extrapolation of their conclusions to our patient population. Later on, studies 2 and 3 have identified important sources of meropenem and piperacillin PK variability that may assist in dose individualization. For meropenem, the main finding of the population PK analysis is the relationship existing between the 24h urine output and meropenem total clearance (CL). Patients with conserved diuresis (>500mL/24h) exhibit at least a 30% increase in meropenem total CL compared to those patients who are anuric (<100mL/24h), increase that is directly proportional to urine volume. Following Monte Carlo simulations based on this population PK model have shown that for maintaining unbound concentrations of meropenem above the minimum inhibitory concentration (MIC) of the bacteria for a 100% of the dosing interval (100% FuT>MIC), oligoanuric patients (residual diuresis 0[500mL/24h) require 500mg/q8h over 30min for the treatment of susceptible bacteria (MIC<2mg/L), while patients with preserved diuresis (>500 mL/24h) require the same dose over a 3h[infusion. If bacteria with MIC close to the resistance breakpoint (2[4mg/L) are to be treated with meropenem, a dose of 500mg/q6h is necessary: over a 30min[bolus for oligoanuric patients and over a 3h[infusion for patients with preserved diuresis. For the attainment of more conservative PD targets (40% FuT>MIC), 500mg/q8h over a 30min[bolus is sufficient regardless of residual diuresis With regards to piperacillin, the main finding of the population PK analysis is the relationship existing among the type of membrane used for CVVHDF, the patient’s weight and piperacillin total CL; for a body weight of 80kg, piperacillin total CL is doubled when a 1.5m2 AN69 acrylonitrile and sodium methallyl sulfonate copolymer filter pre[ coated with heparin and polyethyleneimine (AN69ST) is used compared to the CL for a 0.9m2 AN69 filter. Subsequent Monte Carlo simulations have shown that for a PD target of 100% FuT>MIC, patients receiving CVVHDF with 1.5m2 AN69ST membranes require doses of 4000mg/q8h for the treatment of bacteria with a susceptibility to piperacillin close to the clinical breakpoint (MIC = 8[16mg/L). In contrast, 2000mg/q8h are sufficient for patients with CVVHDF using 0.9m2AN69 membranes. For the treatment of bacteria with high susceptibility to piperacillin (MIC ≤ 4mg/L) or for the attainment of a more conservative PD target (50% FuT>MIC), 2000mg/q8h are sufficient in all cases. CONCLUSIONS: Due to data heterogeneity, current meropenem and piperacillin dosing recommendations for patients with septic shock and CRRT follow a one[size[fits[all fashion, which often translates into a best[guess dosing at the bedside. In this context, we have shown that identification and consideration of clinical and demographic parameters that influence meropenem and piperacillin PK, such as 24h urine output, patient’s weight and type of CRRT membrane, is advantageous for dose titration. As they are characteristics easy to be measured at the bedside, the implementation of our research findings in the real clinical setting is easy and may be helpful in the complex process of optimization of antibiotic use in the Intensive Care Unit.
