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Introduction: Phosphate binders are commonly used in patients receiving kidney replacement therapy (KRT), aiming to reduce and maintain serum phosphorus. Chronic kidney disease-mineral and bone disorder has been linked to reduced lifespan and worsened quality of life. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving KRT., Methods: The data sources examined were MEDLINE (PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with a search deadline of October 2023. We examined randomized controlled trials that compared sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving KRT. We performed a meta-analysis combining the data from trials, using R-studio., Findings: Inclusion criteria were met by five randomized trials. There was no statistically significant difference in the reduction of serum phosphorus between the two groups (MD: -0.07 mmol/L, 95% CI-random effects: -0.15 to 0.02). In the same line, a non-statistically significant difference was observed in serum i-PTH reduction between the two drugs (MD = -1.53 mg/dL, 95% CI = (-4.45, 1.4), p = 0.26, random effects model). No statistically significant difference was observed in all adverse events between the two groups (odds ratio: 1.11, 95% CI: 0.65-1.88, random effects model). Further analysis of gastrointestinal adverse events revealed that sevelamer carbonate increases gastrointestinal adverse events by up to 60% (odds ratio: 1.60, 95% CI: 1.31-1.97, common (fixed) effect model)., Discussion: This meta-analysis of randomized trials showed that both drugs, sucroferric oxyhydroxide and sevelamer equally and effectively controlled serum phosphorus levels, whereas sucroferric oxyhydroxide revealed a better profile in terms of gastrointestinal adverse events. Sucroferric oxyhydroxide is a valuable option for patients receiving KRT when sevelamer carbonate is more difficult to tolerate., (© 2024 The Author(s). Hemodialysis International published by Wiley Periodicals LLC on behalf of International Society for Hemodialysis.)

Introduction: Coronary vascular dysfunction, as assessed by coronary flow reserve (CFR) in the left anterior descending coronary artery, is found in various conditions including end-stage chronic kidney disease (CKD). Currently, we investigated the associations of CFR with echocardiographic indices of systolic and diastolic cardiac function and identified independent predictors of CFR in hemodialysis patients., Methods: End-stage CKD patients treated with hemodialysis (n = 29) without known cardiovascular disease were recruited from a Hemodialysis Unit in Northwestern Greece. A thorough echocardiographic evaluation including CFR measurement following dipyridamole infusion was performed in all participants. Arterial stiffness was assessed by measurement of carotid-femoral pulse wave velocity and aortic augmentation index., Results: The mean age of the patients was 63 years, and mean duration of hemodialysis was 2.9 years. CFR was 1.60 ± 0.37 while dipyridamole caused a significant increase in E' sep , S lat , E' lat , and Stroke volume (P < .05 for all). Independent predictors of CFR were posterior wall thickness (B -0.408, P = .013) and dipyridamole-induced changes in Tei index (B -0.425, P = .007). A severely decreased CFR < 1.5 was observed in 52% of the patients. E/E' ratio (B 10.84, P = .014) was the single independent predictor of severely decreased CFR., Conclusions: In end-stage CKD patients on hemodialysis without known cardiovascular disease, impaired coronary vascular function was prevalent and related to increased left ventricular wall thickness, increased filling pressures, and dipyridamole-induced deteriorated myocardial function independently of the presence of wall-motion abnormalities. Further studies are required to clarify the prognostic role of dipyridamole-induced cardiac changes in hemodialysis patients., (© 2020 Wiley Periodicals, Inc.)

