Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility

Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone-associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone-induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary "pseudolithiasis" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying.     

Monocyte chemoattractant protein-1 is associated with silent cerebral infarction in patients on haemodialysis

Background: In patients with chronic renal failure undergoing haemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of monocyte chemoattractant protein‐1 (MCP‐1) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased MCP‐1 concentration correlate with the occurrence of SCI in HD patients. Methods: Using cranial magnetic resonance imaging (MRI) findings, 52 Japanese patients undergoing HD were divided into two groups: with SCI (61 ± 7 years, mean ± SD, n= 28) and without SCI (60 ± 6 years, n= 24). The gender, metabolic profiles and MCP‐1 concentration were compared between the two groups. Results: The level of MCP‐1 was higher in the with‐SCI group than in the without‐SCI group (P < 0.0001). The proportion of smokers was higher in the with‐SCI group (P < 0.05) than in the without‐SCI group. Plasma level of high‐density lipoprotein cholesterol was lower, while uric acid level was higher, in the with‐SCI group (P < 0.05 and P < 0.05 respectively) compared to the without‐SCI group. Multiple logistic regression analysis identified MCP‐1 level as being significantly associated with the presence of SCI (odds ratio 1.48, 95% confidence interval = 1.10–5.75, P < 0.0001). Conclusions: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI, and that MCP‐1 is significantly associated with the presence of SCI in HD patients.     

Serum Endocan Levels are Associated With Paraoxonase 1 Concentration in Patients With Chronic Kidney Disease

Endocan is a soluble proteoglycan released by the vascular endothelium. The increase of its serum levels is associated with inflammation, endothelial dysfunction and cardiovascular events in patients with chronic kidney disease (CKD). We studied the association of serum endocan with the lipid profile of 105 CKD patients with dyslipidemia, divided in two groups, non‐dialyzed (CKD, N = 57) and hemodialysis (HD, N = 48) in comparison with 30 normal controls (NC). We also analyzed endocan in relation with the concentration of two serum HDL‐linked members of the paraoxonase (PON) family, PON1 and PON3, which have been previously found to have antiatherogenic properties. The results showed that endocan levels were significantly higher in HD patients than in CKD patients (P < 0.001) and NC (P < 0.001). PON1 was significantly decreased only in HD patients compared to NC (P < 0.001), whereas PON3 was significantly increased in both patient groups (P < 0.001). Endocan levels were significantly and positively correlated with total cholesterol and LDL‐C in CKD and additionally were negatively correlated with HDL‐C in HD group. PON1 levels were significantly correlated with endocan in both groups, while no correlation was observed for PON3 in either group. Multiple regression analysis between endocan and the above lipid parameters in the total of patients revealed that endocan was independently associated only with PON1 (β = ?0.513, P = 0.002). It is concluded that the increase of serum endocan levels in patients with CKD may be associated with the decrease of PON1 concentration, irrespective of lipid alterations produced by atherosclerosis development.     

Ceftriaxone-associated Pseudolithiasis in Elderly People: Frequency and Risk Factors

Objective Ceftriaxone (CTRX) is a widely used antibiotic because of its long plasma half-life and good tissue transmission. Many of the reported studies on CTRX-associated pseudolithiasis were performed in children. Although some studies have been published in adults, there are no studies limited to elderly people. The present study investigated CTRX-associated pseudolithiasis and explored its risk factors in the elderly. Methods We retrospectively reviewed 133 elderly patients (≥65 years old) treated with CTRX. Pseudolithiasis was defined as stones or sludge newly appearing in the gallbladder, as detected by computed tomography after the administration of CTRX. We evaluated the risk factors for pseudolithiasis using multivariate regression and inverse probability of treatment weighting analyses. Results Among the 133 patients, 24 (18%) developed CTRX-associated pseudolithiasis. In a multivariate analysis, the CTRX dose [odds ratio (OR) 4.54, 95% confidence interval (CI) 1.36-15.07, p=0.012] and CTRX treatment duration (OR 2.80, 95% CI 1.06-8.04, p=0.043) were significantly associated with pseudolithiasis formation. The cut-off value of the total CTRX dose associated with pseudolithiasis formation was 19 g. A propensity analysis determined that the frequency of pseudolithiasis was increased in patients treated with >19 g total CTRX compared with those who received ≤19 g in total (OR 4.06, 95% CI 1.45-11.32, p=0.008). Conclusion The incidence rate of CTRX-induced pseudolithiasis is high in elderly people, and the CTRX dose and CTRX treatment duration are significant risk factors for pseudolithiasis. A total dose of >19 g increases the likelihood of pseudolithiasis formation in elderly people treated with CTRX.     