L’administració precoç d’antibioteràpia apropiada ha demostrat ser la intervenció més eficaç per reduir la mortalitat en pacients crítics amb xoc sèptic i síndrome de disfunció multiorgànica (SDMO). Malgrat la seva rellevància, però, la dosificació antibiòtica en els pacients amb SDMO incloent insuficiència renal aguda (IRA) que requereixen teràpia continua de suport renal (TCSR) encara representa un repte diari pels professionals de la salut. Al nostre medi, els antibiòtics beta[lactàmics d’ampli espectre meropenem i piperacilelina (en combinació amb tazobactam) són els antibiòtics més prescrits a aquests pacients d’altíssima complexitat i gravetat. L'impacte del xoc sèptic, la IRA i la TCSR en els requeriments de dosis d'aquests fàrmacs és vital, ja que tant la pròpia malaltia com les intervencions mèdiques produeixen alteracions significatives en la seva farmacocinètica (FC), que duen a variacions en els perfils concentració[temps i, conseqüentment, comprometen l'assoliment de concentracions del fàrmac dins del rang terapèutic. No obstant això, individualitzar la dosificació de meropenem i piperacilelina en pacients amb xoc sèptic, IRA i requeriment de TCSR és encara molt complex. HIPÒTESI: La dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR és sub[òptima degut a les variacions en el comportament FC dels fàrmacs produïdes tant per la malaltia com pel maneig mèdic d’aquesta. Aquestes variacions FC poden comprometre l'assoliment de concentracions terapèutiques. OBJECTIUS: 1. Avaluar la idoneïtat de les recomanacions actuals sobre dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR; 2. Identificar les fonts de variabilitat que comprometen l’exposició òptima a aquests antibiòtics en la nostra població de pacients; i 3. Desenvolupar noves recomanacions per individualitzar la dosificació d’aquests antibiòtics tenint en compte aquestes fonts de variabilitat. METODOLOGIA: En base a la hipòtesi i els objectius, s’han desenvolupat els tres estudis següents: Estudi 1: Revisió de la literatura. S’ha realitzat una revisió sistemàtica i avaluació crítica de l'evidència disponible sobre la dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic, IRA i requeriment de TCSR. Estudis 2 i 3: Caracterització de la FC de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR. S’han realitzat dos estudis farmacocinètics multicèntrics, oberts, prospectius observacionals, a les Unitats de Medicina Intensiva de tres hospitals espanyols de tercer nivell. S’han inclòs a l’estudi 30 pacients amb xoc sèptic, IRA i TCSR que rebien meropenem i 19 pacients que rebien piperacilelina. Amb les dades procedents d’aquests pacients, s’han desenvolupat i validat dos models FC poblacionals, a partir dels quals s’han realitzat simulacions de Monte Carlo de diferents esquemes terapèutics (mitjançant el software NONMEM v.7.3®). RESULTATS: La principal troballa de l'estudi 1 és que les recomanacions actuals de dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR es basen en estudis amb algunes limitacions, com ara: 1) diferents nivells de gravetat de la malaltia i de disfunció renal, 2) diferents diagnòstics d’ingrés (mèdic versus quirúrgic versus trauma), 3) diferents maneigs clínics, principalment referent a les característiques de la TCSR, 4) metodologies heterogènies d’anàlisi FC, i 5) diferents objectius farmacodinàmics (FD) en base als quals es fan les recomanacions de dosificació. Això compromet l'extrapolació dels resultats d’aquests estudis a la nostra població de pacients. Posteriorment, els estudis 2 i 3 han identificat importants fonts de variabilitat en la FC de meropenem i piperacilelina, que si es consideren en el moment de la dosificació poden ser útils per individualitzar el tractament antibiòtic. Pel que fa a meropenem, la principal conclusió de l'anàlisi FC poblacional és la relació existent entre la diüresi acumulada de 24h i l’aclariment total de meropenem (CL). Els pacients amb diüresi conservada (>500ml/24h) presenten un increment d’almenys el 30% sobre el CL total de meropenem en comparació amb aquells pacients anúrics (<100mL/24h), sent aquest augment en el CL del fàrmac directament proporcional al volum d'orina. Posteriorment, les simulacions de Monte Carlo basades en aquest model FC poblacional han demostrat que per tal de mantenir les concentracions de meropenem per damunt de la concentració mínima inhibitòria (CMI) dels bacteris durant un 100% de l'interval de dosificació (100% FuT>CMI), els pacients oligo[anúrics (diüresi residual de 0[500mL/24h) requereixen 500mg/q8h administrats en un bolus de 30 minuts per al tractament de microorganismes susceptibles (CMI <2 mg/L), mentre que els pacients amb diüresi conservada (>500mL/24h) requereixen la mateixa dosi administrada mitjançant una perfusió de 3h. Pel tractament de microorganismes amb una CMI propera al límit de susceptibilitat (2[ 4mg/L) és necessària una dosi de 500mg/q6h: administrada en un bolus de 30 minuts de en pacients oligo[anúrics i mitjançant una perfusió de 3h en pacients amb una diüresi conservada. Si s’escull un objectiu FD més conservador, (40% FuT>CMI), una dosi de 500mg/q8h administrada en un bolus de 30 minuts és suficient amb independència de la diüresi residual. Pel que fa a la piperacilelina, la principal conclusió de l'anàlisi FC poblacional és la relació existent entre el tipus de membrana utilitzada per la TCSR, el pes del pacient i el CL total de piperacilelina; per a un pes de 80 kg, el CL total de piperacilelina es duplica quan es fa servir una membrana d’1,5m2 de copolímer d’acrilonitril i sulfat sòdic de metalelil amb un recobriment d’heparina i polietilenimina (AN69ST) en comparació amb el CL total observat quan es fa servir un filtre AN69 convencional de 0,9m2. Posteriors simulacions de Monte Carlo han demostrat que per a un objectiu FD de 100% FuT>CMI, els pacients que reben TCSR amb membranes AN69ST d’1,5m2 requereixen dosis de 4000mg/q8h per al tractament de microorganismes amb CMI properes al límit de susceptibilitat (CMI = 8[ 16mg/L). Per contra, 2000mg/q8h són suficients per als pacients que reben TCSR amb membranes AN69 de 0,9 m2. Per al tractament de soques d’alta susceptibilitat a la piperacilelina (CMI ≤ 4mg/L), o per l’assoliment d'un objectiu FD més conservador (50% FuT>CMI), 2000mg/q8h són suficients en tots els casos.

