Effect of Predialysis Recombinant Human Erythropoietin on Early Survival After Hemodialysis Initiation in Patients With Chronic Kidney Disease: Co‐JET Study

Progression of anemia in patients with chronic kidney disease (CKD) is associated with an increased risk of death and hospitalization. It is not sufficiently clear whether treating renal anemia with recombinant human erythropoietin (rHuEPO) has a beneficial effect on early survival after hemodialysis (HD) initiation in patients with CKD. The study was an open‐label multicenter retrospective cohort study to evaluate the relationship between rHuEPO treatment and early survival after HD initiation in patients with CKD. Predialysis patients with CKD were divided into two groups: an rHuEPO‐treated group (rHuEPO group) and a non‐treatment group. The primary endpoint was all‐cause mortality in the year after HD initiation. A total of 3261 patients were enrolled (2275 in the rHuEPO group and 986 in the non‐treatment group). One‐year survival was 95.36% in the rHuEPO group and 90.36% in the non‐treatment group. The survival rate was significantly higher in the rHuEPO group (P < 0.0001). The results of multivariate analysis confirmed that predialysis treatment with rHuEPO is a predictor for reduced mortality risk (hazard ratio = 0.61, 95% confidence interval: 0.42–0.87, P = 0.006). Risk for the composite event of death/hospitalization was also lower in the rHuEPO group (hazard ratio = 0.88, 95% confidence interval: 0.78–0.98, P = 0.026). The results of this study suggest that treatment with rHuEPO can decrease early mortality risk after initiation of HD in patients with CKD. A prospective study is needed to further investigate early survival after HD initiation.     

Efficacy of Once‐weekly Intravenous Administration of Epoetin‐β as a Maintenance Treatment for Anemia in Japanese Hemodialysis Patients: A Multicenter,Open‐label Clinical Study

Epoetin‐β is extremely useful as a drug for treating anemia in hemodialysis (HD) patients and is widely used for that purpose. The aim of this study was to determine whether once‐weekly intravenous administration of epoetin‐β is as effective in maintaining hemoglobin (Hb) concentration as the same weekly dose administered 2 or 3 times per week as maintenance treatment of anemia in HD patients. The subjects were stable HD patients who had been receiving HD for at least 12 months. Using a fixed weekly dose of 3000 or 6000 IU of epoetin‐β, this study evaluated maintenance of improvement of anemia by comparing Hb concentration in the study period (once‐weekly) with Hb concentration in the prestudy period (2 or 3 times per week). Of the 112 patients treated with epoetin‐β, 111 patients (full analysis set; 3000 IU, 52 patients; 6000 IU, 59 patients) were evaluated, after excluding one patient whose dose was changed immediately before study initiation. The change in the Hb concentration was maintained within ±1.5 g/dL in 89.2% of patients (3000 IU, 88.5%; 6000 IU, 89.8%). The mean Hb concentration was 10.42 ± 0.73 g/dL at study initiation and 10.14 ± 1.00 g/dL at study completion. Adverse reactions occurred in 9.8% of patients (11 out of 112 patients). The main adverse reactions were malaise and increased blood pressure. Once‐weekly intravenous administration of epoetin‐β is useful as maintenance treatment of anemia in HD patients and may be a treatment option.     

Low Hemoglobin Levels and Hypo‐Responsiveness to Erythropoiesis‐Stimulating Agent Associated With Poor Survival in Incident Japanese Hemodialysis Patients

Although erythropoiesis‐stimulating agents (ESAs) are effective at treating anemia, the association between hemoglobin (Hb) levels and survival is still unclear, especially for the incident Japanese hemodialysis (HD) population. The Japan Erythropoietin Treatment (JET) Study is an open multi‐center, prospective, observational study designed to evaluate the relationship between the maintenance of Hb levels and new HD patient prognosis after the first administration of epoetin beta. Landmark analyses were performed to examine the relationship between Hb levels at 6 months and survival. Among a total of 10 310 patients, 6631 completed the initial 6 months of epoetin beta treatment (induction phase) and were followed up for a further 2.5 years (maintenance phase). Three‐year survival rate of patients with <9 g/dL Hb levels after 6 months was 74.1%, which was significantly lower than 89.3% for patients with Hb levels 10 to 11 g/dL; the adjusted hazard ratio (HR) was 2.08 (95% CI, 1.57–2.77; P < 0.0001). Moreover, the 3‐year survival rate for poor responders defined by Hb levels <10 g/dL and weekly epoetin beta doses ≥9000 IU during the induction phase was 71.6%, which was significantly lower than 89.4% for the group, which had Hb levels 10 to 11 g/dL excluding poor responders and those with excursion; the HR was 1.71 (95% CI, 1.13–2.60; P = 0.0118). Adverse events related to the treatment were reported in 71 of 10 310 patients (0.69%). These findings suggest that the achieved low Hb levels and poor response to ESA therapy are significantly associated with high mortality.     

