The purpose of this study was to investigate the impact of Medicare Part D coverage on medication adherence and health outcomes in dialysis patients. A retrospective analysis (2006-2010) using the United States Renal Data System was conducted for Medicare-eligible dialysis patients. Cardiovascular disease morbidity, healthcare utilization and expenditures, medication adherence, and mortality rates were compared, categorized based on patients’ Part D coverage in 2007 for those who: 1) did not reach the coverage gap (cohort 1); 2) reached the coverage gap but not catastrophic coverage (cohort 2); 3) reached catastrophic coverage (cohort 3); and 4) did not reach the coverage gap but received a low-income subsidy (cohort 4). Cox proportional hazards models, Kaplan-Meier methods, logistic regressions, generalized linear models, and generalized estimating equations were used. A total of 11,732 patients were included as meeting inclusion criteria: 1) cohort 1: 3,678 patients had out-of-pocket drug costs <$799; 2) cohort 2: 4,349 patients had out-of-pocket drug costs between $799 and $3,850; 3) cohort 3: 1,310 patients had out-of-pocket drug costs > $3,850; and 4) cohort 4: the remaining 2,395 patients had out-of-pocket drug costs <$799 but received a low-income subsidy. After adjusting for demographic and clinical factors, patients in cohort 2 and cohort 3 had 42 percent and 36 percent increased risk of cardiovascular disease (odds ratio (OR)=1.42, 95% confidence interval (CI):1.20-1.67; OR=1.38, 95% CI:1.10-1.72); and had 36 percent and 37 percent higher death rates compared to those in cohort 4, respectively (hazard ratio (HR)=1.36, 95% CI:1.27-1.44; HR=1.37, 95% CI:1.27-1.48). Patients in cohort 2 were more likely to be nonadherent to medications for diabetes (OR=1.72, 95% CI:1.48-1.99), hypertension (OR=1.69, 95% CI:1.54-1.85), hyperlipidemia (OR=2.01, 95% CI:1.76-2.29), hyperphosphatemia (OR=1.74, 95% CI:1.55-1.95), and hyperparathyroidism (OR=2.08, 95% CI:1.66-2.60) after reaching the coverage gap. These patients had total health care costs that were $2,644 higher due to increased rates of hospitalization and outpatient visits, despite $2,419 lower pharmacy costs compared to patients in cohort 4 after controlling for covariates (p<0.0001). Reaching the Part D coverage gap was associated with decreased medication adherence and unfavorable clinical and economic outcomes in dialysis patients. / text

I dagens samhälle blir människor allt äldre och sjukare. Antalet människor med diabetes och högt blodtryck ökar successivt i samhället vilket på sikt kommer medföra att fler människor insjuknar i kronisk njursvikt. För patienter som lever med kronisk njursvikt och dialysbehandling kan livskvaliteten påverkas. Det är därför av vikt att sjuksköterskan uppmärksammar patientens livssituation och anpassar omvårdnaden utefter individens behov. Att drabbas av kronisk njursvikt innebär en försämrad eller helt utebliven njurfunktion. Syftet med litteraturstudien var att beskriva patienters upplevelser av att leva med dialysbehandling vid kronisk njursvikt. Resultatet är baserat på 13 vetenskapliga artiklar. Efter analys av artiklarna framkom tre teman av patienternas upplevelser: Det förändrade livet, det sociala livet och livet som patient. I resultatet framkom att beroende på dialysmetod upplever patienter olika hinder eller möjligheter som respektive behandling medför. Många patienter beskriver att dialysbehandlingen begränsar det vardagliga livet samtidigt som behandlingen är en livlina. Dialysbehandlingen kan påverka yrkeslivet såväl som resmöjligheter och sociala relationer. Patienter upplevde att de ofta hamnar i en beroendeställning till dialysbehandlingen och sina anhöriga. Upplevelsen av sjuksköterskans bemötande var mestadels positiv och sjuksköterskan har en viktig roll i vårdandet. Litteraturstudien kan användas för att belysa patienters upplevelser av att leva med dialysbehandling. / Today, people are getting older and sicker. The amount of people with diabetes and high blood pressure is gradually increasing, which will ultimately lead to a higher number of people diagnosed with chronic renal failure. The quality of life affects patients living with chronic kidney disease and dialysis treatment. It’s important that the nurse observes the patients life situation to adapt nursing to each individual’s needs. The purpose of the literature review was to portray patients experiences of living with dialysis treatment when living with chronic renal failure. The result consists of 13 articles. Three themes were revealed: the changes of life, the social life and life as a patient. The result showed that patients experienced various barriers and opportunities of the treatment. Dialysis treatment restricts the daily life of the patient but is considered as a lifeline. Dialysis treatment may influence the career, opportunities to travel and social relationships. Patients felt that they often end up in a position of dependence to the dialysis treatment and their relatives. The experiences of care were mostly positive and the nurse had an important role. The literature review can be used to shed light on patients experiences of living with dialysis treatment.

