Menso Nubé - Academia.edu (original) (raw)
Papers by Menso Nubé
Nephrology Dialysis Transplantation, Jun 26, 2009
Background. Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage... more Background. Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Platelet (PLT) dysfunction, which is a wellknown phenomenon in advanced chronic renal failure, corresponds positively with CVD in these patients. The accumulation of retained uraemic toxins might play an important role in this respect. During haemodialysis (HD), both an increase in the expression of the platelet (PLT) cell surface molecule P-selectin (CD62p) and the release of intra-granular substances, such as platelet factor 4 (PF4) and ß-thromboglobulin (BTG), have been described. As the removal of uraemic toxins is superior during haemodiafiltration (HDF), this form of treatment may have quite another impact on PLTs than HD. Methods. Nineteen chronic HD patients who were treated with low-flux HD for at least 2 months were included in the Dutch CONvective TRAnsport STudy (CONTRAST). After randomization, 10 patients continued low-flux HD and 9 patients switched to post-dilution HDF. The present study describes various parameters of PLT activation and degranulation at baseline (during HD) and after 3 months (during HDF) in the latter group of patients. At both time points, multiple blood samples were drawn. During the first 30 min of treatment, differences over the extracorporeal circuit (ECC) were calculated by taking samples from both afferent (arterial) and efferent (venous) lines. Correlations between various parameters were calculated in the total group of patients after 3 months. Results. Immediately after the start of HD, PLT counts dropped over the ECC. During HDF, PLT counts decreased even more and reached a nadir at t30. CD62p expression increased early during HD and returned to baseline thereafter. During HDF, these changes were more pronounced and more protracted. With respect to degranulation, rather dissimilar results were obtained. During HD, both PF4 and BTG increased over time, whereas during HDF, PF4 increased but BTG did not change. Haemoconcentration and transmembrane pressure (TMP) within the dialyser were, respectively, ∼10 and 3× higher during HDF than during HD. There was a striking correlation between the changes in haemoconcentration and the changes in both PLT counts and CD62p over the ECC. Summary and Conclusions. PLT activation, as measured by the expression of CD62p, was more pronounced and more protracted during HDF than during HD. During HDF, PLTs were trapped abundantly within the ECC, not only after first passage, but also thereafter. The degranulation product BTG increased during HD, but did not change during HDF. These observations may well be explained by the greater haemoconcentration and/or higher TMP during HDF on the one hand, and superior convective transport at the other. Whether the potential harmful effects of enhanced PLT activation are counterbalanced by the beneficial effects of an increased convective transport of degranulation products remains to be established.
Clinical Effect of Different Albumin Assays on Calcium and Phosphate Management in Chronic Hemodialysis Patients
Nephrology Dialysis Transplantation, May 1, 2013
Clinical Trials on Hemodiafiltration
In the present chapter, several clinical hemodiafiltration (HDF) studies are discussed, with spec... more In the present chapter, several clinical hemodiafiltration (HDF) studies are discussed, with special emphasis on the reliability of the methodology used. These studies differ widely in design, end points, patient numbers, treatment and comparator groups, and amount of convection volume in the treatment arms. Recently, three large randomized controlled trials (RCT) have been performed comparing survival between online postdilution HDF and hemodialysis (HD). While neither CONTRAST nor the Turkish HDF study showed differences between study arms, in the Spanish ESHOL study the mortality risk was significantly lower in HDF patients (HR 0.70; 95 % CI 0.53–0.92). In all three studies, post-hoc (on-treatment) analysis showed a survival benefit up to 40 % for patients treated with high-volume HDF (convection volume >20–22 L/treatment). Apart from these RCTs, in the last 4 years five meta-analyses on convective therapies have been performed, including four on aggregated study results and one on pooled individual patient data (IPD). Since in the latter approach all individual patient data from trials are ascertained, put together and combined to a new data base, this type of meta-analysis is most reliable for making adjustments and evaluating subgroup results. Notably, in both types of meta-analyses the hazard ratio (HR) for mortality of online HDF (as compared to HD) was about 0.83–0.86, indicating a 15 % lower mortality risk for patients treated with HDF. From the IPD meta-analysis it appeared that the mortality risk was even lower when high convection volumes are applied (HR 0.78; 95 % CI 0.62–0.98). Finally, meta-analysis on modern convective therapies should include only online treatments with a convection volume >20 L/session.
