Japanese Study of the Effects of AMG (α1-Microglobulin) Reduction Rates on Survival (JAMREDS): A Protocol of a Multicenter Prospective Observational Cohort Study.

INTRODUCTION: Recent advances in dialysis therapy have made it possible to remove middle molecules. Removal of small-middle molecules, such as ß2-microglobulin, can now be achieved with conventional hemodialysis (HD), and removal of large-middle molecules has become a target, particularly for α1-microglobulin (AMG, 33 kD). The AMG reduction rate has emerged as a target for improvement of various clinical symptoms, but the effects on prognosis have yet to be determined. The "Japanese study of the effects of AMG (α1-microglobulin) reduction rates on survival" (JAMREDS) was started in April 2020, with the goal of determining if the AMG reduction rate associates with the risk of mortality and cardiovascular disease (CVD) events. METHODS: JAMREDS is a prospective observational study in patients on HD to examine the effects of: (1) AMG reduction rate on survival outcome and CVD events; (2) dialysis treatment modalities (HD, intermittent infusion hemodiafiltration(iHDF), pre/post-dilution online HDF) on survival and CVD events (based on AMG reduction rates with treatment mode); and (3) AMG reduction rates on survival and CVD events in patients undergoing each therapy (iHDF, pre/post-dilution online HDF). The number of planned subjects was 4,000 in preplanning. Data are collected using RED-Cap, which is an EDC system. A total of 9,930 patients were enrolled at the beginning of the study at 59 registered facilities. The JAMREDS observation period will continue until the end of 2023, after which the data will be cleaned and confirmed before analysis. CONCLUSION: This study may provide new evidence for the relationship between the amount of removed large-middle molecules (such as AMG) and the mortality and CVD risk. Comparisons with convection volumes will also be of interest.

Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report.

BACKGROUND: Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy. CASE PRESENTATION: A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia. CONCLUSION: Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.

Removal performance of pre- and post-dilution online hemodiafiltration using identical hemodiafilters in the same patients.

Online hemodiafiltration (OHDF) for renal replacement therapy has two modes: pre- (pre-OHDF) and post-dilution OHDF (post-OHDF). To elucidate the precise differences between the two modes, a clinical study was performed using the same polysulfone hemodiafilters in the same patients. Eight patients were treated with ABH™-22PA for 6 weeks: 3 weeks of pre-OHDF (with substitution volumes of 24, 36, and 48 L) and 3 weeks of post-OHDF (6, 8, and 10 L). The reduction ratios of urea, uric acid (UA), creatinine (CRE), inorganic phosphorus (iP), beta-2-microglobulin (ß2-MG), and alpha-1-microglobulin (α1-MG) were evaluated. The removal amounts of ß2-MG, α1-MG, and albumin were also evaluated by analyzing the spent dialysis fluids. The types and numbers of adverse events (AEs) and device malfunctions were recorded. The reduction ratios of urea, UA, CRE, iP, and ß2-MG were comparable among all conditions, while that of α1-MG tended to be slightly higher in post-OHDF than in pre-OHDF. The removal amounts of α1-MG and albumin in pre-OHDF and post-OHDF were significantly greater with the maximum substitution volume than with the minimum volume. However, the selective removal indices, which were obtained by dividing the amount of α1-MG removed by the albumin level, tended to be slightly higher in pre- than in post-OHDF. No device-related AEs or device malfunctions occurred in either mode. No significant differences in inflammatory responses, evaluated by high-sensitivity C-reactive protein and interleukin-6, were observed. This study provides removal performance and safety data regarding the application of ABH-22PA for pre- and post-OHDF.

X-linked Alport Syndrome with Type IV Collagen α5 Chain Staining Revealing Normal Expression in the Glomerular Basement Membrane and Negative on Bowman's Capsule and Distal Tubular Basement Membrane: A Case Report.

