Dissertations / Theses on the topic 'Kidney replacement therapy (KRT)'

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.

Introduction: The high transmissibility and lethality of the novel coronavirus SARS-CoV-2 (COVID-19) have been catastrophic. Acute kidney injury (AKI) is one of the frequent complications in patients with respiratory insufficiency caused by the virus. The pathogenic mechanism is based on the binding of its S-proteins to the angiotensin-converting enzyme (ACE) receptors, which will trigger a cellular damage. A podocyte and tubular compromise are found in the kidneys which can lead to tubular necrosis and the consequent AKI. Objectives: The objective of this report is to identify the main risk factor to develop AKI in patients infected with SARS-CoV-2 with critical acute respiratory distress. Patients and Methods: We performed this report study, collecting data from 48 ICU patients. Data from 13 of them who developed AKI and needed renal replacement therapy (RRT)were analyzed. Clinical characteristics and laboratory findings were reported using STATA 10.0. Results: AKI was present in 27.08% of patients, mostly male (92.3%) with a mean age of 63.8 years old. Hypertension, diabetes and obesity were the main comorbidities in those patients. Additionally, the meantime between admission and AKI diagnosis was 2.69 days. All patients showed fibrinogen, D-dimer, ALT and values above normal range. Mortality was seen in 61.5% of patients. Conclusion: This report tries to show AKI as an important clinical manifestation in critically ill patients infected with SARS-CoV-2, with high mortality. Further studies are needed to demonstrate if there are independent risk factors.
Revisión por pares

Introdução: Em torno de 30 a 50% dos pacientes críticos desenvolvem insuficiência renal aguda (IRA), sendo que sua progressão leva à necessidade de terapia renal substitutiva (TRS). Dentre os sobreviventes, em torno de 15 a 23% possuem a necessidade de diálise após alta. A ocorrência da insuficiência renal aguda tem sido associada à futura progressão para doença renal crônica. É possível que marcadores tubulares estejam alterados após a recuperação da IRA, antecipando o desenvolvimento de doença renal crônica. Objetivos: Comparar a β2 Microglobulina, as enzimas urinárias N-acetil- β-D-glucosaminidase, lactato desidrogenase e fosfatase alcalina, as frações de excreção de magnésio, fósforo, potássio e ácido úrico e o gradiente transtubular de potássio, bem como a presença de microalbuminúria e proteinúria entre pacientes normais sem qualquer história prévia de dano ou qualquer tipo de disfunção renal, com pacientes sobreviventes de IRA severa com necessidade de hemodiálise que recuperaram função renal de forma a avaliar se existem diferenças entre os 2 grupos. Métodos: Foram incluídos pacientes que apresentaram insuficiência renal aguda com necessidade de hemodiálise internados no centro de terapia intensiva (CTI) do Hospital de Clínicas de Porto Alegre e que receberam alta nos períodos de 2007 a 2010, sem apresentar as seguintes co-morbidades: insuficiência renal crônica, hepatopatia crônica, pacientes HIV positivo, transplantados, doença vascular severa, diabetes com complicações crônicas e rim único funcionante e que apresentavam função renal normal definida por taxa de filtração glomerular > 60 mL/min/1.73m2 calculada pela equação CKD-EPI. Os mesmos foram comparados com voluntários sadios pareados por sexo e idade (+/- 4 anos). Para avaliação das frações de excreção e do gradiente transtubular de potássio foram feitas análises excluindo o uso de medicamentos diuréticos, inibidores da ECA e bloqueadores dos receptores de angiotensina. Resultados: A fração de excreção de magnésio encontrou-se aumentada no grupo com IRA prévia seguida por um menor gradiente transtubular de potássio bem como lactato desidrogenase elevada. O grupo com IRA prévia apresentou proteinúria e microalbuminúria e embora sem significância estatística (P=0,052) uma maior fração de excreção de fósforo. Conclusão: Mesmo com taxa de filtração glomerular normal comparável, os sujeitos do grupo com ira prévia apresentaram sugestivas alterações em nível tubular refletidas por maior fração de excreção de magnésio, elevada lactato desidrogenase e um menor gradiente transtubular de potássio, microalbuminúria e proteinúria que refletem um possível dano renal. Estes achados levam à hipótese de que sujeitos com prévia IRA severa com necessidade de terapia de renal substitutiva, apresentam uma possível sequela relativa à IRA prévia ou uma predisposição para insuficiência renal crônica.
