A questionnaire on prescription patterns of proton pump inhibitors for hemodialysis patients in Japan.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used in the general population often without an endpoint. The practice of prescribing PPIs in the hemodialysis (HD) population is unknown. Thus, we aimed to identify the practice pattern related to PPI prescription for HD patients in Japan through a questionnaire survey. METHODS: We conducted a questionnaire survey for physicians engaged in dialysis practice through email. An email was sent to physicians listed in the Japanese Society of Nephrology (JSN) and iHOPE International registry. RESULTS: We received 187 physicians' answers. One-hundred twelve (60%) physicians would prefer to continuously prescribe PPIs after 8 weeks of treatment for peptic ulcer (PU) or gastroesophageal reflux disease (GERD). The main reason for continuous PPI prescription was the concern for recurrence of PU or GERD. Approximately 20% of physicians responded that they were not accustomed to de-prescribing PPIs for PU or GERD. The reason for PPI de-prescription was the concern for side effects or insurance adaptation period. Even in cases wherein PPIs were prescribed for uncertain reasons, 42% physicians would continuously prescribe PPIs. Most physicians (82%) who answered about stopping PPIs regarded HD patients as a high-risk group for PU. CONCLUSIONS: PPI prescription is often continued in HD patients. De-prescription is not a common practice in Japan. It remains unclear whether discontinuation of PPIs should be recommended in hemodialysis patients who have a high risk of gastrointestinal ulcer. Yet, considering the side effects and polypharmacy in the HD population, more discussions on preferable de-prescription of PPIs are needed.

Correction: Development and Validation of a Clinical Prediction Rule for Bacteremia among Maintenance Hemodialysis Patients in Outpatient Settings.

[This corrects the article DOI: 10.1371/journal.pone.0169975.].

Association Between Staphylococcus aureus Bacteremia and Hospital Mortality in Hemodialysis Patients With Bloodstream Infection: A Multicenter Cohort From Japanese Tertiary Care Centers.

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non-SAB cases. Hospital mortality was higher among SAB cases than non-SAB cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.

Development and Validation of a Clinical Prediction Rule for Bacteremia among Maintenance Hemodialysis Patients in Outpatient Settings.

BACKGROUND: To our knowledge, no reliable clinical prediction rule (CPR) for identifying bacteremia in hemodialysis (HD) patients has been established. The aim of this study was to develop a CPR for bacteremia in maintenance HD patients visiting the outpatient department. METHODS: This multicenter cohort study involved consecutive maintenance HD patients who visited the outpatient clinic or emergency room of seven Japanese institutions between August 2011 and July 2013. The outcome measure was bacteremia diagnosed based on the results of blood cultures. The candidate predictors for bacteremia were extracted through a literature review. A CPR for bacteremia was developed using a coefficient-based multivariable logistic regression scoring method, and calibration was performed. The test performance was then assessed for the CPR. RESULTS: Of 507 patients eligible for the study, we analyzed the 293 with a complete dataset for candidate predictors. Of these 293 patients, 48 (16.4%) were diagnosed with bacteremia. At the conclusion of the deviation process, body temperature ≥ 38.3°C, heart rate ≥ 125 /min, C-reactive protein ≥ 10 mg/dL, alkaline phosphatase >360 IU/L, and no prior antibiotics use within the past week were retained and scored. The CPR had a good fit for the model on calibration. The AUC of the CPR was 0.76, and for score CPR ≥ 2, the sensitivity and specificity were 89.6% and 51.4%, respectively. CONCLUSIONS: We established a simple CPR for bacteremia in maintenance HD patients using routinely obtained clinical information in an outpatient setting. This model may facilitate more appropriate clinical decision making.

Factors Contributing to Erythropoietin Hyporesponsiveness in Patients on Long-Term Continuous Ambulatory Peritoneal Dialysis: A Cross-Sectional Study.