The purpose of this study was to determine if a relationship existed between the change in serum osmolality in the chronic renal failure patient on hemodialysis and the number of clinical symptoms of the dialysis disequilibrium syndrome experienced during hemodialysis. The study was conducted at the Renal Dialysis Unit of an urban medical center located in a southeastern city. Data were collected from May 25, 1978 to June 30, 1978. Data were obtained during 28 hemodialysis procedures performed on 11 subjects. Serum osmolality measurements were collected prior to initiation of the dialysis procedure, at half-hour intervals during dialysis, and prior to termination of dialysis. Clinical symptoms which occurred during dialysis were recorded by the patients and nursing personnel. The hypothesis was that the number of clinical symptoms of the dialysis disequilibrium syndrome experienced by the chronic renal failure patient during hemodialysis will increase as the serum osmolality decreases.

A capacidade reprodutiva de mulheres em tratamento dialítico é reduzida devido alterações hormonais, distúrbios de ovulação e menstruais. A gestação neste grupo é considerada rara e de risco. Nas últimas décadas, mudanças no tratamento para insuficiência renal crônica (IRC) resultaram em um aumento da fertilidade. Estudos relatam as possibilidades de sucesso nas gestações neste grupo. Este estudo, de natureza descritiva propôs investigar as informações que as mulheres urêmicas possuem acerca da gestação em mulheres que fazem tratamento hemodialítico, e identificar se a maternidade é desejada por estas mulheres. Utilizou-se como instrumento de coleta de dados: roteiro de entrevista semidirigida; Escala Diagnóstica Adaptativa Operacionalizada EDAO; as pranchas 1, 2, 3MF, 7MF e 16 do Teste de Apercepção Temática TAT. Participaram do estudo 23 mulheres em tratamento hemodialítico, na faixa etária entre 24 e 43 anos. Dezoito entrevistadas têm um ou mais filhos; apenas cinco entrevistadas não têm filhos. Sessenta e cinco por cento das mulheres manifestam desejo em ser mãe novamente. Vimos que há possibilidade de gravidez neste grupo onde 60% das mulheres têm vida sexual ativa, 60% menstruam mensalmente e apenas 52% fazem uso de método contraceptivo. A EDAO revelou que todas as entrevistadas encontram-se com adaptação ineficaz, sendo 18% com adaptação ineficaz leve, 39% com adaptação ineficaz moderada e 43% com adaptação ineficaz severa. As pranchas do TAT revelaram as dificuldades vivenciadas pela dependência à máquina de hemodiálise e quanto o suporte familiar é fundamental para lidar com as limitações pertinentes a condição de doente renal crônico. Os dados da pesquisa indicam que é importante a atenção da equipe de saúde à sexualidade das mulheres em diálise. Também é importante que o diálogo a respeito do planejamento familiar faça parte das intervenções da equipe / The reproductive capacity of women on hemodialysis is reduced because of hormonal changes, ovulation disturbs and menstrual disturbs. Pregnancy to this group is considered rare and risky. In the last two decades, some changes in the treatment to chronic renal disease have resulted in better life quality to patients, including the increase of fertility. Reports have been put on public relating the possibilities of success. This descriptive study has proposed to investigate how much uremic women are informed about pregnancy in their case, and identify if they wish to be pregnant. It was used as data collect: semi directed interview, Operational Adaptative Diagnostic Scale, and the boards 1, 2, 3MF, 7MF and 16 of Thematic Apperception Test TAT. The study included 23 woman with 24 43 age. Eighteen women have at least one child or more, just five of them do not have any children. The results has demonstrated they are not informed about pregnancy and hemodialysis treatment. Most of the women want to be pregnant, including those who have already been. We observed they are able to be pregnant because 60% of them have active sexual life, 60% menstruate monthly and just 52% avoid pregnancy with contraceptive method. Operational Adaptative Diagnostic Scale revealed that every interviewed woman is not adapted to the treatment (all of them considered their adaptation inefficient), 18% light inefficient adaptation, 39% moderated inefficient adaptation, and 43% severe inefficient adaptation. TAT boards revealed difficulties lived by the dependency to the hemodialysis machine, also revealed how much familiar support is important and fundamental to face the pertinent limits to chronic renal disease. The research data indicate it is important to the doctors to be attempted to womens sexuality. And it is also important that dialogue about familiar plan has to happen among the medical group intervention