High Hemoglobin Levels Maintained by an Erythropoiesis‐Stimulating Agent Improve Renal Survival in Patients with Severe Renal Impairment

Our goal was to investigate the effect modification of maintaining a high Hb target range through erythropoiesis‐stimulating agent therapy on the renal outcome with respect to chronic kidney disease (CKD) stage and concurrent diabetes condition in patients with CKD. We used data from a previously reported randomized controlled trial involving 321 CKD patients not on dialysis, with Hb levels of <10 g/dL, and serum creatinine (Cr) of 2.0 to 6.0 mg/dL, and in which maintaining Hb levels at 11.0–13.0 g/dL with darbepoetin‐α (High Hb group) resulted in a greater renal protective effect than maintaining Hb levels at 9.0–11.0 g/dL with epoetin‐α (Low Hb group). We conducted a post‐hoc analysis of the effects of baseline CKD stage and concurrent diabetic condition on the renal composite endpoint, consisting of death, initiation of renal replacement therapy, and doubling of the serum Cr level. Both groups with stage 4 CKD had a 3‐year cumulative renal survival rate of 53.8%, whereas in patients with stage 5 CKD, the rate in the High Hb group (31.0%) was significantly (P = 0.012) higher than that in the Low Hb group (19.1%). The observations made in patients with stage 5 CKD were maintained on further analysis of non‐diabetic patients, but were not seen in those with diabetes or stage 4 CKD. These results suggest that in patients with stage 5 CKD, especially those without diabetes, achieving a higher target Hb level with erythropoiesis‐stimulating agents is associated with a greater renoprotective effect.     

Bed‐sided short‐duration renal replacement therapy provide a possible option to treat non‐critical coronavirus disease 2019 in maintenance hemodialysis patients in public health crisis

HD care may experience great stress with the coronavirus disease 2019 (COVID‐19) pandemic. A modified HD modality named bed‐sided short‐duration renal replacement therapy (BSRRT) was used in noncritical maintenance HD (MHD) patients diagnosed with COVID‐19 in Wuhan due to extreme situation. To determine the safety and efficacy as a substitution for intermittent HD (IHD), we conducted this study. We used the data of 88 noncritical COVID‐19 MHD patients collected from 65 medical units at the hospitals in Wuhan, China, from January 1 to March 10, 2020. t‐test, Wilcoxon rank sum test, and Fisher exact probability method were used to compare the baseline characteristics, treatment, and death. Log‐rank test and Cox regression multivariate analysis was used to compare the survival of noncritical patients who were transferred to BSRRT modality versus those who were continued on the IHD. Univariate analysis showed the level of reported fatigue symptom at present, bilateral lung computed tomography infiltration and steroid treatment differed between the two groups. The outcome of death of the two groups did not show significant differences in univariate analysis (P = .0563). Multivariate Cox regression analysis dialysis showed modality of treatment after COVID‐19 diagnosis was not a significant predictor of death (P = .1000). These data suggest that for noncritical COVID‐19 MHD patients, the transfer from IHD to BSRRT does not have significant difference in the risk of death compared with IHD group. This finding suggests this modified modality could be an option for the substitution for IHD during the COVID‐19 pandemic period.     

Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Recombinant human erythropoietin (rHuEPO) has been reported to induce hypertension. We investigated the effect of a single injection of rHuEPO on blood pressure in patients receiving hemodialysis (HD) and in patients with predialysis chronic renal failure (CRF). Forty-one patients receiving HD and 36 patients with predialysis CRF received an intravenous injection of rHuEPO, and blood pressure and plasma endothelin-1 were measured before and 30 min after the injection. Mean blood pressure was increased significantly in HD patients, but not in CRF patients (HD: 103+/-5 to 105+/-6 mmHg, p<0.05; CRF: 103+/-4 to 103+/-6, NS). The percentage of patients with increased mean blood pressure of more than 10 mmHg after rHuEPO injection was significantly larger in the HD than in the CRF group (27.0% vs. 5.5%, p<0.01). A positive correlation was found between changes in endothelin-1 level and mean blood pressure in the HD (r=0.43, p<0.01) but not in predialysis chronic renal failure. In conclusion, a single injection of rHuEPO increased blood pressure with a positive correlation with endothelin-1 release in hemodialysis patients, but not in predialysis chronic renal failure patients.     

Excessive Access Cannulation Site Bleeding Predicts Long‐Term All‐Cause Mortality in Chronic Hemodialysis Patients

Our group has previously reported that excessive vascular access bleeding during dialysis treatment in stable hemodialysis (HD) patients was associated with anemia and may indicate poorer health. The association between excessive blood loss from access cannulation site and clinical outcomes was unknown. We hypothesized that excessive access bleeding may have an impact on all‐cause and cardiovascular (CV) mortality in this population. We prospectively conducted an observational, longitudinal study of 360 HD patients. Excessive access bleeding was defined as at least an occurrence of blood loss greater than 4 mL per HD session during a study period of one month. During a median follow‐up of 83 months, all‐cause mortality and CV mortality were registered. Outcomes were analyzed by Kaplan–Meier and Cox proportional hazards regression analyses. A total of 118 (32.8%) participants died and 54 of these were from CV death. Using a multivariate Cox proportional hazards regression, access bleeding was found to be an independent predictor of all‐cause mortality (HR 1.67, 95% CI 0.96–2.91, P = 0.070) but not for CV death (HR 1.53, 95% CI 0.88–2.68, P = 0.135). Our study identified that excessive access cannulation site bleeding could be a novel marker for increased risk of death in HD patients.     

Efficacy of Long‐Term Treatment With Tolvaptan to Prolong the Time Until Dialysis Initiation in Patients With Chronic Kidney Disease and Heart Failure

The short‐term effectiveness of tolvaptan (TLV) against heart failure has been established. TLV is known to decrease the worsening of renal function more than loop diuretics. Long‐term TLV administration decreases the rate of re‐hospitalization in heart failure and prevents deterioration of kidney function. If repeated hospitalization for heart failure can be prevented in patients having concurrent chronic kidney disease (CKD), the period until dialysis initiation may be prolonged. We investigated whether long‐term TLV management can extend the period until dialysis initiation in patients with CKD and heart failure. A retrospective, observational study was conducted among patients with CKD stage G4 and G5 admitted because of heart failure between April 2013 and July 2018. They were divided into those with TLV and those without TLV. They were followed up until August 2018 and relevant data was collected. Data from 115 patients (68 men and 47 women), with a mean age of 73.4 ± 11.9 (median 76.0 and IQR 66.5–82.0) years and a mean eGFR of 11.8 ± 5.7 (median 9.9 and IQR 7.5–14.8) mL/min/1.73m² were included in the analysis. Twenty‐five patients had received long‐term TLV treatment, and 90 had not. Multivariate analysis after adjustment showed that long‐term use of TLV significantly lowered the hazard ratio (HR) for time taken to reach dialysis initiation (HR: 0.3286, 95%CI: 0.1282–0.8423, P = 0.0205). Propensity score‐matched analysis showed similar results (HR: 0.3220, 95%CI: 0.1107–0.9369, P = 0.0376). In patients with CKD G4 and G5 and heart failure, long‐term treatment with TLV can prolong the time until dialysis initiation.     

