Serum Sclerostin Levels and Mortality in Hemodialysis Patients: An 8-Year Prospective Study.

INTRODUCTION: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure. Sclerostin might be involved in the pathogenesis of vascular calcification, but few studies have examined the association between sclerostin and mortality in hemodialysis patients. METHODS: We analyzed a prospective cohort of 654 patients undergoing maintenance hemodialysis. The primary exposure variable was the baseline serum sclerostin level measured at study enrollment. The primary outcome was 8-year all-cause mortality. Mortality risk was assessed using Cox regression models adjusted for potential confounders. RESULTS: During a median follow-up of 7.6 years (interquartile range, 4.1-8.0 years), 229 of the 654 participants died. In a univariate analysis, serum sclerostin levels were not associated with mortality (HR per doubling, 0.94; 95% CI, 0.76-1.17). This result was unchanged after adjustment for age, sex, dialysis vintage, diabetes, prior cardiovascular disease, and body mass index (HR per doubling, 0.92; 95% CI, 0.72-1.17). Similar results were obtained for cardiovascular mortality. CONCLUSION: Serum sclerostin levels were not associated with mortality in maintenance hemodialysis patients. Further research is required to determine the role of sclerostin in vascular calcification and cardiovascular disease in kidney failure.

Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients.

OBJECTIVES: There is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined. METHODS: Baseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients. RESULTS: The maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL. CONCLUSIONS: The presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.

Continuous intradialytic amino acid infusion from the start of dialysis is better to avoid catabolism under the high-volume pre-dilution on-line HDF.

It was reported that amino acid infusion during hemodialysis is useful for improving nutritional status. The optimal administration method of amino acid infusion under the high-volume pre-dilution on-line HDF (HVPO-HDF) was analyzed in this study. Subjects were 10 patients on maintenance dialysis at our clinic. We performed high-volume pre-dilution on-line HDF. We investigated two methods for administration of Neoamiyu® 200-ml total amino acid (TAA) infusion for patients with renal failure: (1) continuous infusion into the dialysis circuit for 4 h from the start of dialysis to its completion (infusion rate 50 ml/h) and (2) continuous infusion started 1 h before completion of dialysis (infusion rate 200 ml/h), and compared pre- and post-dialysis blood concentrations and leakage of TAA, essential amino acids (EAA), and nonessential amino acids (NEAA) between these methods. Pre-dialysis blood concentrations of amino acids showed no difference between both the groups. Post-dialysis blood concentrations of amino acids were higher in all concentrations were significantly higher with continuous infusion starting 1 h before completion of dialysis. Leakage of amino acids showed no difference between both the groups. The continuous intradialytic amino acid infusion from the start of dialysis is better to avoid catabolism under high-volume pre-dilution on-line HDF.

Amino acid losses are lower during pre-dilution on-line HDF than HD of the same Kt/V for urea.

In this study, we investigated differences in amino acid losses between HD and pre-dilution on-line HDF with equal Kt/V for urea to determine which modality removes less amino acids from extravascular pools and ensures better nutrition. The subjects were patients receiving pre-dilution on-line HDF (n = 10) or HD (n = 10) at this hospital. Dialysis time was 4 h for all patients. In patients on HD, the blood flow rate was 200 mL/min and the dialysate flow rate was 463 ± 29.3 mL/min. In patients on pre-dilution on-line HDF, the blood flow rate was 240 ± 20 mL/min, the dialysate flow rate was 565.0 ± 42.5 mL/min, and the substitution flow rate (substitution volume) was 252.8 ± 26.4 mL/min (57.0 ± 6.0 L). Kt/V for urea was comparable between patients on HD and patients on pre-dilution on-line HDF (1.46 ± 0.25 vs. 1.46 ± 0.31). Amino acid loss and clear space were evaluated. Patients on pre-dilution on-line HDF lost significantly less glutamine and arginine (p < 0.01 and p = 0.032) and significantly less nonessential amino acids (NEAAs) than patients on HD (p = 0.013). They also had significantly lower clear space of total amino acids (TAAs), NEAAs, essential amino acids (EAAs), and branched-chain amino acids (BCAAs) than patients on HD (Total AA p = 0.019, NEAA p = 0.018, EAA p = 0.024, BCAA p = 0.042). When Kt/V for urea is equal, pre-dilution on-line HDF ensures better nutrition than does HD.

