Claudia Barth

Interdialytic weight gain, systolic blood pressure, serum albumin, and C-reactive protein levels change in chronic dialysis patients prior to death

Reports from a United States cohort of chronic hemodialysis patients suggested that weight loss, a decline in pre-dialysis systolic blood pressure, and decreased serum albumin may precede death. However, no comparative studies have been reported in such patients from other countries. Here we analyzed dynamic changes in these parameters in hemodialysis patients and included 3593 individuals from 5 Asian countries; 35,146 from 18 European countries; 8649 from Argentina; and 4742 from the United States. In surviving prevalent patients, these variables appeared to have notably different dynamics than in patients who died. While in all populations the interdialytic weight gain, systolic blood pressure, and serum albumin levels were stable in surviving patients, these indicators declined starting more than a year ahead in those who died with the dynamics similar irrespective of gender and geographic region. In European patients, C-reactive protein levels were available on a routine basis and indicated that levels of this acute-phase protein were low and stable in surviving patients but rose sharply before death. Thus, relevant fundamental biological processes start many months before death in the majority of chronic hemodialysis patients. Longitudinal monitoring of these dynamics may help to identify patients at risk and aid the development of an alert system to initiate timely interventions to improve outcomes.

Monitoring dialysis outcomes across the world--the MONDO Global Database Consortium

Background/Aims: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. Methods: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. Results: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. Conclusion: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.

Effect of Pseudomonas aeruginosa exotoxin A on IFN-γ synthesis: expression of costimulatory molecules on monocytes and activity of NK cells

The aim of the study was (1) to evaluate the effect of Pseudomonas aeruginosa Exotoxin A (P-ExA) on the production of IFN-gamma in anti-CD3 induced human peripheral blood mononuclear cells (PBMC) and (2) to establish the effect of P-ExA on the IFN-gamma dependent cellular activities such as the expression of costimulatory molecules on monocytes and cytotoxicity of NK cells. The toxin in a high dose (100 ng/ml) inhibited IFN-gamma synthesis. Inhibitory effect of P-ExA was abolished by IL-1alpha which in a combination with P-ExA exerted a strong synergistic effect on IFN-gamma synthesis. Other monokines such as IL-1beta, IL-6, TNF-alpha neither reversed the inhibitory effect of P-ExA nor induced production of IFN-gamma. P-ExA also inhibited IFN-gamma-induced cellular events: (1) expression of costimulatory molecules on monocytes (CD80, CD86, ICAM-1, HLA-DR); (2) cytotoxic activity of NK cells. Inhibition of NK cells activity by P-ExA was not reversed by cytokines such as IL-2, IFN-alpha and TNF-alpha, which are known to enhance effector functions of NK cells. From these results we conclude that: (1) inhibition of IFN-gamma synthesis, as well as IFN-gamma-induced expression of costimulatory molecules and NK-cell effector functions may lead to suppression of specific and non-specific defense mechanisms, respectively, which are necessary for elimination of PA bacteria; (2) enhancement of IFN-gamma synthesis induced by P-ExA in a combination with IL-1alpha may cause harmful, Th1 cells dependent, inflammatory reactions of the host (septic shock, tissue damage) during infection with Pseudomonas aeruginosa.

Preferences of patients undergoing hemodialysis – results from a questionnaire-based study with 4,518 patients

Background Chronic kidney disease is an increasing health problem worldwide and in its final stage (stage V) can only be treated by renal replacement therapy, mostly hemodialysis. Hemodialysis has a major influence on the everyday life of patients and many patients report dissatisfaction with treatment. Little is known about which aspects of treatment are considered important by hemodialysis patients. The objective of this study was to rate the relative importance of different outcomes for hemodialysis patients and to analyze whether the relative importance differed among subgroups of patients. Patients and methods Within the framework of a yearly questionnaire which is distributed among patients receiving hemodialysis by the largest hemodialysis provider in Germany, we assessed the relative importance of 23 outcomes as rated on a discrete visual analog scale. Descriptive statistics were used to rank the outcomes. Subgroup analyses were performed using Mann–Whitney U or Kruskal–Wallis tests. Results Questionnaires of 4,518 hemodialysis patients were included in the analysis. The three most important outcomes were safety of treatment, health-related quality of life, and satisfaction with care. Further important outcomes were hospital stays, accompanying symptoms, hemodialysis duration, and the improvement or preservation of a good emotional state. Age, profession, and education had the strongest influence on relevant differences of preferences for outcomes; no relevant influence of sex or comorbidity was observed. Conclusion Outcomes concerning the delivery or provision of care and aspects influencing quality of life are rated by patients to be at least as important as clinical outcomes. Many of the outcomes judged to be important by the patients are not regularly considered in research, evaluation studies, or quality programs.