Background: Sudden cardiac death is prevalent in chronic hemodialysis (HD) patients while the dialysis process may have arrhythmogenic potential. We sought to examine the effect of HD on conventional electrocardiographic parameters as well as on novel indexes of repolarization, given that increased spatial dispersion of repolarization is related to ventricular arrhythmias., Methods: We recorded clinical, echocardiographic, and laboratory parameters as well as electrocardiographic indexes before and after a single HD session. Specifically, we calculated the QTc interval, the QRS duration, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio., Results: The study population consisted of 66 chronic HD patients (mean age: 68.9 ± 11.8 years, 40 males). Heart rate, blood pressure, QRS duration, QTc interval, and QT dispersion did not change significantly after the HD session. However, the Tpe interval and the Tpe/QT ratio increased significantly (80 [65-90] ms vs 85 [77.5-100] ms; P = 0.04, and 0.21 [0.18-0.24] vs 0.25 [0.21-0.28]; P = 0.05, respectively). Correlation analysis and multiple regression analysis failed to show significant associations between the baseline parameters and the baseline values of Tpe and Tpe/QT or between the change of the laboratory parameters during HD and the corresponding change of the Tpe and the Tpe/QT values. No significant arrhythmias were observed during the HD sessions., Conclusions: HD induces an increase in novel markers of spatial dispersion of ventricular repolarization. Whether the assessment of these indexes of heterogeneity of repolarization at baseline or their change during HD has a prognostic value with regard to future untoward events, remains to be elucidated., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Dialyzer membrane and the type of heparin used can influence lipid parameters. However, there are limited and debatable data concerning lipid alterations during a single hemodialysis session. Moreover, the role of hemoconcentration after every hemodialysis session confuses the real effect of the heparin on lipid profile. We investigated the acute effect of heparin administration on lipids in hemodialysis patients, but on an off-hemodialysis day in order to eliminate any effect of ultrafiltration. We studied six patients on hemodialysis, six patients on peritoneal dialysis, and six healthy persons. The study was performed in two phases (1 week apart). In phase A, we used unfractionated heparin (5000 IU, intravenous), whereas in phase B, low-molecular-weight heparin (3500 anti-FXa, intravenous) was used. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and Lp(a) were estimated before and 1, 2, 3, and 4 hours after heparin administration. We observed a reduction only in triglycerides (at the first, second, and third hour) in both phases in all groups. The other lipid parameters were not affected. In conclusion, acute administration of both types of heparin seems to affect only triglyceride levels in patients on renal replacement therapy.

Background: Among lipid abnormalities observed in patients with chronic kidney disease (CKD) is a significant decrease in serum high-density lipoprotein cholesterol (HDL-C) levels. In a previously published randomized control trial, we showed that early erythropoietin (EPO) administration in a predialysis population slowed the progression of CKD. In the present nested substudy, we examine whether EPO has an influence on serum HDL-C levels in comparison to other lipid parameters in this population., Methods: Eighty-eight patients with CKD stages 3 and 4 were enrolled in the study. Forty-five patients (group 1) were treated with EPO (50 U/kg/wk), targeting to increase hemoglobin levels to 13 g/dL or greater (>or=130 g/L). The other patients (group 2) remained without treatment until hemoglobin levels decreased to less than 9 g/dL (<90 g/L). The duration of the study was 12 months., Results: At the end of the study, we observed a statistically significant decrease in serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides in both groups. However, serum HDL-C levels significantly increased in only group 1 (from 42.5 +/- 10.4 to 55.9 +/- 8.1 mg/dL [1.10 +/- 0.27 to 1.45 +/- 0.21 mmol/L]; P < 0.001), whereas they were unchanged in group 2. In addition, a significant decrease in atherogenic LDL-C/HDL-C ratio was observed in only group 1. Importantly, the increase in serum HDL-C levels correlated positively with the increase in hemoglobin values in EPO-treated patients., Conclusion: Our results show that EPO treatment of predialysis patients with CKD significantly increases serum HDL-C levels, which may represent an important antiatherogenic effect of this hormone.