Restless legs syndrome effectively treated with constant-pressure predilution online hemodiafiltration.

BACKGROUND: We encountered a case of unstable predilution online HDF due to elevated transmembrane pressure (TMP) when performing constant-speed predilution online hemodiafiltration (HDF) as treatment for restless legs syndrome (RLS) in a dialysis patient. We report the effectiveness of incorporating a newly developed constant-pressure predilution online HDF system as a preventive measure against unstable online HDF and frequent adjustment of settings when treating dialysis patients with RLS. CASE PRESENTATION: A 55-year-old man had suffered from RLS and been undergoing constant-speed online HDF with 45 L target predilution and an ABH-21P hemodiafilter. The symptoms of RLS rated 10 on the International Restless Legs Syndrome Rating Scale (IRLS). The α1-microglobulin (α1-MG) removal rate was only 27.8%, so the hemodiafilter was subsequently replaced with a PEPA hemodiafilter. However, episodes of elevated TMP exceeding 250 mmHg occurred frequently after the replacement and were managed by reducing dialysate flow rate. Therefore, we incorporated a constant-pressure predilution online HDF that maintains TMP below 200 mmHg. The amount of replacement was maintained at approximately 43.5 ± 6.98 L and the α1-MG removal rate was 39.5%, with no need to manually reduce the flow rate. The Alb leakage in dialysate waste was 7.9 g. The patient has maintained an IRLS rating of 0 with no RLS symptoms for the past 4 years. CONCLUSIONS: Using the constant-pressure mode enabled achieved the clinical endpoint, namely, resolution of RLS with no need to manually reduce the flow rate.

Support for Dialysis Therapy in Vietnam, Cambodia, and Myanmar by Japanese Societies in the Field of Blood Purification.

With recent economic development in Southeast Asia, there have been improvements in medical services and healthcare provision. This has led to increased numbers of dialysis patients and increased numbers of dialysis facilities in the region. To assist economically developing countries in managing this change, support projects from Japan have been conducted in the region since around 2007. This article summarizes and discusses Japan's support activities, in which some of the authors were directly involved, in Vietnam, Cambodia, and Myanmar. Initial support was mainly organized by the non-governmental organization Ubiquitous Blood Purification International (NGO UBPI), and currently several organizations in the field of blood purification work together to offer ongoing support in the region. Many positive changes have resulted from these activities in Southeast Asia, but challenges remaining for the future are to establish an educational system for each dialysis specialty and develop dialysis techniques ensuring high treatment quality and safety.

Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis.

BACKGROUND: Hyponatremia is implicated in pathological bone resorption and has been identified as a risk factor for bone fracture in the general population. However, there are limited data on the association between serum sodium levels and fracture risk in patients undergoing hemodialysis (HD). METHODS: We analyzed a historical cohort of 2220 maintenance HD patients to examine the association between serum sodium levels and the risk of fracture and mortality. We also examined the association between serum sodium levels and osteoporosis, based on metacarpal bone mineral density, in a subcohort of 455 patients with available data. In addition, we examined the association between serum sodium levels and bone turnover markers in a separate cross-sectional cohort of 654 maintenance HD patients. RESULTS: During a median follow-up of 5.4 years, 712 patients died, 113 experienced clinical fractures, and 64 experienced asymptomatic vertebral fractures. Lower serum sodium levels were associated with an increased risk of mortality (HR 1.06 per 1 mEq/L decrease; 95% CI 1.03-1.09) but not with the risk of clinical fracture (HR 1.04 per 1 mEq/L decrease; 95% CI 0.97-1.11). A similar lack of association was observed for asymptomatic vertebral fracture and any fracture. Serum sodium levels were also not associated with osteoporosis in a subcohort with available data (n = 455) or with bone alkaline phosphatase or tartrate-resistant acid phosphatase-5b in a separate cross-sectional cohort. CONCLUSION: Serum sodium levels were associated with mortality but not with fracture risk, osteoporosis, or bone turnover markers in maintenance HD patients.