EFFECT OF PSEUDOMONAS AERUGINOSA EXOTOXIN A ON CD3-INDUCED HUMAN T-CELL ACTIVATION

The effect of Pseudomonas aeruginosa (PA) exotoxin A (P-ExA) on CD3-induced T-cell activation was studied on the level of T-cells (proliferation, synthesis of interleukin (IL)-2, expression of IL-2R complex, ICAM-1,2 and LFA-1 molecules), and on the level of monocytes (expression of ICAM-1,2, LFA-1 molecules, as well as FcRI and CD14 receptors). We found that: (1) P-ExA blocked T-cell proliferation and this effect was totally reversed by intact monocytes, and partially by IL-2 or TPA but not by costimulatory cytokines (IL-1alpha, IL-1beta, TNF-alpha or IL-6); (2) P-ExA transiently, in short-term cultures (48 h), inhibited synthesis of IL-2; (3) prolonged stimulation (96 h) of peripheral blood mononuclear cells (PBMC) or CD4 + T-cells with P-ExA in high or low doses (100 and 10 ng/ml, respectively), enhanced the level of IL-2 in the cultures; (4) P-ExA at low dose, combined with IL-1beta, TNF-alpha or IL-6, up-regulated synthesis of IL-2; and (5) stimulation of T-cells with anti-CD3 monoclonal antibody (mAb) and P-ExA at high dose diminished the expression of the p55 chain but not of the p75 chain of IL-2R complex and slightly affected the expression of CD3 complex, ICAM-1,2 and LFA-1 molecules. Hence, P-ExA can regulate the level of IL-2 in cultures of CD3-induced T-cells either by inhibition of IL-2 consumption (when P-ExA is applied in high dose), or by induction of IL-2 production (a costimulatory effect exerted by P-ExA in low dose in combination with monokines). Action of P-ExA on monocytes resulted in: (1) inhibition of the expression of ICAM-1,2 molecules and their ligand LFA-1 molecule; (2) low expression of FcRI receptor (a ligand for Fc part of CD3 mAb); and (3) inhibition (over 90%) of the expression of CD14 molecule. In conclusion, P-ExA-induced anergy of T-cells depends on: (a) decrease in the affinity of IL-2R complex on activated T-cells; and (b) inhibition of the accessory activities of monocytes.

Relationship of Neutrophil-to-Lymphocyte Ratio and Serum Albumin Levels with C-Reactive Protein in Hemodialysis Patients: Results from 2 International Cohort Studies

Background/Aim: The neutrophil-to-lymphocyte ratio (NLR), defined as the neutrophil count divided by lymphocyte count, is an inexpensive and readily available parameter, which may serve as a surrogate for inflammation markers, such as C-reactive protein (CRP). The aim of this study was to determine the utility of NLR in the prediction of elevated CRP levels in hemodialysis (HD) patients. Methods: We analyzed 43,272 HD patients from 2 distinct cohorts within the Monitoring Dialysis Outcomes research collaboration in whom contemporaneous measurements of neutrophil and lymphocyte counts, serum albumin and CRP levels were available. Logistic regression was used to determine the relationship of trichotomized NLR (<2.5, 2.5-5 and >5.0) and albumin levels (<3.1, 3.1-4.0 and >4.0 g/dl) with elevated CRP levels (>10.0, >20.0 and >30.0 mg/l). Congruence of the prediction models was examined by comparing the regression parameters and by cross-validating each regression equation within the other cohort. Results: We found that NLR >5.0 vs. <2.5 (cohort 1: OR 2.3; p < 0.0001 and cohort 2: OR 2.0; p < 0.0001) was associated with CRP levels >10.0 mg/l. Stepwise increase in odds ratio for CRP >10.0 mg/l was observed with the combination of high NLR and low albumin levels (NLR >5.0 and albumin <3.1) (cohort 1: OR 7.6; p < 0.0001 and cohort 2: OR 11.9; p < 0.0001). Cross-validation of the 2 regression models revealed a predictive accuracy of 0.68 and 0.69 in the respective cohorts. Conclusion: This study suggests that NLR could serve as a potential surrogate marker for CRP. Our results may add to diagnostic abilities in settings where CRP is not measured routinely in HD patients. NLR is easy to integrate into daily practice and may be used as a marker of systemic inflammation.

Dialysis Access as an Area of Improvement in Elderly Incident Hemodialysis Patients: Results from a Cohort Study from the International Monitoring Dialysis Outcomes Initiative

Background: Commencing hemodialysis (HD) using a catheter is associated with a higher risk of adverse outcomes, and early conversion from central-venous catheter (CVC) to arteriovenous fistula/graft (non-CVC) improves outcomes. We investigated CVC prevalence and conversion, and their effects on outcomes during the first year of HD in a multinational cohort of elderly patients. Methods: Patients ≥70 years from the MONDO Initiative who commenced HD between 2000 and 2010 in Asia-Pacific, Europe, North-, and South-America and survived at least 6 months were included in this investigation. We stratified by age (70-79 years [younger] vs. ≥80 years [older]) and compared access types (at first and last available date) and their changes. We studied the association between access at initiation and conversion, respectively, and all-cause mortality using Kaplan-Meier curve and Cox regression, and predicted the absence of conversion from catheter to non-CVC using adjusted logistic regression. Results: In 14,966 elderly, incident HD patients, survival was significantly worse when using a CVC at all times. In Europe, the conversion frequency from CVC to non-CVC was higher in the younger fraction. Conversion from non-CVC to CVC was associated with worsened outcomes only in the older fraction. Conclusion: These results corroborate the need for early HD preparation in the elderly HD population. Treatment of elderly patients who commence HD with a CVC should be planned considering aspects of individual clinical risk assessment. Differences in treatment practices in predialysis care specific to the elderly as a population may influence access care and conversion rate.

Knowing What We Do and Doing What We Should: Quality Assurance in Hemodialysis

An international group of around 50 nephrologists and scientists, including representatives from large dialysis provider organisations, formulated recommendations on how to develop and implement quality assurance measures to improve individual hemodialysis patient care, population health and cost effectiveness. Discussed were methods thought to be of highest priority, those clinical indicators which might be most related to meaningful patient outcomes, tools to control treatment delivery and the role of facilitating computerized expert systems. Emphasis was given to the use of new technologies such as measurement of online dialysance and ways of assessing fluid status. The current evidence linking achievement of quality criteria with patient outcomes was reviewed. This paper summarizes useful processes and quality measures supporting quality assurance that have been agreed across the expert panel. It also notes areas where more understanding is required.

[Shared decision-making as a new quality indicator in nephrology: a nationwide survey in Germany].

ZusammenfassungHintergrund und Ziel:Partizipative Entscheidungsfindung (Shared Decision-Making) gewinnt als Modell der Arzt-Patienten-Beziehung auch im deutschen Gesundheitssystem zunehmend an Bedeutung. Insbesondere im Bereich chronischer Erkrankungen erwartet man sich von diesem Konzept mittel- bis langfristige Verbesserungen der Behandlungsergebnisse. Bislang liegen der deutschen Versorgungsforschung jedoch kaum empirische Daten zum Stand und zu den Entwicklungstendenzen der partizipativen Entscheidungsfindung vor. Diese Studie liefert aktuelle Ergebnisse zu dieser Fragestellung aus einer deutschlandweiten Befragung von terminal niereninsuffizienten Patienten.Methodik:Im Rahmen des Programms Qualität in der Nephrologie (QiN) wurden in einer schriftlichen, deutschlandweiten Erhebung 6 614 Patienten mit terminaler Niereninsuffizienz befragt. Der Fragebogen enthielt ein zuvor übersetztes und validiertes Instrument zur Erfassung der wahrgenommenen Einbeziehung in die Therapie (PICS).Ergebnisse:82% der Befragten fühlen sich durch ihre Ärzte für eine Beteiligung an Entscheidungen motiviert. 81% der Patienten informieren sich aktiv bei ihren Ärzten über ihre Erkrankung und Behandlungsmöglichkeiten. 69% geben an, dass eine gemeinsame Entscheidungsfindung von Arzt und Patient stattgefunden hat. Das Lebensalter, die Dialysejahre und das Geschlecht stehen im Zusammenhang mit der wahrgenommenen Einbeziehung.Schlussfolgerung:Dieser Aufsatz bietet eine valide Grundlage für die prospektive Erforschung der partizipativen Entscheidungsfindung in der Behandlung der terminalen Niereninsuffizienz. Die Ergebnisse der vorliegenden Studie deuten auf eine hohe Bereitschaft von Dialysepatienten hin, sich aktiv am Prozess der Entscheidungsfindung zu beteiligen. Spezifische Patientencharakteristika und die Präferenzen der Patienten sollten nicht nur bei der alltäglichen klinischen Interaktion mit den Patienten Berücksichtigung finden. Sie könnten darüber hinaus im Rahmen der Qualitätssicherung systematisch erfasst und als Verbesserungspotential genutzt werden.AbstractBackground and Purpose:Shared decision-making (SDM) as a model in physician-patient interaction is gaining relevance in the German health system. By applying this model, mid- and long-term improvements are expected especially in the outcomes of chronic diseases. Up to now, there has hardly been any empirical data available in German health services research regarding the state and development of SDM. This study establishes a baseline and provides actual data on this subject based on a German-wide survey of end-stage renal disease (ESRD) patients.Methods:Standardized German-wide survey of 6,614 patients with ESRD. The questionnaire included an instrument to measure the patients’ perceived involvement in care (PICS) which had been translated and validated before.Results:82% of the questioned patients feel their physicians facilitated involvement in decision making. 81% of the patients actively inform themselves concerning their disease and treatment options. 69% state that SDM has taken place. Age, years on dialysis and gender correlate with perceived involvement.Conclusion:This paper provides a valid baseline for the prospective research of SDM in ESRD. The results indicate that dialysis patients are willing to participate in the process of medical decision-making. Characteristics and preferences of the patients should be taken into account not only in everyday clinical interactions. They could be monitored systematically within the framework of quality management and used as potential for quality improvement.