Introdução: A hemodiálise é um procedimento invasivo, para pacientes em falência renal onde se realiza a filtração do sangue continuamente, utilizando-se circulação extracorpórea em um filtro hemodialisador. No Brasil, a prática do reuso de hemodialisadores atinge quase 100% nos serviços de diálise. Uma das justificativas para o reuso são os limitados recursos para a assistência à saúde. No entanto, esta prática, causa questionamentos relacionados à segurança. Erros técnicos no reprocessamento, qualidade da água e alteração da integridade da membrana do hemodiliasador podem afetar a qualidade do processamento expondo os pacientes ao risco de bacteriemia e sepse. Objetivo: Avaliar a contaminação microbiana dos hemodialisadores após o número máximo de reusos permitidos, comparando os resultados conforme tipo de processamento: manual e automatizado. Método: Esta pesquisa caracterizou-se como estudo de campo, transversal, de caráter exploratório comparativo em dois serviços de diálise. A composição da amostra foi por conveniência conforme a disponibilidade destas, pelas instituições doadoras, sendo os grupos experimentais compostos por 11 hemodialisadores processados pelo método automatizado e quatro hemodialisadores processados manualmente. As amostras foram coletadas após o processamento obedecendo ao número máximo de reusos permitidos pela RDC ANVISA nº 11/2014, sendo 12 reusos para processamento manual e 20 reusos para processamento automatizado. Em Cabine de Proteção Biológica a solução salina e dialisadora foram drenadas dos compartimentos de sangue e dialisato, respectivamente, e injetados 150 mL de meio de cultura Tioglicolato de Sódio Fluido em cada compartimento. As amostras foram incubadas em estufa microbiológica por 14 dias, a temperatura de 35 ºC ±2ºC. Após esse período alíquotas do meio de cultura foram semeadas em meios de ágar sangue, anaerinsol e sabouraud, capazes de recuperar a maioria dos microrganismos aeróbios, anaeróbios, bolores e leveduras. As placas foram incubadas por 48 horas a 35 ºC ±2ºC, e procedida a identificação de gênero dos micorganismos. Realizados controles positivos com hemodialisadores contaminados intencionalmente e controles negativos, com novos esterilizados. Resultados: Das amostras submetidas ao processamento automatizado três amostras (3/11-27,3%) apresentaram crescimento microbiano no compartimento de sangue, sendo identificados dois diferentes microrganismos: de Sphingomonas paucimobilis (66,67%) e de Penicillium sp. (33,33%). Todas as amostras 11/11 (100%) apresentaram crescimento microbiano no compartimento de dialisato, sendo identificados 5 diferentes microrganismos: Sphingomonas paucimobilis (43,75%), Strenotrophomonas maltophilia (25%), Pseudomonas aeruginosa (18,75%), Acinectobacter baumannii (6,25%) e Candida sp (6,25%). Dos quatro hemodialisadores submetidos ao processamento manual, uma amostra (25%) apresentou crescimento de bacilo Gram-positivo no compartimento de sangue e uma amostra (25%) apresentou crescimento no compartimento do dialisato contaminados por três microrganismos distintos: de Bacillus sp, Rhizobium radiobacter, Burkholderia sp. Comparando os resultados da contaminação microbiana segundo os dois métodos de processamento analisados não houve diferença estatisticamente significante (p=1) para o compartimento de sangue. Para o compartimento do dialisato o método automatizado apresentou maior número amostras positivas em relação ao manual (p=0,008791). Conclusão: Os resultados demonstraram que o reuso dos hemodialisadores não é uma prática recomendada, podendo causar bacteriemia e sepse em pacientes em tratamento hemodialítico. Ressalta-se que a pesquisa foi conduzida no pior cenário após o número máximo de reusos permitidos sem determinar em qual número de reusos a contaminação aconteceu. / Introduction: Hemodialysis is an invasive procedure for patients with kidney failure in which blood is continuously filtered using a dialyzer filter through extracorporeal blood flow. In Brazil dialyzers are nearly 100% reused in dialysis facilities. One of the main justifications to reuse dialyzers is economical. However, this practice often leads to concerns related to patient safety. Technical errors in reprocessing, water quality and the membrane dialyzer degradation may lead to different risks including bacteremia and sepsis. Objective: To evaluate dialyzers regarding microbiological contamination after maximal number of reuses, comparing results in accordance with the type of reprocessing: manual and automated. Method: This research was characterized as a transversal, exploratory and comparative in two dialysis facilities. The sample was composed as convenience according to the availability of the facilities which donated the samples. The experimental groups were composed