X-linked Alport syndrome is a hereditary progressive renal disease resulting from the disruption of collagen α3α4α5 (IV) heterotrimerization caused by pathogenic variants in the COL4A5 gene. This study aimed to report a male case of X-linked Alport syndrome with a mild phenotype accompanied by an atypical expression pattern of type IV collagen α5 [α5 (IV)] chain in glomerulus. A 38-year-old male presented with proteinuria (2.3 g/day) and hematuria. He has been detected urinary protein and occult blood since childhood. A renal biopsy was performed at the age of 29 years; however, a diagnosis of Alport syndrome was not considered. A renal biopsy 9 years later revealed diffuse thinning and lamellation of the glomerular basement membrane. Α staining for α5 (IV) revealed a normal expression pattern in the glomerular basement membrane and a complete negative expression in Bowman's capsule and distal tubular basement membrane. Using next-generation sequencing, we detected a COL4A5 missense variant within exon 35 (NM_000495.5: c.3088G>A, p. G1030S). The possibility of X-linked Alport syndrome should be considered when negative expression of α5 (IV) staining on Bowman's capsule was observed.

Splenic abscess diagnosed following relapsing sterile peritonitis in a peritoneal dialysis patient: A case report with literature review.

Peritoneal dialysis (PD)-related peritonitis is sometimes complicated with other infections; however, few cases of splenic abscess have been reported. We present the case of a 64-year-old PD patient with complicated splenic abscesses diagnosed following relapsing sterile peritonitis. After PD induction, he presented with turbid peritoneal fluid and was diagnosed with PD-related peritonitis. A plain abdominal computed tomography (CT) did not reveal any intra-abdominal focus of infection. After empiric intravenous antibiotics, the peritoneal dialysate was initially cleared, with a decrease in dialysate white blood cells (WBC) to 20/µL. However, WBC and C-reactive protein (CRP) levels remained elevated. A contrast-enhanced abdominal CT showed two areas of low-density fluid with no enhancement in a mildly enlarged spleen, making it difficult to distinguish abscesses from cysts. Due to relapsing sterile peritonitis, we performed an abdominal ultrasonography, and suspected splenic abscesses due to rapid increase in size. Repeated imaging tests were useful in establishing a diagnosis of splenic abscesses. Considering the persistent elevation of WBC and CRP levels, imaging findings, and episodes of relapsing peritonitis, we comprehensively formed the diagnosis, and performed a splenectomy as a rescue therapy. We should consider the possibility of other infectious foci with persistent inflammation after resolving PD-related peritonitis.

Clinical Characteristics and Risk Factors for Mortality due to Bloodstream Infection of Unknown Origin in Hemodialysis Patients: A Single-Center, Retrospective Study.

INTRODUCTION: Hemodialysis patients are at a high risk of bloodstream infection (BSI). The risk factors for BSI-associated mortality, especially of unknown origin, remain uncertain. BSI of unknown origin is highly prevalent and related to high mortality. The present study aimed to investigate the clinical and microbiological characteristics of BSI and risk factors for BSI-associated mortality, including BSI of unknown origin, in hemodialysis patients. METHODS: This study was a single-center, retrospective study conducted from August 2012 to July 2019 in hemodialysis patients with BSI at Kawashima Hospital. Data related to demographics, clinical parameters, BSI sources, causative microorganisms, and initial treatments were collected from the medical records. The predictors for mortality associated with BSI were evaluated by logistic regression. RESULTS: Among 174 patients, 55 (30.9%) had the infection from unknown origin. The most frequent bacterium was Staphylococcus aureus. Low serum albumin level was an independent predictor of mortality due to BSI (odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.13-0.59). A lower serum albumin level (≤2.5 g/dL) was associated with poorer mortality. Methicillin-resistant Staphylococcus aureus (MRSA) was independently associated with mortality due to BSI of unknown origin (OR: 6.20, 95% CI: 1.04-37.1); 87.5% cases with BSI of unknown origin due to MRSA were not initially administrated anti-MRSA antibiotics, and in such patients, the mortality rate was 85.7%. CONCLUSIONS: Serum albumin level of 2.5 g/dL is a cutoff value, which could predict the mortality due to BSI in hemodialysis patients. Considering the high mortality rate of MRSA-associated BSI of unknown origin, wherein no focus of infection was identified in the present study, initial empiric treatment should be considered for MRSA-associated BSI of unknown origin.