Nephrology Dialysis Transplantation, Oct 26, 2004
Erythropoiesis activity, iron availability and reticulocyte hemoglobinization during treatment with hemodialysis and in subjects with uremia
PubMed, 2006
In hemodialysis subjects correction of anemia is facilitated by combined supplementation of intra... more In hemodialysis subjects correction of anemia is facilitated by combined supplementation of intravenous iron and recombinant human erythropoietin. Reticulocyte hemoglobin content (RET-He) is considered to be an actual indicator reflecting functional iron availability for erythropoiesis. In the present study, interdependence between biochemical analytes reflecting iron status and hemocytometric parameters indicating the degree of hemoglobinization of reticulocytes and red blood cells, respectively, is established. Participants of the study were reference subjects (n=75), subjects with iron deficiency anemia (n=52), subjects with uremia (n=19) and subjects undergoing hemodialysis treatment (n=43). If compared with the reference subjects the results for RBC counts and MCHC are statistically significantly decreased in case of subjects with hemodialysis and uremia, whereas increased results are established with regard to RDW-sd values. Significantly increased results for absolute reticulocyte counts and immature reticulocyte fractions (IRF) are also observed in case of subjects with hemodialysis and uremia. Slightly increased values for the ZPP/heme ratio in combination with elevated reticulocyte count reflect increased activity of erythropoiesis. At a definite MCV value, decreased levels for the hemoglobin content of reticulocytes (RET-He) and hemoglobin content of red blood cells (RBC-He) are observed in case of subjects treated with hemodialysis and in subjects with uremia if compared with identical MCV values of the group of reference subjects. For the ratio of RET-He and RBC-He obviously decreased results are demonstrated in case of subjects with iron deficiency anemia (1.02 +/- 0.08, mean +/- SD), hemodialysis (1.05 +/- 0.05) and uremia (1.02 +/- 0.10) if compared with the group of reference subjects (1.11 +/- 0.02). From the combined interpretation of the MCV values within the reference range and decreased values for RET-He and RET-He/RBC-He ratios, respectively, a decreased degree of hemoglobinization is concluded in the case of subjects with hemodialysis or uremia. The conclusion implicating the presumption of reduced functional availability of iron for hemoglobin synthesis is supported by the detection of increased results for sTfR concentrations and ZPP/heme ratios.
Why Is High Volume Online Post-dilution Hemodiafiltration Associated with Improved Survival?
Springer eBooks, Nov 6, 2015
Retention of middle molecular weight (MMW) uremic toxins has been related to mortality in patient... more Retention of middle molecular weight (MMW) uremic toxins has been related to mortality in patients with end-stage kidney disease (ESKD). Therefore, interest has shifted from pure diffusive dialysis techniques, such as low-flux hemodialysis (HD), which remove only small water solutes, towards convective therapies, such as hemodiafiltration (HDF), which remove larger compounds as well. Controversy exists, however, as to whether the positive effect of HDF on MMW solutes translates in a superior clinical outcome. Here, we describe the results of three recent large randomized controlled trials (RCT), comparing online post-dilution HDF with HD, and four systematic reviews on convective therapy, and discuss the discrepancies between these studies. Actually, it appears that the concept of ‘convective therapy’ is confusing, as it is not strictly defined and differently interpreted. When convection volumes >21 L/session are applied, especially cardiovascular (CV) mortality is markedly reduced, while the incidence non-CV death due to infections or malignancies, remains unaltered. Echocardiographic analysis suggests that left ventricular (LV) function and structure worsen in HD and remain stable in HDF. Moreover, intradialytic hemodynamic stability appears better preserved during HDF. Currently, there is no convincing evidence that HDF lowers CV mortality by improvements in inflammation, nutrition, CKD-mineral and bone disease, dyslipidemia and anemia control.