of 11 automated reprocessed dialyzers and four manually reprocessed dialyzers. The samples were collected after reprocessing in dialysis facilities according to the maximal number of reuses permited by law (12 in manual reprocessing and 20 in automated reprocessing) and prepared in Biosafety Cabinets. Saline Solution and dialysate solution were drained from both the blood and the dialysate chambers, respectively, by applying suction and filled with 150 mL of culture medium sodium thioglicolato fluid in each chamber and they were incubated at a temperature of 35 º C + or -2 ° C for 14 days. After this period, the samples were cultured in medium adequate for the growth of aerobic and anaerobic organisms as well as fungi and yeasts.The samples were incubated for 48 hours at 35 º C + or -2 ° C and identification of microorganisms was carried. Results: The analyzed samples which were automated reprocessed, 3/11(27.3%) showed microbiological growth in the blood chamber, of this total, we identified two different microorganisms: S.paucimobilis (66,67%) and Penicillium sp. (33,33%). In the dialysate chamber 11/11 (100%) of microbiological growth was identified, of this total we identified five different microorganisms: S.paucimobilis (43,75%) , S. maltophilia (25%) , P. aeruginosa (18,75%) , A. baumannii (6,25%) and Candida sp. (6,25%). The four analyzed samples which were manually reprocessed, 1/4(25%) showed microbiological growth in the blood chamber. One sample with Gram-positive Bacillus was identified in the dialysate chamber and contaminated by Bacillus sp, R. Radiobacter and Burkholderia sp. Comparing the results related to microbiological growth according to the two methods in the blood chamber, we concluded that there was no statistically significant difference (p=1) and in the dialysate chamber, there was a higher number of positive samples among those which were automated reprocessed compared to manually reprocessed (p = 0.008791) Conclusion: The results showed that dialyzers reuse is not a recommended practice and may cause bacteremia and sepsis for patients with chronical kidney disease. We highlight that this study was carried out considering the worst case scenario ,i.e. after the maximal number of reuses permitted by law, without specifying in which number of reuses the contamination occurred.

Dialysis patients are operated to have AV Fistula which is a joint junction of an artery and vein in the arm, operated to increase the blood flow through the dialyzer machine. AV- fistula is a type of vascular access which is a path into the body to connect/disconnect devices, but in this case, it is mainly Dialyzer. To reduce the failure rate during maturation period of AV Fistula, doctors recommend squeezing ball exercise as a necessary precaution for AV Fistula failure. Doing Squeezable interaction for about 3-4 times a day is recommended based on patient’s health condition. Hence, the proposed architecture adopts this squeezable exercise by embedding with sensor and measuring the angle at which the sensor is bent. The framework also proposes a new care coordination system having the hardware layer which has key components such as raspberry Pi, sensor which help in recording the pressure values when user presses the ball and software layer which solely focuses on data sync among the applications used by the user. It has been recorded that 53 % of patients having AV-Fistula fail because of negligence and lack of care. The maturation period is so critical and important which made us to build a gamification platform to monitor the exercise and track the activity through android application to keep users motivated and disciplined. In further chapters of the study will focus on different clinical like procedure around AV-Fistula and technical information such as different technologies used and implemented in the proposed system along with sensor circuit. This project goal is to present a way of monitoring patients and to keep track of the compliance whether the patient is active doing exercise daily. This way we are trying to present a care monitoring system for patients to help prevent AV Fistula failure. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