Serum YKL-40 Level is Associated with Geriatric Nutritional Risk Index (GNRI) and γ-GTP in Hemodialysis Patients.

Chitinase-3-like protein 1 (YKL-40) is a glycoprotein associated with inflammation and tissue remodeling that has recently been used as a marker of inflammation in hemodialysis (HD) patients. In this study, we aimed to determine whether YKL-40 has potential to serve as a nutritional parameter in Japanese HD patients. The serum YKL-40 concentration, hematological parameters, inflammatory marker levels, anthropometric measurements, and laboratory values were measured in 88 patients receiving HD. The geriatric nutritional risk index (GNRI) was used as a nutritional assessment tool. 45.4% of patients were malnourished. YKL-40 correlated positively with age, alkaline phosphatase, alanine transaminase and γ-glutamyl transpeptidase (γ-GTP) levels, but not with nutritional status, and correlated inversely with ankle brachial index score, a predictor of atherosclerosis. Furthermore, multiple regression analysis confirmed that γ-GTP, GNRI and age correlated with YKL-40. YKL-40 elevation was associated with γ-GTP, GNRI and age in HD patients. J. Med. Invest. 69 : 101-106, February, 2022.

Present status of renal replacement therapy in lower-middle-income Asian countries: Cambodia, Myanmar, Laos, Vietnam, Mongolia, and Bhutan as of June 2019 (before COVID-19), from the interviews of leading doctors in every country: (duplicated English publication from "the special Japanese edition of educational lectures in the 64th annual meeting of the Japanese Society for Dialysis Therapy").

The present status of Cambodia, Myanmar, Laos, Vietnam, Mongolia, and Bhutan as of June 2019 was reviewed from the interviews of leading doctors in every country. The timing was until just 6 months before the COVID-19 pandemic broke out. The cost per hemodialysis session was 25-70 US dollar and expensive if it is compared with average monthly income of every country. In Cambodia and Laos, patients must cover 100% of expenses for maintenance hemodialysis, in Myanmar, the government covers the cost of once-weekly dialysis sessions, in Vietnam, the government covers 80% of the cost, and in Mongolia and Bhutan, the cost is fully covered by the government. Continuous ambulatory peritoneal dialysis was widely available in Vietnam and Mongolia, which have achieved a relative standard of social infrastructure, but is far from common in any of the other countries. The number of patients on dialysis is increasing with economic development in all countries. Diabetic nephropathy is a common primary reason for dialysis. None of the countries discussed in this article had clinical engineers who could maintain hemodialysis equipment and carry out clinical tasks in dialysis centers. Hospitals were not maintaining their equipment, and damaged units were kept in storage to be used for spare parts. None of the countries had dieticians to provide patients with dietary guidance. Establishment and training of both clinical engineers and registered dietitians are major projects that must be undertaken.

Retraction Note: Impact of the third wave of the COVID-19 pandemic and interventions to contain the virus on society and patients with kidney disease in Cambodia.

[This retracts the article DOI: 10.1186/s41100-021-00372-6.].

Interrelationships Between Sclerostin, Secondary Hyperparathyroidism, and Bone Metabolism in Patients on Hemodialysis.

