Zsófia K. Németh

Serum 25(OH)-Cholecalciferol Concentration Is Associated with Hemoglobin Level and Erythropoietin Resistance in Patients on Maintenance Hemodialysis

Background: Resistance to erythropoiesis-stimulating agents (ESAs) has been observed in patients with chronic kidney disease (CKD) and it is associated with clinical outcomes. The presence of ESA resistance cannot always be explained by the known risk factors of the condition, suggesting that additional factors may be involved. We wanted to test the hypothesis that vitamin D insufficiency is associated with lower hemoglobin (Hb) and ESA resistance in patients on maintenance hemodialysis (HD). Methods: Data from patients receiving maintenance HD in a single dialysis center were extracted from the medical records in a retrospective chart review. Basic patient characteristics and laboratory data including Hb, serum albumin, intact parathyroid hormone and serum 25(OH)-cholecalciferol (25(OH)D3) levels were collected. ESA dose and Kt/V were extracted from the dialysis charts. Correlation analysis and multivariate linear regression analysis were used to reveal potential independent associations between clinical and laboratory parameters and ESA resistance. Results: Data from 142 patients were analyzed. Serum 25(OH)D3 concentration was significantly correlated with Hb (ρ = 0.186, p < 0.05) and also with ESA dose/Hb index (ρ = 0.230, p < 0.01). In multivariable regression analyses, serum 25(OH)D3 concentration remained significantly associated with both Hb and ESA dose/Hb index after controlling for potentially important confounders. Conclusion: Serum 25(OH)D3 concentration is independently associated with erythropoietin responsiveness in CKD patients on maintenance HD. If this association will be confirmed, treatment trials looking at the effect of vitamin D supplementation on anemia treatment in CKD patients may be warranted.

Serum osteoprotegerin level, carotid-femoral pulse wave velocity and cardiovascular survival in haemodialysis patients

BACKGROUND Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in haemodialysis patients. The link between OPG and aortic stiffening--a consequence of arterial calcification--has not been previously evaluated in this population, and it is not known whether OPG-related mortality risk is mediated by arterial stiffening. METHODS At baseline, OPG and aortic pulse wave velocity (PWV) were measured in 98 chronic haemodialysis patients who were followed for a median of 24 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related cardiovascular mortality was evaluated by including both OPG and PWV in the same survival model. RESULTS At baseline mean (standard deviation) PWV was 11.2 (3.3) m/s and median OPG (interquartile range) was 11.1 (7.5-15.9) pmol/L. There was a strong, positive, linear relationship between PWV and lnOPG (P = 0.009, model R(2) = 0.540) independent of covariates. During follow-up 23 patients died of cardiovascular causes. In separate univariate survival models both PWV and lnOPG were related to cardiovascular mortality [hazard ratios 1.31 (1.14-1.50) and 8.96 (3.07-26.16), respectively]. When both PWV and lnOPG were entered into the same model, only lnOPG remained significantly associated with cardiovascular mortality [hazard ratio 1.11 (0.93-1.33) and 7.18 (1.89-27.25), respectively). CONCLUSION In haemodialysis patients OPG is strongly related to PWV and OPG related cardiovascular mortality risk is, in part, mediated by increased PWV.

Evaluation of the Tensioday ambulatory blood pressure monitor according to the protocols of the British Hypertension Society and the Association for the Advancement of Medical Instrumentation.

BackgroundThe validation of ambulatory blood pressure monitoring devices is necessary to obtain information on their accuracy. The objective of the present study was to evaluate the accuracy of the Tensioday oscillometric ambulatory blood pressure monitor according to the protocols of the British Hypertension Society and the Association for the Advancement of Medical Instrumentation (AAMI). DesignWe followed the phases recommended by the British Hypertension Society protocol: before-use calibration, in-use assessment, after-use calibration, static device validation and report of the evaluation. However, we expanded on the protocol to accommodate features required by the AAMI. MethodThe accuracy of calibration of three Tensioday devices was tested before and after the in-use phase when each of three devices was performing 10 24 h sessions of ambulatory monitoring. As all three devices passed these phases, the accuracy of blood pressure measurement was tested in one arbitrarily selected device on 85 subjects for systolic and 85 for diastolic blood pressure values. This was done by comparing three sequential same-arm blood pressure readings obtained by the device with three readings obtained by two observers using standard mercury sphygmomanometer. The comparisons were carried out while resting in the seated, supine and standing positions for all subjects. The results were used to grade the performance of the device according to the British Hypertension Society protocol and to calculate the mean ± standard deviation of the difference between the device and the observers, as required by the AAMI. ResultsThe Tensioday device achieved an overall grade of A for both the systolic and diastolic measurements, and had a mean difference compared with the observer-measured blood pressure of 1.4 ± 5.3/1.0 ± 4.7 mmHg, which satisfies the AAMI criteria for accuracy. The British Hypertension Society grading did not change when patients with low, medium, and high blood pressure were analysed separately. The AAMI accuracy criteria were fulfilled in the standing and lying positions as well. ConclusionOn the basis of these results, the Tensioday ambulatory blood pressure monitoring device can be recommended for clinical use for ambulatory monitoring. The accuracy of the device needs, however, further testing in special situations, such as in pregnancy, in elderly patients and during exercise.

The Method of Distance Measurement and Torso Length Influences the Relationship of Pulse Wave Velocity to Cardiovascular Mortality

BACKGROUND The method of estimating distance traveled by the pulse wave, used in the calculation of pulse wave velocity (PWV), is not standardized. Our objective was to assess whether different methods of distance measurement influenced the association of PWV to cardiovascular mortality in hemodialysis (HD) patients. METHODS Ninety-eight chronic HD patients had their PWV measured using three methods for distance estimation; PWV1: suprasternal notch-to-femoral site minus suprasternal notch-to-carotid site, PWV2: carotid-to-femoral site, PWV3: carotid-to-femoral site minus suprasternal notch-to-carotid site. Carotid-to-femoral distance was used to approximate torso length. Patients were followed for a median of 30 months and the association of PWV and cardiovascular mortality was assessed using survival analysis before and after stratification for torso length. RESULTS The three methods resulted in significantly different PWV values. During follow-up 50 patients died, 32 of cardiovascular causes. In log-rank tests, only tertiles of PWV1 was significantly related to outcome (P values 0.017, 0.257, 0.137, for PWV1, PWV2, and PWV3, respectively). In adjusted Cox, proportional hazards regression only PWV1 was related to cardiovascular mortality. In stratified analysis, however, among patients with below median torso length all PWV values were related to outcome, whereas in patients with above median torso length none of the PWV methods resulted in significant relationship to outcome. CONCLUSIONS PWV calculated using suprasternal notch-to-femoral distance minus suprasternal notch-to-carotid distance provides the strongest relationship to cardiovascular mortality. Longer torso weakens the predictive value of PWV, possibly due to more tortuosity of the aorta hence, more error introduced when using surface tape measurements.

Bone mineral density in patients on maintenance dialysis

Disorders of bone and mineral metabolism affect almost all patients with advanced chronic kidney disease (CKD). High prevalence of decreased bone mineral density has been reported in this population; however, the role and diagnostic utility of bone density measurements are not well established. The incidence of bone fractures is high in patients with ESRD, but the association between fractures and bone density is not obvious. A recent meta-analysis suggested that decreased density at the radius might be associated with higher overall fracture risk. Changes in bone mineral density reflect several underlying pathological processes, such as vitamin D deficiency, estrogen deficiency and changes in bone turnover. The response of bone to these factors and processes is not uniform: it can vary in different compartments of the same bone or in different bones of the skeleton. Therefore, it is important to differentiate between the various types of bone. This may be possible by proper selection of the measurement site or using methods such as quantitative bone computed tomography. Previous studies used different methods and measured bone mineral density at diverse sites of the skeleton, which makes the comparison of their results very difficult. The association between changes in bone mineral metabolism and cardiovascular mortality is well known in ESRD patients. Studies also suggest that low bone density itself might be an indicator for high risk of cardiovascular events and poor overall outcome in this population. Some of the risk factors of low bone mineral density, such as vitamin D or estrogen deficiency, are potentially modifiable. Further studies are needed to elucidate if interventions modifying these risk factors will have an impact on clinical outcomes. In this review, we discuss the options for and problems of assessment of bone density and summarize the literature about factors associated with low bone density and its link to clinical outcomes in patients on maintenance dialysis.

Sociodemographic factors and patient perceptions are associated with attitudes to kidney transplantation among haemodialysis patients

BACKGROUND Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude. METHODS In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript. RESULTS Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to increasing age, with unwillingness to consider transplantation. CONCLUSIONS Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions.