Orientador: Priscylla Tatiana Chalfun Guimarães Okamoto / Resumo: A doença renal crônica (DRC) é uma enfermidade comum em cães idosos. No insucesso do tratamento clínico tem-se a opção das terapias de substituição renal, onde se destaca a hemodiálise intermitente (HDI). Tanto a técnica de HDI como o estado clínico dos cães com DRC podem desencadear uma reação inflamatória. A proteína C reativa (CRP) é uma proteína de fase aguda que pode ser utilizada como marcador da resposta inflamatória em cães. O objetivo deste estudo foi de avaliar o uso da proteína C reativa como um biomarcador de lesão inflamatória na monitoração da resposta inflamatória de cães com DRC no estádio IV submetidos a hemodiálise intermitente e comparar dois métodos de dosagem da proteína C reativa em cães com doença renal crônica IV. Foram selecionados 16 cães com doença renal crônica IV, divididos em dois grupos: 8 animais no grupo tratamento clínico, 8 animais no grupo hemodiálise intermitente e 7 animais sadios no grupo controle. Foram coletadas amostras de sangue antes da primeira e da última sessão de tratamento de ambos os grupos, para avaliação de hemograma, bioquímica sérica (ureia, creatinina, albumina, potássio, fósforo). Para determinação das concentrações da proteína C reativa foi utilizado o método de ELISA (Dog CRP ELISA (CRP-4), Life Diagnostics Inc.) método de ELISA sanduíche (Kit CATALYST CRP TEST , IDEXX Catalyst®), ambos conforme as recomendações do fabricante. Foi observado elevada concentração de proteína C reativa no GHDI quando comparado com GC (p= ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Chronic Kidney Disease (CKD) is a common disease in older dogs. When the clinical treatment is unsuccessful, kidney replacement therapies become an option, the most prevalent of which is Intermittent Hemodialysis (IHD). Both the IDH technique and the clinical condition of the CKD patients may trigger an inflammatory reaction. C-reactive protein (CRP) is an acute phase protein that may be used as a marker for inflammatory response in dogs. This study aims at evaluating the use of C-Reactive Protein as a biomarker for inflammatory injuries in the monitoring process of the inflammatory response in dogs affected by Stage IV Chronic Kidney Disease undergoing intermittent hemodialysis, in addition to comparing the two different tests to measure CRP in these patients. Sixteen dogs with Stage IV chronic kidney disease were selected for the study and divided into two groups: 8 animals in the clinical treatment group; and 8 animals in the intermittent hemodialysis group. In addition, seven healthy animals were included in a third group as a control. Blood samples were collected before the first and the last treatment session for both groups for a full blood count and serum biochemistry assay (urea, creatinine, albumin, potassium and phosphorus). A canine CRP ELISA Kit (Dog CRP ELISA (CRP-4), Life Diagnostics Inc.) and the CATALYST CRP TEST device (IDEXX Catalyst®) were used to determine the concentration of C-Reactive protein according to the manufacturer’s instructions. We observed an... (Complete abstract click electronic access below) / Mestre

Renewed momentum in the microalgae industry due to commercial interest in biofuels and bioproducts is driving the need to increase the economic competitiveness of large-scale microalgal production. Current knowledge of membrane systems common in other disciplines, such as environmental engineering, marine science, and biomedicine, are relevant to algae production. With pore sizes ranging from microns to angstroms, membranes provide tailored functions for solid/liquid separation (cell retention, biomass concentration and dewatering), gas/liquid separation (gas delivery and removal), and solute/liquid separation (bioproduct recovery, feedstock preparation and effluent recycling) that are problematic or not possible with other technologies. Though membranes have great potential to facilitate cultivation and harvesting, challenges in energy reduction and fouling mitigation need to be overcome for long-term, cost-effective applications. This body of research includes a thorough literature review of membrane applications in the algal industry and three experimental studies investigating ways to improve the cultivation and harvesting of microalgal species in wastewater. The first study investigated the growth of native and augmented algal communities in various growth media. Algal monocultures (Chlorella sorokiniana and Botryococcus braunii) and algal communities native to clarifiers of a wastewater treatment plant were batch cultivated in 1) clarified effluent following a BOD removal reactor (PBCE), 2) clarified effluent following a nitrification reactor (PNCE), and 3) a reference medium (RM). After 12 days, all algal species achieved nitrogen removal between 68-82% in PBCE and 37-99% in PNCE, and phosphorus removal between 91-100% in PBCE and 60-100% in PNCE. The pH of the wastewater samples increased above 9.8 after cultivation of each species, which likely aided ammonia volatilization and phosphorous adsorption. Both monocultures grew readily with wastewater as a feedstock, but B. braunii experienced significant crowding from endemic fauna. In most cases, native algal species' nutrient removal efficiency was competitive with augmented algal monocultures, and in some cases achieved a higher