Background: About 30 to 50% of the critically ill patients develop acute renal failure (ARF) and the progression leads to the need of renal replacement therapy. Between the survivors 15 to 23% has the need of dialysis after discharge. The severity of the ARF is a robust predictor for the development of a future chronic kidney disease. The occurrence of acute renal failure has been associated with future progression of chronic kidney disease. Objective: Compare β2-microglobulin, the urinary enzymes N-acetyl-β- D-glucosaminidase, lactate dehydrogenase, alkaline phosphatase fractional excretion of magnesium, phosphorous, potassium and uric acid transtubular potassium gradient, including the presence of microalbuminuria and proteinuria between subjects with normal renal function without any previous history of acute renal injury or any kind of renal dysfunction with survivors of severe ARF with the needed of hemodialysis that recovered renal function in order to evaluate if there are differences between the 2 groups. Methods: It was enrolled patients that presented acute renal failure with the need of hemodialysis hospitalized on intensive care unit (ICU) and discharged on the period of 2007 to 2010 at Hospital de Clínicas de Porto Alegre, without the following co-morbidities chronic renal failure, chronic hepatopathy, positive HIV, transplants, severe vascular disease, diabetes with chronic complications and single functioning kidney that presented normal renal function defined as glomerular filtration rate (GFR) > 60 mL/min/1.73m2 calculated by CKD EPI formula The subjects were compared with healthy volunteers and paired by sex and age (+/- 4 years). To evaluate fractional excretions and transtubular potassium gradient, analyses were made excluding subjects that were taken diuretic medication, ACE inhibitors and angiotensin block receptors. Results: The fractional excretion of magnesium was finding increased on the previous ARF group followed by a lower transtubular potassium gradient and elevated lactate dehydrogenase. The previous ARF group showed proteinuria and microalbuminuria and although without statistical significance (p=0.052) an elevated phosphorous excretion. Conclusion: Although normal glomerular filtration rate, the subjects with previous ARF, showed suggested tubular alterations reflected by a higher fractional excretion of magnesium, elevated lactate dehydrogenase and a lower transtubular potassium gradient, microalbuminuria and proteinuria that reflects a possible renal damage. Those findings lead to the hypothesis that subjects with previous severe ARF with the need of renal replacement therapy present a possible sequel related to previous ARF or a predisposition to chronic kidney disease.

Поширеність і захворюваність на хронічну хворобу нирок (ХХН) є важливою проблемою охорони здоров’я як в Україні, так і в усьому світі. Прогресуючий перебіг ХХН супроводжується розвитком термінальної хвороби, яка потребує лікування методами ниркової замісної терапії (НЗТ).

Hintergrund: Die regionale Citrat-Antikoagulation im Rahmen der Nierenersatztherapie hat bei interdisziplinären Intensivpatienten in den letzten Jahren zunehmend an Bedeutung gewonnen. Für Schwerbrandverletzte existieren bislang kaum Untersuchungen zu diesem Verfahren. Ziel dieser Arbeit war es, die kontinuierliche Nierenersatztherapie mit Citrat-Antikoagulation bei Intensivpatienten mit akutem Nierenversagen nach schwerem Verbrennungstrauma im Hinblick auf Praktikabilität, Effektivität und Komplikationshäufigkeit sowie die Stabilität von Elektrolyt- und Säure-Basen-Haushalt und Gerinnung zu untersuchen. Daneben