Poor Compliance with Guidelines on Anemia Treatment in a Cohort of Chronic Hemodialysis Patients
Blood Purification, 2012
Background/Aims: Guidelines for the management of anemia and iron deficiency in chronic hemodialy... more Background/Aims: Guidelines for the management of anemia and iron deficiency in chronic hemodialysis (HD) patients have been developed to standardize therapy and improve clinical outcome. The present study evaluated compliance with anemia guidelines and investigated whether differences between centers were present. Methods: Data on anemia management from patients in the baseline cohort of the CONTRAST study (NCT00205556) were analyzed. 598 chronic HD patients (62% male, age 63.6 ± 14.0 years) from 26 Dutch dialysis centers were included. Results: Mean hemoglobin (Hb) level was 11.9 ± 1.3 g/dl and Hb was ≥11.0 g/dl in 81% of the patients. Compliance with all anemia targets (Hb 11.0–12.0 g/dl, transferrin saturation ratio ≥20%, ferritin 100–500 ng/ml) was reached in 11.6% (95% CI 7.8–17.0) of the patients, with a wide range among centers (4–26%, adjusted for case mix, treatment-related factors and center-specific characteristics). Conclusion: Compliance with anemia targets in stable HD patients was poor and showed a wide variation between treatment facilities.
Ndt Plus, Apr 1, 2020
Background. Previous studies in patients on haemodialysis (HD) have shown an association of fibro... more Background. Previous studies in patients on haemodialysis (HD) have shown an association of fibroblast growth factor 23 (FGF23) with all-cause mortality. As of yet, the result of FGF23 lowering on mortality is unknown in this population. Methods. FGF23 was measured in a subset of 404 patients from the Dutch CONvective TRansport STudy (CONTRAST study) [a randomized trial in prevalent dialysis patients comparing HD and haemodiafiltration (HDF) with clinical outcome] at baseline and Months 6 and 12. A substantial decline of FGF23 change over time was anticipated in patients randomized to HDF since HDF induces higher dialytic clearance of FGF23. The associations of both baseline FGF23 and 6-months change in FGF23 with all-cause mortality were analysed. In addition, the difference in FGF23 change between HD and HDF was explored. Furthermore, the role of dialysis modality in the association between FGF23 change and outcome was analysed. Results. No association was observed between quartiles of baseline FGF23 and all-cause mortality. Over 6 months, FGF23 declined in patients on HDF, whereas FGF23 remained stable in patients on HD. A decrease in FGF23 was not associated with improved survival compared with a stable FGF23 concentration. However, increasing FGF23 was associated with a significantly higher mortality risk, both in crude and fully adjusted models [hazard ratio 2.01 (95% confidence interval 1.30-3.09)]. Conclusion. Whereas no association between a single value of FGF23 and all-cause mortality was found, increasing FGF23 concentrations did identify patients at risk for mortality. Since lowering FGF23 did not improve outcome, this study found no argument for therapeutically lowering FGF23.
Influence of erythropoietin treatment on urea kinetic parameters in hemodialysis patients
PubMed, Apr 1, 1991
Urea kinetic parameters were studied by means of dialysate collection in 8 stable hemodialysis pa... more Urea kinetic parameters were studied by means of dialysate collection in 8 stable hemodialysis patients before and after treatment with recombinant human erythropoietin (r-HuEPO), in order to investigate the impact of a rising hematocrit (Ht) on dialyzer performance and nutritional status. After 6 months, the average in vivo dialyzer urea clearance had fallen from 152 to 132 ml/min and consequently Kt/V values had become undesirably low in most of the patients in whom the relatively short dialysis regimens had been kept unchanged. There was also a significant decrease of protein intake. As a result of both changes there was only a moderate increase of predialysis mean blood urea concentration. These findings indicate that after correction of anemia by r-HuEPO dialyzer performance decreased. The concomitant decrease of protein intake seems to contrast to the improved general physical condition and appetite as indicated in the questionnaires. Although body weight remained the same, there might have been a tendency to avoid protein consumption with maintained total calory intake as a result of slight underdialysis. Therefore, in individual cases dialysis prescriptions may need reconsideration when Ht levels rise after r-HuEPO administration, especially in short dialysis regimens.