BACKGROUND: Factors contributing to erythropoietin (EPO) hyporesponsiveness in patients on long-term continuous ambulatory peritoneal dialysis are not well understood. Therefore, we investigated the factors contributing to EPO hyporesponsiveness using the EPO resistance index (ERI). METHODS: A total of 14 patients (7 males and 7 females, age 65.0 ± 11.9 years) were selected for this study. We defined ERI as the weekly dose of EPO per body weight divided by hemoglobin (U/kg/g/dl/week). Bioelectrical impedance analysis was used to assess the patients' body composition and fluid status. We examined associations between ERI and clinical parameters, such as physiological, chemical and nutrition status, by correlation and multiple linear regression analyses. RESULTS: Peritoneal dialysis duration was 95 ± 23 months, and all patients underwent peritoneal dialysis for >5 years. Hemoglobin, blood pressure and ultrafiltration volume of peritoneal dialysis were 11.5 ± 1.2 g/dl, 123 ± 14/72 ± 8 mm Hg and 834 ± 317 ml/day, respectively. Renal Kt/V and peritoneal Kt/V, which are indices of dialysis adequacy, were 0.32 ± 0.31 and 1.70 ± 0.31, respectively. Age and extracellular water/total body water (ECW/TBW) ratio had significant positive correlations with ERI (both p < 0.05). Levels of C-reactive protein, serum albumin, parathyroid hormone and normalized protein catabolic rate were not significantly correlated with ERI. In a multiple regression analysis, ECW/TBW was independently associated with ERI (p < 0.05). CONCLUSIONS: This study demonstrates that ECW/TBW was a factor contributing to ERI and that appropriate maintenance of body fluid volume could contribute to low EPO dosing.

Nephrology pre-dialysis care affects the psychological adjustment, not only blood pressure, anemia, and phosphorus control.

Several studies have suggested that pre-dialysis care is associated with clinical outcomes. However, little has been reported on the influence of pre-dialysis care on the psychological adjustment to dialysis. The purpose of this study was to evaluate the impact of pre-dialysis care on psychological adjustment to dialysis and clinical characteristics. In this cross-sectional study, we enrolled 52 patients who started hemodialysis at our hospital. They were divided into two groups according to the time of referral to our hospital: the early referral group (over 1 year prior to first dialysis: 19 patients, mean age 69.3 ± 11.1) and the late referral group (within 1 year prior to first dialysis: 33 patients, mean age 72.3 ± 8.9). We measured the clinical characteristics and evaluated the psychological adjustment to dialysis by Shontz's stage theory. Compared with the late referral group, the early referral group had a significantly better clinical characteristics concerning blood pressure (140.2 ± 23.7 vs. 156.9 ± 23.3 mmHg, P = 0.0150), hemoglobin (10.3 ± 1.5 vs. 9.4 ± 1.0 g/dL, P = 0.0078), and phosphorus (4.5 ± 1.5 vs. 5.5 ± 1.3 mg/dL, P = 0.0166). In addition, psychological adjustment to dialysis evaluated by Shontz's stage theory was significantly better in the early referral group (P = 0.017). Our results indicate that nephrology pre-dialysis care affects not only blood pressure, anemia, and phosphorus control but also the psychological adjustment to dialysis.

Impact of hydration and nutrition status on the Watson formula in peritoneal dialysis patients.

Urea clearance (Kt/V urea), adjusted for total body water (TBW) using the Watson formula (TBW(Watson)), is widely used to guide peritoneal dialysis (PD) prescription and to ensure dialysis adequacy. The impact of body composition on the determination of TBW(Watson) is well established, but the effect of hydration and nutrition status on TBW(Watson) is not understood. We therefore studied the effects of hydration and nutrition status on TBW(Watson) in PD patients. Our study enrolled 195 PD patients and 33 healthy control subjects. Multiple-frequency bioelectrical impedance spectroscopy (MF-BIS) was used to measure TBW and the result was compared with TBW(Watson). Patients were divided into three groups according to their degree of overhydration [deltahydration status (OH) in liters]: normally hydrated group (OH: < 2.0 L), mildly overhydrated group (OH: 2.0 - 4.0 L), and severely overhydrated group (OH: > 4.0 L). Compared with MF-BIS, the Watson formula overestimated TBW in normally hydrated patients, but underestimated TBW in severely overhydrated patients. In addition, of the normally hydrated patients, 22 were malnourished by subjective global assessment, and the TBW(Watson) overestimation was much greater in them than in the well-nourished patients. Our study suggests that hydration and nutrition status both strongly affect TBW(Watson) in PD patients.

Diurnal variations of blood glucose by continuous blood glucose monitoring in peritoneal dialysis patients with diabetes.