sollten Aussagen zur Prävalenz des akuten Nierenversagens in dieser Patientengruppe und zu dessen Einfluss auf die Letalität getroffen werden. Methode: Im Rahmen einer retrospektiven Untersuchung wurden unter Verwendung von Patientenakten und Patientendatenmanagementsystem (PDMS) Daten von 27 Schwerbrandverletzten (VKOF ≥ 20% oder ABSI ≥ 8) mit akutem Nierenversagen ausgewertet, die zwischen Januar 2004 und Dezember 2009 im Verbrennungszentrum des Klinikums Sankt Georg Leipzig mit einer kontinuierlichen Nierenersatztherapie behandelt wurden. Bei allen Patienten kam ein Dialysegerät Prisma CFM (Gambro Hospal GmbH, Deutschland) mit einer Polyacrylnitril-Filtermembran (AN 69, Filterset M 100) der gleichen Firma zum Einsatz. Standardverfahren war eine kontinuierliche veno-venöse Hämodiafiltration (CVVHDF) im Prädilutionsmodus. Bei 18 Patienten wurde eine regionale Citrat-Antikoagulation als Antikoagulationsverfahren eingesetzt, bei 7 Patienten eine systemische Heparin-Antikoagulation, bei 2 Patienten kamen alternierend beide Verfahren zum Einsatz. Für die 18 Patienten unter regionaler Citrat-Antikoagulation erfolgte eine detaillierte Analyse des akuten Nierenversagens unter Einbeziehung des klinischen Verlaufes, der Laborparameter und der Behandlungsdaten des Nierenersatzverfahrens. Ergebnisse: Die Prävalenz eines akuten Nierenversagens mit Notwendigkeit zur Nierenersatztherapie bei Schwerbrandverletzten betrug 15,5%. Die Sterblichkeitsrate war in der Patientengruppe mit Nierenversagen etwa fünffach erhöht (25,9 vs. 4,8%). Die Letalitätsrate bei den Patienten unter systemischer Heparin-Antikoagulation war bei vergleichbarem Verbrennungsausmaß etwa fünfmal höher als unter regionaler Citrat-Antikoagulation (57,1 vs. 11.1%). Die Nierenersatztherapie wurde im Median nach 6 Tagen begonnen, die mediane Behandlungsdauer pro Patient betrug 7 Tage. Bei Start der CVVHDF wiesen 94,4% der Patienten einen Schockzustand mit Notwendigkeit einer Vasopressortherapie auf, 83,3% zeigten schwere Dysfunktionen in mindestens 3 Organsystemen, der SOFA-score lag im Median bei 14. Bei einer mittleren Citratkonzentration von 3,6 mmol/l Blut im Extrakorporalkreiskauf konnte eine mediane effektive Filterlaufzeit von 67 Stunden erreicht werden. Hypocalcämien (<0,9 mmol/l) fanden sich in 1,1%, Hypercalcämien (>1,3 mmol/l) in 0,4%. Hypernatriämien (<150 mmol) waren mit 0,4% ebenso selten wie metabolische Alkalosen (pH >7,50 und BE >4) mit 0,2%. Im Gesamtdialysezeitraum von 3790 Stunden gab es nur ein Blutungsereignis, die Gerinnungsparameter zeigten bis auf einen passageren Abfall der Thrombozytenzahl keine signifikanten Veränderungen. Die erzielte mittlere Dialysedosis war mit 35,1 ml/kg Körpergewicht/h ausreichend hoch. Neben einer Reduktion der Nierenretentionsparameter Serum-Creatinin und Serum-Harnstoff fanden sich unter dem Nierenersatzverfahren verbesserte Oxygenierungsindices und sinkende SOFA-scores. Keiner der überlebenden Patienten war zum Zeitpunkt der Entlassung dialysepflichtig. Zusammenfassung: Die CVVHDF unter regionaler Citrat-Antikoagulation ist bei Schwerbrandverletzten ein effektives und in Bezug auf Säure-Basen-Haushalt, Elektrolyte und Gerinnung sicheres Verfahren. Neben einer effektiven Elimination harnpflichtiger Substanzen konnten eine exzellente Stabilität von Elektrolyten und metabolischen Parametern sowie eine suffiziente Antikoagulation im Extrakorporalkreislauf mit niedrigem Blutungsrisiko und konstant langen Filterlaufzeiten nachgewiesen werden. Die Prävalenz des akuten Nierenversagens bei Schwerbrandverletzten ist hoch, die Letalität bei Vorliegen des Organversagens vier-bis fünffach erhöht.