Background. The incidence of starting renal replacement therapy (RRT) among young people (< 20 years of age) in 2013 in Scotland was 7.7 per million (age-related) population. Little knowledge exists about cardiovascular risk factors (CVRFs), long-term survival and cardiovascular disease (CVD) outcomes in patients who initiated RRT in childhood. The main source of routine data for these patients is available from the European Society of Paediatric Nephrology/European Renal Association- European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry. In Scotland nationally comprehensive data on patients receiving RRT is available from the Scottish Renal Registry (SRR). Aim and objectives. The overall aim of the thesis is to review relevant literature and conduct retrospective cohort studies describing CVRF prevalence, all-cause mortality and incidence of CVD outcomes in patients who initiated RRT in childhood. ESPN/ERA-EDTA registry data were used to describe the prevalence of anaemia, hypertension, dyslipidaemia and BMI categories and their association with all-cause and CV mortality. SRR data were used to describe all-cause mortality and CVD incidence and their association with age at start of RRT, sex, primary renal disease (PRD), type of RRT and period of start of RRT. Methods. Systematic searches were performed to identify relevant literature. For the ESPN/ERA-EDTA analyses patients who started RRT between 0 and 20 years of age and who had CVRF data were included. Patients were followed from date of first CVRF measurement until the earliest of death, loss to follow-up, reaching 20 years of age or the end of follow-up (December 31st 2012). Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality, comparing patients with and without each CVRF. For the SRR analyses, patients who started RRT under 18 years of age in the period from 1963 to 2013 were included in the analyses. To describe CVD incidence the SRR data were linked to national registers for death and CVD hospital admissions available from 1981 onwards. These analyses, therefore, included patients who started RRT between 1981 and 2013 with follow-up until first CVD event after start of RRT, end of follow-up period or censoring at death. Cox proportional hazard models were used to examine the association of age at initiation of RRT, sex, PRD, type of RRT and period of initiation of RRT with all-cause mortality and CVD incidence. Results. The systematic reviews revealed a gap in current knowledge about CVD incidence and the association of CVRFs with CVD outcomes in patients who initiated RRT in childhood. In total, 7,845 patients were included in the ESPN/ERA-EDTA registry analysis. The mean age of the patients was 9.5 (SE 0.06) years, 58.9% were male, and the most common PRD was congenital anomalies of kidney and urinary tract (CAKUT). The prevalence of dyslipidaemia, hypertension, anaemia overweight/obesity and underweight was 87.5%, 79.3%, 36.0%, 29.9% and 4.3%, respectively. During median follow-up of 3.7 (IQR 1.7-6.8) years 357 patients died. HRs for anaemia were 2.19 (95% CI 1.64-2.93) and 2.55 (95% CI 1.27-5.12) for all-cause and CVD mortality, respectively. The HR for all-cause mortality for underweight was 1.81 (95% CI 1.30-2.53). No other studied CVRFs were statistically significantly associated with all-cause and CVD mortality. In total, 479 patients were included in the SRR analyses of all-cause mortality. The most common PRD was CAKUT and 55.3% of patients were male. During a median follow-up of 18.3 (IQR 8.7-27.0 years) years 126 patients died. Twenty-year survival among patients initiated RRT