Self-Monitoring and Self-Efficacy in Patients with Chronic Kidney Disease During Low-Sodium Diet Self-Management Interventions: Secondary Analysis of the ESMO and SUBLIME Trials.

BACKGROUND: Patients with chronic kidney disease are often requested to engage in self-monitoring sodium (i.e. salt) intake, but it is currently unknown how self-monitoring would empower them. This study aims to assess: (1) how frequent self-monitoring tools are being used during low-sodium diet self-management interventions; (2) whether self-efficacy (i.e. trust in own capability to manage the chronic disease) is associated with self-monitoring frequency; and (3) whether higher self-monitoring frequency is associated with an improvement in self-efficacy over time. METHOD: Data from two multicenter randomized controlled trials (ESMO [n = 151] and SUBLIME [n = 99]) among adult Dutch patients with chronic kidney disease (eGFR ≥ 20-25 mL/min/1.73 m2) were used. In both studies, routine care was compared to a 3-month low-sodium diet self-management intervention with several self-monitoring tools (online food diary, home blood pressure monitor, and urinary sodium measurement device [only ESMO]). Data was collected on usage frequency of self-monitoring tools. Frequencies during the interventions were compared between low and high baseline self-efficacy groups using the Mann-Whitney U test and T-test and associated with changes in self-efficacy during the interventions using Spearman correlation coefficients. RESULTS: Large variations in self-monitoring frequency were observed. In both interventions, usage of self-monitoring tools was highest during the first month with sharp drops thereafter. The online food diary was the most frequently used tool. In the ESMO intervention, low baseline self-efficacy was associated with a higher usage frequency of self-monitoring tools. This finding was not confirmed in the SUBLIME intervention. No significant associations were found between usage frequency of self-monitoring tools and changes in self-efficacy over time. CONCLUSION: Patients with low self-efficacy might benefit most from frequent usage of self-monitoring tools when sufficient guidance and support is provided.

Trends in home dialysis use differ among age categories in past two decades: A Dutch registry study.

BACKGROUND: Although the number of patients with end-stage kidney disease is growing, the number of patients who perform dialysis at home has decreased during the past two decades. The aim of this study was to explore time trends in the use of home dialysis in the Netherlands. METHODS: Dialysis episodes of patients who started dialysis treatment were studied using Dutch registry data (RENINE). The uptake of home dialysis between 1997 through 2016 was evaluated in time periods of 5 years. Home dialysis was defined as start with peritoneal dialysis or home haemodialysis, or transfer to either within 2 years of dialysis initiation. All analyses were stratified for age categories. Mixed model logistic regression analysis was used to adjust for clustering at patient level. RESULTS: A total of 33 340 dialysis episodes in 31 569 patients were evaluated. Mean age at dialysis initiation increased from 62.5 ± 14.0 to 65.5 ± 14.5 years in in-centre haemodialysis patients, whereas it increased from 51.9 ± 15.1 to 62.5 ± 14.6 years in home dialysis patients. In patients <65 years, the uptake of home dialysis was significantly lower during each 5-year period compared with the previous period, whereas kidney transplantation occurred more often. In patients ≥65 years, the incidence of home dialysis remained constant, whereas mortality decreased. CONCLUSIONS: In patients <65 years, the overall use of home dialysis declined consistently over the past 20 years. The age of home dialysis patients increased more rapidly than that of in-centre dialysis patients. These developments have a significant impact on the organization of home dialysis.

Differences in hospitalisation between peritoneal dialysis and haemodialysis patients.