This report seeks to describe the status of kidney disease and renal replacement therapy in lower-resource settings, particularly sub-Saharan Africa. Acute kidney injury and transplantation are included on a limited basis because it is impossible consider the renal replacement therapy landscape at the exclusion of either. As in the rest of the developing world, chronic kidney disease and end-stage renal disease place a sizable and rapidly growing burden on sub-Saharan Africa, and Africans face a double-burden of disease from communicable and non-communicable diseases. Meanwhile, renal replacement therapy and the subspecialty of nephrology are expanding in sub-Saharan Africa, from non-existence in many countries to a limited, tentative subsistence, largely with the support of international organizations and the dedication of local nephrologists. Hemodialysis is the most common form of renal replacement therapy in sub-Saharan Africa, but peritoneal dialysis services, particularly for acute kidney injury, are growing and renal transplants are performed in a few sub-Saharan countries. Nonetheless, in the majority of sub-Saharan Africa, maintenance dialysis is still only available to the wealthy urban few. Although peritoneal dialysis may seem more feasible in the developing world than hemodialysis for multiple reasons, it is still fraught with challenges that make widespread implementation presently unadvisable. As renal replacement therapy is costly and currently unaffordable on a large scale for most of these countries, emphasis must be on identifying at-risk populations through screening and low-cost treatment or management of risk factors to mitigate chronic kidney disease.

A introdução da terapêutica substitutiva da função renal (TSFR) é consensual na presença de complicações potencialmente fatais associadas à insuficiência renal aguda (IRA). Contudo, na ausência de indicações urgentes, o timing ideal para a introdução da TSFR continua a ser debatido. Esta revisão sistemática e meta-análise pretende comparar a introdução precoce e tardia da TSFR em doentes críticos com IRA. O outcome primário é a mortalidade após 28 dias de seguimento. Os outcomes secundários incluem a mortalidade global, a recuperação da função renal (RFR) e diversos efeitos adversos associados à TSFR. Os estudos incluídos na revisão sistemática foram obtidos a partir de três bases de dados (MEDLINE, CENTRAL e SCOPUS). Não foram aplicadas restrições com base na data de publicação dos estudos e, a última pesquisa foi realizada em Setembro de 2020. Treze ensaios clínicos randomizados foram incluídos na análise, contemplando um total de 5193 pacientes. Não foi detetada uma diferença estatisticamente significativa entre os dois grupos relativamente ao outcome primário (risco relativo (RR) 1.00; intervalo de confiança (IC) de 95% entre 0.89 e 1.12, P = 1.00; I²=30%), à mortalidade global (RR 1.00; IC 95% entre 0.90 e 1.12; P = 0.98, I² = 42%), e à RFR (RR 1.02, 95% IC 95% entre 0.92 e 1.13, P = 0.75, I² =53%). Contudo, o início precoce da TSFR parece estar significativamente associado a uma maior incidência de efeitos adversos, nomeadamente hipotensão (RR 1.34; IC 95% entre 1.17 a 1.53, P < 0.0001, I²=6%) ou infeção (RR 1.83; IC 95% entre 1.11 a 3.02, P = 0.02, I²=0%). No geral, uma introdução precoce da TSFR não se traduz numa melhoria na mortalidade após 28 dias de seguimento, na mortalidade global e na RFR. No entanto, está associada a uma maior incidência de efeitos adversos relacionados com a TSFR, como a hipotensão e a infeção.
Renal replacement therapy (RRT) is consensual in the presence of life-threatening complications associated with acute kidney injury (AKI). In the absence of urgent indications, the optimal timing for RRT initiation is still under debate. This systematic review and meta-analysis aims to compare early and late RRT initiation strategies in critically ill patients with AKI. The selected primary outcome was 28-day mortality. Secondary outcomes included overall mortality, recovery of renal function (RRF) and several RRT associated-adverse events. Studies were obtained from three databases (MEDLINE, CENTRAL and SCOPUS), searched from inception to September 2020.Thirteen randomized controlled trials (RCTs) were included, with 5193 patients in total. No significant difference was found between the two groups regarding 28-day mortality (Risk Ratio (RR) 1.00; 95% confidence interval (CI) 0.89 to 1.12; P = 1.00, I²=30%), overall mortality (RR 1.00; 95% CI 0.90 to 1.12; P = 0.98, I² = 42%) and RRF (RR 1.02, 95% CI 0.92 to 1.13, P = 0.75, I² =53%). However, early RRT initiation was associated with a significantly higher incidence of hypotensive (RR 1.34; 95% CI 1.17 to 1.53, P < 0.0001, I²=6%) and infectious events (RR 1.83; 95% CI 1.11 to 3.02, P = 0.02, I²=0%).In general, early RRT initiation does not seem to significantly improve the 28-day and overall mortality, neither the likelihood of RRF in critically ill patients with AKI. Moreover, it is associated with an increased risk for RRT-associated adverse events, namely hypotension and infection.