Ultrafiltration volume by once‐weekly hemodialysis is a predictor of technique survival of combination therapy with peritoneal dialysis and hemodialysis

Overhydration is a major cause of technique failure of peritoneal dialysis (PD). Hence, we investigated the impact of ultrafiltration (UF) volume by once‐weekly hemodialysis (HD), excess volume beyond their dry weight, on technique survival of PD and HD combination therapy (PD+HD). Forty‐six anuric PD+HD patients were divided into three groups according to baseline UF volume by HD: low‐UF (<mean ? 1SD), middle‐UF (≥mean ? 1SD and <mean + 1SD), and high‐UF (≥mean + 1SD). High‐UF group showed larger extracellular water normalized to height (P = .038) and longer HD sessions (P < .001) compared with low‐UF group, whereas low‐UF group was older than middle‐UF group (P = .001). Technique survival rate was significantly lower in high‐UF group than in low and middle‐UF groups (P < .001), and the rates at 44 months were 80%, 90%, 20% in low, middle, and high‐UF groups, respectively. Chronic overhydration was the leading cause of technique failure for all. This study suggests that fluid overload remains a major cause of technique failure of PD even after once‐weekly HD is added.     

Tuberculosis spondylitis in patients on hemodialysis: Clinical features,risk factors,and outcomes in 12 patients

The aim of this study was to investigate the clinical features, risk factors and outcomes of tuberculosis spondylitis (TBS) in patients on hemodialysis (HD). We systematically reviewed medical records from 12 HD patients with TBS admitted to our hospital from April 2008 to April 2018. A total of 120 age‐ and sex‐matched HD patients without infections were randomly selected as controls. The incidence of TBS in our patient group was 1.5/1000 per year. The average duration from initial symptoms to diagnosis was 45.4 days (range, 11‐180 days). Neurosurgery was performed in 4 (33.3%) patients. TBS was cured or improved in 11 (91.7%) patients. HD patients with TBS had significantly lower albumin and Hb levels than controls (P = .03 and P = .01). These findings indicated that lower albumin and Hb levels were possible risk factors for TBS in patients on HD, most HD patients with TBS had a good outcome after anti‐TB therapy with or without surgery.     

Effect of albumin infusion on preventing the deterioration of renal function in patients with spontaneous bacterial peritonitis

OBJECTIVE : To determine whether plasma volume expansion with albumin could prevent impairment of renal function and reduce mortality in cirrhotic patients with either acute spontaneous bacterial peritonitis (SBP) or patients complicated with SBP. METHODS : A total of 112 patients was randomly allocated to two groups: 56 patients were allocated to be treated with ceftriaxone and 56 patients were allocated to treatment with ceftriaxone plus intra‐venous albumin in 3 weeks. Serum creatinine and blood urea nitrogen levels were monitored. RESULTS : Of the 56 patients (group 2) treated with ceftriaxone and albumin, five patients had renal impairment. Of the 56 patients (group 1) treated with ceftriaxone alone, 19 had renal impairment. The incidence of renal impairment was significantly lower in patients treated with ceftriaxone and albumin (5/56; 10%) than in patients treated with ceftriaxone alone (19/56; 34%; P = 0.002). In addition, in‐hospital mortality in group 2 was 10% (5/56), but was 33% (17/56) in group 1. Thus, in‐hospital mortality was significantly reduced from 33% (17/56) in patients treated with ceftriaxone to 10% (5/56) in patients treated with ceftriaxone and albumin (P = 0.01). CONCLUSIONS : The addition of intravenous albumin to an antibiotic regimen reduces the incidence of renal impairment and mortality in cirrhotic patients with SBP.     