Exaggerated postprandial increase in blood glucose has been postulated to be associated with cardiovascular injury. The concentration of blood glucose is altered by glucose absorption from peritoneal dialysis (PD) fluids. In PD patients, we used continuous blood glucose monitoring (CGM) to analyze diurnal variations in blood glucose. Diurnal blood glucose was determined in 10 diabetic PD patients who used CGM (iPro2: Medtronic, Northridge, CA, U.S.A.) for 3 days. Blood glucose concentrations before and after glycemic control were monitored in 5 patients. Correlations between CGM parameters [standard deviation of blood glucose (SDG)], peritoneal function [dialysate-to-plasma ratio of creatinine (D/P Cr) and end-to-initial dialysate (D/D0) glucose], 24-hour peritoneal glucose absorption, and glycemic index were determined. In 5 patients, CGM was performed again after adjustments to antidiabetic drugs. A large diurnal variation, especially at night, was observed in this patient cohort. No correlation of HbA1c with mean blood glucose concentration was observed. Although SDG had no association with 24-hour peritoneal glucose absorption, it did show an association with D/P Cr and D/D0 glucose. The SDG was significantly lower after treatment with a dipeptidyl peptidase IV inhibitor or an increase in insulin dose. Results of the present study indicate that diurnal variations in glucose depend on the speed of peritoneal glucose absorption rather than the net glucose absorption.

The Prevalence of the Risk Factors for Atherosclerosis among Type 2 Diabetic Patients Is Greater in the Progressive Stages of Chronic Kidney Disease.

BACKGROUND/AIMS: The prevalence of the risk factors for atherosclerosis, other than diabetes mellitus, among type 2 diabetic patients with different stages of chronic kidney disease (CKD) determined by glomerular filtration rate (GFR) was investigated. METHODS: The prevalence of ten risk factors (age ≥65 years, history of smoking, male gender, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia) was determined in 2,107 Japanese type 2 diabetic patients with different stages of CKD (six stages according to GFR). RESULTS: The risk factors for age ≥65 years and male gender were found in 49 and 62% of the study subjects, respectively. The percentages of subjects with a current history of smoking, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia were 35, 44, 47, 70, 61, 13, 21 and 26%, respectively. The prevalence of age ≥65 years, male gender, albuminuria, hypertension, hypo-HDL-cholesterolemia, hyperuricemia and anemia was greater in the later stages of GFR, whereas the prevalence of hypercholesterolemia and obesity did not differ between stages. The prevalence of a current history of smoking was lower in the later stages of GFR. The cumulative number of risk factors increased from 3.1 to 6.8 in the later stages of GFR. CONCLUSION: Among type 2 diabetic patients with CKD, the total number of risk factors increases with the progression of renal dysfunction. It is important to pay attention to newly recognized risk factors for hyperuricemia and anemia, in addition to hypertension, albuminuria and hypo-HDL-cholesterolemia, in monitoring diabetic patients with later stages of CKD.

Vildagliptin is Effective for Glycemic Control in Diabetic Patients Undergoing either Hemodialysis or Peritoneal Dialysis.

INTRODUCTION: Vildagliptin can be used in patients with type 2 diabetes mellitus and renal impairment. However, there have been few reports investigating the clinical effectiveness of vildagliptin in diabetic patients undergoing hemodialysis. No previous studies have evaluated the use of vildagliptin in patients undergoing peritoneal dialysis. The authors determined the usefulness of vildagliptin for treating type 2 diabetic patients receiving chronic dialysis, including peritoneal dialysis. METHODS: A retrospective study of ten diabetic patients undergoing peritoneal dialysis and five diabetic patients undergoing hemodialysis who were treated with 50 mg/day of vildagliptin was performed. Clinical parameters were investigated for a period of 6 months starting from the vildagliptin therapy. RESULTS: The hemoglobin A1c (HbA1c) levels were significantly reduced after baseline in both the peritoneal dialysis and hemodialysis groups, whereas the hemoglobin levels did not change during the follow-up period. The mean change in the HbA1c level (ΔHbA1c) was -0.6 ± 0.9% and -0.5 ± 0.7% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. The glycated albumin (GA) levels were also significantly reduced compared with baseline in the peritoneal dialysis group, although the serum albumin levels did not change. The mean change in the GA level (ΔGA) was -3.4 ± 3.1% and -2.1 ± 2.5% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. Stepwise multivariate analyses demonstrated the level of HbA1c at baseline to be significantly associated with the ΔHbA1c and that the level of GA at baseline was significantly associated with the ΔGA. CONCLUSION: Vildagliptin exhibits effectiveness in patients with type 2 diabetes mellitus undergoing peritoneal dialysis or hemodialysis. The degree of improvement in the HbA1c and GA levels was dependent on these levels at baseline, similar to the findings of previous reports of subjects without end-stage kidney disease.

Hypoglycemia observed during continuous glucose monitoring in patients with type 2 diabetes mellitus treated by subcutaneous insulin injection.