A introdução da terapêutica substitutiva da função renal (TSFR) é consensual na presença de complicações potencialmente fatais associadas à insuficiência renal aguda (IRA). Contudo, na ausência de indicações urgentes, o timing ideal para a introdução da TSFR continua a ser debatido. Esta revisão sistemática e meta-análise pretende comparar a introdução precoce e tardia da TSFR em doentes críticos com IRA. O outcome primário é a mortalidade após 28 dias de seguimento. Os outcomes secundários incluem a mortalidade global, a recuperação da função renal (RFR) e diversos efeitos adversos associados à TSFR. Os estudos incluídos na revisão sistemática foram obtidos a partir de três bases de dados (MEDLINE, CENTRAL e SCOPUS). Não foram aplicadas restrições com base na data de publicação dos estudos e, a última pesquisa foi realizada em Setembro de 2020. Treze ensaios clínicos randomizados foram incluídos na análise, contemplando um total de 5193 pacientes. Não foi detetada uma diferença estatisticamente significativa entre os dois grupos relativamente ao outcome primário (risco relativo (RR) 1.00; intervalo de confiança (IC) de 95% entre 0.89 e 1.12, P = 1.00; I²=30%), à mortalidade global (RR 1.00; IC 95% entre 0.90 e 1.12; P = 0.98, I² = 42%), e à RFR (RR 1.02, 95% IC 95% entre 0.92 e 1.13, P = 0.75, I² =53%). Contudo, o início precoce da TSFR parece estar significativamente associado a uma maior incidência de efeitos adversos, nomeadamente hipotensão (RR 1.34; IC 95% entre 1.17 a 1.53, P < 0.0001, I²=6%) ou infeção (RR 1.83; IC 95% entre 1.11 a 3.02, P = 0.02, I²=0%). No geral, uma introdução precoce da TSFR não se traduz numa melhoria na mortalidade após 28 dias de seguimento, na mortalidade global e na RFR. No entanto, está associada a uma maior incidência de efeitos adversos relacionados com a TSFR, como a hipotensão e a infeção.
Renal replacement therapy (RRT) is consensual in the presence of life-threatening complications associated with acute kidney injury (AKI). In the absence of urgent indications, the optimal timing for RRT initiation is still under debate. This systematic review and meta-analysis aims to compare early and late RRT initiation strategies in critically ill patients with AKI. The selected primary outcome was 28-day mortality. Secondary outcomes included overall mortality, recovery of renal function (RRF) and several RRT associated-adverse events. Studies were obtained from three databases (MEDLINE, CENTRAL and SCOPUS), searched from inception to September 2020.Thirteen randomized controlled trials (RCTs) were included, with 5193 patients in total. No significant difference was found between the two groups regarding 28-day mortality (Risk Ratio (RR) 1.00; 95% confidence interval (CI) 0.89 to 1.12; P = 1.00, I²=30%), overall mortality (RR 1.00; 95% CI 0.90 to 1.12; P = 0.98, I² = 42%) and RRF (RR 1.02, 95% CI 0.92 to 1.13, P = 0.75, I² =53%). However, early RRT initiation was associated with a significantly higher incidence of hypotensive (RR 1.34; 95% CI 1.17 to 1.53, P < 0.0001, I²=6%) and infectious events (RR 1.83; 95% CI 1.11 to 3.02, P = 0.02, I²=0%).In general, early RRT initiation does not seem to significantly improve the 28-day and overall mortality, neither the likelihood of RRF in critically ill patients with AKI. Moreover, it is associated with an increased risk for RRT-associated adverse events, namely hypotension and infection.

A high-performance liquid chromatography was developed to assay levofloxacin and vancomycin. Fluorescence polarization immunoassay was to assay amikacin. The oseltamivir carboxylate and telavancin concentrations were assayed by high-performance liquid chromatography coupled with tandem mass spectrometry.