Skeletal Muscle Loss Is Negatively Associated With Single‐Pool Kt/V and Dialysis Duration in Hemodialysis Patients

We evaluated the skeletal muscle loss in hemodialysis (HD) patients by bioelectrical impedance analysis (BIA) and handgrip strength test. Thirty‐four HD patients and 16 healthy subjects (control group) were measured for skeletal muscle mass normalized as the skeletal muscle mass index (SMI), calculated as skeletal muscle mass (kg)/height (m)² using a tetrapolar bioelectrical impedance plethysmograph. Handgrip strength test was also performed using a hand dynamometer in both groups. In HD patients, the associations of SMI and handgrip strength with age, sex, HD conditions, and HD parameters such as body mass index (BMI), single‐pool Kt/V (spKt/V), normalized protein catabolic rate (nPCR), creatinine generation rate (CGR) and serum albumin level (Alb) were investigated. SMI of HD patients (4.58 ± 0.95 kg/m²) was significantly lower than that of the control group (5.55 ± 0.80 kg/m², P < 0.01). The handgrip strength of HD patients (19.9 ± 7.74 kg) was also significantly lower than that of the control group (33.0 ± 8.94 kg, P < 0.01). In HD patients, HD duration was associated with both SMI and handgrip strength. Among HD parameters, spKt/V was negatively associated with both SMI and handgrip strength, BMI and Alb were positively associated with SMI, while nPCR and CGR were associated with neither SMI nor handgrip strength. HD duration independently contributed to skeletal muscle loss and the value of spKt/V may be affected by skeletal muscle loss in HD patients.     

Correlation of Coronary Artery Calcification With Pre‐Hemodialysis Bicarbonate Levels in Patients on Hemodialysis

Coronary artery calcification (CAC) leads to a significant increase in cardiovascular morbidity and mortality in hemodialysis (HD) patients. Metabolic acidosis, which is common in HD patients, promotes bone resorption in human and animals as a result of buffer function of bone, and calcium and phosphate elute from bone into blood stream. However, the effect of acidosis on CAC in HD patients has never been precisely investigated. This is a cross‐sectional observational study performed in a single center. One hundred and seven prevalent HD patients (35 women and 72 men) underwent electron‐beam computed tomography (EBCT) to evaluate CAC score (CACS), and then we evaluated associated factors of CACS with clinical and laboratory parameters including pre‐HD pH and bicarbonate levels. Pre‐HD pH and bicarbonate levels were 7.35 ± 0.04, and 17.6 ± 1.8mmol/L, respectively. The pre‐HD pH had no significant correlation to CACS (r = ?0.025, P = 0.81). CACS was significantly negatively correlated with pre‐HD bicarbonate levels (r = ?0.329, P = 0.0009) and serum albumin levels (r = ?0.298, P = 0.0467), while it was positively correlated with age (r = 0.319, P = 0.0008) and HD duration (r = 0.385, P = 0.0004). Serum levels of calcium, phosphorus, intact parathyroid hormone, and use of phosphorus binders were not related to CACS. Multivariate analysis indicated that plasma pre‐HD bicarbonate level was independently associated with CACS. The present study showed that blood levels of pre‐HD bicarbonate were significantly associated with CAC in HD patients. Further studies are needed to confirm these results and to determine whether correction of metabolic acidosis prevents the development of CAC, one of the features of accelerated atherosclerosis in HD patients.     

Dialysis Method Alters the Expression of MicroRNA‐33a and Its Target Genes ABCA1, ABCG1 in THP‐1 Macrophages