Circulating FGF23 is not associated with cardiac dysfunction, atherosclerosis, infection or inflammation in hemodialysis patients.

Fibroblast growth factor (FGF) 23 is a bone-derived hormone regulating serum inorganic phosphate (Pi) concentration. FGF23 is also involved in the development of chronic kidney disease (CKD)-mineral and bone disorder. Serum FGF23 concentration begins to increase early in the progression of CKD and can be remarkably high in hemodialysis patients with end-stage renal disease. It has been reported that high FGF23 concentration is a risk factor for cardiac dysfunction, atherosclerosis, infection or systemic inflammation in CKD patients. FGF23 was also shown to induce cardiac hypertrophy directly acting on cardiomyocytes. However, it is still controversial whether high FGF23 is causing cardiac dysfunction, atherosclerosis, infection or systemic inflammation in CKD patients. In the current study, we investigated whether FGF23 concentration is associated with cardiac dysfunction, atherosclerosis, infection or systemic inflammation in Japanese hemodialysis patients. We recruited 119 hemodialysis patients and examined the association between serum FGF23 concentration and several parameters concerning mineral metabolism, cardiac dysfunction, atherosclerosis, infection, and systemic inflammation. Serum FGF23 concentration was independently associated with serum calcium and Pi concentration (ß = 0.276, p < 0.001; ß = 0.689, p < 0.001). However, serum FGF23 concentration was not associated with parameters of cardiac dysfunction, atherosclerosis, infection, and systemic inflammation, either. Our results do not support the hypothesis that high FGF23 in dialysis patients is the cause of cardiac dysfunction, atherosclerosis, infection or systemic inflammation.

A Clinical Significance of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared to Hemodialysis: A Multicenter Randomized Controlled Crossover Trial.

BACKGROUND: Intermittent infusion hemodiafiltration -(I-HDF) using repeated infusion of ultrapure dialysis fluid through a dialysis membrane or sterile nonpyrogenic substitution fluid was developed to prevent a rapid decrease in blood pressure by increasing the patient's circulating blood volume, to enhance the plasma refilling rate by improving peripheral circulation, and to enhance solute transfer from the extravascular space to the intravascular space by enhancing the plasma refilling rate. Furthermore, the effect of fouling caused by attachment of proteins to the membrane as a result of ultrafiltration can be reduced by backflushing of the membrane with the purified dialysate in I-HDF. Although there have been several clinical trials of I-HDF, there have been no comparisons of the clinical significance of and indications for -I-HDF with those of conventional hemodialysis (HD). OBJECTIVE: The aim of this multicenter randomized controlled crossover trial was to compare the clinical significance of -I-HDF with that of HD in Japan. METHOD: Patients were randomized to receive HD, I-HDF, and HD (group A) or I-HDF, HD, and I-HDF (group B) in that order for 14 weeks each. The sample size of 70 was determined based on the operability and patient availability. Treatment outcomes were evaluated 5 and 14 weeks after the start of each treatment period. The patients received 4-h treatment sessions with no changes in session duration or anticoagulant therapy during the study. I-HDF was performed using a GC-110N dialysis machine. Two hundred milliliters of ultrapure dialysis fluid were infused at a rate of 150 mL/min by backfiltration every 30 min during treatment. The first and last infusions were performed 30 min after the start and 30 min before the end of treatment, respectively. The total estimated infusion volume per session was 1.4 L (i.e., 200 mL × 7 infusions). I-HDF is a type of online HDF with a small fluid replacement volume. An ABH-P polysulfone membrane hemodiafilter was used for -I-HDF and a class 1 or 2 hemodialyzer with a polysulfone membrane not coated with vitamin E and approved by the Japanese reimbursement system was used for HD. The primary outcomes were the Short Form-36 version 2 summary scores for quality of life and the visual analog scale scores for clinical symptoms. Secondary outcomes were vital signs, number of interventions, and pre-treatment blood test results. These variables were evaluated 1 week before at the start of the study, and at 5 and 14 weeks after the start of each treatment period. The removal characteristics of the various solutes were evaluated when possible on the first day of each treatment period. All patients provided written informed consent to participate. RESULTS: Thirty-two patients in group A and 32 patients in group B completed the trial. There were no differences in the primary or secondary outcomes between I-HDF and HD. Serum α1-microglobulin (MG) levels at 14 weeks were significantly lower for I-HDF than for HD. During treatment, the removal rates for urea and creatinine, which are low molecular weight substances, were significantly lower during I-HDF than during HD. In contrast, the ß2-MG and α1-MG removal rates were significantly higher during I-HDF than during HD. Furthermore, there was significantly less albumin leak during I-HDF than during HD. The solute removal results reflect the difference in pore size between the hemodiafilter used for I-HDF and the hemodialyzer used for HD and the difference in convective transport attributable to filtration between the 2 methods. CONCLUSIONS: These findings show that the removal rates of low molecular weight substances are significantly lower and those of medium to high molecular weight substances are significantly higher with I-HDF than with HD. They also indicate that there is significantly less albumin leak during I-HDF than during HD, meaning that I-HDF may be a particularly suitable dialysis modality for patients with malnutrition and the elderly in Japan.

Influence of albumin leakage on glycated albumin in patients with type 2 diabetes undergoing hemodialysis.

Glycated albumin (GA) is recommended as a better glycemic indicator than HbA1c in patients undergoing hemodialysis, because the red blood cell lifespan is generally faster than that in normal subjects. However, GA can be also affected by protein loss in urine and hemodialysis fluid. Therefore, in this study, we investigated the effect of albumin leakage induced by hemodialysis on GA. Nine patients undergoing hemodialysis with a large or small amount of albumin leakage were observed for 9 months in a crossover manner. As a result, it was shown that albumin leakage could affect GA, but the effect was practically small considering the prescription of diabetic drugs. The correlations between HbA1c and blood glucose levels and between GA and blood glucose levels were similar in our study. In conclusion, GA was a reliable indicator, even with the change of hemodialysis modality. The influence of albumin leakage induced by hemodialysis on GA was negligible practically. We should recognize that the preferable glycemic indicator in patients undergoing hemodialysis depends on the hemoglobin and albumin metabolism of each patient.

Cilostazol-induced acute tubulointerstitial nephritis accompanied by IgA nephropathy: a case report.

BACKGROUND: Cilostazol is an antiplatelet drug that is widely prescribed for the prevention of secondary stroke. Adverse reactions to cilostazol include headaches, palpitations, and diarrhea. Little is known about the nephrotoxicity of cilostazol, such as acute kidney injury. We report a biopsy-proven case of diffuse tubulointerstitial nephritis induced by cilostazol. CASE PRESENTATION: A 69-year-old woman prescribed cilostazol was hospitalized for acute kidney injury. On admission, her renal function deteriorated, with an increased serum creatinine level. Urinalysis showed hematuria, proteinuria, and hyper-beta2-microglobulinuria. A renal biopsy revealed diffuse tubulointerstitial nephritis associated with IgA nephropathy, and gallium-67 scintigraphy showed uptake in the bilateral kidneys. A drug lymphocyte stimulation test for cilostazol was positive, and the patient was diagnosed with cilostazol-induced acute tubulointerstitial nephritis. Despite discontinuation of cilostazol, her renal function rapidly worsened and steroid pulse therapy was initiated, followed by oral high-dose glucocorticoid therapy. After steroid treatment, her serum creatinine level normalized in parallel with urine beta2-microglobulin. CONCLUSION: Cilostazol can induce acute tubulointerstitial nephritis.

Prognostic factors for mortality in middle-aged and older hemodialysis patients: a 5-year observational study.

Clinical guidelines for hemodialysis therapy have been described in an evidence-based manner with most evidence from randomized control trials or retrospective studies in which all generations of the hemodialysis patients were enrolled. Therefore, the question still remains whether these guidelines can be applied to increasing older patients. This study is an observational study, including 735 patients who received maintenance hemodialysis in April 2006. At baseline, the participants' age was 62.1 ± 12.8 years (mean ± SD). Hemodialysis duration was 103.7 ± 89.3 months. In a 5-year observation period (actual follow-up period: 1551 ± 499 days), 175 patients died. Prognostic factors were investigated by multivariate analysis with Cox proportional hazard model. Next, we stratified the patients according to their age. 363 patients were included in the middle-aged patient's category between 40 and 64 years, and 314 were involved in the older patient's category between 65 and 84 years old. As a subanalysis, significant predictors of 5-year survival were examined in the age-stratified cohort. Then, Kt/V, serum ß2-microglobulin and calcium concentration were significant predictors in our entire cohort, as well as body mass index, neutrophil count, and serum sodium concentration even after adjustment for age, gender, diabetic status and hemodialysis duration. However, Kt/V, serum ß2-microglobulin and calcium concentration controlled by hemodialysis prescriptions were independent risk factors especially in older patients, not in middle-aged patients. In conclusion, hemodialysis prescriptions for lowering uremic toxins and managing mineral-bone disorder are important to decrease the risk of death even in older hemodialysis patients.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Henoch-Schönlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome.

A 37-year-old pregnant woman developed purpura which was subsequently diagnosed as Henoch-Schönlein purpura (HSP). After childbirth, the patient developed proteinuria and hematuria. Further examination revealed that the HSP nephritis (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase syndrome. The onset of HSPN during pregnancy or after childbirth is rare. Moreover, to our knowledge, this is the first case to describe renal involvement in anti-synthetase syndrome.

The effect of albumin leakage in hemodialysis patients on redox status of serum albumin.

Human mercaptoalbumin (HMA) is a reduced form of albumin that is associated with cardiovascular disease in dialysis patients. Albumin-leaky hemodialysis (HD) is increasingly recognized as a gold standard therapy because it is correlated with better prognosis compared to conventional HD. However, albumin-leaky HD induces low serum albumin concentration because of albumin leakage, which is a classical risk factor for mortality. The aim of this study was to explain the preferable prognosis in patients undergoing albumin-leaky HD with low serum albumin concentration. Ten HD patients were enrolled. They were preconditioned with albumin-non-leaky HD (mean albumin leakage: 1.0 g) for 2 months. Subsequently, albumin-leaky HD (9.1 g) was performed for 6 months, followed by relatively non-leaky HD (within 3.0 g). The ratio and level of HMA were evaluated. The amount of albumin leakage was related to the ratio of HMA, and inversely correlated with serum albumin concentration. The level of HMA was maintained regardless of albumin leakage. Regarding HMA level, a moderate amount of albumin leakage was acceptable. A stably maintained HMA level in albumin-leaky HD patients can contribute to preferable prognosis even if they have low serum albumin concentration.

Treatment of renal anaemia with erythropoiesis-stimulating agents in predialysis chronic kidney disease patients: Haemoglobin profile during the 6 months before initiation of dialysis.

AIM: Erythropoiesis-stimulating agents (ESAs) are all effective for renal anaemia in patients with chronic kidney disease (CKD). However, it was reported that the haemoglobin (Hb) concentration decreases to 8.4 g/dL during the initial phase of dialysis despite treatment with recombinant human erythropoietin (rHuEPO). This study compared Hb at the initiation of dialysis among patients treated with three different ESAs (rHuEPO, darbepoetin alfa [DA], and a continuous erythropoietin receptor activator [CERA]). METHODS: The subjects were 82 CKD patients who started dialysis at Kawashima Hospital between 1 January 2009 and 28 February 2015 and who received only one kind of ESA for at least 6 months before initiation of dialysis. Baseline characteristics and laboratory data at initiation of dialysis were compared among the three groups. Then changes of the Hb, ESA dose, and erythropoiesis resistance index were assessed over time during the 6 months before initiation of dialysis. Differences of Hb at the initiation of dialysis were also assessed. RESULTS: Among the 82 patients, 36 received rHuEPO, 13 received DA, and 33 received CERA. Baseline characteristics and laboratory data of the patients showed no significant differences among the three groups. The monthly Hb decreased gradually during the 6-month period before initiation of dialysis in all three groups. Hb was significantly higher in the CERA group than the rHuEPO group at the initiation of dialysis. CONCLUSION: Long-acting ESAs may be more useful for predialysis patients with CKD because they do not attend hospital frequently, unlike haemodialysis patients.

The First-Known Case of Hereditary Heterozygous Butyrylcholinesterase Deficiency in a Patient on Dialysis.

Serum levels of butyrylcholinesterase (BChE) are commonly used to assess liver function. Its levels have been reported to be significantly lower in patients undergoing dialysis. To the best of our knowledge, this is the first report of hereditary heterozygous BChE deficiency in a patient undergoing dialysis. Medical staff involved in the care of patients with BChE deficiency should be aware of anesthetic usage, because prolonged neuromuscular paralysis following the administration of succinylcholine or mivacurium may occur. However, in the heterozygotes, BChE activity is not completely absent. Therefore, differentiating patients undergoing dialysis is challenging. A 52-year-old man underwent living-related kidney transplantation for focal segmental glomerulosclerosis at 22 years of age. As the renal function gradually worsened, the patient began to receive combined hemodialysis and peritoneal dialysis therapy. No problems with anesthesia were observed in past surgeries. The patient's BChE levels fluctuated between 76 and 170 U/L (reference range: 198-495 U/L); however, they had never been previously investigated. We suspected hereditary heterozygous BChE deficiency because the patient's sister was also diagnosed with it. DNA sequencing revealed a heterozygous missense mutation (Gly365Arg) and a K-variant (Ala539Thr). Patients on dialysis with low serum BChE levels often present with low albumin levels which may be overlooked as malnutrition. Thus, BChE deficiency should be suspected in patients on dialysis with unexplained low serum BChE levels. In the case of heterozygous BChE deficiency, the reference value is low, and continuous monitoring is crucial.

Impact of Albumin Leakage on the Mortality of Patients Receiving Hemodialysis or Online Hemodiafiltration.

Background: Online hemodiafiltration (OHDF) has a lower mortality rate than hemodialysis (HD). We aimed to investigate the impact of the albumin leakage on the mortality of patients receiving HD or OHDF. Methods: In this single-center study, consecutive patients receiving renal replacement therapy between January and April 2018 were retrospectively registered. Using (1:1) propensity score matching, 3-year all-cause mortality was compared between patients receiving HD and OHDF, and the impact of albumin leakage on the mortality rate in both groups was investigated. Results: Of the 460 patients, 137 patients receiving HD were matched with an equal number of patients receiving OHDF. OHDF was associated with higher albumin leakage (p < 0.001) and a lower mortality than HD (log-rank test, p < 0.001). Albumin leakage was associated with mortality in patients receiving HD (per 1 g increase, hazard ratio (HR): 0.495, 95% confidence interval (CI): 0.275-0.888) and patients receiving OHDF (per 1 g increase, HR: 0.734, 95% CI: 0.588-0.915). Patients receiving HD, with the highest albumin leakage tertile (>3 g), had a similar mortality rate to patients receiving OHDF, with similar albumin leakage. Conclusions: The negative relationship between albumin leakage and mortality suggests the benefit of removing middle- to -large-molecular-weight substances to improve survival.