American Journal of Kidney Diseases, Nov 1, 2014
Nephrology Dialysis Transplantation, Mar 1, 2002
Our knowledge of erythropoiesis and iron in renal disease is limited. The accepted view of the co... more Our knowledge of erythropoiesis and iron in renal disease is limited. The accepted view of the control of erythropoiesis was founded on observations made in a variety of disorders, but the control mechanism in healthy individuals may not be quite the same. Evidence suggests that mechanisms other than erythropoietic stimulation may play a role in increased red blood cell production. Measuring erythropoiesis is complex. The quantitative reticulocyte count is probably the closest practical assessment of erythropoietic activity we can achieve, yet there is very little correlation between circulating erythropoietin level and reticulocyte count in normal and near normal subjects. Oxygen transport in humans depends entirely upon iron. In renal disease, the failure of the erythropoietin positive feedback mechanism can be readily and directly remedied; recombinant human erythropoietin therapy can replace the missing erythropoietin, but this will be negated if iron supply to the erythroid marrow falls short of demand. Measurement of iron stores is also complex. The use of serum ferritin concentration as a direct quantitative estimate of iron in the stores is not advisable, and in practice we have not found the transferrin receptor assay to be useful in identifying patients who require iron therapy. Use of percentage hypochromia as a measure of iron deficiency is complicated by the fact that hypochromic cells are not exclusively a consequence of functional iron deficiency. There are clearly lessons still to be learned in this field and there is much that we do not yet understand about the control of erythropoiesis and iron metabolism in humans.
Tissue Antigens, Dec 11, 2008
Twenty non-transfused dialysis patients received a small number of HLA-A and-B matched pre-transp... more Twenty non-transfused dialysis patients received a small number of HLA-A and-B matched pre-transplant leukocyte-poor blood transfusions. Currently, in 10 of these patients transplanted with a cadaveric kidney, graft survival at 3 months is
[Proatherogenic changes induced by hemodialysis; probably a result of bio-incompatibility]
PubMed, Dec 30, 2000
Chronic haemodialysis patients have a disproportionately high risk for developing cardiovascular ... more Chronic haemodialysis patients have a disproportionately high risk for developing cardiovascular disease, which can only in part be explained by known risk factors such as dyslipidaemia, hypertension, hyperhomocysteinemia, diabetes mellitus and chronic volume expansion. A possible cause is that the haemodialysis treatment itself contributes to the accelerated atherosclerosis, observed in these patients. Nowadays, atherosclerosis is considered an inflammatory process, mediated by a dysfunction of the vascular endothelium. As a result, blood cells adhere to the vascular surface and release a variety of vasoactive mediators, cytokines, growth factors and free radicals. Due to the contact between blood and dialyzer, humoral systems and cellular elements are stimulated, and this may be viewed as an inflammatory reaction. As a consequence of this, the vascular surface of haemodialysis patients is repeatedly exposed to the influences of cytokines, coagulation products, vasoactive mediators, stimulated leukocytes and thrombocytes, and oxidative stress. It is therefore conceivable that the haemodialysis treatment itself enhances the greatly increased cardiovascular risk in chronic haemodialysis patients.
Reappraisal of Hemodiafiltration for Managing Uremic Complications
Clinical Journal of The American Society of Nephrology, Sep 1, 2021
![Research paper thumbnail of Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]](https://attachments.academia-assets.com/118426116/thumbnails/1.jpg)
](Current Controlled Trials in Cardiovascular Medicine, May 20, 2005
Background: The high incidence of cardiovascular disease in patients with end stage renal disease... more Background: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. Methods: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and lowflux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. Conclusion: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD.
Blood Purification, 2007
11.1, 2.64 vs. 4.01, and 5.61 vs. 9.74, respectively). Conclusion: Dialysis with a polysulfone me... more 11.1, 2.64 vs. 4.01, and 5.61 vs. 9.74, respectively). Conclusion: Dialysis with a polysulfone membrane seems to lead to more platelet activation than dialysis with a cuprammonium membrane.
Nephrology Dialysis Transplantation, Oct 1, 2001
PLOS ONE, Nov 23, 2015
Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome,... more Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a posthoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77-94), the HR for cardiovascular mortality 0.73 (95% CI 0.62-0.85) and for sudden death 0.76 (95% CI 0.62-0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ-0.011 mmol/L/year, 95% CI-0.017 to-0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time.
Nephrology Dialysis Transplantation, Jun 23, 2016
Background: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may ... more Background: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated. Methods: In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl. Results: The mean (6standard deviation) age of 396 test subjects was 63.6 (613.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P ¼ 0.01)]. Stratified models showed a stable sScl in patients treated with HD (D þ2.9 pmol/L/year, 95% CI À0.5 to þ6.3, P ¼ 0.09) and a decreasing concentration in those treated with HDF (D À4.5 pmol/L/year, 95% CI À8.0 to À0.9, P ¼ 0.02). The relative change in the latter group was related to the magnitude of the convection volume. Conclusions: (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume.