An in vitro model was utilized to examine adsorption of antibiotics onto haemofilters. In order to test antibiotics from a range of classes, levofloxacin, amikacin, vancomycin, telavancin, and oseltamivir carboxylate were studied.
In summary, the antibiotic adsorption by haemofilters is a complex process. Both characteristics of antibiotics and haemofilters may determine adsorption. Among the studied antibiotics, in vitro adsorption of amikacin by PAN filters may have clinical significance, thus the routine monitoring of amikacin peak concentration in vivo during CRRT is recommended.
In the in vitro model, blood was pumped from an agitated, glass mixing chamber (heated using an automatic water bath), around a circuit and returned to the mixing chamber using a haemofiltration machine. Ultrafiltrate was also returned to the mixing chamber to constitute a closed circuit. As a result any decrease in drug concentration could only be due to adsorption to the filter and extracorporeal circuit, spontaneous degradation or metabolism by red cells.
The main findings were: (1) low adsorption of levofloxacin and vancomycin by haemofilters at clinically relevant concentrations; (2) significant absolute adsorption of amikacin by polyacrylonitrile haemofilters; (3) the adsorption of antibiotics was membrane-material dependent with greater adsorption by polyacrylonitrile filters; (4) lack of relationship between membrane surface area and amikacin adsorption; (5) the adsorption of levofloxacin is reversible, contrary to irreversibility of vancomycin and amikacin; (6) sieving coefficient of oseltamivir is very near to 1.0.
This thesis investigated: (1) the extent of antibiotic adsorption (levofloxacin, vancomycin, amikacin, telavancin and oseltamivir carboxylate) by haemofilters; (2) the time course of antibiotic adsorption by haemofilters; (3) the effects of plasma albumin concentration, initial dosage, pH, filter membrane material, filter membrane surface area and repeated dosing on adsorption; (4) the reversibility or irreversibility of adsorption; (5) clearance of oseltamivir carboxylate and telavancin by ultrafiltration.
Up to 25% of critically ill patients develop acute renal failure with sepsis being the most common cause. Outside of North and South America, these patients usually receive continuous renal replacement therapy (CRRT) which utilizes high flux haemofilter membranes. Thus it is common for these patients to be concurrently receiving antibiotics and CRRT. However, information about the adsorptive capacity of various haemofilters for most drugs is lacking.
"September 2007."
Advisers: Charles Gomersall; Tony Gin.
Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4659.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2007.
Includes bibliographical references (p. 147-164).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract in English and Chinese.
School code: 1307.

Hintergrund: Die regionale Citrat-Antikoagulation im Rahmen der Nierenersatztherapie hat bei interdisziplinären Intensivpatienten in den letzten Jahren zunehmend an Bedeutung gewonnen. Für Schwerbrandverletzte existieren bislang kaum Untersuchungen zu diesem Verfahren. Ziel dieser Arbeit war es, die kontinuierliche Nierenersatztherapie mit Citrat-Antikoagulation bei Intensivpatienten mit akutem Nierenversagen nach schwerem Verbrennungstrauma im Hinblick auf Praktikabilität, Effektivität und Komplikationshäufigkeit sowie die Stabilität von Elektrolyt- und Säure-Basen-Haushalt und Gerinnung zu untersuchen. Daneben sollten Aussagen zur Prävalenz des akuten Nierenversagens