ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD) Patients, But Not with Iron Storage.

OBJECTIVE: It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA. DESIGN AND METHOD: We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI). RESULTS: A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level. CONCLUSION: Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.

How to monitor vascular access in our hospital.

BACKGROUND: The number of dialysis patients in Japan has amounted to approximately 310,000. Most of the patients undergo hemodialysis. The reason why they can undergo hemodialysis is because maintaining and managing vascular access (VA) has improved. Recently, thanks to the progress of medical equipment, a variety of monitoring systems have been developed. It is important to make good use of these monitoring systems. RESULTS: In our hospital, we have been monitoring with an ultrasonic device and HD02. We measure blood flow of brachial artery with an ultrasonic device during nondialysis treatment. We examine real blood flow and blood recirculation with HD02 and evaluate the function of VA during dialysis. CONCLUSIONS: In order to provide good dialysis care, good use of monitoring devices of VA is significant.

The Impact of Buttonhole Cannulation on Patients and Staff in Hemodialysis Facilities.

The two reasons that patients desire buttonhole cannulation are avoidance of puncture pain and extension of arteriovenous fistula life. Despite the desire to receive buttonhole cannulation by many patients, medical staff at most local hemodialysis facilities tend to hesitate to implement the cannulation method. This method is used on patients in the dialysis unit at Saitama Medical Center, but tends to be discontinued for those patients upon their transfer to local hemodialysis facilities. Medical staff members of one local hemodialysis facility report the percentage of patients on the buttonhole method was 53% in 2007, but that it sharply decreased to 17% in 2013. Hesitation by local hemodialysis facilities to adopt the buttonhole method is due to, but not limited to, several factors. These factors include the frequently occurring trampoline effect, the difficulty of removing scabs, formation of a false buttonhole track, and the pain from insertion of a dull needle. Perceived differences in the value of buttonhole cannulation may potentially affect communication between patients and staff in local hemodialysis facilities.

Clinical significance of fractional magnesium excretion (FEMg) as a predictor of interstitial nephropathy and its correlation with conventional parameters.

BACKGROUND: Elevated urine Mg excretion and its correlation with histological damage in tubulo-interstitial nephropathy (TIN) were reported. Here we investigated the clinical significance of the fractional excretion of Mg (FEMg) for the prediction of TIN. METHODS: We enrolled and assessed 94 adult patients with various renal diseases diagnosed principally by renal biopsy. RESULTS: Our stratified analysis based on the value of the conventional TIN parameter N-acetylglucosaminidase (NAG) excretion showed that the high-NAG index group (more than median value of NAG-to-Cr ratio, n = 47) demonstrated significantly high FEMg values (p = 0.017). A univariate analysis revealed a significant correlation between the FEMg and the NAG index (R = 0.60) but not for other parameters. A multivariate regression analysis confirmed the significance of the FEMg as an effective predictor of the NAG index. The FEMg showed a significant correlation with the estimated glomerular filtration rate (eGFR) in the patients with eGFR ≤ 30 mL/min. The correlation of FEMg with the NAG index was not observed in the primary glomerulonephritis patients but was apparent in the patients with hypertensive nephrosclerosis or interstitial nephritis. CONCLUSION: Our findings may indicate that the combination of the FEMg and the NAG index can provide a specific, sensitive assessment for TIN in patients without renal insufficiency.

Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients.

In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations.

Adrenomedullin in peritoneal effluent expressed by peritoneal mesothelial cells.

BACKGROUND: Adrenomedullin (AM) possesses vasodilative and cell-protective properties. Glycine combines with the C-terminal of AM to form mature, physiologically active AM (mAM). AM is reportedly induced by high glucose condition in vascular endothelial or smooth muscle cells; however, little is known on how AM is activated by amidation. To investigate the behavior of AM in patients undergoing peritoneal dialysis (PD), the concentrations of AM, mAM and CA125 were measured. The mAM to AM ratio (mAM/AM ratio) was also evaluated as a marker of amidation activity. METHODS: Twenty patients were recruited for this study. The effluent at the time of the peritoneal equilibration test was collected and AM, mAM and CA125 concentrations were measured. The expression of AM in peritoneal mesothelial cells (PMCs) collected from effluent was also examined with an indirect immunofluorescent method. RESULTS: Mean values of AM and mAM in effluent were 18.1 ± 1.6 and 4.1 ± 0.3 fmol/mL, respectively. In plasma, they were 42.6 ± 3.3 and 5.6 ± 0.6 fmol/mL, respectively. AM concentrations in effluent did not correlate with plasma AM level but correlated well with the dialysate-to-plasma ratio of creatinine (D/P ratio of creatinine). Moreover, in 7 of 20 cases, concentrations of the mAM and mAM/AM ratio in effluent were higher than in plasma. In effluent, AM concentration but not the mAM/AM ratio correlated with CA125 concentration. Immunocytological study revealed diffuse, cytoplasmic expression of AM in PMCs which were collected from effluent during PD. CONCLUSION: AM is expressed by PMCs and actively amidated in the abdominal cavity of patients undergoing PD.