CONTEXT: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure, but its role in the pathogenesis of renal bone disease remains unknown. OBJECTIVE: We aimed to explore the association of serum sclerostin with bone metabolism in patients undergoing hemodialysis, with a particular focus on parathyroid hormone (PTH)-dependent and PTH-independent pathways. METHODS: This cross-sectional and prospective cohort study included 654 patients undergoing hemodialysis at 10 facilities in Japan. We employed multivariable linear regression to explore whether sclerostin levels were associated with metacarpal bone mineral density (BMD), intact PTH, bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b). We employed mediation analyses to explore whether and to what extent the association of PTH with bone turnover markers is mediated by sclerostin. We also compared sclerostin levels between patients with and without previous or incident fractures. RESULTS: The median sclerostin level in hemodialysis patients was 3- to 4-fold higher than that in healthy individuals. Higher sclerostin levels were associated with higher metacarpal BMD and lower levels of intact PTH, BAP, and TRACP-5b. However, the relationships of sclerostin with bone turnover markers were substantially attenuated after adjustment for PTH. Mediation analysis suggested that the effects of PTH on bone turnover markers were mainly direct rather than mediated by sclerostin. Sclerostin levels were not associated with previous or incident fractures. CONCLUSION: These findings suggest that in patients undergoing dialysis, sclerostin has only a limited role in bone metabolism and may not mediate the effect of PTH on bone turnover.

Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients.

BACKGROUND: Some trials have indicated that coronary artery calcification progresses more slowly in sevelamer-treated dialysis patients than in those using calcium-based binders. Effects of phosphate binders on circulating advanced glycation end products (AGEs) are unknown. STUDY DESIGN: Randomized trial with parallel-group design. SETTING & PARTICIPANTS: 183 adult (aged >20 years) patients on maintenance hemodialysis therapy at 12 dialysis facilities with a mean vintage of 118 ± 89 (median, 108) months. Dialysate calcium concentration was 2.5 mEq/L, and dietary calcium was not controlled. INTERVENTION: Patients were randomly assigned to 12 months of treatment with sevelamer (n = 91) or calcium carbonate (n = 92). OUTCOMES & MEASUREMENTS: Primary outcome measures were change from baseline in coronary artery calcification score (CACS) determined at study entry and completion using multislice computed tomography and the proportion of patients with a ≥ 15% increase in CACS. Blood parameters were determined at study entry and 2-week intervals, and levels of plasma pentosidine, a representative AGE, were determined at study entry, 6 months, and study completion. RESULTS: 79 (86.8%) and 84 (91.3%) patients in the sevelamer and calcium-carbonate arms completed the treatment, respectively. Both binders were associated with an increase in mean CACS: 81.8 (95% CI, 42.9-120.6) and 194.0 (139.7-248.4), respectively (P < 0.001 for both). After adjustment for baseline values, the increase in the sevelamer group was 112.3 (45.8-178) less (P < 0.001). Percentages of patients with a ≥ 15% increase in CACS were 35% of the sevelamer group and 59% of the calcium-carbonate group (P = 0.002). Plasma pentosidine levels increased with calcium carbonate but not [corrected] sevelamer treatment (P < 0.001). Sevelamer use was associated with decreased risk of a ≥ 15% increase in CACS regardless of baseline blood parameters, pentosidine level, and CACS. LIMITATIONS: Treatment duration was relatively short, some sevelamer-treated patients (7 of 79) received calcium carbonate, and washout could not be performed. CONCLUSIONS: The data suggest that sevelamer treatment slowed the increase in CACS and suppressed AGE accumulation.

Impact of the third wave of the COVID-19 pandemic and interventions to contain the virus on society and patients with kidney disease in Cambodia.