MO663: No Translocation of Intact Intestinal Bacteria During Intermittent Dialysis Therapies
Nephrology Dialysis Transplantation, May 1, 2022
Nephrology Dialysis Transplantation, Jun 26, 2009
Background. Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage... more Background. Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Platelet (PLT) dysfunction, which is a wellknown phenomenon in advanced chronic renal failure, corresponds positively with CVD in these patients. The accumulation of retained uraemic toxins might play an important role in this respect. During haemodialysis (HD), both an increase in the expression of the platelet (PLT) cell surface molecule P-selectin (CD62p) and the release of intra-granular substances, such as platelet factor 4 (PF4) and ß-thromboglobulin (BTG), have been described. As the removal of uraemic toxins is superior during haemodiafiltration (HDF), this form of treatment may have quite another impact on PLTs than HD. Methods. Nineteen chronic HD patients who were treated with low-flux HD for at least 2 months were included in the Dutch CONvective TRAnsport STudy (CONTRAST). After randomization, 10 patients continued low-flux HD and 9 patients switched to post-dilution HDF. The present study describes various parameters of PLT activation and degranulation at baseline (during HD) and after 3 months (during HDF) in the latter group of patients. At both time points, multiple blood samples were drawn. During the first 30 min of treatment, differences over the extracorporeal circuit (ECC) were calculated by taking samples from both afferent (arterial) and efferent (venous) lines. Correlations between various parameters were calculated in the total group of patients after 3 months. Results. Immediately after the start of HD, PLT counts dropped over the ECC. During HDF, PLT counts decreased even more and reached a nadir at t30. CD62p expression increased early during HD and returned to baseline thereafter. During HDF, these changes were more pronounced and more protracted. With respect to degranulation, rather dissimilar results were obtained. During HD, both PF4 and BTG increased over time, whereas during HDF, PF4 increased but BTG did not change. Haemoconcentration and transmembrane pressure (TMP) within the dialyser were, respectively, ∼10 and 3× higher during HDF than during HD. There was a striking correlation between the changes in haemoconcentration and the changes in both PLT counts and CD62p over the ECC. Summary and Conclusions. PLT activation, as measured by the expression of CD62p, was more pronounced and more protracted during HDF than during HD. During HDF, PLTs were trapped abundantly within the ECC, not only after first passage, but also thereafter. The degranulation product BTG increased during HD, but did not change during HDF. These observations may well be explained by the greater haemoconcentration and/or higher TMP during HDF on the one hand, and superior convective transport at the other. Whether the potential harmful effects of enhanced PLT activation are counterbalanced by the beneficial effects of an increased convective transport of degranulation products remains to be established.
Clinical Effect of Different Albumin Assays on Calcium and Phosphate Management in Chronic Hemodialysis Patients
Nephrology Dialysis Transplantation, May 1, 2013
Clinical Trials on Hemodiafiltration
In the present chapter, several clinical hemodiafiltration (HDF) studies are discussed, with spec... more In the present chapter, several clinical hemodiafiltration (HDF) studies are discussed, with special emphasis on the reliability of the methodology used. These studies differ widely in design, end points, patient numbers, treatment and comparator groups, and amount of convection volume in the treatment arms. Recently, three large randomized controlled trials (RCT) have been performed comparing survival between online postdilution HDF and hemodialysis (HD). While neither CONTRAST nor the Turkish HDF study showed differences between study arms, in the Spanish ESHOL study the mortality risk was significantly lower in HDF patients (HR 0.70; 95 % CI 0.53–0.92). In all three studies, post-hoc (on-treatment) analysis showed a survival benefit up to 40 % for patients treated with high-volume HDF (convection volume >20–22 L/treatment). Apart from these RCTs, in the last 4 years five meta-analyses on convective therapies have been performed, including four on aggregated study results and one on pooled individual patient data (IPD). Since in the latter approach all individual patient data from trials are ascertained, put together and combined to a new data base, this type of meta-analysis is most reliable for making adjustments and evaluating subgroup results. Notably, in both types of meta-analyses the hazard ratio (HR) for mortality of online HDF (as compared to HD) was about 0.83–0.86, indicating a 15 % lower mortality risk for patients treated with HDF. From the IPD meta-analysis it appeared that the mortality risk was even lower when high convection volumes are applied (HR 0.78; 95 % CI 0.62–0.98). Finally, meta-analysis on modern convective therapies should include only online treatments with a convection volume >20 L/session.
Nephrology Dialysis Transplantation, Oct 26, 2004
Erythropoiesis activity, iron availability and reticulocyte hemoglobinization during treatment with hemodialysis and in subjects with uremia
PubMed, 2006
In hemodialysis subjects correction of anemia is facilitated by combined supplementation of intra... more In hemodialysis subjects correction of anemia is facilitated by combined supplementation of intravenous iron and recombinant human erythropoietin. Reticulocyte hemoglobin content (RET-He) is considered to be an actual indicator reflecting functional iron availability for erythropoiesis. In the present study, interdependence between biochemical analytes reflecting iron status and hemocytometric parameters indicating the degree of hemoglobinization of reticulocytes and red blood cells, respectively, is established. Participants of the study were reference subjects (n=75), subjects with iron deficiency anemia (n=52), subjects with uremia (n=19) and subjects undergoing hemodialysis treatment (n=43). If compared with the reference subjects the results for RBC counts and MCHC are statistically significantly decreased in case of subjects with hemodialysis and uremia, whereas increased results are established with regard to RDW-sd values. Significantly increased results for absolute reticulocyte counts and immature reticulocyte fractions (IRF) are also observed in case of subjects with hemodialysis and uremia. Slightly increased values for the ZPP/heme ratio in combination with elevated reticulocyte count reflect increased activity of erythropoiesis. At a definite MCV value, decreased levels for the hemoglobin content of reticulocytes (RET-He) and hemoglobin content of red blood cells (RBC-He) are observed in case of subjects treated with hemodialysis and in subjects with uremia if compared with identical MCV values of the group of reference subjects. For the ratio of RET-He and RBC-He obviously decreased results are demonstrated in case of subjects with iron deficiency anemia (1.02 +/- 0.08, mean +/- SD), hemodialysis (1.05 +/- 0.05) and uremia (1.02 +/- 0.10) if compared with the group of reference subjects (1.11 +/- 0.02). From the combined interpretation of the MCV values within the reference range and decreased values for RET-He and RET-He/RBC-He ratios, respectively, a decreased degree of hemoglobinization is concluded in the case of subjects with hemodialysis or uremia. The conclusion implicating the presumption of reduced functional availability of iron for hemoglobin synthesis is supported by the detection of increased results for sTfR concentrations and ZPP/heme ratios.
Why Is High Volume Online Post-dilution Hemodiafiltration Associated with Improved Survival?
Springer eBooks, Nov 6, 2015
Retention of middle molecular weight (MMW) uremic toxins has been related to mortality in patient... more Retention of middle molecular weight (MMW) uremic toxins has been related to mortality in patients with end-stage kidney disease (ESKD). Therefore, interest has shifted from pure diffusive dialysis techniques, such as low-flux hemodialysis (HD), which remove only small water solutes, towards convective therapies, such as hemodiafiltration (HDF), which remove larger compounds as well. Controversy exists, however, as to whether the positive effect of HDF on MMW solutes translates in a superior clinical outcome. Here, we describe the results of three recent large randomized controlled trials (RCT), comparing online post-dilution HDF with HD, and four systematic reviews on convective therapy, and discuss the discrepancies between these studies. Actually, it appears that the concept of ‘convective therapy’ is confusing, as it is not strictly defined and differently interpreted. When convection volumes >21 L/session are applied, especially cardiovascular (CV) mortality is markedly reduced, while the incidence non-CV death due to infections or malignancies, remains unaltered. Echocardiographic analysis suggests that left ventricular (LV) function and structure worsen in HD and remain stable in HDF. Moreover, intradialytic hemodynamic stability appears better preserved during HDF. Currently, there is no convincing evidence that HDF lowers CV mortality by improvements in inflammation, nutrition, CKD-mineral and bone disease, dyslipidemia and anemia control.
Poor Compliance with Guidelines on Anemia Treatment in a Cohort of Chronic Hemodialysis Patients
Blood Purification, 2012
Background/Aims: Guidelines for the management of anemia and iron deficiency in chronic hemodialy... more Background/Aims: Guidelines for the management of anemia and iron deficiency in chronic hemodialysis (HD) patients have been developed to standardize therapy and improve clinical outcome. The present study evaluated compliance with anemia guidelines and investigated whether differences between centers were present. Methods: Data on anemia management from patients in the baseline cohort of the CONTRAST study (NCT00205556) were analyzed. 598 chronic HD patients (62% male, age 63.6 ± 14.0 years) from 26 Dutch dialysis centers were included. Results: Mean hemoglobin (Hb) level was 11.9 ± 1.3 g/dl and Hb was ≥11.0 g/dl in 81% of the patients. Compliance with all anemia targets (Hb 11.0–12.0 g/dl, transferrin saturation ratio ≥20%, ferritin 100–500 ng/ml) was reached in 11.6% (95% CI 7.8–17.0) of the patients, with a wide range among centers (4–26%, adjusted for case mix, treatment-related factors and center-specific characteristics). Conclusion: Compliance with anemia targets in stable HD patients was poor and showed a wide variation between treatment facilities.
Ndt Plus, Apr 1, 2020
Background. Previous studies in patients on haemodialysis (HD) have shown an association of fibro... more Background. Previous studies in patients on haemodialysis (HD) have shown an association of fibroblast growth factor 23 (FGF23) with all-cause mortality. As of yet, the result of FGF23 lowering on mortality is unknown in this population. Methods. FGF23 was measured in a subset of 404 patients from the Dutch CONvective TRansport STudy (CONTRAST study) [a randomized trial in prevalent dialysis patients comparing HD and haemodiafiltration (HDF) with clinical outcome] at baseline and Months 6 and 12. A substantial decline of FGF23 change over time was anticipated in patients randomized to HDF since HDF induces higher dialytic clearance of FGF23. The associations of both baseline FGF23 and 6-months change in FGF23 with all-cause mortality were analysed. In addition, the difference in FGF23 change between HD and HDF was explored. Furthermore, the role of dialysis modality in the association between FGF23 change and outcome was analysed. Results. No association was observed between quartiles of baseline FGF23 and all-cause mortality. Over 6 months, FGF23 declined in patients on HDF, whereas FGF23 remained stable in patients on HD. A decrease in FGF23 was not associated with improved survival compared with a stable FGF23 concentration. However, increasing FGF23 was associated with a significantly higher mortality risk, both in crude and fully adjusted models [hazard ratio 2.01 (95% confidence interval 1.30-3.09)]. Conclusion. Whereas no association between a single value of FGF23 and all-cause mortality was found, increasing FGF23 concentrations did identify patients at risk for mortality. Since lowering FGF23 did not improve outcome, this study found no argument for therapeutically lowering FGF23.
Influence of erythropoietin treatment on urea kinetic parameters in hemodialysis patients
PubMed, Apr 1, 1991
Urea kinetic parameters were studied by means of dialysate collection in 8 stable hemodialysis pa... more Urea kinetic parameters were studied by means of dialysate collection in 8 stable hemodialysis patients before and after treatment with recombinant human erythropoietin (r-HuEPO), in order to investigate the impact of a rising hematocrit (Ht) on dialyzer performance and nutritional status. After 6 months, the average in vivo dialyzer urea clearance had fallen from 152 to 132 ml/min and consequently Kt/V values had become undesirably low in most of the patients in whom the relatively short dialysis regimens had been kept unchanged. There was also a significant decrease of protein intake. As a result of both changes there was only a moderate increase of predialysis mean blood urea concentration. These findings indicate that after correction of anemia by r-HuEPO dialyzer performance decreased. The concomitant decrease of protein intake seems to contrast to the improved general physical condition and appetite as indicated in the questionnaires. Although body weight remained the same, there might have been a tendency to avoid protein consumption with maintained total calory intake as a result of slight underdialysis. Therefore, in individual cases dialysis prescriptions may need reconsideration when Ht levels rise after r-HuEPO administration, especially in short dialysis regimens.