biomass yield, demonstrating the potential to utilize native species for nutrient polishing and algal biomass production. In the second study, the isolated cultivation of algal resource utilizing selectivity (ICARUS) process was conceived and developed. ICARUS integrates a passive membrane photobioreactor configuration with wastewater as a growth medium. Eleven membranes of varying porosity and materials were examined based on characteristics and resulting algae productivity. Four ICARUS series (40kDa-PVDF, 0.53 g L-1, 14.1 mg; 0.1µm-PVDF, 0.43 g L-1, 16.6 mg; 12kDa-RC, 0.35 g L-1, 14.5 mg; 0.2 µm-CA, 0.41 g L-1, 14.5 mg) had a final cell density and mass yield that was significantly higher than that of suspended culture (0.25 g L-1, 9.1 mg). Optimal pore size range was identified to be 50-1000 kDa. Six additional series (0.2µm-CA, 0.1µm-PVDF, 40kDa-PVDF, 12kDa-RC, 3.5kDa-PVDF, and 3kDa-RC) also sustained significantly longer exponential growth phases than the suspended cultures. The ICARUS series maintained an average pH of 9.55, which was significantly lower than the average pH of 10.21in the suspended culture. Membrane characteristics affecting the variability in microalgae productivity were evaluated in 2D and generalized linear models. In the third study, select membranes from the laboratory experiments in Chapter 5 (12kDa-RC, 40kDa-PVDF, 7µm-NY) were tested in extended field conditions at a wastewater treatment plant, where the movement of dissolved constituents and biomass productivity were compared to that of closed suspended series. All ICARUS series had higher biomass productivity (RC, 2.87 g L-1; PVDF, 10.6 g L-1; NY, 8.45 g L-1) than the suspended series (0.38 g L-1), which was due to both a longer exponential growth phase and passive dewatering in the ICARUS series. Dissolved ions passed readily across each membrane, and no nutrient limitation was apparent in any series. Gas exchange was slower than expected, which may have been due to external and internal attached growth utilizing gases at the membrane surface. However, dissolved oxygen concentration did not limit algal growth, and adequate carbon dioxide was available to regulate ICARUS pH. In fact, the ICARUS series maintained an average pH of 7.6, whereas the pH of the control series reached 9.8-10.5. The invasion of endemic wastewater species was dependent on pore size; the RC and PVDF series maintained a monoculture, but the NY series had severe contamination. The resulting research has demonstrated a proof-of-concept of a new microalgal cultivation method which may reduce the cost of large-scale cultivation efforts integrated at wastewater treatment plants or within existing algal production facilities. Investigating various wastewater effluents, membranes, and algal strains has allowed for recommendations for the operation of scaled-up systems. Future research should focus on mechanisms and characteristics of biofouling as well as the operation of a field scale prototype. By improving large scale algal cultivation, algal biofuels may become more economically competitive with fossil fuels or other renewables, enhancing their participation in the country's diverse energy portfolio.

Thesis (M. Nurs.)--University of Hong Kong, 2006.

Le traitement de lanémie par érythropoïétine humaine recombinante est efficace et entraîne une amélioration de la survie et de la qualité de vie et une diminution du risque de complications cardio-vasculaires chez les patients insuffisants rénaux chroniques et dialysés. Lefficacité de ce traitement dépend toutefois principalement dune fourniture adéquate de fer à la moelle érythropoïétique. Chez les sujets sains, chez qui les besoins en fer sont moindres que dans linsuffisance rénale, la nécessité dune supplémentation martiale a été démontrée dans la stimulation érythropoïétique. Lors de stimulations érythropoïétiques importantes, comme celles créées par le don de sang autologue dans les programmes dautotransfusion supporté par rHuEPO, la disponibilité du fer peut également limiter lérythropoïèse. En labsence de supplémentation martiale, le succès de tels programmes est conditionné par la quantité de fer circulant mobilisable de départ mais ne dépend que peu du fer de réserve dont la mobilisation est trop lente. Cela démontre limportance dun apport extérieur de fer chez les sujets normaux engagés dans un programme dautotransfusion. Nos travaux montrent que, malgré une utilisation dune partie du fer de réserve, les collectes de sang étaient dépendantes dune absorption digestive de fer qui augmentait de façon considérable. Nous avons démontré que lactivité érythropoïétique était un stimulant de labsorption digestive de fer au moins aussi puissant que la déplétion des réserves. Labsorption digestive de fer chez les patients hémodialysés