Assessing protein and albumin recovery rates in different ascites filtration membrane washing methods for cell-free and concentrated ascites reinfusion therapy.

Objectives: In cell-free and concentrated ascites reinfusion therapy (CART), the protein recovery rate decreases when the filtration membrane gets clogged. Employing a device with a filtration membrane washing feature prevents clogging, but it leads to the loss of ascites within the filter, resulting in reduced protein recovery. This study employed a device with a membrane washing function to investigate the relationship between protein recovery rate and the quantity of washing solution used, depending on the selected washing method. Methods: We analyzed cases of CART conducted at Fujita Health University Hospital between May 2021 and November 2022. The cases were divided and compared between two groups: one using flush and rinse as the washing method (flush+rinse group) and another using only flushing (flush group). Results: We identified nine cases and 16 sessions. In the flush+rinse group, the median amount of washing solution used per membrane washing was 259 mL per cycle, whereas it was 54 mL per cycle in the flush group. This difference was statistically significant (p<0.0001). The median total protein recovery rate was 53.8% for the flush+rinse group and 78.8% for the flush group, with the latter showing a significantly higher value (p=0.0199). Conclusions: In CART using a membrane washing function, adopting a washing method that reduces the amount of washing solution leads to an increase in the total protein recovery rate.

Additional renoprotective effect of the SGLT2 inhibitor dapagliflozin in a patient with ADPKD receiving tolvaptan treatment.

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD). Vasopressin plays a pivotal role in ADPKD progression; therefore, the selective vasopressin V2 receptor antagonist tolvaptan is used as a key drug in the management of ADPKD. On the other hand, sodium-glucose cotransporter-2 inhibitors (SGLT2i), which may possibly stimulate vasopressin secretion due to the diuretic effect of the drug, have been shown to have both renal and cardioprotective effects in various populations, including those with non-diabetic chronic kidney disease. However, the effect of SGLT2i in patients with ADPKD have not been fully elucidated. Herein, we report the case of a patient with ADPKD on tolvaptan who was administered the SGLT2i dapagliflozin. The patient was a Japanese woman diagnosed with ADPKD at age 30. Despite the treatment with tolvaptan, eGFR was gradually declined from 79.8 to 50 ml/min/1.73 m2 in almost 5 years and 10 mg of dapagliflozin was initiated in the hope of renoprotective effects. Although a small increase in vasopressin levels was observed, eGFR decline rate was moderated after dapagliflozin initiation. This case suggested an additional renoprotective effect of dapagliflozin in patient with ADPKD receiving tolvaptan. Although there is no evidence about the renal protective effect of SGLT2i in patients with ADPKD, we hereby report a case successfully treated with dapagliflozin for approximately 2 years. Further research, including clinical trials, is needed to evaluate whether SGLT2i are effective in patients with ADPKD.

Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol.

INTRODUCTION: Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population. METHODS AND ANALYSIS: This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse. ETHICS AND DISSEMINATION: The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: jRCTs041220126.

Sodium zirconium cyclosilicate reconciles management of hyperkalemia and continuity of renin-angiotensin-aldosterone system inhibitors: a retrospective observational study.

BACKGROUND: Sodium zirconium cyclosilicate, a non-absorbed non-polymer zirconium silicate, is a new potassium binder for hyperkalemia. A previous report showed that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows a higher continuation rate of renin-angiotensin-aldosterone system inhibitors. However, no studies have compared sodium zirconium cyclosilicate with existing potassium binders for renin-angiotensin-aldosterone system inhibitor continuity. The purpose of this study was to evaluate the effect of sodium zirconium cyclosilicate on angiotensin-converting enzyme inhibitor /angiotensin receptor blocker continuation in patients with hyperkalemia compared to that of calcium polystyrene sulfonate. METHODS: Patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly prescribed sodium zirconium cyclosilicate or calcium polystyrene sulfonate to treat hyperkalemia at a tertiary referral hospital between August 2020 and April 2022 were enrolled in this single-center, retrospective observational study. The primary outcome measure was angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription three months after initiating potassium binders. RESULTS: In total, 174 patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly administered sodium zirconium cyclosilicate (n = 62) or calcium polystyrene sulfonate (n = 112) were analyzed. The prescription rate of angiotensin-converting enzyme inhibitors /angiotensin receptor blockers at 3 months was significantly higher in the sodium zirconium cyclosilicate group than in the calcium polystyrene sulfonate group (89 vs. 72%). Multivariate logistic regression models showed that sodium zirconium cyclosilicate was independently associated with the primary outcome (odds ratio 2.66, 95% confidence interval 1.05-7.43). The propensity score-matched comparison also showed a significant association between sodium zirconium cyclosilicate and the primary outcome. CONCLUSIONS: Our study suggests that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows for a higher continuation rate of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers than calcium polystyrene sulfonate. These findings suggest that sodium zirconium cyclosilicate has potential benefits for patients with chronic kidney disease receiving renin-angiotensin-aldosterone system inhibitors.