American Journal of Kidney Diseases, Nov 1, 2014
Nephrology Dialysis Transplantation, Mar 1, 2002
Our knowledge of erythropoiesis and iron in renal disease is limited. The accepted view of the co... more Our knowledge of erythropoiesis and iron in renal disease is limited. The accepted view of the control of erythropoiesis was founded on observations made in a variety of disorders, but the control mechanism in healthy individuals may not be quite the same. Evidence suggests that mechanisms other than erythropoietic stimulation may play a role in increased red blood cell production. Measuring erythropoiesis is complex. The quantitative reticulocyte count is probably the closest practical assessment of erythropoietic activity we can achieve, yet there is very little correlation between circulating erythropoietin level and reticulocyte count in normal and near normal subjects. Oxygen transport in humans depends entirely upon iron. In renal disease, the failure of the erythropoietin positive feedback mechanism can be readily and directly remedied; recombinant human erythropoietin therapy can replace the missing erythropoietin, but this will be negated if iron supply to the erythroid marrow falls short of demand. Measurement of iron stores is also complex. The use of serum ferritin concentration as a direct quantitative estimate of iron in the stores is not advisable, and in practice we have not found the transferrin receptor assay to be useful in identifying patients who require iron therapy. Use of percentage hypochromia as a measure of iron deficiency is complicated by the fact that hypochromic cells are not exclusively a consequence of functional iron deficiency. There are clearly lessons still to be learned in this field and there is much that we do not yet understand about the control of erythropoiesis and iron metabolism in humans.
Tissue Antigens, Dec 11, 2008
Twenty non-transfused dialysis patients received a small number of HLA-A and-B matched pre-transp... more Twenty non-transfused dialysis patients received a small number of HLA-A and-B matched pre-transplant leukocyte-poor blood transfusions. Currently, in 10 of these patients transplanted with a cadaveric kidney, graft survival at 3 months is
[Proatherogenic changes induced by hemodialysis; probably a result of bio-incompatibility]
PubMed, Dec 30, 2000
Chronic haemodialysis patients have a disproportionately high risk for developing cardiovascular ... more Chronic haemodialysis patients have a disproportionately high risk for developing cardiovascular disease, which can only in part be explained by known risk factors such as dyslipidaemia, hypertension, hyperhomocysteinemia, diabetes mellitus and chronic volume expansion. A possible cause is that the haemodialysis treatment itself contributes to the accelerated atherosclerosis, observed in these patients. Nowadays, atherosclerosis is considered an inflammatory process, mediated by a dysfunction of the vascular endothelium. As a result, blood cells adhere to the vascular surface and release a variety of vasoactive mediators, cytokines, growth factors and free radicals. Due to the contact between blood and dialyzer, humoral systems and cellular elements are stimulated, and this may be viewed as an inflammatory reaction. As a consequence of this, the vascular surface of haemodialysis patients is repeatedly exposed to the influences of cytokines, coagulation products, vasoactive mediators, stimulated leukocytes and thrombocytes, and oxidative stress. It is therefore conceivable that the haemodialysis treatment itself enhances the greatly increased cardiovascular risk in chronic haemodialysis patients.
Reappraisal of Hemodiafiltration for Managing Uremic Complications
Clinical Journal of The American Society of Nephrology, Sep 1, 2021
Current Controlled Trials in Cardiovascular Medicine, May 20, 2005
Background: The high incidence of cardiovascular disease in patients with end stage renal disease... more Background: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. Methods: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and lowflux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. Conclusion: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD.
Blood Purification, 2007
11.1, 2.64 vs. 4.01, and 5.61 vs. 9.74, respectively). Conclusion: Dialysis with a polysulfone me... more 11.1, 2.64 vs. 4.01, and 5.61 vs. 9.74, respectively). Conclusion: Dialysis with a polysulfone membrane seems to lead to more platelet activation than dialysis with a cuprammonium membrane.
Nephrology Dialysis Transplantation, Oct 1, 2001
PLOS ONE, Nov 23, 2015
Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome,... more Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a posthoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77-94), the HR for cardiovascular mortality 0.73 (95% CI 0.62-0.85) and for sudden death 0.76 (95% CI 0.62-0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ-0.011 mmol/L/year, 95% CI-0.017 to-0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time.
Nephrology Dialysis Transplantation, Jun 23, 2016
Background: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may ... more Background: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated. Methods: In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl. Results: The mean (6standard deviation) age of 396 test subjects was 63.6 (613.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P ¼ 0.01)]. Stratified models showed a stable sScl in patients treated with HD (D þ2.9 pmol/L/year, 95% CI À0.5 to þ6.3, P ¼ 0.09) and a decreasing concentration in those treated with HDF (D À4.5 pmol/L/year, 95% CI À8.0 to À0.9, P ¼ 0.02). The relative change in the latter group was related to the magnitude of the convection volume. Conclusions: (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume.
MO663: No Translocation of Intact Intestinal Bacteria During Intermittent Dialysis Therapies
Nephrology Dialysis Transplantation, May 1, 2022