in dieser Patientengruppe und zu dessen Einfluss auf die Letalität getroffen werden. Methode: Im Rahmen einer retrospektiven Untersuchung wurden unter Verwendung von Patientenakten und Patientendatenmanagementsystem (PDMS) Daten von 27 Schwerbrandverletzten (VKOF ≥ 20% oder ABSI ≥ 8) mit akutem Nierenversagen ausgewertet, die zwischen Januar 2004 und Dezember 2009 im Verbrennungszentrum des Klinikums Sankt Georg Leipzig mit einer kontinuierlichen Nierenersatztherapie behandelt wurden. Bei allen Patienten kam ein Dialysegerät Prisma CFM (Gambro Hospal GmbH, Deutschland) mit einer Polyacrylnitril-Filtermembran (AN 69, Filterset M 100) der gleichen Firma zum Einsatz. Standardverfahren war eine kontinuierliche veno-venöse Hämodiafiltration (CVVHDF) im Prädilutionsmodus. Bei 18 Patienten wurde eine regionale Citrat-Antikoagulation als Antikoagulationsverfahren eingesetzt, bei 7 Patienten eine systemische Heparin-Antikoagulation, bei 2 Patienten kamen alternierend beide Verfahren zum Einsatz. Für die 18 Patienten unter regionaler Citrat-Antikoagulation erfolgte eine detaillierte Analyse des akuten Nierenversagens unter Einbeziehung des klinischen Verlaufes, der Laborparameter und der Behandlungsdaten des Nierenersatzverfahrens. Ergebnisse: Die Prävalenz eines akuten Nierenversagens mit Notwendigkeit zur Nierenersatztherapie bei Schwerbrandverletzten betrug 15,5%. Die Sterblichkeitsrate war in der Patientengruppe mit Nierenversagen etwa fünffach erhöht (25,9 vs. 4,8%). Die Letalitätsrate bei den Patienten unter systemischer Heparin-Antikoagulation war bei vergleichbarem Verbrennungsausmaß etwa fünfmal höher als unter regionaler Citrat-Antikoagulation (57,1 vs. 11.1%). Die Nierenersatztherapie wurde im Median nach 6 Tagen begonnen, die mediane Behandlungsdauer pro Patient betrug 7 Tage. Bei Start der CVVHDF wiesen 94,4% der Patienten einen Schockzustand mit Notwendigkeit einer Vasopressortherapie auf, 83,3% zeigten schwere Dysfunktionen in mindestens 3 Organsystemen, der SOFA-score lag im Median bei 14. Bei einer mittleren Citratkonzentration von 3,6 mmol/l Blut im Extrakorporalkreiskauf konnte eine mediane effektive Filterlaufzeit von 67 Stunden erreicht werden. Hypocalcämien (<0,9 mmol/l) fanden sich in 1,1%, Hypercalcämien (>1,3 mmol/l) in 0,4%. Hypernatriämien (<150 mmol) waren mit 0,4% ebenso selten wie metabolische Alkalosen (pH >7,50 und BE >4) mit 0,2%. Im Gesamtdialysezeitraum von 3790 Stunden gab es nur ein Blutungsereignis, die Gerinnungsparameter zeigten bis auf einen passageren Abfall der Thrombozytenzahl keine signifikanten Veränderungen. Die erzielte mittlere Dialysedosis war mit 35,1 ml/kg Körpergewicht/h ausreichend hoch. Neben einer Reduktion der Nierenretentionsparameter Serum-Creatinin und Serum-Harnstoff fanden sich unter dem Nierenersatzverfahren verbesserte Oxygenierungsindices und sinkende SOFA-scores. Keiner der überlebenden Patienten war zum Zeitpunkt der Entlassung dialysepflichtig. Zusammenfassung: Die CVVHDF unter regionaler Citrat-Antikoagulation ist bei Schwerbrandverletzten ein effektives und in Bezug auf Säure-Basen-Haushalt, Elektrolyte und Gerinnung sicheres Verfahren. Neben einer effektiven Elimination harnpflichtiger Substanzen konnten eine exzellente Stabilität von Elektrolyten und metabolischen Parametern sowie eine suffiziente Antikoagulation im Extrakorporalkreislauf mit niedrigem Blutungsrisiko und konstant langen Filterlaufzeiten nachgewiesen werden. Die Prävalenz des akuten Nierenversagens bei Schwerbrandverletzten ist hoch, die Letalität bei Vorliegen des Organversagens vier-bis fünffach erhöht.