et IRC est souvent diminuée et il a été démontré quelle est insuffisante pour rencontrer les besoins associés à un traitement par rHuEPO. De plus la tolérance digestive est mauvaise et la compliance est donc médiocre. Ladministration intraveineuse de fer est, de ce fait, nécessaire, mais non dépourvu de risques. Le dépistage du déficit martial fonctionnel est donc indispensable mais les paramètres classiques utilisés dans ce but peuvent se révéler sub-optimaux. La ferritine sérique, utilisée pour lestimation du fer de réserve, est une protéine de la phase aiguë de linflammation. Elle peut donc surévaluer les réserves de fer dans lurémie, considérée comme un état inflammatoire. Dans une population de sujets sains, nous avons montré que lactivité érythropoïétique et ladministration intraveineuse de fer pouvaient également fausser lévaluation des réserves de fer. Lactivité érythropoïétique diminue le pool labile de fer contenu dans les macrophages et la diminution de la production de ferritine qui sensuit peut donner une sous-estimation des réserves en fer. Lors dune stimulation érythropoïétique intense, dans un état déquilibre martial entre entrées et sorties, nous avons observé une augmentation de la FRT et donc une surestimation de lévaluation du fer de réserve qui en est dérivée. Alors que dans ces conditions, la FRT devrait rester stable ou diminuer suite à la mobilisation du fer pour lérythropoïèse stimulée, ladministration de fer intraveineux semble entraîner une augmentation de ce pool labile de fer intracellulaire, avec une stimulation de la production de ferritine qui ne représente alors plus de façon précise les stocks de fer de lorganisme. Le pourcentage de globules rouges hypochromes est considéré comme le meilleur prédicteur simple de la réponse à une charge martiale chez les patients hémodialysés traités par rHuEPO, témoignant de sa valeur diagnostique dans le déficit martial. Ce paramètre serait également le meilleur prédicteur en présence dun syndrome inflammatoire. Nous avons pu démontrer, pour la première fois, que la présence dune CRP augmentée influence positivement %HYPO. Dans cette étude, établissant les facteurs modulant %HYPO, ce paramètre était, comme attendu, influencé par les paramètres du monitoring martial, principalement le fer sérique et la saturation de la transferrine, mais moins la ferritine, pour les raisons déjà exposées. Des valeurs pathologiques de %HYPO étaient dailleurs retrouvées pour toutes les valeurs de ferritine jusquà 900 ng/mL. %HYPO était également corrélé à la dose de rHuEPO, reflétant le déficit martial induit par la stimulation érythropoïétique mais également la stimulation érythropoïétique en tant que telle. Le meilleur prédicteur simple de %HYPO était le taux de récepteurs solubles de la transferrine. Ce paramètre, connu pour être plus influencé par lactivité érythropoïétique que par le déficit martial, était lui-même corrélé, dans cette étude, à la fois à TSAT et à la réticulocytose. %HYPO semblait donc positivement influencé par lactivité érythropoïétique. Cette observation représente un désavantage pour le monitoring des besoins en fer des patients traités par rHuEPO chez qui le déficit martial fonctionnel cohabite avec laugmentation de lactivité érythropoïétique. Chez les patients donneurs de cellules souches, chez qui la stimulation érythropoïétique a été poussée à lextrême par de hautes doses de rHuEPO et des phlébotomies répétées, %HYPO sélevait de manière très importante jusquà des valeurs de 40%. Cette élévation était présente malgré une supplémentation martiale adéquate, comme en témoignent les courbes superposables de fer prélevé et de fer injecté. De plus, laugmentation de %HYPO débutait plus précocément que la chute de CHr. Il ne peut être exclu que le déficit martial participe à ce phénomène mais nous avons démontré que le rôle de la stimulation érythropoïétique était plus important. Nous avons établi une corrélation entre la production érythrocytaire et lapparition de nouveaux globules rouges hypochromes, confirmant cette hypothèse. Lactivité érythropoïétique induite par le traitement de lanémie rénale est, cependant, nettement moins importante que dans la situation précédente. Dans la population de patients dialysés, nous avons montré une augmentation moindre de %HYPO en réponse à lintroduction de rHuEPO malgré une supplétion martiale adéquate (CHr constant). Cette augmentation était due à lapparition dune population érythrocytaire plus jeune avec un volume cellulaire plus grand et un contenu en hémoglobine normal, résultant en une diminution artificielle de la concentration en hémoglobine. Grâce à la technologie des nouveaux compteurs cellulaires, les indices cellulaires peuvent être déterminés séparément dans les populations réticulocytaires et érythrocytaires matures. Létude des paramètres des érythrocytes matures semblait pouvoir répondre aux biais causés par lactivité érythropoïétique. Nous en avons donc determiné les valeurs de référence. La comparaison entre les indices réticulocytaires et ceux des globules rouges matures montrent que les réticulocytes sont 20% plus grands avec une concentration en hémoglobine 10% inférieure aux érythrocytes matures. Ces différences expliquent les biais qui peuvent être rencontrés dans linterprétation des paramètres de routine. Par létude de diverses pathologies hématologiques, nous avons pu valider linterprétation de ces paramètres. Dans lanémie hémolytique autoimmune, dans laquelle lactivité érythropoïétique est importante sans déficit martial, linterprétation des paramètres de routine menait à penser à un statut ferriprive alors que les paramètres des érythrocytes matures montraient une anémie plutôt macrocytaire et hyperchrome. Dans lanémie ferriprive %HYPO et %HYPOm augmentaient de façon superposable en raison de la faible réticulocytose. De manière générale, toutes les pathologies étudiées, dans lesquelles la réticulocytose est normale ou basse, présentent les mêmes caractéristiques pour les indices des érythrocytes matures que pour les paramètres déterminés sur la population érythroïde globale. Létude de corrélations a également montré que %HYPO était corrélé avec la réticulocytose mais pas avec le fer sérique, alors que %HYPOm était corrélé avec le fer sérique mais pas avec la réticulocytose. Ce paramètre rencontrait donc le but que nous recherchions. La détermination de la sensibilité et de la spécifité des indices globulaires matures dans la prédiction de la réponse à une charge martiale plaide en faveur de lutilisation de %HYPOm dans ce but. Le fait que les patients inclus dans cette étude soient dans la phase de maintenance du traitement par rHuEPO fait que les différences entre les paramètres de routine et les paramètres des érythrocytes matures sont peu importantes et non significatives. Une étude dans la phase dinduction du traitement par rHuEPO pourrait augmenter la différence entre ces paramètres. Une telle étude est toutefois difficile à réaliser car les critères de réponse à la charge martiale devraient être établis différemment. Pour confirmer lintérêt de ces paramètres dans le monitoring martial des patients dialysés traités par rHuEPO, une étude pharmaco-économique comparant les coûts du traitement par rHuEPO et des doses de fer administrées soit en fonction des directives internationales soit en fonction de %HYPOm pourrait être réalisée. Cependant, un nombre important de patients devraient être inclus pour que les résultats soient significatifs. En conclusion, ce travail confirme la nécessité, même dans une population considérée comme saine, dun apport extérieur de fer lors de la stimulation érythropoïétique par érythropoïétine humaine recombinante, étant donné la mobilisation trop lente du fer de réserve. Dans cette situation, labsorption digestive de fer est régulable et lactivité érythropoïétique semble être un stimulateur au moins aussi puissant que la déplétion martiale pour labsorption intestinale de fer. La ferritine, habituellement utilisée dans le monitoring des réserves de fer, est un paramètre médiocre dans lanémie rénale traitée par rHuEPO. En effet, en plus de leffet bien connu de linflammation sur ce marqueur, nous avons montré que ladministration intraveineuse de fer entraîne une production de ferritine sérique inadéquate, probablement en réponse à laugmentation du pool labile de fer. Ce phénomène semble plus important que leffet de la diminution de ce pool labile en réponse à la stimulation érythropoïétique. La mesure de la ferritine surestime donc le fer de réserve dans lanémie rénale traitée par rHuEPO et fer intraveineux. Le pourcentage de globules rouges hypochromes est un paramètre sensible et spécifique du déficit martial fonctionnel. Toutefois, nous avons démontré linfluence de linflammation et de lactivité érythropoïétique sur ce paramètre, pouvant biaiser son interprétation, pour le moins dans la phase de correction de lanémie, quand une réticulocytose élevée cohabite avec un nombre dérythrocytes matures faible. Les paramètres des érythrocytes matures ont été démontrés comme plus fiables pour linterprétation des données dans diverses pathologies hématologiques. Ils présentent lavantage dexclure, au moins en grande partie, les biais entraînés par une réticulocytose élevée. La sensibilité et la spécificité de %HYPOm dans la prédiction de la réponse à une supplémentation martiale étaient supérieures à celles des autres paramètres habituellement utilisés, mais cette différence nétait pas significative en raison de la stabilité des patients étudiés. Son intérêt en clinique quotidienne reste à démontrer.