Age and Pre-operative HbA1c levels affect renal function compensation in living kidney donors.

OBJECTIVES: About 90% of Japanese kidney transplantations are conducted from living donors, and their safety and the maintenance of their renal function are critical. This study aims to identify factors that affect the compensation of renal function in living kidney donors after donor nephrectomy. METHOD: In a retrospective cohort study, we reviewed data from 120 patients who underwent nephrectomy as living kidney transplant donors in our department from 2012 to 2021. Univariable and multivariable linear regression analyses were performed for donor factors affecting renal function after donor nephrectomy. RESULT: The multivariable linear regression model revealed that the donor's age (p = 0.025), preoperative estimated Glomerular Filtration Rate (eGFR) (p < 0.001), and hemoglobin A1c (HbA1c) (p = 0.043) were independent risk factors for eGFR at six months after nephrectomy. The eGFR deterioration was more strongly associated with age in females than in males, whereas higher HbA1c values were more strongly associated with eGFR deterioration in males. Higher donor age and higher HbA1c each enhance the deterioration of eGFR six months after living donor nephrectomy. The data suggest that old age in especially female donors and preoperative higher HbA1c in male donors have a harmful impact on their renal function compensation.

Predictors of damage accrual in patients with antineutrophil cytoplasmic antibody-associated vasculitis: A nationwide prospective study.

OBJECTIVES: This study elucidated the prognosis and risk factors associated with damage accrual during long-term remission maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We obtained data from 120 patients registered in a nationwide prospective cohort study on remission induction therapy in Japanese patients with AAV and rapidly progressive glomerulonephritis (RemIT-JAV-RPGN), who achieved remission at 24 months after treatment initiation and were followed up for additional 24 months. The primary outcome was the vasculitis damage index (VDI) score at Month 48, and the secondary outcome included risk factors associated with increased total VDI at Month 48. RESULTS: The understudied patients comprised 52 men and 68 women aged 68 ± 13 years. Between Months 25 and 48, the patients' survival rate was 95% (114/120). End-stage renal disease developed in seven patients by Month 48, and 64 cases had increased VDI. The multivariable analysis results revealed that oral prednisolone (PSL) doses at Month 24 were associated with damage accrual between Months 24 and 48. CONCLUSIONS: VDI accrual was observed in more than half of patients with AAV during maintenance therapy, and increased VDI scores were associated with oral PSL doses 24 months after initiating remission induction therapy in Japan.

Comparison of the Serial Humoral Immune Response according to the Immunosuppressive Treatment after SARS-CoV-2 mRNA Vaccination.

Objective The objective of this study was to estimate the humoral immune response evaluated by immunoglobulin G (IgG) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD-IgG) following the third mRNA coronavirus disease 2019 (COVID-19) vaccination in patients with kidney disease who received immunosuppressive treatment. Methods The primary outcome was RBD-IgG levels after the third SARS-CoV-2 vaccination. The primary comparison was the RBD-IgG levels between patients with kidney disease who received immunosuppressive treatment (n=124) and those who did not (n=33). Results The RBD-IgG levels were significantly lower in the patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. The RBD-IgG levels were lower in patients treated with glucocorticoid monotherapy than in those who did not receive immunosuppressive treatment. Even in patients who received ≤5 mg prednisolone, the RBD-IgG levels were significantly lower. Nine of the 10 patients who received rituximab within one year before the first vaccination did not experience seroconversion after the third vaccination. Meanwhile, all nine patients who received rituximab only after the second vaccination experienced seroconversion, even if B cell recovery was insufficient. Patients treated with mycophenolate mofetil plus glucocorticoid plus belimumab had significantly lower RBD-IgG levels than those treated with mycophenolate mofetil plus glucocorticoid. Conclusion The RBD-IgG levels were lower in patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. Low-dose glucocorticoid monotherapy affected the humoral immune response following the third mRNA COVID-19 vaccination.