in childhood was 77.6% (95% CI 73.8-81.3). Age at start of RRT, PRD and type of RRT were significantly associated with all-cause mortality. HR for all-cause mortality for patients who started RRT under 2 years of age was 2.50 (95% CI 1.19-5.25) compared to patients who started RRT at 12 to 18 years old. HR for all-cause mortality for patients with PRD other than CAKUT or glomerulonephritis (GN) was 1.58 (95% CI 1.05-2.39) compared to patients with CAKUT. HRs for all-cause mortality for patients who only received either HD or PD during follow-up were 19.4 (95% CI 10.4-36.4 and 19.5 (9.65-39.7), respectively, compared to patients who received a renal transplant. In total, 381 patients were included in the SRR analyses of CVD incidence. During a median of 12.9 (IQR 5.6-21.5) years of follow-up after initiation of RRT 134 patients (35.2%) developed CVD. The overall crude CVD incidence was 2.6 (95% CI 2.2-3.0) per 100 person-years. HRs for CVD were 1.69 (95% CI 1.05-2.74) for males compared to females, 1.72 (95% CI 1.02-2.91) for PRD other than CAKUT or GN compared to CAKUT and 8.38 (95% CI 3.31-21.23) and 7.30 (95% CI 2.30-23.16) for patients who only received either HD or PD during follow-up, respectively, compared to patients who received a renal transplant. Conclusions. This thesis has contributed to knowledge about CVRF prevalence, longer-term survival and CVD outcomes in patients who initiated RRT in childhood by identifying high prevalence of CVRFs and that CVD is a common complication. This study did not investigate whether anaemia, hypertension, dyslipidaemia and obesity are associated with a higher risk of developing CVD after start of RRT. Future research is needed to study whether treatment of anaemia, hypertension, dyslipidaemia and controlling body weight will reduce the risk of CVD and mortality in patients who initiated RRT in childhood.

A terapia renal substitutiva contínua (TRSC) é amplamente utilizada em pacientes criticamente enfermos com insuficiência renal aguda (IRA). O meropenem é um carbapenêmico usado em pacientes críticos que tem uma atividade antibacteriana dependente do tempo. O objetivo do estudo foi avaliar a farmacocinética do meropenem infundido em três horas em pacientes submetidos à TRSC. Estudamos as concentrações plasmáticas e de efluente em cinco pacientes submetidos à TRSC. As amostras foram coletadas em momentos 0, 30 min, e 1, 2, 4, 6 e 8 horas após o início de uma infusão de 3 horas. As determinações de meropenem foram feitas por cromatografia líquida de alta eficiência. Quatro pacientes do sexo masculino e um feminino, idade de 53,0 ± 19,7 (23 a 80 anos), 62,1 ± 10,6 kg, foram estudados. Parâmetros farmacocinéticos apresentados em mediana (amplitude): concentrações plasmáticas, 34.86mg / L (10,08-139,27); tempo de meia vida (t ½), 1,8 h (1,4-3,0); volume de distribuição (Vd), 8,29 L (5,8-15,3); depuração total (Dept ) 3,98 L / h (2,51-4,35); concentração máxima (Cmax) 48,5 mg/L (37,0-105,8); concentração mínima (Cmin) 20,1 mg / L (14,0-16,6); constante de eliminação (Kel), 0,38 (0,34-0,43); área sob a curva de concentração versus tempo (AUC 0 a 8 h), 251,1 mg / Lh (229,7-398,4); (AUC de 0a∞), 275,1 mg /Lh (263,8-453,6).A depuração total pela TRSC variou de 8,46 a 18,33 ml/min. No efluente as concentrações máximas foram 24,35 e 74,81 mg /L. A eliminação de meropenem por TRSC é semelhante ao que é relatado pelo rim normal, quando é infundido por 3 horas a cada 8 h. Os níveis plasmáticos foram sempre acima do MIC necessário. Podemos concluir que não houve necessidade de ajuste de dose do meropenem com a dose de TRSC prescrita.