Release from glomerular overload by the addition of low-dose thiazide in patients with angiotensin receptor blocker-resistant hypertension.

BACKGROUND/AIMS: This multicenter, prospective, observational study assessed the renoprotective effects of losartan/thiazide combination therapy in terms of lowering the estimated glomerular filtration rate (eGFR). METHODS: Adult patients with angiotensin receptor blocker (ARB)-resistant essential hypertension (n = 104) were enrolled and switched to combination therapy with losartan (50 mg/day) and hydrochlorothiazide (12.5 mg/day). RESULTS: eGFR values declined significantly during the first 3 months, and changes in eGFR were assessed according to tertiles of the eGFR decrease ratio at 3 months. Only the high eGFR decrease (1st tertile) group showed significantly greater decreases in baseline eGFR and albumin-to-creatinine ratio (ACR) during the first 3 months. Additionally, the assessment according to tertiles of the baseline eGFR showed a signifcant decrease in eGFR and ACR during the first 3 months in the high baseline eGFR (1st tertile) group, but not in the moderate (2nd tertile) and low baseline eGFR (3rd tertile) groups. CONCLUSION: The present results revealed that losartan/thiazide combination therapy attenuated glomerular overload, indicating that this therapy may provide glomerular protection in patients with an elevated GFR without causing prolonged damage to renal function.

Prevention of lipopolysaccharide-induced peritoneal damage by eplerenone in rats undergoing peritoneal dialysis.

BACKGROUND: Bacterial peritonitis in patients undergoing peritoneal dialysis (PD) is a major cause of therapy interruption due to peritoneal insufficiency. Here we studied the effect of a selective mineralocorticoid receptor (MR) blocker, eplerenone, on the prevention of peritoneal damage.
 METHODS: Male Sprague-Dawley rats were treated with a daily infusion of human use PD solution (100 mL/kg i.p., PD group, n = 5), or with PD solution and intermittent intraperitoneal injections of lipopolysaccharide (LPS group, n = 5) or with LPS and eplerenone (100 mg/kg/d, po, Ep group, n = 5) for 4 weeks. Peritoneal samples were subjected to assessment following the peritoneal equilibration test (PET). RESULTS: Histological observations revealed that LPS treatment resulted in significant peritoneal thickening associated with increased ED-1-positive cell infiltration and the number of transforming growth factor (TGF)-ß1-positive cells, and that eplerenone reduced these changes. LPS administration also evoked significant upregulation of monocyte chemotactic protein-1 and TGF-ß1, which were inhibited by eplerenone. PET revealed that ultrafiltration and transperitoneal osmotic diffusion were significantly impaired by LPS and restored by eplerenone. Increased value of the mass transfer area coefficients for creatinine values was also recovered by Ep (0.10 ± 0.01 in the PD, 0.14 ± 0.02 in the LPS and 0.08 ± 0.0 in the Ep groups). Immunostaining for von Willebrand factor showed a significant increase by LPS and its restoration by Ep.
 CONCLUSIONS: Ep effectively diminished LPS-induced peritoneal insufficiency. A selective blockade of MR might prevent peritoneal insufficiency associated with bacterial peritonitis.

A case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with lupus erythematosus in the central nervous system.