Atherosclerosis and accompanying cardiovascular disease are the first causes of mortality in patients undergoing maintenance hemodialysis. Anti‐atherosclerotic effects of hemodiafiltration (HDF) have been reported. Our study aimed to investigate the effect of serum derived from a healthy group (n = 23), before and after hemodialysis (HD) therapy (n = 23), and before and after HDF therapy (n = 17) on the expression of microRNA‐33a and its target genes adenosine triphosphate‐binding cassette transporter A1,G1 (ABCA1, ABCG1) in THP‐1 macrophages. Meanwhile, blood lipids and high‐sensitivity C‐reactive protein (hs‐CRP) were measured in these groups. Our data showed that the expression of miRNA‐33a was lower (P < 0.05) and ABCA1 and ABCG1 were higher (P < 0.05) in the healthy group than pre‐HD and pre‐HDF. miR‐33a was significantly decreased (P < 0.05) but ABCA1, ABCG1 was significantly increased (P < 0.05) in post‐HDF compared with pre‐HDF, while these parameters in pre‐ and post‐ HD groups did not show any significant change (P > 0.05). High density lipoprotein cholesterol (HDL‐C) was higher and hs‐CRP was lower in the healthy group than pre‐HD and pre‐HDF groups. Moreover, a significant increase of HDL‐C (P < 0.05) and decrease (P < 0.05) of hs‐CRP was shown in post‐HDF compared with pre‐HDF, but HD appeared to have no significant change in these subjects. HDF therapy can downregulate miR‐33a expression, and then result in ABCA1, ABCG1 upregulation and an increase in circulating HDL‐C, leading to a possible anti‐atherosclerosis effect to some extent.     

Excessive Fall of Blood Pressure During Maintenance Hemodialysis in Patients With Chronic Renal Failure Is Induced by Vascular Malfunction and Imbalance of Autonomic Nervous Activity

Acute hypotension during maintenance hemodialysis (HD) is not only a critical complication, but also an independent risk factor for mortality in patients with chronic renal failure (CRF). This study was designed to clarify the mechanisms underlying excessive fall of blood pressure during HD. Fifty‐six CRF patients with HD thrice a week were divided into two groups according to the intradialytic hypotension episodes after 4 weeks of the observation period; the hypotension group, showing four or more episodes of intradialytic hypotension, and the non‐hypotension group, showing three episodes of intradialytic hypotension or less. The intradialytic hypotension was defined as a fall of ≥30 mm Hg in the systolic blood pressure during HD. The brachial‐ankle pulse wave velocity (ba‐PWV), serum high‐sensitivity (hs)‐CRP, reactive oxygen species (ROS) generation, and serum malondialdehyde‐modified LDL (MDA‐LDL) were measured before HD. The high‐ frequency (HF) and low‐frequency components (LF) of the heart rate variability and entropy were analyzed by the maximal entropy method. The ba‐PWV, hs‐CRP, ROS generation, and MDA‐LDL were significantly higher in the hypotension group than in the non‐hypotension group. HF, LF/HF, and entropy during HD increased significantly in the non‐hypotension group, while entropy during HD decreased significantly in the hypotension group as compared with the baseline. LF/HF and entropy during HD were significantly lower in the hypotension group than in the non‐hypotension group. These findings suggest that the major factors causing excessive fall of blood pressure during HD in patients with CRF might be vascular malfunction and imbalance of autonomic nervous activity.     

Outcome of patients with reactive amyloidosis associated with rheumatoid arthritis in dialysis treatment

The aim was to analyze the clinical outcome of a group of 51 patients diagnosed with systemic amyloidosis associated with rheumatoid arthritis who received hemodialysis (HD) as renal replacement therapy. We monitored the clinical course of the disease and factors that could influence survival. Determination of the onset of the underlying disorder was made retrospectively by reviewing the patient’s chart when a diagnosis of amyloid was confirmed. During a 96.9 person-year follow-up, 42 patients died. Survival of these 51 patients from the initiation of HD at 251 days was 50%. Poor prognosis in amyloid patients was mainly due to a large number of sudden deaths immediately following HD therapy. Out of 51 patients 21 needed unplanned initiation of HD. The unplanned initiation was significantly associated with poor survival. Seventy-five percentile of creatinine clearance (Ccr) was 9.7 ml/min, and 75% of these patients who initiated HD had highly impaired renal functional states. These data indicated that amyloidotic patients with HD showed a high mortality rate; therefore, planned initiation of HD was highly recommended to improve the patient’s survival. Particular attention was given to the Ccr levels, because the levels of serum creatinine may not be a useful marker for some patients with amyloidosis.     

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.     