Continuous renal replacement therapy (CRRT) is widely used in critically ill patients with acute kidney injury (AKI). Meropenem is a carbapenem used in critically ill patients, which has a time dependent antibacterial activity. The aim of the study was to assess the pharmacokinetics of meropenem on a 3-hour infusion in patients undergoing CRRT due to AKI. We studied the plasmatic and effluent concentrations in five patients undergoing CRRT. The samples were collected at moments 0, 30 minutes, and 1, 2, 4, 6 and 8 hours after the beginning of the 3-hour infusion. The meropenem determinations were made through high performace efficiency liquid chromatography (HPLC). Four male patients and one female patient, with a mean age of 53,0 ± 19,7 (23 to 80 years), weighing 62,1 ± 10,6 kgs were studied. Pharmacokinetic parameters presented in medians (range): plasmatic concentrations, 34.86mg / L (10,08-139,27); half-life (t ½), 1,8 h (1,4-3,0); volume of distribution (Vd), 8,29 L (5,8-15,3); total clearance (CLT) 3,98 L / h (2,51-4,35); (Cmax) (maximum plasma concentration), 48,5 mg / L (37,0-105,8); Cmin (minimum plasma concentration)20,1 mg / L (14,0-16,6); elimination constant (Kel), 0,38 (0,34-0,43); area under the concentration versus time curve (AUC 0 a 8 h), 251,1 mg / Lh (229,7-398,4); (AUC 0 a ∞) 275,1 mg / Lh (263,8-453,6). In the effluent, the maximum concentrations varied from 24,35 to 74,81 mg/L, and the clearance from the therapy varied from 8,46 to 18,33 ml/min. The elimination of meropenem through CRRT is similar to that of a normal kidney, given a 3-hour infusion every 8 hours. Plasmatic levels were always above the necessary MICs. We can conclude there was no need for dose adjustment of meropenem with the prescribed CRRT dose.

This chapter summarizes current best practice with respect to intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for those with acute kidney injury. These modalities can be delivered using a variety of technology platforms. These platforms for the most part use online dialysate, and water quality needs to be monitored and maintained to current standards. Intermittent haemodialysis and SLED provide reasonable outcomes in experienced hands, and ameliorate morbidity and mortality resulting from the ‘acute uraemic syndrome’: that is, intractable infection, non-resolving shock, and haemorrhage.Careful consideration needs to be given to appropriate modality selection for patients. Lower-efficiency modalities such as continuous therapies or SLED are more appropriate for patients at risk from dialysis disequilibrium syndrome, those with abdominal compartment syndrome, and those who are haemodynamically unstable (including cardiogenic shock). Care should be taken to avoid complications related to rapid fluid and solute removal, anticoagulation, and vascular access. Intradialytic hypotension is detrimental for both general and renal recovery of critically ill patients, and can be mitigated by sodium and ultrafiltration profiling, and frequent treatments and prolonged treatment time to minimize ultrafiltration goals and rates.Irrespective of the modality applied, an adequate dialysis dose must be achieved. This is facilitated through the use of optimally placed and technically superior central venous catheters, and well-considered prescription of haemodialysis and SLED operating parameters. Dose should be monitored regularly through urea kinetic modelling, either using Kt/V for thrice-weekly schedules or the corrected equivalent renal urea clearance (EKRc) for more frequent ones.