Arterial Stiffness in Hemodialysis: Which Parameter to Measure to Predict Cardiovascular Mortality?

In previous studies, different parameters of arterial stiffness were related to cardiovascular mortality in hemodialysis patients, but their relative prognostic value has not previously been evaluated in 1 cohort. Carotid-femoral pulse wave velocity (PWV), the carotid augmentation index, carotid pulse pressure (CPP) and carotid-brachial pulse pressure amplification (AMP) were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1–34) and the association of these parameters with cardiovascular mortality were assessed using log-rank tests and Cox proportional hazards regressions. During follow-up, 25 patients died of cardiovascular causes. Increasing pre- and postdialysis PWV tertiles and decreasing predialysis AMP tertiles were significantly related to cardiovascular mortality (p = 0.012 and 0.011 for PWV, respectively; < 0.001 for AMP). Neither the carotid augmentation index nor carotid pulse pressure were related to cardiovascular mortality. The adjusted hazard ratios for 1 m/s higher pre- and postdialysis PWV were 1.24 (1.07–1.44) and 1.17 (1.06–1.28), respectively. The hazard ratio for 10% lower predialysis AMP was 1.41 (1.03–1.92). When included in the same model, both predialysis PWV and AMP remained significantly associated with cardiovascular mortality. Among different stiffness parameters, PWV is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis AMP seems to provide additional prognostic information.

Serum osteoprotegerin is associated with pulse pressure in kidney transplant recipients

Pulse pressure (PP) reflects increased large artery stiffness, which is caused, in part, by arterial calcification in patients with chronic kidney disease. PP has been shown to predict both cardiovascular and cerebrovascular events in various patient populations, including kidney transplant (KTX) recipients. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in hemodialysis patients. Here we tested the hypothesis that OPG is associated with increased pulse pressure. We cross-sectionally analyzed the association between serum OPG and PP in a prevalent cohort of 969 KTX patients (mean age: 51 +/− 13 years, 57% male, 21% diabetics, mean eGFR 51 +/− 20 ml/min/1.73 m2). Independent associations were tested in a linear regression model adjusted for multiple covariables. PP was positively correlated with serum OPG (rho = 0.284, p < 0.001). Additionally, a positive correlation was seen between PP versus age (r = 0.358, p < 0.001), the Charlson Comorbidity Index (r = 0.232, p < 0.001), serum glucose (r = 0.172, p < 0.001), BMI (r = 0.133, p = 0.001) and serum cholesterol (r = 0.094, p = 0.003). PP was negatively correlated with serum Ca, albumin and eGFR. The association between PP and OPG remained significant after adjusting for multiple potentially relevant covariables (beta = 0.143, p < 0.001). We conclude that serum OPG is independently associated with pulse pressure in kidney transplant recipients.

The role of laser Doppler flowmetry tests, serum angiopoietin-2, asymmetric and symmetric dimethylarginine to predict outcome in chronic kidney disease.

Objective: The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients. Methods: Postocclusive reactive hyperemia area (PORHHA), acetylcholine and sodium nitroprusside-mediated flow changes were estimated by laser Doppler flowmetry, and Ang-2, asymmetric and symmetric dimethylarginin were assessed in 105 CKD patients at baseline. Multiple failure time Cox-regression analyses with backward elimination were performed to determine the predictors of the combined endpoint of cardiovascular mortality and cardiovascular events or all-cause mortality and cardiovascular events during a median of 66.6 (interquartile range 39.8–80.4) months of follow-up. Results: In univariate models lnAng-2 and lnPORHHA both predicted the cardiovascular outcome besides age, diabetes, baseline cardiovascular disease, brachial pulse pressure and log C-reactive protein. In multivariate analysis lnPORHHA [hazard ratio: 0.66 (95% confidence interval: 0.49–0.89) per ln(mU s)], age [1.03 (1.01–1.06) per year], log C-reactive protein [1.31 (1.06–1.64) per ln(mg/l)] and diabetes [3.33 (1.70–6.53)] remained significant predictors of the cardiovascular outcome, whereas lnAng-2 did not enter the model. Neither of the microvascular variables were an independent predictor of all-cause mortality and cardiovascular events. Conclusion: Among the functional and biochemical microvascular parameters PORHHA seems to improve cardiovascular risk assessment in CKD. Nevertheless the robustness of traditional risk factors seems to outweigh the role of microvascular biomarkers on all-cause mortality and cardiovascular events at this time.