Super high‐flux hemodialysis provides comparable effectiveness with high‐volume postdilution online hemodiafiltration in removing protein‐bound and middle‐molecule uremic toxins: A prospective cross‐over randomized controlled trial

Although high‐volume postdilution online hemodiafiltration (ol‐HDF) is superior to high‐flux HD in removing all kinds of uremic toxins and improving survival, this treatment is not available in most HD centers. The present study was conducted to compare the effectiveness in removals of protein‐bound (indoxyl sulfate [IS]), middle‐molecule [beta‐2 microglobulin (B2M) and alpha‐1 microglobulin (A1MG)], and small‐molecule uremic toxins between super high‐flux HD (SHF‐HD), HD with a novel SHF dialyzer and high‐volume postdilution ol‐HDF in a noninferiority fashion. Fifteen prevalent HD patients were randomly allocated into two sequences of 12‐week treatment periods of SHF‐HD treatment and later high‐volume postdilution ol‐HDF period or vice versa. Each treatment period was divided by a wash‐out phase of 4‐week high‐flux HD. Twelve of 15 patients could complete the study. When compared with high‐volume postdilution ol‐HDF (convective volume of 24.4 ± 3.52 L), SHF‐HD provided comparable reduction ratio values of IS, B2M, and A1MG with mean difference of 5.87 (95% confidence interval [CI] ‐1.63, 13.37), 1.98 (95% CI,‐0.21, 4.18), and 22.96 (95% CI, ‐1.91, 47.83), respectively. The spKt/Vurea was not different. The predialysis levels of all uremic toxins at baseline and after 12‐week treatment did not differ between both groups. Although albumin loss in dialysate in SHF‐HD was greater than high‐volume postdilution ol‐HDF, the serum albumin levels after 12‐week SHF‐HD treatment were significantly higher than baseline. In conclusion, SHF‐HD provides noninferior effectiveness to high‐volume postdilution ol‐HDF in removing various uremic toxins with significantly increased serum albumin levels despite higher albumin loss. SHF‐HD might be an effectively alternative treatment when high‐volume postdilution ol‐HDF is not available.     

Soluble P-selectin during a single hemodialysis session in patients with chronic renal failure and erythropoietin treatment.

In several studies, hemodialysis (HD) patients treated with recombinant human erythropoietin (rHuEPO) because of renal anemia showed increased levels of soluble adhesion molecules. The purpose of the study was to investigate the changes of soluble P-selectin (sSELP) and its relationship to platelet activation during a single HD session in patients with long-term rHuEPO treatment. Fifty-two HD patients with chronic renal failure were involved--26 with rHuEPO treatment (EPO group) and 26 without (non-EPO group). Thirty healthy subjects served as the control group. The sSELP, beta-thromboglobulin, and platelet factor 4 plasma levels were measured before and after a single 4-hour HD session on a cuprophane dialyzer. The basal beta-thromboglobulin and platelet factor 4 plasma levels were significantly increased in both HD groups compared with healthy controls but did not change after a single HD session, except for a significant decrease of platelet factor 4 in the non-EPO group. The predialysis sSELP plasma levels did not differ significantly compared with those of the healthy controls, but there was a significant increase of sSELP levels after a single HD session in both groups (EPO, P < .005; non-EPO, P < .05, respectively). These results suppose that the increased sSELP level was released from platelets during the course of a single HD session. The more significant increase of the sSELP plasma levels in EPO group during HD indicates that platelets are more activated in patients with long-term rHuEPO treatment, and this fact could partially explain the suspected tendency for thrombosis in these patients.     

The effects of hypertension and diabetes on new‐onset chronic kidney disease: A prospective cohort study

The study aimed to determine the different status of hypertension and diabetes on the risk of new‐onset chronic kidney disease (CKD) events in Kailuan Study. A total of 21 905 individuals were enrolled in the study. The new‐onset incidents of CKD, hypertension, and diabetes were collected in the follow‐ups. All the individuals were divided into five groups according to baseline and follow‐up hypertension and diabetes status: baseline hypertension (BH), baseline hypertension and incidence of diabetes (BHID), baseline diabetes (BD), baseline diabetes and incidence of hypertension (BDIH), and baseline hypertension and diabetes (BHD). The risk of new‐onset CKD of the five groups was calculated using the Cox regression analysis. In the median follow‐up of 7.05 ± 2.59 years, the prevalence of new‐onset CKD in the group of BH, BHID, BD, BDIH, and BHD were 27.1, 43.79, 25.4, 36.6, and 45.1 per 1000 years, respectively. When adjusted possible confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) of new‐onset CKD were 1.50 (95% CI: 1.38‐1.63), 1.25(95% CI: 1.07‐1.47), and 1.52 (95% CI: 1.35‐1.7) in the group of BHID, BDIH, and BHD, respectively, as referred to the BH group (P < .001). No obvious difference was observed in the group of BH and BD for the incidence of new‐onset CKD. Sensitivity analysis still showed the similar results among the five groups. The study showed that the effect of simple hypertension or simple diabetes on new‐onset CKD was not significantly different, but the incidence of new‐onset hypertension or diabetes increased the risk of new‐onset CKD. Hypertension and diabetes had a synergistic influence on the risk of new‐onset CKD.     

Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized,Phase 3, Multicenter,Open‐Label Study

Roxadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor developed to treat anemia in chronic kidney disease (CKD) patients. This Phase 3, randomized, open‐label, 24‐week study investigated the efficacy and safety of roxadustat in Japanese CKD patients with anemia on peritoneal dialysis (PD) who were previously treated or not treated with erythropoiesis stimulating agents (ESAs). Patients not previously receiving ESA (ESA‐Naïve group) were randomized to roxadustat at a starting dose of 50 or 70 mg three times weekly; patients previously receiving ESA (ESA‐Converted group) switched from ESA to roxadustat 70 or 100 mg three times weekly depending on the prior ESA dose. Outcomes included maintenance rate of average hemoglobin (Hb) level within 10–12 g/dL at weeks 18–24, cumulative response rate at end of treatment (Hb thresholds, 10.0 g/dL or 10.5 g/dL; Hb increase, ≥1.0 g/dL), and average Hb levels at weeks 18–24. Safety was assessed by occurrence of treatment‐emergent adverse events (TEAEs). Fifty‐six patients were enrolled (ESA‐Naïve, n = 13; ESA‐Converted, n = 43). Maintenance rates (weeks 18–24) were 92.3% (95% CI: 64.0–99.8; ESA‐Naïve) and 74.4% (95% CI: 58.8–86.5; ESA‐Converted). Cumulative response rate was 100.0% in the ESA‐Naïve group. Average Hb levels (weeks 18–24) were 11.05 g/dL (95% CI: 10.67–11.42; ESA‐Naïve) and 10.93 g/dL (95% CI: 10.73–11.13; ESA‐Converted). Common TEAEs included nasopharyngitis and back pain. Roxadustat was well tolerated and effective in maintaining target Hb levels in CKD patients on PD who were previously treated or not treated with ESA.     

Evaluation of Long‐Term Combination Therapy With Peritoneal Dialysis and Hemodialysis

It is well known that a combination therapy with peritoneal dialysis (PD) and hemodialysis (HD) is feasible and may improve clinical status in patients for whom adequate solute and fluid removal is difficult to achieve with PD alone. The objective of the present study was to evaluate whether the therapy is useful in the likelihood of long‐term peritoneal membrane and cardiac function. The therapy was 6 days of PD and one session of HD per week. Physical, biochemical, dialysate‐to‐plasma ratio of creatinine (D/P Cr), arteriovenous fistula (AVF) blood flow, and left ventricular mass index (LVMI) data were prospectively analyzed in 30 patients with measurements performed at 0 and 6 months, and for 21 patients, 12 or 18 months after initiation of the therapy. The levels of hemoglobin (Hb) after therapy were significantly higher than those at the initiation of therapy. The levels of LVMI and human atrial natriuretic peptide (hANP) after therapy were significantly lower than those at the initiation of therapy, whereas AVF blood flow did not change significantly. D/P Cr levels at 6 months after the therapy were significantly lower than those at the initiation of therapy. D/P Cr levels at 12 or 18 months after the therapy were not aggravated. It appears that the therapy improves Hb levels and cardiac function because of adjusting body fluid status. It was indicated that peritoneal function after therapy may be improved. Therefore, combination therapy is useful from the lifestyle viewpoint of patients in the transition period of PD to HD with end‐stage kidney disease.     