Drug dosing in acute kidney injury (AKI) is one of the broadest topics in human medicine. It requires an understanding of markedly altered and constantly changing physiology under many disease situations, the use of the drugs to treat those variety of diseases, and the concept of drug removal during blood cleansing therapies. Early in AKI kidney function may be supraphysiologic, while later in the course there may be no kidney function. As function deteriorates other metabolic pathways are altered in unpredictable ways. Furthermore, the underlying disorders that lead to AKI alter metabolic pathways. Heart failure is accompanied by vasoconstriction in the muscle, skin and splanchnic beds, while brain and cardiac blood flow proportionally increase. Third spacing occurs and lungs can become congested. As either kidney or liver function deteriorates, there may be increased or decreased drug sensitivity at the receptor level. Acidosis accompanies several failing organs. Protein synthesis is qualitatively and quantitatively altered. Sepsis affects tissue permeability. All these abnormalities influence drug pharmacokinetics and dynamics. AKI is accompanied by therapeutic interventions that alter intrinsic metabolism which is in turn complicated by kidney replacement therapy (KRT). So metabolism and removal are both altered and constantly changing. Drug management in AKI is exceedingly complex and is only beginning to be understood. Thus, we approach this discussion in a physiological manner. Critically ill patients pass through phases of illness, sometimes rapidly, other times slowly. The recognition of the phases and the need to adjust medication administration strategies is crucial to improving outcomes. An early phase involving supraphysiologic kidney function may be contributory to therapeutic failures that result in the complication of later AKI and kidney function failure.

The incidence of acute kidney injury (AKI) is commonly seen in critically ill children, the origins of which may be traced to a wide range of conditions such as inborn errors of metabolism, sepsis, congenital heart defects, bone marrow and organ transplantation, and to a lesser extent from multiple organ dysfunction syndrome (MODS) [1]. It is vital to provide a form of fluid and electrolyte clearance in these patients until native renal function improves. Nearly 3,600 critically ill children per year with acute kidney injury receive life-saving continuous renal replacement therapy (CRRT) in the United States. However, there is no CRRT device approved by the Food and Drug Administration for use in pediatric patients. Thus, clinicians unsafely adapt adult CRRT devices for use in the pediatric patients due to lack of safer alternatives. Complications observed with using adult adapted CRRT devices in children include hypotension, hemorrhage, thrombosis, temperature instability, inaccurate fluid balance between ultrafiltrate (UF) removed from and replacement fluid (RF) delivered to the patient, electrolyte disorders, and alteration of drug clearance. This research addresses this unmet clinical need through the design, mechanical and biological characterization of a pediatric specific Kidney Injury and Dysfunction Support (KIDS) CRRT device that provides high accuracy in fluid balance, reduces extracorporeal blood volume, and eliminates other problems associated with using adapted adult CRRT devices in children.

The clinical results of thromboembolism (TE) in Patients with prosthetic valVe endocarditis (PVE) and anticoagulant therapy were studied. 22 PVE patients (ll males and females each from 4 to 59 years old, average 32.7) were selected from 1939 patients who had undergone valve replacement at this hospital from 1964 and 1985. The complication frequency of TE and its clinical results, anticoagulant therapy and coagulation tests were investigated. Diagnostic criterion was determined in either of the following two: l) those patients who experienced valve replacement, with at least gradual pyrogenic symptons and inflammation factors such as a large increase in white blood cells, the progress of ESR and positive CRP, also with the same bacterium found more than twice in blood culture, also with the same bacterium found more than twice in blood culture, or 2) those patients who experienced valve replacement, with bacterial verruca found at re-valve replacement or at pathological anatomy. PVE onset took 2 days to 6.5 years (average 407 days) to appear after valve replacement. 8 out of the 22 PVE patients (36.3%) showed complications at TE onset, and 5 out of the 8 patients repeated. Embolism was found in 6 cases of brain, 4 cases of kidney, 2 cases of lung, 2 cases of limbs and 1 case of spleen, and 8 patients all died. On the other hand, 5 complications (22.7%) at bleeding were found in 3 cases of brain, 1 case of duodenum and 1 case of site of replaced aortic valve, and 4 patients died. Anticoagulant therapy was given to 21 out of the 22 PVE patients, and thrombotest (TT) values at TE onset were all less than 30%. Warfarin was administered as anticoagulant. 2 patients were administered with aspirin, but one was given with 250mg aspirin per day together with warfarin, and the other with 330mg aspirin per day alone. TT values at the onset of bleeding were from 10 to 56%. Anticoagulant therapy had been performed to the PVE patients since PVE onset did not yet appear, but complications coagulability by TT values, and all the patients died. In addition to this, complications at bleeding were found many and most of patients died even when the TT values were not so low. Therefore, we believe that the anticoagulant therapy that had been performed after PVE onset still needs further studies.