Partizipative Entscheidungsfindung als neuer Qualitätsindikator in der Nephrologie

ZusammenfassungHintergrund und Ziel:Partizipative Entscheidungsfindung (Shared Decision-Making) gewinnt als Modell der Arzt-Patienten-Beziehung auch im deutschen Gesundheitssystem zunehmend an Bedeutung. Insbesondere im Bereich chronischer Erkrankungen erwartet man sich von diesem Konzept mittel- bis langfristige Verbesserungen der Behandlungsergebnisse. Bislang liegen der deutschen Versorgungsforschung jedoch kaum empirische Daten zum Stand und zu den Entwicklungstendenzen der partizipativen Entscheidungsfindung vor. Diese Studie liefert aktuelle Ergebnisse zu dieser Fragestellung aus einer deutschlandweiten Befragung von terminal niereninsuffizienten Patienten.Methodik:Im Rahmen des Programms Qualität in der Nephrologie (QiN) wurden in einer schriftlichen, deutschlandweiten Erhebung 6 614 Patienten mit terminaler Niereninsuffizienz befragt. Der Fragebogen enthielt ein zuvor übersetztes und validiertes Instrument zur Erfassung der wahrgenommenen Einbeziehung in die Therapie (PICS).Ergebnisse:82% der Befragten fühlen sich durch ihre Ärzte für eine Beteiligung an Entscheidungen motiviert. 81% der Patienten informieren sich aktiv bei ihren Ärzten über ihre Erkrankung und Behandlungsmöglichkeiten. 69% geben an, dass eine gemeinsame Entscheidungsfindung von Arzt und Patient stattgefunden hat. Das Lebensalter, die Dialysejahre und das Geschlecht stehen im Zusammenhang mit der wahrgenommenen Einbeziehung.Schlussfolgerung:Dieser Aufsatz bietet eine valide Grundlage für die prospektive Erforschung der partizipativen Entscheidungsfindung in der Behandlung der terminalen Niereninsuffizienz. Die Ergebnisse der vorliegenden Studie deuten auf eine hohe Bereitschaft von Dialysepatienten hin, sich aktiv am Prozess der Entscheidungsfindung zu beteiligen. Spezifische Patientencharakteristika und die Präferenzen der Patienten sollten nicht nur bei der alltäglichen klinischen Interaktion mit den Patienten Berücksichtigung finden. Sie könnten darüber hinaus im Rahmen der Qualitätssicherung systematisch erfasst und als Verbesserungspotential genutzt werden.AbstractBackground and Purpose:Shared decision-making (SDM) as a model in physician-patient interaction is gaining relevance in the German health system. By applying this model, mid- and long-term improvements are expected especially in the outcomes of chronic diseases. Up to now, there has hardly been any empirical data available in German health services research regarding the state and development of SDM. This study establishes a baseline and provides actual data on this subject based on a German-wide survey of end-stage renal disease (ESRD) patients.Methods:Standardized German-wide survey of 6,614 patients with ESRD. The questionnaire included an instrument to measure the patients’ perceived involvement in care (PICS) which had been translated and validated before.Results:82% of the questioned patients feel their physicians facilitated involvement in decision making. 81% of the patients actively inform themselves concerning their disease and treatment options. 69% state that SDM has taken place. Age, years on dialysis and gender correlate with perceived involvement.Conclusion:This paper provides a valid baseline for the prospective research of SDM in ESRD. The results indicate that dialysis patients are willing to participate in the process of medical decision-making. Characteristics and preferences of the patients should be taken into account not only in everyday clinical interactions. They could be monitored systematically within the framework of quality management and used as potential for quality improvement.