Introduction to the issue: Stay in an intensive care unit or anaesthesiology and resuscitation department has a demonstrable effect on the quality of life, whether mental, physical, or mental. A large percentage of patients experience post intensive care syndrome. The huge challenge for nursing care is to reduce this percentage and enable patients to recover in the best possible way and return to normal life of the same quality as before the hospitalization Methodology: The aim of this work is to find out how the quality of life of patients is affected after hospitalization in the intensive care unit or anaesthesiology and resuscitation department, with a proportion of acute renal failure and the need for continuous renal replacement. First, patients were evaluated with APACHE II score, SOFA and TISS 2. Next, questionnaires in which they responded to the period before hospitalization (SF 36, DEMMI, ADL, IADL) were filled, when released from ARO they went through the test of physical capability, (30s sit-up test, 6-minute walk test), further measurements when released from ICU took place (HADS, MAF, DEMMI, ADL, 30s sit-p test, 6-minute walk test), and after three months (SF 36, HADS, MAF, DEMMI, IADL, ADL 30s sit-up test, 6-minute walk test and a week of wearing a Garmin vivofit bracelet). Main...

Introduction : La mortalité associée à l’insuffisance rénale aiguë (acute kidney injury ‘’AKI’’) aux soins intensifs pédiatriques (SIP) dépasse les 50%. Des études antérieures sur la thérapie de remplacement rénal (TRR) ont fait ressortir plusieurs facteurs de risque de mortalité dont le syndrome de défaillance multiviscérale (SDMV) et la surcharge liquidienne ≥ 10 à 20% avant l’initiation de la TRR. L’objectif de cette étude était d’identifier les principaux facteurs de risque de mortalité à 28 jours après l’initiation de la TRR chez les patients atteints d’AKI aux SIP. Méthode : Il s’agit d’une étude de cohorte rétrospective aux SIP d’un centre tertiaire. Tous les enfants ayant reçus de la TRR continue ou de l’hémodialyse intermittente pour AKI, entre janvier 1998 et décembre 2014, ont été inclus. Les facteurs de risque de mortalité ont été préalablement identifiés par quatre intensivistes et deux néphrologues pédiatres et analysés à l’aide d’une régression logistique multivariée. Résultats : Quatre-vingt-dix patients ont été inclus. L’âge médian était de 9 [2-14] ans. La principale indication d’initiation de la TRR était la surcharge liquidienne (64,2%). La durée médiane d’hospitalisation aux SIP était de 18,5 [8,0-31,0] jours. Quarante patients (44,4%) sont décédés dans les 28 jours suivant l’initiation de la TRR et quarante-cinq (50,0%) avant la sortie des SIP. Le score de PELOD ≥ 20 (OR 4,66 ; 95%CI 1,68-12,92) et la surcharge liquidienne ≥ 15% (OR 9,31; 95%CI 2,16-40,11) à l’initiation de la TRR étaient associés de façon indépendante à la mortalité. Conclusion : Cette étude a permis de faire ressortir deux facteurs de risque de mortalité à 28 jours à l’initiation de la TRR : la surcharge liquidienne et la sévérité du SDMV mesurée par le score de PELOD.
Introduction: Mortality rate associated with acute kidney injury (AKI) in pediatric intensive care units (PICU) exceeds 50%. Prior studies on renal replacement therapy (RRT) have highlighted different mortality risk factors including the presence of a multiple organ dysfunction syndrome (MODS) and fluid overload ≥ 10 to 20% before starting RRT. The aim of this study was to identify most important risk factors of 28-day mortality in patients with AKI at RRT initiation in PICU. Methods: We conducted a retrospective cohort study in a tertiary care pediatric center. All critically ill children who underwent acute continuous RRT or intermittent hemodialysis for AKI between January 1998 and December 2014 were included. A case report form was developed and specific risk factors were identified by a panel of four pediatric intensivists and two nephrologists. Risk factors analysis was made using logistic regression in SPSS and SAS software. Results: Ninety patients were included. The median age was 9 [2-14] years. The most common indication for RRT initiation was fluid overload (FO) (64.2%). The median PICU length of stay was 18.5 [8.0-31.0] days. Forty of the 90 patients (44.4%) died within 28 days after RRT initiation and forty-five (50.0%) died before PICU discharge. In a multivariate logistic regression analysis, a PELOD score ≥ 20 (OR 4.66; 95%CI 1.68-12.92) and percentage of FO ≥ 15% (OR 9.31; 95%CI 2.16-40.11) at RRT initiation were independently associated with mortality. Conclusion: This study suggests that fluid overload and severity of MODS measured by PELOD score are two risk factors of 28-day mortality in PICU patients on RRT.