Effects of N-acetyl-L-tryptophan on desorption of the protein-bound uremic toxin indoxyl sulfate and effects on uremic sarcopenia.

INTRODUCTION: Indoxyl sulfate (IS) is a protein-bound uremic toxin that causes uremic sarcopenia. IS has poor dialysis clearance; however, the addition of a binding competitor improves its removal efficiency. METHODS: Dialysis experiments were performed using N-acetyl-l-tryptophan (L-NAT) instead of l-tryptophan (Trp) using pooled sera obtained from dialysis patients. The molecular structures of L-NAT and Trp were similar to that of IS. Therefore, we examined whether Trp and L-NAT were involved in muscle atrophy in the same manner as IS by performing culture experiments using a human myotube cell line. RESULTS: The removal efficiency of L-NAT was the same as that of Trp. However, L-NAT concentrations in the pooled sera increased at the end of the experiment. Trp (1 mM) decreased the area of human myocytes, similar to IS, whereas L-NAT did not. CONCLUSION: L-NAT is a binding competitor with the ability to remove protein-bound IS while preventing sarcopenia.

Impact of B Cell Depletion on COVID-19 in Kidney Transplant Recipients.

Kidney transplant recipients are patients at high risk for coronavirus disease 2019 (COVID-19) due to being on immunosuppressive therapy. B cell depletion therapy, including rituximab, is an important strategy for ABO-incompatible transplants. However, knowledge about the effect of B cell depletion therapy on COVID-19 is lacking. Thirty kidney transplant recipients who developed COVID-19 were included in this study. To examine the impact of B cell depletion therapy, we retrospectively investigated the relationship between the background of the patients and the clinical outcome. Of the 30 patients, 13 received B cell depletion therapy. The median time between transplant and onset of COVID-19 was 6.1 years after transplantation; however, nine cases remained markedly depleted of CD19(+) cells (<4.0%). The patients were assigned to the normal (n = 21) and depletion groups (n = 9). Progression rates in the depletion and normal groups were 55.6% and 9.5%, respectively (p = 0.014). Furthermore, the survival rate was significantly lower in the depletion group (100% in the normal group vs. 66.7% in the depletion group; p = 0.021). B cell depletion therapy may have long-term effects and increase the risk of COVID-19 in kidney transplant recipients.

Tolvaptan's Association with Low Risk of Acute Kidney Injury in Patients with Advanced Chronic Kidney Disease and Acute Decompensated Heart Failure.

INTRODUCTION: Furosemide, a loop diuretic, is often empirically used to treat acute decompensated heart failure (ADHF) initially. Conversely, decongestion using tolvaptan, an aquaretic, is thought to maintain renal function compared to furosemide. However, it has not been investigated in patients with advanced chronic kidney disease (CKD) at high risk of developing acute kidney injury (AKI). This study aimed to investigate AKI incidence using tolvaptan add-on treatment, compared to increased furosemide treatment for patients with ADHF complicated by advanced CKD. METHODS: We retrospectively studied patients with advanced CKD (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m2) who developed ADHF under outpatient furosemide treatment. The exposure was set to tolvaptan add-on treatment, and the control was set to increased furosemide treatment. RESULTS: Of the 163 patients enrolled, 79 were in the tolvaptan group and 84 in the furosemide group. The mean age was 71.6 years, the percentage of males was 63.8%, the mean eGFR was 15.7 mL/min/1.73 m2, and patients with CKD stage G5 were 61.9%. AKI incidence was 17.7% in the tolvaptan group and 42.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.13-0.86], p = 0.023 in multivariate logistic regression analysis). Persistent AKI incidence was 11.8% in the tolvaptan group and 32.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.10-1.06], p = 0.066 in the multinomial logit analysis). CONCLUSION: This study suggests that tolvaptan may be better than furosemide in patients with ADHF experiencing complicated advanced CKD.