We report on a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with lupus erythematosus in the central nervous system (CNS). A 73-year-old woman with essential hypertension suddenly demonstrated consciousness disturbance. Upon her admission, laboratory data showed significant hyponatremia (114 mEq/L) and a lack of body fluid loss. Diminished free water excretion (urine osmolality 684 mOsm/kg) and normal urine Na excretion (FENa 1.70 %) were consistent with the diagnosis of SIADH, which was confirmed by an inappropriately high concentration of plasma antidiuretic hormone (ADH) (15.3 pg/mL at 256 mOsm/kg of plasma osmolality). The hyponatremia was corrected by a combination of oral water intake restriction and saline infusion with furosemide administration until the 20th hospital day. Simultaneously, the presence of exudative pleural effusion in both chest cavities, suggesting the existence of pleuritis, and high titer of anti-nuclear antibody (ANA, 5120×) and anti-double-strand DNA antibody (6500 IU/mL), indicated the subclinical development of systemic lupus erythematosus (SLE), although the diagnostic criteria were not satisfied at that time. On the 34th hospital day, the sudden onset of unknown consciousness disturbance confirmed the diagnosis of SLE as CNS lupus. In previous case reports on SLE and/or SIADH, a few cases in which SLE and SIADH developed concomitantly regularly showed high immunological activities, as in our case. Some common pathophysiological bases might be involved in the concomitant appearance of those disorders.

A case of water intoxication with prolonged hyponatremia caused by excessive water drinking and secondary SIADH.

Water intoxication is a life-threatening disorder accompanied by brain function impairment due to severe dilutional hyponatremia. We treated a 22-year-old man without psychotic illness who had been put in a detention facility. He drank 6 liters of water over a 3-hour period at the facility as a game's penalty, and he showed progressive psychiatric and neurological signs including restlessness, peculiar behavior and convulsions. On his admission, 15 h after the discontinuation of the water drinking, he was in a coma, showing intermittent convulsions and remarkable hyponatremia (120 mmol/l). Because his laboratory tests showed hypertonic urine and normal sodium excretion, the diagnosis of secondary development of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was strongly suggested and later confirmed by the suppression of the renin-aldosterone system and the inappropriately elevated secretion of ADH. Saline infusion and an initial administration of furosemide in addition to dexamethasone as treatments for the patient's brain edema successfully improved his laboratory data and clinical signs by the 3rd hospital day, and he was returned to the facility without physical or psychiatric abnormalities on the 6th day. The secondary SIADH might have been due to the prolonged emesis, recurrent convulsions and rapid elevation of intracranial pressure.

The efficacy of intensive granulocyte and monocyte adsorption apheresis in a patient with Crohn's disease complicated by extensive subcutaneous aseptic neutrophilic abscesses.

BACKGROUND AND AIMS: Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohn's disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). METHODS: The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. RESULTS: On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patient's CDAI fell to <150, and the skin lesions re-epithelialized. CONCLUSIONS: In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.

Dialysate purification after introduction of automated hot water disinfection system to central dialysis fluid delivery system.

Most dialysis clinics in Japan have mainly adopted the central dialysis fluid delivery system (CDDS) to provide constant treatment to many patients. Chemical disinfection is the major maintenance method of the CDDS. Our clinic introduced an automated hot water disinfection system that used the heat conduction effect to disinfect a reverse osmosis (RO) device and dialysis fluid supply equipment. Endotoxin level and the amount of viable bacteria often showed abnormal values before introduction of this system. After its introduction, weekly disinfection resulted in endotoxin levels and the amount of viable bacteria lower than measurement sensitivity. In hot water disinfection, water heated to 90°C in the RO tank flows into the dialysis fluid supply equipment. The maximum temperature inside the tank of the supply equipment is 86.3°C. (We confirmed that the temperature was maintained at 80°C or more for 10 minutes or more during the monitoring.) Dialysate purification was maintained even after introduction of the automated hot water disinfection system and the dialysate could be supplied stably by the CDDS. Therefore, this disinfection system might be very useful in terms of both cost and safety, and can be used for dialysis treatment of multiple patients.

Early use of brachial-basilic arteriovenous fistula.

PURPOSE: The aim of this study was to evaluate the long-term patency rate and complications associated with the use of the BBAVF in the early period. METHODS: The records of all patients undergoing BBAVFs for hemodialysis access between June 2001 and June 2011 were retrospectively evaluated. We allowed the use of the BBAVF beginning two weeks after the fistula creation. The primary and secondary patencies were estimated using the Kaplan-Meier method. RESULTS: A total of 44 BBAVFs were created for 41 patients. Most (73.2%) of the patients had previously been on hemodialysis. A previous history of AVG creation was noted in 36.6% and previous insertion of a catheter was reported for 72.7% of the patients, respectively. The mean time to the first cannulation of the BBAVF was 18.8 days (13-42 days). In two cases, the BBAVFs were not used. Postoperative complications were noted in 2 cases, and included prolonged arm edema and thrombosis. There was no infection of the wound or steal syndrome. The primary and secondary patency rates were 68.1% and 84.2% at 1 year, 55.0% and 80.7% at 2 years, and 38.1% and 70.1% at 5 years, respectively. CONCLUSIONS: In this study, the patency rates following the early use of the BBAVFs were not inferior to the previously reported patency rates in the literature. In cases where the patients already have an inserted central catheter, the early use of the BBAVFs decreases the complications associated with catheters.

Endogenous factors modified by hemodialysis may interfere with the accuracy of blood glucose-measuring device.

In Japan, self-monitoring of blood glucose (SMBG) devices are widely used both at home and in hospitals, but many analytical errors and safety concerns have been reported about the SMBG devices used in hospitals. Analytical performances of StatStrip (Nova Biomedical Corporation, MA, USA), a new point-of-care testing device and Glutest (Sanwa Chemical, Aichi, Japan), a routinely used SMBG device were compared in glucose measurement of pre- and postdialysis blood samples and we evaluated which factors in blood modified by hemodialysis affect accuracy of these devices. Subjects in this study were 44 hemodialysis patients. Blood samples were obtained from patients just before and just after the hemodialysis. Blood glucose concentrations of samples were measured by StatStrip and Glutest. Hematocrit and plasma concentrations of electrolytes, metabolites, etc. of the samples were measured in the central laboratory. StatStrip showed no difference between pre- and postdialysis blood samples and showed very little bias from reference method. On the other hand, Glutest showed difference between pre- and postdialysis samples. Although there is no problem in the data of predialysis blood samples by Glutest, however, these of the postdialysis blood samples by Glutest were >10% less than reference method. Factors in blood modified by hemodialysis such as hematocrit, uric acid, albumin, potassium, and calcium affected glucose readings by Glutest. Glucose readings by Glutest of samples from hemodialysis patients were affected by hematocrit and several factors, which were modified by hemodialysis. StatStrip is considered as a better device in dialysis hospitals.

Renoprotective effect of pioglitazone by the prevention of glomerular hyperfiltration through the possible restoration of altered macula densa signaling in rats with type 2 diabetic nephropathy.

BACKGROUND/AIMS: Pioglitazone (PGZ), one of the thiazolidinediones, has been known to show renoprotective effects. In this study, we focused on the effect of PGZ on glomerular hyperfiltration (GHF), resultant glomerular injury and altered macula densa signaling as a cause of sustained GHF through modified tubuloglomerular feedback in rats with diabetic nephropathy. METHODS: Kidneys from 24-week-old male OLETF rats and LET rats, nondiabetic controls, were used for the experiment. PGZ was administered (10 mg/kg/day, p.o.) for 2 weeks from 22 to 24 weeks of age in some of the OLETF rats (OLETF+PGZ). RESULTS: Parameters relating GHF, kidney weight, creatinine clearance, urine albumin/creatinine ratio and glomerular surface were all increased in OLETF rats and partially restored in OLETF+PGZ rats. Expressions of desmin and TGF-ß were also increased in OLETF rats and restored in OLETF+PGZ rats. The changes in TGF-ß expression were confirmed to be independent of podocyte number. Finally, the immunoreactivity of neuronal nitric oxide synthase (nNOS) and cyclooxygenase 2 (COX-2) in the macula densa was assessed for the evaluation of macula densa signaling. Altered intensities of nNOS and COX-2 in OLETF rats were restored in OLETF+PGZ rats, which agreed with the gene expression analysis (nNOS: 100.2 ± 2.9% in LET, 64.2 ± 2.7% in OLETF, 87.4 ± 12.1% in OLETF+PGZ; COX-2: 100.8 ± 7.4% in LET, 249.2 ± 19.4% in OLETF, 179.9 ± 13.5% in OLETF+PGZ; n = 5) and the semiquantitative analysis of nNOS/COX-2-positive cells. CONCLUSION: PGZ effectively attenuated the GHF and hyperfiltration-associated glomerular injury in diabetic nephropathy. The restoration of altered macula densa signaling might be involved in the renoprotective effect of PGZ.

Treatment of refractory Crohn's disease by intensive granulocyte and monocyte adsorption apheresis: a report on two drug refractory cases.

Granulocyte and monocyte adsorption apheresis (GMA) is one therapeutic option for induction of remission in patients with inflammatory bowel diseases. Recently intensive GMA (2 sessions per week) was reported to be strikingly better than weekly GMA, both in remission rate and time to remission. Here we report two cases of Crohn's disease refractory to weekly GMA who responded to intensive GMA. One patient had not received immunosuppressive therapy while the other had been refractory to combination therapy with infliximab and azathioprine. Intensive GMA induced remission in these 2 patients. Intensive GMA may represent a therapeutic choice for remission induction and maintenance with infliximab.

Contribution of residual renal function on peritoneal solute transport in dialysis patients.

BACKGROUND: Increased peritoneal solute transport rate (PSTR) is primarily a consequence of continuous exposure to bioincompatible glucose-based peritoneal dialysis (PD) solutions. However, relationships between increasing PSTR and dialysate glucose load remain unclear. As some PD patients with preserved residual renal function do not show increased PSTR despite long-term PD, we examined whether loss of residual renal function is associated with increased PSTR on long-term PD. METHODS: We evaluated 35 patients who started PD between 1997 and 2002 and received continuous PD treatment for >6 years. Data included baseline clinical data, residual renal function, urea and creatinine clearance, dialysate glucose load, ultrafiltration, and the use of icodextrin and renin-angiotensin system inhibitors. Peritoneal equilibration test results and data were collected annually for 6 years. RESULTS: Both the glomerular filtration rate and urine volume at 6 years on PD showed significant negative correlations with the dialysate-to-plasma creatinine ratio (D/P Cr) at 6 years (r = -0.716 and r = -0.717, respectively). Multivariate analysis showed only urine volume at 6 years on PD as an independent covariate of the D/P Cr at 6 years on PD. CONCLUSIONS: Loss of residual renal function is directly associated with increased PSTR in patients on long-term PD.

[Predictive value of ultrasonographical assessments of carotid artery for cardiovascular events in patients under hemodialysis: add on comparison with stroke patients].

BACKGROUND: The prognosis of patients on hemodialysis (HD) was determined with respect to cardiovascular disease. We analyzed the relationships between several parameters of carotid artery echograms and cardiovascular events (CVE) in patients on HD. We also compared the characteristic findings of carotid artery echography in patients with stroke and patients on HD. METHOD: We enrolled 104 patients on HD (male : female, 72: 32; mean age, 63.0 +/- 11.2 years) and 48 with stroke (male : female, 36: 12; mean age, 66.0 +/- 7.7 years) who were admitted to our hospital between 1998 and 2004. We measured intima media thickness (IMT), plaque score (PS), resistive index (RI), common carotid artery (CCA) stenosis and plaque echogenicity using B-mode ultrasonography. The correlation between carotid artery echographic findings and CVE were analyzed over a period of 37.5 +/- 22.9 months of follow-up. The characteristic findings of carotid artery echography were compared among groups of patients on initial HD (iHD) and maintenance HD (mHD) and with stroke accompanied by eGFR > 60 mL/min/1.73 m2. RESULTS: Both PS and RI significantly correlated with CVE (p < 0.005 and p < 0.05, respectively), and CVE occurred at the early phase of follow up in patients with increased PS. Both PS and RI were also higher in mHD than in stroke (p < 0.005). Both PS and CCA stenosis were higher in mHD than in iHD (p < 0.01, p< 0.05). More hard plaques were identified in patients on mHD than in those with stroke (p < 0.005). Multivariate analysis showed that the numbers of soft and hard plaques were significantly associated with CCA stenosis(p < 0.05) and the duration of dialysis (p < 0.05), respectively. CONCLUSIONS: Increasing PS and RI were powerful predictors of CVE in patients on HD. Atherosclerotic changes were equal in patients on iHD and those with stroke. Plaque score, the numbers of hard plaques and CCA stenosis were increased in mHD, suggesting the development of atherosclerotic changes in patients on HD.