Bioimpedance Spectroscopy‐Based Fluid Status in Combined Dialysis Compared With Hemodialysis and Peritoneal Dialysis: A Cross‐Sectional Study

Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used in Japan for PD patients with decreased residual renal function. However, fluid status in PD+HD patients has not been well studied. In this cross‐sectional study, we compared fluid status in 41 PD+HD patients with that in 103 HD and 92 PD patients using the bioimpedance spectroscopy. Extracellular water normalized to patient height (NECW, kg/m) was the highest in pre‐HD (8.3 ± 1.6) followed by PD (7.9 ± 2.7), PD+HD (7.5 ± 2.5), and post‐HD patients (6.9 ± 1.5) (P < 0.01). By multiple linear regression analysis, PD+HD was associated with a significantly lower NECW than pre‐HD (β = ?0.8, P = 0.03) and similar to PD (β = ?0.5, P = 0.24) and post‐HD (β = 0.6, P = 0.08) after adjustment for age, sex, diabetic nephropathy, ischemic heart disease, dialysis period, and daily urine volume. There was no correlation between NECW and daily urine volume in all dialysis groups. Average daily fluid removal (a sum of urine volume and ultrafiltration volume by dialysis) was positively correlated with NECW in PD+HD and pre‐HD, but not in PD and post‐HD patients. Our results suggest that fluid status in PD+HD patients with decreased residual renal function is acceptable as compared with that in HD and PD patients.     

High Target Hemoglobin With Erythropoiesis‐Stimulating Agents Has Advantages in the Renal Function of Non‐Dialysis Chronic Kidney Disease Patients

We investigated the long‐term effects of maintaining high hemoglobin (Hb) on renal function in patients with chronic kidney disease not on dialysis. Subjects (Hb < 10 g/dL and serum creatinine (Cr) 2–6 mg/dL) were randomized to either a high Hb group (N = 161, 11.0 ≤ Hb < 13.0 g/dL) receiving darbepoetin alfa or to a low Hb group (N = 160, 9.0 ≤ Hb < 11.0 g/dL) with epoetin alfa, stratified according to baseline Hb and serum Cr levels, comorbidity of diabetes, and study centers. Primary endpoints were composites of the following events: doubling of serum Cr, initiation of dialysis, renal transplantation, or death. Three‐year cumulative renal survival rates (95% CI) were 39.9% (30.7–49.1%) and 32.4% (24.0–40.8%) in the high and low Hb groups, respectively (log‐rank test; P = 0.111). A Cox proportional‐hazards model adjusted by age, sex and the randomization factors showed a significantly lower event rate in the high Hb group (P = 0.035). The estimated hazard ratio (95% CI) for the high versus the low Hb group was 0.71 (0.52–0.98), the risk reduction was 29% in the high Hb group. Incidences of serious adverse cardiovascular events did not differ significantly between the high and low Hb groups (3.1% and 4.4%, respectively). No safety issues were noted in either group. Maintaining higher Hb levels with darbepoetin alfa better preserved renal function in patients with chronic kidney disease not on dialysis.     

Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients With Severe Artery Calcification

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima‐media thickness (CCA‐IMT). Moreover, we studied the relationship between OPG levels and all‐cause and cardiovascular (CV) mortality during a 5‐year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C‐reactive protein, interleukin‐6, tumor necrosis factor receptor II (TNFRII), transforming growth factor‐β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA‐IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39–20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA‐IMT values (OR 6.56; 95%CI 1.06–40.6; P = 0.036). OPG levels above the median were associated with higher CCA‐IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84–72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA‐IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow‐up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA‐IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all‐cause mortality in CKD patients with advanced medial arterial calcification.     

Long‐Term Safety and Efficacy of Bixalomer in Hyperphosphatemic Patients With Chronic Kidney Disease Not on Dialysis