Combination of brain natriuretic peptide and urinary albumin as a predictor of cardiovascular-renal events in outpatients with chronic kidney disease.

Objectives: Cardiovascular and renal diseases are closely related. Brain natriuretic peptide (BNP) and urinary albumin are established predictors for cardiac and renal morbidities, respectively. To date, no reports have investigated the combined predictive value of BNP and urinary albumin for long-term cardiovascular-renal events in patients with chronic kidney disease (CKD). The aim of this study was to investigate this theme. Methods: Four hundred eighty-three patients with CKD were enrolled into this study and followed-up for 10 years. The endpoint was cardiovascular-renal events. Results: During the median follow-up period of 109 months, 221 patients developed cardiovascular-renal events. Log-transformed BNP and urinary albumin were identified as independent predictors for cardiovascular-renal events, with a hazard ratio of 2.59 (95% confidence interval [CI], 1.81-3.72) and 2.27 (95% CI, 1.82-2.84) for BNP and urinary albumin, respectively. For the combined variables, the group with high BNP and urinary albumin had a markedly higher risk (12.41-times; 95% CI 5.23-29.42) of cardiovascular-renal events compared with that of the group with low BNP and urinary albumin. Adding both variables to a predictive model with basic risk factors improved the C-index (0.767, 0.728 to 0.814, p=0.009), net reclassification improvement (0.497, p<0.0001), and integrated discrimination improvement (0.071, p<0.0001) more than each of them alone. Conclusions: This is the first report to demonstrate that the combination of BNP and urinary albumin can stratify and improve the predictability of long-term cardiovascular-renal events in CKD patients.

Outcomes of Pancreas Transplantation for Lower-Ranked Candidates.

BACKGROUND: To perform more pancreas transplantation (PTx), our center sometimes performs pancreas transplantation for candidates ranked sixth place or lower. In this study, we analyzed the outcomes of PTx performed in our center to compare the outcomes of higher- and lower-ranked candidates. METHODS: Seventy-two cases in which PTx was performed at our center were divided into 2 groups according to the candidate's rank. Cases in which PTx was performed for candidates up to fifth place were classified into the higher rank candidate group (HRC group; n = 48), whereas PTx for candidates who were ranked sixth place or lower were classified into the lower rank candidate group (LRC group; n = 24). The outcomes of PTx were retrospectively compared. RESULTS: Although the LRC group included a greater number of older donors (age ≥60 years), a greater number of donors with deteriorated renal function, and a greater number of HLA mismatches, the 1- and 5-year patient survival rates in the HRC group were 91.6% and 91.6%, respectively, compared with 95.8% and 87.0%, respectively, in the LRC group (P = .755). In terms of both pancreas and kidney graft survival, there were no significant differences between the 2 groups. Additionally, there were no significant differences between the 2 groups regarding the glucagon stimulation test and 75 g OGTT results, insulin independence rate, HbA1c, or serum creatinine level after transplantation. CONCLUSIONS: In Japan, where there is a severe donor shortage, the performance of transplantation for lower-ranked candidates would increase the number of opportunities for patients to receive PTx.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia.

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (ß coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

SOX9 and SRY binding sites on mouse mXYSRa/Enh13 enhancer redundantly regulate Sox9 expression to varying degrees.

Sox9 plays an essential role in mammalian testis formation. It has been reported that gene expression in the testes is regulated by enhancers. Among them, mXYSRa/Enh13-which is located at far upstream of the transcription start site-plays a critical role, wherein its deletion causes complete male-to-female sex reversal in mice. It has been proposed that the binding sites (BSs) of SOX9 and SRY, the latter of which is the sex determining gene on the Y chromosome, are associated with mXYSRa/Enh13. They function as an enhancer, whereby the sequences are evolutionarily conserved and in vivo binding of SOX9 and SRY to mXYSRa/Enh13 has been demonstrated previously. However, their precise in vivo functions have not been examined to date. To this end, this study generated mice with substitutions on the SOX9 and SRY BSs to reveal their in vivo functions. Homozygous mutants of SOX9 and SRY BS were indistinguishable from XY males, whereas double mutants had small testes, suggesting that these functions are redundant and that there is another functional sequence on mXYSRa/Enh13, since mXYSRa/Enh13 deletion mice are XY females. In addition, the majority of hemizygous mice with substitutions in SOX9 BS and SRY BS were female and male, respectively, suggesting that SOX9 BS contributes more to SRY BS for mXYSRa/Enh13 to function. The additive effect of SOX9 and SRY via these BSs was verified using an in vitro assay. In conclusion, SOX9 BS and SRY BS function redundantly in vivo, and at least one more functional sequence should exist in mXYSRa/Enh13.

Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy.

Galactose (Gal)-deficient IgA1 (Gd-IgA1) is involved in IgA nephropathy (IgAN) pathogenesis. To reflect racial differences in clinical characteristics, we assessed disease- and race-specific heterogeneity in the O-glycosylation of the IgA1 hinge region (HR). We determined serum Gd-IgA1 levels in Caucasians (healthy controls [HCs], n = 31; IgAN patients, n = 63) and Asians (HCs, n = 20; IgAN patients, n = 60) and analyzed profiles of serum IgA1 HR O-glycoforms. Elevated serum Gd-IgA1 levels and reduced number of Gal residues per HR were observed in Caucasians. Reduced number of N-acetylgalactosamine (GalNAc) residues per HR and elevated relative abundance of IgA1 with three HR O-glycans were common features in IgAN patients; these features were associated with elevated blood pressure and reduced renal function. We speculate that the mechanisms underlying the reduced GalNAc content in IgA1 HR may be relevant to IgAN pathogenesis.

An Examination of Donor Factors That Impact the Results of the Glucagon Stimulation Test as an Assessment of the Pancreatic Graft Endocrine Function.

OBJECTIVES: Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors. METHODS: Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors. RESULTS: The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function ( P < 0.001). CONCLUSIONS: To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered.

First-in-human study of blood amyloid ß removal from early Alzheimer's disease patients with normal kidney function.

INTRODUCTION: Amyloid ß (Aß) is a brain protein that causes Alzheimer's disease (AD). This study aimed to verify whether hemadsorption using a hexadecyl-alkylated cellulose bead (HexDC) column removes blood Aß and brain Aß accumulation in mild cognitive impairment/mild AD cases with normal kidney function. METHODS: Two patients with positive Aß on brain imaging underwent HexDC hemadsorption weekly for 6 months. RESULTS: The Aß removal efficiency of HexDC was 87-99%. Aß1-40 /Aß1-42 influx into the blood in one session was 596/56 and 489/48 ng for Case A and Case B, respectively. Although brain Aß accumulation did not clearly change after 6 months of hemadsorption, cognitive functions measured by the two tests were maintained or slightly improved. CONCLUSION: Blood Aß removal was performed in two early AD patients with normal kidney function without adverse events, and it slightly improved or maintained cognitive function.

The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

Relationship between selection of dosage forms of vitamin D receptor activators and short-term survival of patients on hemodialysis.

BACKGROUND: The benefits of vitamin D receptor activators (VDRAs) for patients with chronic kidney disease are well recognized. However, the optimal criteria for patient selection, dosage forms, and duration providing the highest benefit and the least potential risk remain to be confirmed. MATERIALS AND METHODS: The study population was derived from the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis, a multicenter prospective cohort study of 1520 incident dialysis patients. According to the VDRA usage status in March 2015 (interim report), the 967 patients surviving after March 2015 were classified into three groups: without VDRA (NV, n = 177), oral VDRA (OV, n = 447), and intravenous VDRA (IV, n = 343). Mortality rates were compared using the log-rank test, and factors contributing to all-cause mortality were examined using both univariate and multivariate Cox proportional hazard regression analyses. RESULTS: There were 104 deaths (NV, n = 27; OV, n = 53; IV, n = 24) during the follow-up period (1360 days, median), and significant differences in cumulative survival rates were observed between the three groups (p = 0.010). Moreover, lower all-cause mortality was associated with IV versus NV (hazard ratio, 0.46 [95% confidence interval 0.24-0.89]; p = 0.020). CONCLUSION: This study demonstrated the impact of the VDRA dosage form on the short-term survival of incident hemodialysis patients during the introduction period. Our results suggest that relatively early initiation of intravenous VDRA in patients beginning hemodialysis may have some clinical potential.