Clinical Efficacy and Safety of Low-Dose Pemafibrate in Patients With Severe Renal Impairment: A Retrospective Study.

BACKGROUND: The management of hypertriglyceridemia in patients with chronic kidney disease (CKD) is important. Pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator with less toxic effects on liver and kidney function than those of other fibrates, has recently been approved for the treatment of patients with an estimated glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m2. However, the efficacy and safety of pemafibrate in patients with severe renal impairment have not yet been established. METHODS: This single-center, retrospective observational study included 12 outpatients with CKD and hypertriglyceridemia, who were newly started on low-dose pemafibrate (0.1 mg/day) treatment between December 2021 and May 2023 and whose eGFRs were less than 30 mL/min/1.73 m2 at baseline. Blood samples were collected before and at 12 weeks after pemafibrate treatment. RESULTS: After 12 weeks of treatment, the serum triglyceride level was significantly decreased, whereas the high-density lipoprotein cholesterol level was significantly increased. The serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and uric acid levels were also significantly decreased, without worsening of the eGFR and serum creatinine levels. In the subgroup analysis, there were no significant differences in the changes in clinical parameters regardless of statin use and CKD stage at baseline. CONCLUSIONS: Low-dose pemafibrate administration in patients with severe renal impairment resulted in significant improvements in triglyceride, high-density lipoprotein cholesterol, and serum uric acid levels, and liver function, without adverse events.

Low-density Lipoprotein Receptor Activities, Lipids, Apolipoprotein, and Clinical Course of Patients with Steroid-resistant Nephrotic Syndrome Treated with Low-density Lipoprotein Apheresis: A Case Series.

We herein report three cases of steroid-resistant nephrotic syndrome successfully treated with low-density lipoprotein apheresis (LDL-A). All patients were treated with a combination of steroids, cyclosporine, and LDL-A. In all cases, the serum concentrations of LDL, total and high-density lipoprotein cholesterol, and triglycerides were significantly lowered following LDL-A administration. Furthermore, the estimated LDL receptor activity increased, while both serum LDL and total cholesterol levels decreased, suggesting that LDL-A increases LDL receptor activity by driving changes in serum cholesterol concentration. This case series suggests that LDL-A increases LDL receptor activity, which may improve the intracellular uptake of cyclosporine.

Polymorphism in the human matrix Gla protein gene is associated with the progression of vascular calcification in maintenance hemodialysis patients.

BACKGROUND: Matrix Gla protein (MGP) is one of the important proteins inhibiting vascular calcification (VC). Single nucleotide polymorphisms (SNPs) located in the promoter and coding regions of the MGP gene affect the transcriptional activity. In this study, we investigated the relationship between the SNPs and progression of VC in patients undergoing maintenance hemodialysis (MHD). METHODS: This was a retrospective, longitudinal cohort study of 134 MHD patients whose VC could be followed by multi-detector computed tomography (MDCT) examinations. MGP-SNPs (T-138C, rs1800802 and G-7A, rs1800801) were determined. The progression speed of VC was examined by plotting the abdominal aortic calcium volume scores. RESULTS: The progression speed of VC of patients with the CC genotype of T-138C was significantly slower than that of patients with the CT or TT genotype. Multiple regression analysis showed that CT/TT genotype, greater age at the beginning of MHD, male sex, high levels of calcium × phosphate, low levels of high-density lipoprotein cholesterol, high levels of low-density lipoprotein cholesterol, low levels of ferritin and non-use of angiotensin II receptor blockers were significantly associated with progression of VC. CONCLUSIONS: The MGP-138CC genotype may be associated with slower progression of VC in MHD patients. The genotype of the MGP gene will be a genomic biomarker that is predictive of VC progression.