Cambodia detected its first case of COVID-19 just 3 days before WHO declared that the outbreak constituted as PHEIC. As of February 15, 2021, and after two major outbreaks, only 479 cases had been reported, 396 (83%) of which were imported. This small number of cases was largely thanks to stringent measures and policies put in place by the government to curb the spread. Despite these efforts, a third cluster outbreak was declared on February 20, 2021. It has disrupted all aspects of life in Cambodia. As in many other countries affected by the virus, economic hardship, lockdowns in cities, and food insecurity ensued. Against the backdrop of this widespread impact on the citizens of Cambodia, we conducted this review article to better understand the situation of healthcare workers in nephrology and dialysis patients and the challenge they face in providing and receiving essential medical care. Healthcare providers have continued working to serve their patients despite facing a high risk of catching SARS-CoV-2 and other challenges including difficulties in traveling to work, increased physical and mental burden, and higher stress due to measures taken to minimize the risk of transmission during patients' care. Some healthcare workers have been discriminated against by neighbors. The most difficult mission is when having to deal with families whose loved one is denied access to a hemodialysis session due to suspected COVID-19 while waiting for PCR test results. Hemodialysis patients reported facing economic hardship and increasingly difficult circumstances. When access to food is limited, patients have eaten canned or dried salted food rather than an appropriate hemodialysis diet. Because hemodialysis centers are concentrated in a few cities, access has become even harder during the travel ban. In-center hemodialysis rules are stricter and does not allow family members or escorts to enter the unit. Only a few hemodialysis patients have been vaccinated. Before COVID-19, hemodialysis patients already faced major burdens. The pandemic appears to be decreasing their quality of life and survival even further. Through this study, we have revealed current hardships and the need to improve the situations for both healthcare workers in nephrology and hemodialysis patients in Cambodia.

[Clinical significance of risedronate for patients with prostate cancer receiving androgen deprivation therapy].

PURPOSE: Androgen deprivation therapy (ADT) in patients with prostate cancer is associated with bone loss. We investigated the effectiveness of risedronate about a decreasing bone mineral density in patients with prostate cancer on ADT. MATERIAL AND METHOD: A prospective study was conducted in Kitasato University Hospital from April 2004 to October 2006. A total of 69 men with prostate cancer were assigned to receive either oral risedronate or none during ADT (hormone naïve). The treatment group was 58 men and taking 2.5 mg risedronate per day. The control group was 11 men. At baseline, we assessed BMD (bone mineral density) by DEXA and urinary NTX, and measured for these changes every 6 months. RESULT: At baseline, each BMDs had no significant difference at the lumber and total hip. At the first 6-month stage, the change in BMD percentage between the 2 groups was statistically significantly different at lumber (p = 0.002) and total hip (p = 0.038). At the 12-month stage, the change in the BMD percentage between the 2 groups was statistically significantly different at the lumber (p = 0.038). And each difference made out that the risedronate group was preserving BMD. In urinary NTX, bone turn over was statistically significantly decreased with the risedronate group compared with the control group at the 12-month stage (p = 0.017). CONCLUSION: We assure the beginning of bone loss at an early date (6 months) with ADT. Daily oral risedronate in patients with receiving ADT reduces bone mineral loss and maintain BMD.

Japan's Support of Hemodialysis in Southeast Asia.

BACKGROUND: With continuing economic development in the developing countries of Southeast Asia, the numbers of dialysis facilities and patients are increasing every year. However, dialysis-related devices tend to be provided with financial support from developed countries and/or donations from nonprofit organizations, and some donated devices are disposed of, without attempts at repair, when they break down. Device management and dialysate quality can also be problematic. SUMMARY: To help address these issues, Japan started to provide technical guidance and support for dialysate purification in these countries. As a result, dialysate quality improved and local medical staff can now perform dialysis therapy using purified dialysate. At the same time, education was provided to staff, and their improved knowledge and skills have contributed to appropriate device maintenance, ensuring the dialysate used is of sufficient quality. Currently, approaches for human resource development are being actively provided in these countries through cooperation with local academic societies or other organizations in the field. Key Messages: A review of the current status of management of dialysis-related devices and dialysate quality in developing countries reveals that financial support and donations for medical devices alone are insufficient and the development of local human resources is crucial. Nurturing and training of clinical engineers, who directly operate today's advanced medical devices for patients, as well as device maintenance and management are urgent issues to address.

Carbohydrate Counting: A Simple Method of Dietary Management for Glycemic Control in Japanese Diabetic Hemodialysis Patients.

BACKGROUND: Carbohydrate counting used in dietary therapy for diabetes is based on the concept that the postprandial rise in blood glucose levels is primarily affected by ingested carbohydrates. This method has been widely accepted and used since 1993, when its usefulness was demonstrated in the United States, largely due to the ease with which patients can understand the method. However, in Japan, there is a common misunderstanding that energy intake determines postprandial blood glucose levels. SUMMARY: We examined the effectiveness of using basic carbohydrate counting and advanced carbohydrate counting with Japanese diabetic dialysis patients. With both methods, predialysis blood glucose and HbA1c levels were significantly decreased at the final follow-up compared with preinstruction values. There were no significant changes in other parameters. The carbohydrate counting method was able to be applied independently of, but concurrently with, the control of potassium and phosphorus intake, which is the basis of dietary therapy for dialysis patients. Moreover, those patients who completed the basic carbohydrate counting instruction sessions had a mean relative carbohydrate intake (% of total energy) of 51.0 ± 4.7% per meal, indicating they did not consume a low-carbohydrate diet. Key Messages: At present, there is no literature on carbohydrate counting performed by dialysis patients. Carbohydrate counting is a useful method of dietary management for glycemic control that can be applied independently of, but concurrently with, the control of potassium and phosphorus intake in dietary therapy for dialysis patients.

Immediate effect of Shakuyaku-kanzo-to on muscle cramp in hemodialysis patients.

We administered 2.5 g of Shakuyaku-kanzo-to granule to 61 patients who had muscle cramp during hemodialysis (HD) sessions and examined its immediate effects. We selected 10 patients who wanted to take the drug at home, out of cases, for whom the drug was effective on the study described above and had them take the drug in the same way at the beginning of muscle cramp at home examined the effects. In the study during HD sessions, muscle cramp and its associated pain disappeared in 5.3 +/- 3.9 min on average in 54 out of 61 cases. In the study of patients who took the drug at home, muscle cramp disappeared within 10 min in all cases. Shakuyaku-kanzo-to is thought to be very useful for muscle cramp during HD sessions of hemodialized patients because it has immediate effects by its oral administration on the occasion of cramp. With regard to the muscle cramp, which appears at home after HD sessions, the patients can cope with it by taking the drug by themselves. This is an epoch-making therapy, for it was impossible to cope with muscle cramp except in hospitals because the therapy of muscle cramp was limited to intravenous infusion of hypertonic solutions of dextrose, mannitol, and saline during HD sessions.

A Prospective Multicenter Randomized Controlled Study on Interleukin-6 Removal and Induction by a new Hemodialyzer With Improved Biocompatibility in Hemodialysis Patients: A Pilot Study.

We compared interleukin-6 (IL-6) removal and induction between conventional polysulfone (Con) and TORAYLIGHT NV (NV) dialyzers in hemodialysis patients. Twenty patients on Con with high IL-6 concentrations (2.7-8.5 pg/mL) were randomized to Con or NV group. Dialyzer performance was determined in NV group while patients were on Con and after being switched onto NV. Erythropoiesis-stimulating agent (ESA) response index (ERI) was assessed every 4 months for one year. IL-6 clearance was comparable between Con and NV. IL-6 removal rates were comparable for the first 1 h, but were higher with NV for the entire session (P = 0.03). Before-to-during-dialysis IL-6 concentration ratios were lower with NV on the venous side after the session (P = 0.03). During the one-year study, hemoglobin was lower in Con group than in NV group at month 8 (P = 0.046). ERI decreased in NV and increased in Con group, with a significant difference between the groups (P = 0.002). NV and Con are comparable in removing IL-6 and both induce IL-6. However, the data suggest that NV induces less IL-6, which may reduce the risk of ESA hyporesponsiveness.