Perilipin‐1 in Hemodialyzed Patients: Association With History of Coronary Heart Disease and Lipid Profile

Perilipin‐1 surrounds lipid droplets in both adipocytes and in atheroma plaque foam cells and controls access of lipases to the lipid core. In hemodialysis (HD) patients, dyslipidemia, malnutrition, inflammation and atherosclerosis are common. Thirty‐six HD patients and 28 healthy volunteers were enrolled into the study. Ten HD patients suffered from coronary heart disease (CHD). Perilipin‐1, triglycerides, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol (HDL‐C), body mass index, albumin, geriatric nutritional risk index, normalized protein catabolic rate, interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) were measured. Perilipin‐1 did not differ between HD patients and healthy volunteers. IL‐6 and TNF‐α were higher in HD patients. The evaluated nutritional markers and the markers of inflammation did not differ between HD patients with high perilipin‐1 levels and HD patients with low perilipin‐1 levels. Regarding the lipid profile, only HDL‐C differed between HD patients with high perilipin‐1 levels and HD patients with low perilipin‐1 levels, and it was higher in the first subgroup. Perilipin‐1 was significantly higher in HD patients without CHD. Perilipin‐1 is detectable in the serum of HD patients and it is associated with increased HDL‐C and decreased incidence of CHD.     

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.     

Changes in Serum Asymmetric Dimethylarginine and Endothelial Markers Levels With Varying Periods of Hemodialysis

Asymmetric dimethylarginine (ADMA) as a uremia toxin is accumulated in end‐stage renal disease (ESRD) patients. Elevated ADMA level has been shown to be predictive of cardiovascular diseases (CVDs) and all‐cause mortality in ESRD. Therefore, we investigated the effect of prolonged hemodialysis (HD) treatment on the levels of serum ADMA, arginine, nitric oxide (NO), soluble intercellular adhesion molecule‐1 (sICAM‐1) and soluble vascular cell adhesion molecule‐1 (sVCAM‐1). Seventy‐five patients (M/F = 40/35) with chronic renal failure (CRF) and who were on HD were divided into five groups with differing treatment periods of HD; from 6 to 24 months to 97–120 months. Fifteen apparently healthy subjects acted as controls. The serum levels of ADMA, sICAM‐1 and sVCAM‐1 were increased in all patient groups compared to the control group. No significant difference was observed when the patient groups were compared in terms of HD treatment periods. Nitric oxide levels were lower in the three groups who were treated for periods of 49–72, 73–96, 97–120 months compared to the control group. The L‐arginine to ADMA ratio was decreased in all patient groups compared to controls. Consequently, our investigations have shown that in HD continued for more than 4 years NO levels began to decrease significantly and the levels of serum ADMA, sICAM‐1 and sVCAM‐1 levels increased although this increase was not affected by the period in which hemodialysis treatment was applied.     

Cardiovascular Protective Effects of On‐Line Hemodiafiltration: Comparison With Conventional Hemodialysis

Atherosclerotic complications have a significant effect on mortality in patients undergoing hemodialysis (HD) therapy. However, anti‐atherosclerotic and cardioprotective effects of on‐line hemodiafiltration (HDF) remain to be elucidated. We prospectively compared the anti‐atherosclerotic and cardioprotective effects in two randomly divided groups, i.e. on‐line HDF group (n = 13) and conventional HD group (n = 9) for 1 year. Surrogate markers were brachial‐ankle pulse wave velocity (baPWV), intima‐media thickness (IMT) of carotid artery as an atherosclerosis marker, and cardiac functional surrogate markers included left ventricular mass index (LVMI), ejection fraction (EF), and LV diastolic capacity represented as E/A and deceleration time (DT). LVMI in on‐line HDF patients showed significant regression after 1 year of treatment (131.9 ± 25.8 to 116.5 ± 24.7 g/m², P = 0.03), while LVMI in HD patients did not show any significant change (148.0 ± 47.1 to 142.3 ± 35.5 g/m²). Levels of baPWV in HD patients showed a significant increase (11.4%) from basal levels, while on‐line HDF groups showed no significant increase. Furthermore, HD patients showed significant worsening of LV diastolic capacity (E/A: from 0.87 ± 0.12 to 0.79 ± 0.08, P = 0.03), while it was not shown in on‐line HDF patients. Ejection fraction and IMT did not show any significant change in both groups. Serum albumin, C‐reactive protein, β2 microglobulin, blood pressure, and anti‐hypertensive drug use did not change in both groups. On‐line HDF showed a significant improvement in LVMI and prevented a significant worsening of baPWV or LV diastolic capacity compared with patients on conventional HD therapy.     

Role of Uremic Toxins on Apoptosis With Varying Periods of Hemodialysis

Increased apoptotic cell death in uremic patients has been confirmed by a variety of studies. The present study aimed to investigate the effect of uremic toxins and duration of hemodialysis (HD) therapy on apoptosis by means of measuring serum caspase cleaved CK18 (CCCK‐18) levels. Seventy chronic HD patients were recruited and divided into three groups with differing periods of HD, from 6 months to 10 years. Twelve healthy subjects served as controls. Serum CCCK‐18 level was found significantly higher in HD patient groups (Group 2; 189 ± 71 IU/L, Group 3; 182 ± 65 IU/L, Group 4; 204 ± 111 IU/L) as compared to the control group (122 ± 20 U/L) (P < 0.05). When all hemodialysis patients considered together serum CCCK‐18 showed positive correlation with serum uric acid and phosphorus (P < 0.05). In conclusion, our results suggest that apoptosis is enhanced in HD patients, phosphorus and uric acid might play a role in this increment, but duration of HD therapy has no effect on apoptosis.     

Usefulness of combined application of double‐filtration plasmapheresis and twice‐daily injections of interferon‐β in hemodialysis patients with hepatitis C virus genotype 1b infection and a high viral load

Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and has been recognized as an important prognostic factor. Therefore, the aggressive antiviral therapy is necessary for HCV infection in HD patients. However, various treatment limitations exist in HD patients such as the inability to use ribavirin. We have previously reported that HCV RNA can be eradicated by administration of interferon (IFN)‐β during HD in patients with HCV infection caused by genotypes known to be sensitive to IFN therapy and low serum HCV RNA levels. In this case report, we tried to clarify the efficacy of combined application of double‐filtration plasmapheresis (DFPP) and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. We report two HD patients with HCV genotype 1b infection and high viral loads who were successfully treated by five sessions of DFPP undertaken prior to treatment with IFN‐β (twice‐daily injections for 2 weeks). HCV was eradicated by this combination therapy in both patients. We revealed the efficacy of combined application of DFPP and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. This combined therapy may be useful for the HD patients who are resistant to conventional IFN monotherapy.     

Beneficial Effect of Endovascular Therapy and Low‐Density Lipoprotein Apheresis Combined Treatment in Hemodialysis Patients With Critical Limb Ischemia due to Below‐Knee Arterial Lesions

To assess the clinical benefit of combined treatment of below‐knee endovascular therapy (BK‐EVT) plus low‐density lipoprotein apheresis (LDLA) compared with BK‐EVT monotherapy, we retrospectively evaluated the clinical outcome of hemodialysis (HD) patients with critical limb ischemia (CLI) due to isolated BK arterial lesions who underwent BK‐EVT or BK‐EVT plus short‐term LDLA. Between October 2011 and September 2014, 62 HD patients underwent isolated BK‐EVT monotherapy (BK‐EVT group), and 25 HD patients underwent BK‐EVT plus LDLA (BK‐EVT + LDLA group). LDLA was started within 1 week after BK‐EVT and performed four times in total within next 2 weeks. Major adverse limb events (MALE) including major amputation and re‐intervention, and all‐cause mortality were examined by Kaplan–Meier method and the log‐rank test. Baseline characteristics were not different other than low ABI and low dorsal SPP in BK‐EVT + LDLA group. Cumulative MALE‐free rate was significantly improved in BK‐EVT + LDLA group over the BK‐EVT group (72.0% and 45.1% respectively at 30 months after treatment, P = 0.04). All‐cause mortality did not differ between the two groups. Major causes of death were heart failure and sepsis in both groups. Short‐term LDLA hybrid treatment immediately after BK‐EVT might improve the outcome of ischemic limbs after re‐vascularization therapy.