BACKGROUND: The relationship between hypoglycemia and the dose of insulin used in patients with type 2 diabetes mellitus was investigated by continuous glucose monitoring (CGM). PATIENTS AND METHODS: In total, 83 CGM studies were performed in 70 outpatients with type 2 diabetes receiving treatment by subcutaneous insulin injection. RESULTS: The total dose of insulin, bolus insulin dose, and basal insulin dose used in the subjects were 32±18 units, 19±13 units, and 13±8 units, respectively. The proportion of time in the hypoglycemic range (blood glucose<3.9 mmol/L) during CGM was positively correlated with the bolus insulin ratio (bolus/total insulin dose, r=0.22, P=0.04), although it was not associated with the total dose of insulin or the hemoglobin A1c (HbA1c) level. It was negatively correlated with the mean blood glucose (r=-0.38, P<0.01), whereas it was not associated with the SD or the mean amplitude of glycemic excursions (MAGE). The proportion of time in the hypoglycemic range was significantly greater in the subjects with a bolus insulin ratio of ≥0.6 (3.2±4.4%, n=42) than a ratio of <0.6 (1.2±3.0%, n=41), although the HbA1c level, total dose of insulin, mean blood glucose, SD, and MAGE were not significantly different between the two groups. CONCLUSIONS: An excessive dose of bolus insulin might increase the duration of hypoglycemia, independently from the HbA1c levels, in patients with type 2 diabetes mellitus receiving subcutaneous insulin injection.

Development of Wernicke's encephalopathy during initiation of hemodialysis in an elderly non-alcoholic patient.

A 79-year-old man with chronic renal failure developed general fatigue and loss of appetite. He was diagnosed with endstage renal disease and was started on hemodialysis (HD). The symptoms improved immediately, but the mental status deteriorated gradually, reaching Glasgow Coma Scale (GCS) 5. Computed tomography showed no significant intracranial lesion, but magnetic resonance images showed symmetric high-intensity changes in the periaqueductal area, suggestive of Wernicke's encephalopathy (WE). He was immediately treated with intravenous infusion of thiamine. Five days later, the mental status level improved up to GCS 14, and the above MRI findings disappeared. To our knowledge, this is the first report describing the clinical outcome of a non-alcoholic patient who developed WE during initiation of HD. WE should be suspected in patients who are on chronic HD as well as those on initiation of HD with unexplained neurological abnormalities.

Repeated Epstein-Barr virus-associated hemophagocytic syndrome in a lupus nephritis patient.

A 55-year-old Japanese female was diagnosed with systemic lupus erythematosus (SLE) and developed nephrotic syndrome. She was diagnosed with lupus nephritis by a percutaneous renal biopsy. She was treated with intravenous steroid pulse therapy twice, but it proved to be ineffective. She achieved a complete remission after intravenous cyclophosphamide pulse (CPAIV) therapy. Thereafter, her lupus nephritis was well controlled and demonstrated only a low activity. However, she suffered Epstein- Barr virus (EBV)-associated hemophagocytic syndrome (HPS) twice, and in each case she was treated with anticancer drugs and achieved a complete remission. This was a rare case of lupus nephritis who showed repeated EBV-associated HPS.

Left ventricular mass index is an independent determinant of diastolic dysfunction in patients on chronic hemodialysis: a tissue Doppler imaging study.

BACKGROUND: Diastolic heart failure is the most common clinical form of heart failure. Tissue Doppler imaging (TDI) is often used to quantitate left ventricular (LV) diastolic function. The purpose of this study was to identify the determinant(s) of diastolic dysfunction in patients with end-stage renal disease on hemodialysis (HD), using the TDI method. METHODS: The study subjects were 53 patients with end-stage renal disease and preserved LV systolic function on maintenance HD. LV function was assessed by conventional echocardiography. The ratio of early trans-mitral flow velocity to early mitral annular velocity (E/e') was measured by TDI. Patients were stratified into two groups based on E/e' value (≤15 and >15 groups). Arterial stiffness was evaluated by pulse wave velocity and cardio-ankle vascular index. RESULTS: Patients of the E/e' >15 group were older (p = 0.025). There were no significant differences in blood pressure, ejection fraction, E/A, deceleration time, and pulse wave velocity between the E/e' >15 and E/e' ≤15 groups. However, there were significant differences in LV mass index (LVMI; p < 0.001) and cardio-ankle vascular index (p = 0.048) between the two groups. Multiple regression analysis identified that LVMI was an independent determinant of E/e' (p = 0.003). CONCLUSIONS: Our findings suggest that LVMI is an independent determinant of LV diastolic dysfunction in patients on HD.