BACKGROUND: Dialysis is associated with frequent hospitalisations. Studies comparing hospitalisations between peritoneal dialysis (PD) and haemodialysis (HD) report conflicting results and mostly analyse data of patients that remain on their initial dialysis modality. This cohort study compares hospitalisations between PD and HD patients taking into account transitions between modalities. METHODS: The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes collected hospitalisation data of patients who started dialysis between 2012 and 2017. Primary outcome was hospitalisation rate, analysed with a multi-state model that attributed each hospitalisation to the current dialysis modality. RESULTS: In total, 695 patients (252 PD, 443 HD) treated in 31 Dutch hospitals were included. The crude hospitalisation rate for PD was 2.3 ( ± 5.0) and for HD 1.4 ( ± 3.2) hospitalisations per patient-year. The adjusted hazard ratio for hospitalisation rate was 1.1 (95%CI 1.02-1.3) for PD compared with HD. The risk for first hospitalisation was 1.3 times (95%CI 1.1-1.6) higher for PD compared with HD during the first year after dialysis initiation. The number of hospitalisations and number of hospital days per patient-year were significantly higher for PD. The most common causes of PD and HD hospitalisations were peritonitis (23%) and vascular access-related problems (33%). CONCLUSION: PD was associated with higher hospitalisation rate, higher risk for first hospitalisation and higher number of hospitalisations compared with HD. Since the PD hospitalisations were mainly caused by peritonitis, more attention to infection prevention is necessary for reducing the number of hospitalisations in the future.

Dietary magnesium supplementation inhibits abdominal vascular calcification in an experimental animal model of chronic kidney disease.

BACKGROUND: Vascular calcification is a key process involved in cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Magnesium supplementation may counteract vascular calcification. In this study we aimed to determine whether increased dietary magnesium intake inhibits vascular calcification in CKD in vivo and explore the mechanisms underlying these effects. METHODS: Sprague Dawley rats were partially nephrectomized and fed a diet with high phosphate and either high or normal magnesium content for 16 weeks. The primary outcome was the tissue calcium content of the aorta in the high versus normal dietary magnesium group. In addition, we analysed plasma mineral concentrations, aortic vascular calcification identified with von Kossa staining, calcium apposition time and aortic expression of genes related to vascular calcification. RESULTS: The number of animals in the highest tissue calcium content tertile was significantly lower in the abdominal aorta [1 (10%) versus 6 (55%); P = .03] in the high versus normal dietary magnesium group, but did not differ in the aortic arch and thoracic aorta. Von Kossa staining and calcium apposition time corresponded to these results. The median tissue calcium content was not significantly different between the groups. Serum phosphate concentrations and expression of osteogenic markers in the aorta did not differ between the groups. CONCLUSIONS: This study demonstrates that increased dietary magnesium inhibits abdominal vascular calcification in an experimental animal model of CKD in vivo. These are promising results for CKD patients and further study is needed to identify the mechanisms involved and to determine the clinical relevance in patients.

Magnesium intake and vascular structure and function: the Hoorn Study.

PURPOSE: Circulating and dietary magnesium have been shown to be inversely associated with the prevalence of cardiovascular disease (CVD) and mortality in both high and low-risk populations. We aimed to examine the association between dietary magnesium intake and several measures of vascular structure and function in a prospective cohort. METHODS: We included 789 participants who participated in the vascular screening sub-cohort of the Hoorn Study, a population-based, prospective cohort study. Baseline dietary magnesium intake was estimated with a validated food frequency questionnaire and categorised in energy-adjusted magnesium intake tertiles. Several measurements of vascular structure and function were performed at baseline and most measurements were repeated after 8 years of follow-up (n = 432). Multivariable linear and logistic regression was performed to study the cross-sectional and longitudinal associations of magnesium intake and intima-media thickness (IMT), augmentation index (Aix), pulse wave velocity (PWV), flow-mediated dilatation (FMD), and peripheral arterial disease (PAD). RESULTS: Mean absolute magnesium intake was 328 ± 83 mg/day and prior CVD and DM2 was present in 55 and 41% of the participants, respectively. Multivariable regression analyses did not demonstrate associations between magnesium intake and any of the vascular outcomes. Participants in the highest compared to the lowest magnesium intake tertile demonstrated in fully adjusted cross-sectional analyses a PWV of -0.21 m/s (95% confidence interval -1.95, 1.52), a FMD of -0.03% (-0.89, 0.83) and in longitudinal analyses an IMT of 0.01 mm (-0.03, 0.06), an Aix of 0.70% (-1.69, 3.07) and an odds ratio of 0.84 (0.23, 3.11) for PAD CONCLUSION: We did not find associations between dietary magnesium intake and multiple markers of vascular structure and function, in either cross-sectional or longitudinal analyses.

Comorbidity is not associated with dialysis modality choice in patients with end-stage kidney disease.

AIM: Over the past years the proportion of home dialysis patients has decreased in the Netherlands. In addition, the home dialysis use varies significantly among centres. It is unclear whether this is the result of differences in comorbidity, or other factors. Our aim was to investigate the association between comorbidity and dialysis modality choice. METHODS: The multi-centre DOMESTICO cohort study collected comorbidity data of patients who started dialysis in 35 Dutch centres from 2012 to 2016. Comorbidity was assessed by the Charlson comorbidity index. Home dialysis was defined as any peritoneal dialysis or home haemodialysis treatment during follow-up. Multivariable logistic regression analysis was used to assess the association between comorbidity and dialysis modality, with a mixed model approach to adjust for clustering of patients within dialysis centres. RESULTS: A total of 1358 patients were included, of whom 628 were treated with home dialysis. In crude mixed model analyses, the probability of receiving home dialysis was lower when comorbidity score was higher: having a high comorbidity score resulted in an odds ratio of 0.74 (95% CI 0.54-1.00) when compared with patients without comorbidities. After adjustments for age, sex, ethnic background, body mass index and dialysis vintage, there was no association between comorbidity and home dialysis. CONCLUSION: Comorbidity was not significantly associated with home dialysis choice, after adjustment for several confounding factors including age and body mass index. Future studies should aim at unravelling the centre-specific characteristics that probably play a role in dialysis modality choice.

Dialysis withdrawal in The Netherlands between 2000 and 2019: time trends, risk factors and centre variation.

BACKGROUND: Dialysis withdrawal is a common cause of death in dialysis-dependent patients. This study aims to describe dialysis withdrawal practice in The Netherlands, focussing on time trends, risk factors and centre variation. METHODS: Data were retrieved from the Dutch registry of kidney replacement therapy patients. All patients who started maintenance dialysis and died in the period 2000-2019 were included. The main outcome was death after dialysis withdrawal; all other causes of death were used for comparison. Time trends were analysed as unadjusted data (proportion per year) and the year of death was included in a multivariable logistic model. Univariable and multivariable analyses were performed to identify factors associated with withdrawal. Centre variation was compared using funnel plots. RESULTS: A total of 34 692 patients started dialysis and 18 412 patients died while on dialysis. Dialysis withdrawal was an increasingly common cause of death, increasing from 18.3% in 2000-2004 to 26.8% in 2015-2019. Of all patients withdrawing, 26.1% discontinued treatment within their first year. In multivariable analysis, increasing age, female sex, haemodialysis as a treatment modality and year of death were independent factors associated with death after dialysis withdrawal. Centre variation was large (80.7 and 57.4% within 95% control limits of the funnel plots for 2000-2009 and 2010-2019, respectively), even after adjustment for confounding factors. CONCLUSIONS: Treatment withdrawal has become the main cause of death among dialysis-dependent patients in The Netherlands, with large variations between centres. These findings emphasize the need for timely advance care planning and improving the shared decision-making process on choosing dialysis or conservative care.

Funnel plots of patient-reported outcomes to evaluate health-care quality: Basic principles, pitfalls and considerations.

A funnel plot is a graphical method to evaluate health-care quality by comparing hospital performances on certain outcomes. So far, in nephrology, this method has been applied to clinical outcomes like mortality and complications. However, patient-reported outcomes (PROs; eg, health-related quality of life [HRQOL]) are becoming increasingly important and should be incorporated into this quality assessment. Using funnel plots has several advantages, including clearly visualized precision, detection of volume-effects, discouragement of ranking hospitals and easy interpretation of results. However, without sufficient knowledge of underlying methods, it is easy to stumble into pitfalls, such as overinterpretation of standardized scores, incorrect direct comparisons of hospitals and assuming a hospital to be in-control (ie, to perform as expected) based on underpowered comparisons. Furthermore, application of funnel plots to PROs is accompanied by additional challenges related to the multidimensional nature of PROs and difficulties with measuring PROs. Before using funnel plots for PROs, high and consistent response rates, adequate case mix correction and high-quality PRO measures are required. In this article, we aim to provide insight into the use and interpretation of funnel plots by presenting an overview of the basic principles, pitfalls and considerations when applied to PROs, using examples from Dutch routine dialysis care.

Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe.

The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk with the use of ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe from February 1, 2020, to April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from 7 European countries encompassing 4298 patients. COVID-19-attributable mortality was calculated using propensity score-matched historic control data and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%-21.4%) in 3285 patients receiving dialysis and 19.9% (17.5%-22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants ≥75 years of age, 44.3% (35.7%-53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02-1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy, a highly vulnerable population due to underlying chronic kidney disease and a high prevalence of multimorbidity.

Cardiovascular events in anti-neutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of observational studies.

OBJECTIVES: Several chronic inflammatory diseases are associated with cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly quantified. The aim of the present study was to review the evidence for an increased cardiovascular risk, including ischaemic heart disease, cerebrovascular accidents and peripheral arterial disease, in patients with ANCA-associated vasculitis. METHODS: A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies comparing vasculitis patients with at least one control group. Summary estimates were derived with a random-effects model and reported as relative risks. RESULTS: One thousand three hundred and seventy-five studies were identified. Seven studies were included, comprising almost 14 000 ANCA-associated vasculitis patients vs general population controls in six studies and chronic kidney disease patients in one study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23, 2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates. CONCLUSION: This meta-analysis of observational studies supports an increase in cardiovascular risk in patients with ANCA-associated vasculitis of ∼65%, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis.

Coronary Artery Calcification in Hemodialysis and Peritoneal Dialysis.

BACKGROUND: Vascular calcification is seen in most patients on dialysis and is strongly associated with cardiovascular mortality. Vascular calcification is promoted by phosphate, which generally reaches higher levels in hemodialysis than in peritoneal dialysis. However, whether vascular calcification develops less in peritoneal dialysis than in hemodialysis is currently unknown. Therefore, we compared coronary artery calcification (CAC), its progression, and calcification biomarkers between patients on hemodialysis and peritoneal dialysis. METHODS: We measured CAC in 134 patients who had been treated exclusively with hemodialysis (n = 94) or peritoneal dialysis (n = 40) and were transplantation candidates. In 57 of them (34 on hemodialysis and 23 on peritoneal dialysis), we also measured CAC progression annually up to 3 years and the inactive species of desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, osteoprotegerin. We compared CAC cross-sectionally with Tobit regression. CAC progression was compared in 2 ways: with linear mixed models as the difference in square root transformed volume score per year (ΔCAC SQRV) and with Tobit mixed models. We adjusted for potential confounders. RESULTS: In the cross-sectional cohort, CAC volume scores were 92 mm3 in hemodialysis and 492 mm3 in peritoneal dialysis (adjusted difference 436 mm3; 95% CI -47 to 919; p = 0.08). In the longitudinal cohort, peritoneal dialysis was associated with significantly more CAC progression defined as ΔCAC SQRV (adjusted difference 1.20; 95% CI 0.09 to 2.31; p = 0.03), but not with Tobit mixed models (adjusted difference in CAC score increase per year 106 mm3; 95% CI -140 to 352; p = 0.40). Peritoneal dialysis was associated with higher osteoprotegerin (adjusted p = 0.02) but not with dp-ucMGP or fetuin-A. CONCLUSIONS: Peritoneal dialysis is not associated with less CAC or CAC progression than hemodialysis, and perhaps with even more progression. This indicates that vascular calcification does not develop less in peritoneal dialysis than in hemodialysis.