Background: Platelet activating factor acetylhydrolase (PAF-AH) is a Ca2+-independent phospholipase A2 that is secreted mainly from monocytes/macrophages. In human plasma, PAF-AH is associated primarily with low-density lipoprotein (LDL), while a small proportion of enzyme is associated with high-density lipoprotein (HDL). The ratio of HDL-PAF-AH to total plasma enzyme activity may represent a potential marker of atherogenicity. We evaluated possible alterations of lipoprotein-associated enzyme activity in Chronic Kidney Disease (CKD) patients, stages 3-4, and further investigated whether long-term therapy with recombinant human erythropoietin (epoetin) has any influence on the plasma PAF-AH activity in vivo or on the enzyme activity secreted from peripheral blood monocytes (PBMs), in vitro., Methods: Forty-eight patients, 28 men and 20 women, with CKD (stages 3-4) participated in the study. Patients were randomized into groups I and II. Patients of group I (n = 28) were administered subcutaneously epoetin, 50 units/kg once per week. The Hb target was 13 g/dl. In group II (n = 20), epoetin was initiated only when the Hb levels decreased during follow-up to less than 9 g/dl. All patients were seen on an outpatient basis at 2, 4 and 6 months. Twenty-two normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls., Results: The PAF-AH activity in plasma of both patient groups at baseline was higher compared to controls, whereas no difference in the HDL-PAF-AH activity was observed among the studied groups. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly lower in both patient groups compared to controls. Epoetin administration in the patients of group I was associated with a significant increase in the plasma PAF-AH and in HDL-PAF-AH activities 2 months after treatment, which remained stable for up to 6 months of therapy, a phenomenon not observed in untreated patients of group II. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly increased in patients of group I compared to the baseline values, a phenomenon not observed in patients of group II. In vitro treatment with epoetin of PBMs from patients of group I (undergoing therapy with epoetin) resulted in a dose-dependent increase in total and secreted enzyme activity, a phenomenon not observed in patients of group II who did not receive therapy with epoetin. This suggests that the in vivo increase in lipoprotein-associated PAF-AH observed in patients treated with epoetin may be attributed to the drug-induced enhanced secretion of PAF-AH from PBMs of these patients., Conclusions: CKD patients of stages 3-4 are characterized by an increase in plasma PAF-AH activity and a low ratio of HDL-PAF-AH to total plasma enzyme activity. Long-term therapy with epoetin may improve this atherogenic ratio thus this drug may play an important antiatherogenic role in CKD.

Background: Erythrocytes represent an important component of the antioxidant capacity of blood, comprising, in particular, intracellular enzymes, including platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease (CKD), and further investigated whether erythropoietin (EPO) administration in these patients has any influence on the enzyme activities., Methods: Thirty-six patients (19 men and 17 women) with CKD (stages 1 to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2 (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized into two groups (i.e., groups II and III). Patients of group II (N= 11) were administered EPO subcutaneously, 50 units per kg once per week. In group III (N= 12), EPO was initiated only when the hemoglobin (Hb) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. The PAF-AH and Gpx activities were determined in isolated washed erythrocytes., Results: The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls, the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied populations, both enzyme activities were negatively correlated with the creatinine clearance values. Importantly, the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO (group III), a phenomenon not observed in patients receiving EPO (group II), or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III., Conclusion: Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients. Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency, thus preserving the erythrocyte defense mechanisms against oxidative stress.

Background: Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia., Methods: We conducted a randomized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to <9 g/dL. The primary end point was a composite of doubling of creatinine, renal replacement, or death., Results: Eighty-eight patients were randomized (early treatment N= 45, deferred treatment N= 43) and followed for a median of 22.5 months. During follow-up, 13 versus 23 patients reached the primary end point in the two arms, respectively (log-rank P= 0.0078). The relative hazard for reaching an end point was 0.42 (P= 0.012). Adjusting for baseline serum creatinine, the adjusted relative hazard was 0.37 (P= 0.004), while the risk increased 2.23-fold (P < 0.001) per 1 mg/dL higher creatinine at baseline. The benefit was similar regardless of the baseline hemoglobin and proteinuria. No patients had any severe adverse events., Conclusion: Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy.