Tiny Hoekstra

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 β-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 β-trace protein and β2-microglobulin equations and the accuracy was significantly greater for β-trace protein, β2-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 β-trace protein, β2-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.

Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Abstract The chronic infection status suffered by HIV-infected individuals promotes chronic arterial inflammation and injury, which leads to dysfunction of the endothelium, atherosclerosis and thrombosis. Although HIV-1 subtype C is prevalent in South Africa and accounts for almost a third of the infections worldwide, this subtype differs genetically from HIV-1 subtype B on which the majority of studies have been done. The objective of this study was to assess whether newly identified, never-treated, HIV-1-infected South African participants showed signs of endothelial dysfunction, accelerated atherosclerosis and increased blood coagulation. We compared 300 newly diagnosed (never antiretroviral-treated) HIV-infected participants to 300 age-, gender-, body mass index- and locality-matched uninfected controls. Levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, interleukin-6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), fibrinogen and plasminogen activator inhibitor-1 (PAI-1), and carotid radialis pulse wave velocity (cr-PWV) were determined. The HIV-infected participants showed lower HDL-C and higher IL-6, CRP, ICAM-1 and VCAM-1 levels compared to the uninfected controls. No differences in fibrinogen and PAI-1 levels were detected. A continuous positive trend of increasing age with cr-PWV was detected in the HIV-infected group. Our findings suggest inflammatory injury of the endothelium, pointing to endothelial dysfunction of never-treated HIV-1-infected South Africans of African ancestry. Although no indication of a prothrombotic state could be detected, there was an indication of accelerated vascular aging and probable early atherosclerosis in the older HIV-infected participants.

Perceived Barriers and Support Strategies for Reducing Sodium Intake in Patients with Chronic Kidney Disease: a Qualitative Study

BackgroundReducing sodium intake can prevent cardiovascular complications and further decline of kidney function in patients with chronic kidney disease. However, the vast majority of patients fail to reach an adequate sodium intake, and little is known about why they do not succeed.PurposeThis study aims to identify perceived barriers and support strategies for reducing sodium intake among both patients with chronic kidney disease and health-care professionals.MethodA purposive sample of 25 patients and 23 health-care professionals from 4 Dutch medical centers attended 8 focus groups. Transcripts were analyzed thematically and afterwards organized according to the phases of behavior change of self-regulation theory.ResultsMultiple themes emerged across different phases of behavior change, including the patients’ lack of practical knowledge and intrinsic motivation, the maladaptive illness perceptions and refusal skills, the lack of social support and feedback regarding disease progression and sodium intake, and the availability of low-sodium foods.ConclusionsThe results indicate the need for the implementation of support strategies that target specific needs of patients across the whole process of changing and maintaining a low-sodium diet. Special attention should be paid to supporting patients to set sodium-related goals, strengthening intrinsic motivation, providing comprehensive and practical information (e.g., about hidden salt in products), increasing social support, stimulating the self-monitoring of sodium intake and disease progression, and building a supportive patient–professional relationship that encompasses shared decision making and coaching. Moreover, global programs should be implemented to reduce sodium levels in processed foods, introduce sodium-related product labels, and increase consumer awareness.

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

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.

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 ratios 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.

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.

Association of Ethnicity and Survival in Peritoneal Dialysis: A Cohort Study of Incident Patients in Brazil

BACKGROUND There are no available epidemiologic studies about the impact of ethnicity on outcomes of patients treated with peritoneal dialysis (PD) in South America. This study aims to assess the effect of ethnicity on the mortality of incident PD patients in Brazil. STUDY DESIGN Prospective observational cohort study of incident patients treated with PD. SETTINGS & PARTICIPANTS Patients 18 years or older who started PD therapy between December 2004 and October 2007 in 114 Brazilian dialysis centers. PREDICTORS Self-reported ethnicity defined by the Brazilian Institute of Geography and Statistics as black and brown versus white patients and baseline demographic, socioeconomic, clinical, and laboratory data were collected at baseline. OUTCOME Mortality, using cumulative mortality curves in which kidney transplantation and transfer to hemodialysis therapy were treated as competing end points. Multivariate Cox proportional hazards analysis was used to adjust for gradually more potential explanatory variables, censored for kidney transplantation and transfer to hemodialysis therapy. Analyses were performed for all patients, as well as stratified for elderly (aged ≥65 years) and nonelderly patients. RESULTS 1,370 patients were white, 516 were brown, and 273 were black. The competing-risk model showed higher mortality in white patients compared with black and brown patients. With white patients as the reference, Cox proportional hazards analysis showed a crude HR for mortality of 0.77 (95% CI, 0.56-1.05) for black and 0.74 (95% CI, 0.59-0.94) for brown patients. After adjusting for potential explanatory factors, HRs were 0.67 (95% CI, 0.48-0.95) and 0.77 (95% CI, 0.43-1.01), respectively. The same results were observed in elderly and nonelderly patients. LIMITATIONS Ethnicity was self-determined and some misclassification might have occurred. CONCLUSIONS Black and brown Brazilian incident PD patients have a lower mortality risk compared with white patients.

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.

The association between dialysis modality and the risk for dialysis technique and non-dialysis technique-related infections

BACKGROUND Infections are a major cause of morbidity and mortality among dialysis patients. Dialysis modality has been hypothesized to be a potential immunomodulatory factor. The objective of this study was to determine the influence of the first dialysis modality on the risk for infections on dialysis. METHODS Our study was conducted utilizing the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) cohort of incident dialysis patients. Medical records of all patients from two tertiary care university hospitals and three regional hospitals were reviewed using pre-specified criteria. Information about infections was collected from the start of dialysis until death, modality switch, study withdrawal, kidney transplantation or at the end of the study. Age-standardized incidence rates for infections were calculated. Poisson regression analysis was used to calculate adjusted incidence rate ratios (IRRs). RESULTS In total, 452 patients, of whom 285 started with haemodialysis (HD) and 167 with peritoneal dialysis (PD), were included. The median follow-up time on the first dialysis modality was similar for HD and PD, 1.8 and 2.0 dialysis years, respectively. During the first 6 months, the age-standardized infection incidence rate was higher on HD compared with PD patients (P = 0.02). Overall, PD patients had a higher infection risk [adjusted IRR: 1.65, 95% confidence interval (CI): 1.34-2.03], which could be attributed to a 4-fold increased risk for dialysis technique-related infections. The risk for non-dialysis technique-related infections was lower in PD patients (adjusted IRR: 0.56, 95% CI: 0.40-0.79). CONCLUSIONS Overall, PD patients carry a higher risk for infections. Interestingly, the risk for non-dialysis technique-related infections was higher in HD patients. The links between dialysis modality and the immune system are expected to explain this difference, but future studies are needed to test these assumptions.

In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.