Perceived Sodium Reduction Barriers Among Patients with Chronic Kidney Disease: Which Barriers Are Important and Which Patients Experience Barriers?

PURPOSE: The purposes of this study were to assess the importance of perceived sodium reduction barriers among patients with chronic kidney disease (CKD) and identify associated sociodemographic, clinical, and psychosocial factors. METHOD: A total of 156 patients with CKD completed a questionnaire assessing sodium reduction barriers (18 self-formulated items), depressive symptoms (Beck Depression Inventory), perceived autonomy support (Modified Health Care Climate Questionnaire), and self-efficacy (Partners in Health Questionnaire). Factor analysis was used to identify barrier domains. Correlation coefficients were computed to examine relationships between barrier domains and patient characteristics. RESULTS: Nine barrier domains were identified. Barriers perceived as important were as follows: high sodium content in products, lack of sodium feedback, lack of goal setting and discussing strategies for sodium reduction, and not experiencing CKD-related symptoms (mean scores > 3.0 on 5-point scales, ranging from 1 'no barrier' to 5 'very important barrier'). Other barriers (knowledge, attitude, coping skills when eating out, and professional support) were rated as moderately important (rated around midpoint), and the barrier 'intrinsic motivation' was rated as somewhat important (mean score = 1.9). Sodium reduction barrier domains were not associated with gender and kidney function, but were associated with age, level of education, number of comorbidities, perceived autonomy support, depressive symptoms, and self-efficacy (range r = 0.17-0.35). Patients with lower self-efficacy and perceived autonomy support scores experienced most sodium reduction barriers. CONCLUSION: Patients with CKD experience multiple important sodium reduction barriers and could benefit from support strategies that target various sodium reduction barriers and strengthen beliefs regarding self-efficacy and autonomy support. Additionally, environmental interventions should be implemented to reduce sodium levels in processed foods.

Sodium Restriction in Patients With CKD: A Randomized Controlled Trial of Self-management Support.

BACKGROUND: To evaluate the effectiveness and sustainability of self-managed sodium restriction in patients with chronic kidney disease. STUDY DESIGN: Open randomized controlled trial. SETTING & PARTICIPANTS: Patients with moderately decreased kidney function from 4 hospitals in the Netherlands. INTERVENTION: Regular care was compared with regular care plus an intervention comprising education, motivational interviewing, coaching, and self-monitoring of blood pressure (BP) and sodium. OUTCOMES: Primary outcomes were sodium excretion and BP after the 3-month intervention and at 6-month follow-up. Secondary outcomes were protein excretion, kidney function, antihypertensive medication, self-efficacy, and health-related quality of life (HRQoL). RESULTS: At baseline, mean sodium excretion rate was 163.6±64.9 (SD) mmol/24 h; mean estimated glomerular filtration rate was 49.7±25.6mL/min/1.73m2; median protein excretion rate was 0.8 (IQR, 0.4-1.7) g/24 h; and mean 24-hour ambulatory systolic and diastolic BPs were 129±15 and 76±9mmHg, respectively. Compared to regular care only (n=71), at 3 months, the intervention group (n=67) showed reduced sodium excretion rate (mean change, -30.3 [95% CI, -54.7 to -5.9] mmol/24 h), daytime ambulatory diastolic BP (mean change, -3.4 [95% CI, -6.3 to -0.6] mmHg), diastolic office BP (mean change, -5.2 [95% CI, -8.4 to -2.1] mmHg), protein excretion (mean change, -0.4 [95% CI, -0.7 to -0.1] g/24h), and improved self-efficacy (mean change, 0.5 [95% CI, 0.1 to 0.9]). At 6 months, differences in sodium excretion rates and ambulatory BPs between the groups were not significant, but differences were detected in systolic and diastolic office BPs (mean changes of -7.3 [95% CI, -12.7 to -1.9] and -3.8 [95% CI, -6.9 to -0.6] mmHg, respectively), protein excretion (mean changes, -0.3 [95% CI, -0.6 to -0.1] g/24h), and self-efficacy (mean change, 0.5 [95% CI, 0.0 to 0.9]). No differences in kidney function, medication, and HRQoL were observed. LIMITATIONS: Nonblinding, relatively low response rate, and missing data. CONCLUSIONS: Compared to regular care only, this self-management intervention modestly improved outcomes, although effects on sodium excretion and ambulatory BP diminish over time.

Estimating residual kidney function in dialysis patients without urine collection.

Residual kidney function contributes substantially to solute clearance in dialysis patients but cannot be assessed without urine collection. We used serum filtration markers to develop dialysis-specific equations to estimate urinary urea clearance without the need for urine collection. In our development cohort, we measured 24-hour urine clearances under close supervision in 44 patients and validated these equations in 826 patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. For the development and validation cohorts, median urinary urea clearance was 2.6 and 2.4 ml/min, respectively. During the 24-hour visit in the development cohort, serum ß-trace protein concentrations remained in steady state but concentrations of all other markers increased. In the validation cohort, bias (median measured minus estimated clearance) was low for all equations. Precision was significantly better for ß-trace protein and ß2-microglobulin equations and the accuracy was significantly greater for ß-trace protein, ß2-microglobulin, and cystatin C equations, compared with the urea plus creatinine equation. Area under the receiver operator characteristic curve for detecting measured urinary urea clearance by equation-estimated urinary urea clearance (both 2 ml/min or more) were 0.821, 0.850, and 0.796 for ß-trace protein, ß2-microglobulin, and cystatin C equations, respectively; significantly greater than the 0.663 for the urea plus creatinine equation. Thus, residual renal function can be estimated in dialysis patients without urine collections.

Trends in haemoglobin, erythropoietin-stimulating agents and iron use in Swedish chronic kidney disease patients between 2008 and 2013.

BACKGROUND: The guidelines for anaemia management in chronic kidney disease (CKD) patients have changed substantially during the past 10 years. We here evaluate whether these changes are followed by subsequent modifications in physicians' anaemia management in Sweden. METHODS: We included patients incident to the Swedish Renal Registry for CKD non-dialysis (CKD-ND, referred patients with an estimated glomerular filtration rate <45 mL/min/1.73 m(2)) and haemodialysis (HD) between 2008 and 2013. Time trends in anaemia management were investigated in relation to prescribed medication, laboratory measures and other relevant clinical characteristics. Linear and binominal regression models were used to describe trends across three predefined time periods (2008-09, 2010-11 and 2012-13). RESULTS: Erythropoiesis-stimulating agents (ESAs) use decreased over time among both CKD-ND and HD patients [risk ratio (RR) 2012-13 compared with 2008-09 for CKD-ND 0.88, 95% confidence interval (CI) 0.81-0.96; RR for HD 0.95, 95% CI 0.93-0.97]. Mean ESA dose decreased significantly among HD patients (7% in 2010-11 compared with 2008-09 and another 3% during 2012-13). Over the time periods studied, ESA doses increased slightly in the CKD-ND population. Mean haemoglobin (Hb) levels decreased in CKD-ND patients, among both ESA users and non-users, whereas it decreased to a lesser degree, albeit significantly, among HD ESA users. The risk of having an Hb >120 g/L decreased, especially between 2008-09 and 2010-11. Iron use increased over time, mainly in the HD population, but also among CKD-ND ESA non-users. CONCLUSIONS: Changes in guidelines have influenced the clinical anaemia practice of Swedish nephrology care, resulting in lower ESA use and lower Hb levels.

Phosphorus metabolism in peritoneal dialysis- and haemodialysis-treated patients.

BACKGROUND: Phosphorus control is generally considered to be better in peritoneal dialysis (PD) patients as compared with haemodialysis (HD) patients. Predialysis phosphorus concentrations are misleading as a measure of phosphorus exposure in HD, as these neglect significant dialysis-related fluctuations. METHODS: Parameters of mineral metabolism, including parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23), were determined in 79 HD and 61 PD patients. In PD, phosphorus levels were determined mid-morning. In HD, time-averaged phosphorus concentrations were modelled from measurements before and after the mid-week dialysis session. Weekly renal, dialytic and total phosphorus clearances as well as total mass removal were calculated from urine and dialysate collections. RESULTS: Time-averaged serum phosphorus concentrations in HD (3.5 ± 1.0 mg/dL) were significantly lower than the mid-morning concentrations in PD (5.0 ± 1.4 mg/dL, P < 0.0001). In contrast, predialysis phosphorus concentrations (4.6 ± 1.4 mg/dL) were not different from PD. PTH and FGF-23 levels were significantly higher in PD. Despite higher residual renal function, total phosphorus clearance was significantly lower in PD (P < 0.0001). Total phosphorus mass removal, conversely, was significantly higher in PD (P < 0.05). CONCLUSIONS: Our data suggest that the time-averaged phosphorus concentrations in patients treated with PD are higher as compared with patients treated with HD. Despite a better preserved renal function, total phosphorus clearance is lower in patients treated with PD. Additional studies are needed to confirm these findings in a population with a different demographic profile and dietary background and to define clinical implications.

Diuretics, Limited Ultrafiltration, and Residual Renal Function in Incident Hemodialysis Patients: A Case Series.

The effect of diuretics on residual renal function expressed as residual GFR (rGFR) and urine volume (rUV) using 24-hour urine collections has not been well examined in hemodialysis (HD) patients. We present a small (seven patient) but provocative case series describing a strikingly low rate of decline in rUV and rGFR (average of creatinine and urea clearances, 24-hour urine collections) in patients treated with increasing doses of furosemide (up to 360 mg/day) during the first 2 years after initiation of HD. Between 6 and 12 months, the mean rUV fell by 1 ml/month, whereas rGFR declined by 0.03 ml/min/1.73 m(2) /month. The mean rate of decline from 12 to 24 months for rUV (33 ml/month) and rGFR (0.02 ml/min/1.73 m(2) /month) were also low. While data are clearly limited and the observation retrospective, they are consistent with the better documented benefit of diuretics observed in end-stage renal disease patients treated with peritoneal dialysis.

Genetic polymorphisms influencing total and γ' fibrinogen levels and fibrin clot properties in Africans.

Inter-ethnic variation in fibrinogen levels is hypothesized to be the result of differences in genetic background. No information is available regarding the contribution of genetics to fibrinogen γ' in Africans. Only limited information is available regarding the interaction between genotypes and total and γ' fibrinogen concentration in determining fibrin clot properties. Our aim was to investigate the effect of polymorphisms in the fibrinogen and Factor XIII genes on total and γ' fibrinogen and clot properties (turbidimetry) in 2010 black Africans as well as to determine their interactions. Significant associations were observed between rs1049636 (FGG gene), with total fibrinogen levels and between rs2070011 (FGA promoter area) and fibrinogen γ' levels. Significant associations were observed between single nucleotide polymorphisms (SNPs) in the FGA (rs2070011), FGB (rs1800787) and FGG (rs1049636) genes and fibre size. Significant interactions were found between total and/or γ' fibrinogen levels and SNPs in the FGA (rs2070011), FGB (rs2227385, rs1800787, rs1800788, rs4220) and F13A1 genes (rs5985) in determining clot properties. The different SNPs influenced the relationships between total and γ' fibrinogen levels with clot properties in opposing directions. Genetic influences may be ethnic-specific and should not only focus on fibrinogen concentration, but also on functionality in determining its role in CVD.

Short-Form 12 or Short-Form 36 to measure quality-of-life changes in dialysis patients?

BACKGROUND: Short-Form 36 (SF-36) is a self-report health-related quality-of-life (HRQOL) questionnaire, widely used in dialysis patients. It consists of physical and mental component scores (PCS/MCS), ranging from 0 to 100. To improve efficiency, the Short-Form 12 (SF-12) was developed to reproduce PCS and MCS. We assessed the ability of SF-12 versus SF-36 to detect change over time, and the association of SF-12 versus SF-36 with short-term and long-term mortality in dialysis patients. METHODS: Patients were selected from the Netherlands Cooperative Study on the Adequacy of Dialysis (N = 1379), a prospective follow-up study among incident dialysis patients (62.1% HD) who completed SF-36 measurements every 6 months. Changes in scores of SF-12 versus SF-36 were compared with intra-class correlation coefficients (ICCs). Subsequently, Bland-Altman plots were used to assess limits of agreement. Relationship with mortality was assessed with Cox models with and without a time-dependent variable, adjusted for age, sex, ethnicity, comorbidity and dialysis modality at baseline. RESULTS: ICC for change in scores was 0.90 for MCS and 0.84 for PCS. Mean difference was -0.1 and 0.2, respectively, and limits of agreement were -8.3 to 8.4 for MCS change in scores and -8.8 to 9.2 for PCS. Adjusted hazard ratio's for mortality per 5 units increment were 0.87 (95% CI: 0.84-0.91) for MCS12, 0.87 (95% CI: 0.84-0.90) for MCS36, 0.79 (95% CI: 0.76-0.83) for PCS12 and 0.75 (95% CI: 0.71-0.78) for PCS36. CONCLUSIONS: SF-12 can be used to detect change in HRQOL in cohort studies on dialysis patients. SF-12 and SF-36 were similarly associated with short-term and long-term mortality. However, the wide limits of agreement indicate that SF-12 and SF-36 can give different scores on the individual level, suggesting that for individual purposes SF-36 instead of SF-12 should be used.

Treatment with high dose of erythropoiesis-stimulating agents and mortality: analysis with a sequential Cox approach and a marginal structural model.

BACKGROUND: Anemia-correction trials indicated higher mortality rates in chronic kidney disease patients assigned to higher hemoglobin targets. The safety of the high erythropoiesis-stimulating agent (ESA) doses that these patients received has therefore been questioned. However, no trial that directly compares treatment with different ESA doses has been published. We thus aimed to estimate the effect of high ESA dose on mortality in an observational cohort of dialysis patients. METHODS: The Netherlands Cooperative Study on the Adequacy of Dialysis is a Dutch cohort study of incident dialysis patients in which ESA dose, comorbidities, and laboratory parameters were collected every 6 months. Mortality in patients with a high ESA dose (above median 6000 units/week) was compared with that in patients with no or low ESA dose with Cox regression analyses. To handle time-dependent confounding, a sequential Cox approach was used conditional on baseline covariates, with inverse probability of censoring weights (IPCW) for dependent censoring. Analyses were repeated with a marginal structural model (MSM) with inverse probability of treatment weights and IPCW. RESULTS: Hazard ratio (HR) for high ESA dose was 1.20 (95%CI 0.83-1.73) with a sequential Cox and 1.54 (95%CI 1.08-2.18) with an MSM. Truncation of weights in the MSM did not affect estimates. To compare, conventional Cox analyses indicated a baseline adjusted HR of 1.66 (95%CI 1.20-2.31). CONCLUSION: Patients treated with high ESA dose have a 1.2-1.5 increased risk of mortality. Our analyses support guidelines advising a conservative ESA dosing regimen, which carefully weighs the patients' benefits and risks.