Bixalomer, a metal‐free, nonabsorbable phosphate binder, is approved in Japan to treat hyperphosphatemia in dialysis patients. Bixalomer is effective and has a favorable safety profile in predialysis patients with hyperphosphatemia. This study examined the long‐term effectiveness and safety of bixalomer in predialysis patients with hyperphosphatemia. This was a 48‐week, multicenter, open‐label, phase 3 study in Japanese predialysis patients with hyperphosphatemia. Patients received bixalomer at an initial dose of 1500 mg/day, which was titrated to a maximum of 7500 mg/day depending on patients’ serum phosphorus responses to bixalomer. A total of 105 patients received bixalomer treatment, and 39 completed the study. The most common reason for discontinuation was initiation of dialysis. Mean serum phosphorus concentrations decreased from 5.15 mg/dL at baseline to 4.67 mg/dL at Week 12 and then fluctuated slightly around this level until it reached 4.58 mg/dL at Week 48. The proportion of total patients achieving the target serum phosphorus concentration (≥2.5 to <4.6 mg/dL) increased after treatment to a maximum of 66.2% at Week 20 and subsequently decreased to 51.3% by Week 48. Most adverse events (AEs) occurred in the first 12 weeks of treatment. The incidence of AEs did not increase with long‐term treatment. Common AEs reported included nasopharyngitis (29.5%), constipation (19%), and upper respiratory tract inflammation (12.4%). These findings suggest that long‐term treatment with bixalomer is effective, well tolerated, and has no new safety concerns. Bixalomer may be an alternative treatment option for the long‐term management of hyperphosphatemia in patients with chronic kidney diseases.     

Arterial hypertension in patients with chronic kidney insufficiency in hemodialysis with erythropoietin

The purpose of this study was to evaluate the effect of the partial correction of anaemia with recombinant human erythropoietin (rHuEPO) on the blood pressure (BP) of patients on chronic haemodialysis (HD). A group of 50 patients (26 men and 24 woman, mean age of 50 +/- 19.0 and range of 21 to 67) with basal levels of haemoglobin (Hb) less than or equal to 8 g/dl was evaluated before and during treatment with rHuEPO. Recombinant erythropoietin was started at 50 U/kh I.V. 3 times a week, immediately after each session of HD, for 4 weeks, and this dose was increased in steps of 25 U/kg until and Hb level of 12 g/dl or a maximum dose of 100 U/kg were reached. Before the administration of rHuEPO 33 patients (67.3%) were normotensives and 16 (32.6%) were hypertensives treated and well controlled. During the period of administration of rHuEPO 10 of the normotensives (30.3%) and 5 (31.3%) of the hypertensives patients showed an increase in the B.P. There was no correlation between the frequency of increase in B.P. and sex, age, length of time on HD and previous levels of B.P., but that frequency was higher in the patients with the lowest basal levels of haematocrit (Hct) and with the greatest increases in Hct (delta Hct). An immediate effect of I.V. administration of rHuE-PO on B.P. levels was not found. Finally we discuss the etiopathologic factors eventually responsible for the increase in BP and suggest some rules to be observed in the therapeutic use of rHuEPO.     

Effect of early correction of anemia with erythropoietin on left ventricular mass in predialysis patients: a multi-center trial

Objective To assess the effects of early correction of anemia with recombinant human erythropoietin (rHuEPO) on the development and progression of left ventricular hypertrophy (LVH) in patients with mild-to-moderate chronic renal insufficiency (CRI) who are not on hemodialysis. Methods A total of 158 patients with serum creatinine from 147μmol/L to 400μmol/L were enrolled in this prospective, multicenter study. Eighty-six patients with hemoglobin (Hb)<110g/L received rHuEPO treatment with a target Hb of > 110g/L (Group A). Forty patients with comparable Hb concentration ( <110g/L) but did not receive rHuEPO (Group B) and 32 patients with Hb≥110g/L and without rHuEPO treatment (Group C) were served as controls. Left ventricular mass index (LVMI) was evaluated by echocardiography at baseline and every 3 months for 2 years. Results There was no difference in age, gender, etiology of renal failure, blood pressure and cardiovascular risk factors among the 3 groups. At baseline, the prevalence of LVH was 72.1 % in group A, 72.5% in group B and 59.4% in group C. LVMI was inversely correlated with Hb levels (r=0.70, P<0.01). During the 2-year period, the mean LVMI decreased from 142.6±25.7g/m2 to 132.4±18.5 g/m2 in group A, while increased significantly in both group B and group C. The mean Hb concentration increased from 93.8±14.6g/L to 111.2±10.3g/L(P<0.05) in group A, but tended to decrease in group B and group C. There was no significant change of the mean blood pressure, number of anti-hypertensive drugs and serum creatinine concentrations in all 3 groups. However, patients' serum creatinine doubled more often in group B and group C than in group A. Conclusions LVH was common in predialysis CRI patients and was associated with the severity of anemia. Early intervention with rHuEPO may reverse LVH in these patients.