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Background We assessed the anti-SARS-CoV-2 spike antibody response to the third dose of BNT162b2 mRNA COVID-19 vaccine in Japanese hemodialysis patients and determined factors associated with the anti-SARS-CoV-2 spike antibody titer after the third dose of COVID-19 vaccine. Methods Overall, 64 patients were enrolled in this single-center, prospective, longitudinal study. Anti-SARS-CoV-2 spike antibody titers were compared between hemodialysis patients and 18 healthcare workers. Multiple linear regression analysis was used to identify factors associated with the anti-SARS-CoV-2 spike antibody titer after the third vaccination. Results There was no significant difference in anti-SARS-CoV-2 spike antibody titer 4 weeks after the third vaccination between hemodialysis patients and healthcare workers (18,500 [interquartile range, 11,000–34,500] vs. 11,500 [interquartile range, 7,918–19,500], all values in AU/mL; p = 0.17). Uric acid (standard coefficient [β] = −0.203, p = 0.02), transferrin saturation (β = −0.269, p = 0.003), and log–anti-SARS-CoV-2 spike antibody titer 1 week before the third vaccination (β = 0.440, p < 0.001) correlated with the log–anti-SARS-CoV-2 spike antibody titer 4 weeks after the third vaccination. In contrast, only the log–anti-SARS-CoV-2 spike antibody titer 1 week before the third vaccination (β = 0.410, p < 0.001) correlated with the log–anti-SARS-CoV-2 spike antibody titer 12 weeks after the third vaccination. Conclusion The anti-SARS-CoV-2 spike antibody titer after the third dose of COVID-19 vaccine was comparable between hemodialysis patients and healthcare workers. Uric acid concentration, transferrin saturation, and anti-SARS-CoV-2 spike antibody titer before the third dose were associated with the anti-SARS-CoV-2 spike antibody titer after the third dose in Japanese hemodialysis patients.

Abstract Background Minimal change nephrotic syndrome (MCNS) can be complicated by thymoma; however, no standard therapy for thymoma-associated MCNS has yet been established. We herein describe a case of steroid-resistant MCNS associated with thymoma, treated effectively with rituximab. Case presentation A 71-year-old Japanese man was referred to our department with severe proteinuria (20 g/gCr). Renal biopsy showed minimal change disease and computed tomography revealed an anterior mediastinal mass. Based on these findings, he was diagnosed with thymoma-associated MCNS. He was treated with oral prednisolone (50 mg/day) and cyclosporine, and underwent thymectomy and plasma exchange. However, no improvement in proteinuria was observed. He therefore received intravenous rituximab 500 mg, resulting in a marked decrease in proteinuria from 5328 to 336 mg/day after 1 week. Conclusions This case suggests that rituximab might be an effective therapy in patients with steroid-resistant MCNS associated with thymoma.

Introduction: Clinical studies on differences among changes in cerebral and hepatic oxygenation during hemodialysis (HD) in patients with and without intradialytic hypotension (IDH) are limited. We investigated changes in intradialytic cerebral and hepatic oxygenation before systolic blood pressure (SBP) reached the nadir during HD and compared these differences between patients with and without symptomatic IDH. Methods: We analyzed data from 109 patients with (n=23) and without (n=86) symptomatic IDH who were treated with HD. Cerebral and hepatic regional oxygen saturation (rSO2), as a marker of tissue oxygenation and circulation, was monitored during HD using an INVOS 5100c oxygen saturation monitor. Changes in cerebral or hepatic rSO2 when SBP reached the nadir during HD were compared between the groups of patients. Results: The cerebral rSO2 before HD in patients with and without symptomatic IDH was 49.7 ± 11.2% and 51.3 ± 9.1% (p = 0.491). %Changes in cerebral rSO2 did not significantly differ between the two groups from 60 min before the SBP nadir during HD. Hepatic rSO2 before HD in patients with and without symptomatic IDH were 58.5 ± 15.4% and 57.8 ± 15.9% (p = 0.869). The %changes in hepatic rSO2 were significantly lower in patients with symptomatic IDH than in those without throughout the observational period (p < 0.001). We calculated the area under the receiver operating characteristic curve (AUC) and estimated cut-off values for changes in hepatic rSO2 as a symptomatic IDH predictor. The predictive ability at 5 and 40 min before symptomatic IDH onset was excellent, with AUCs and cut-off values of 0.847 and 0.841, and -10.9% and -5.0%, respectively. Conclusions: Hepatic oxygenation significantly decreased more in patients with symptomatic IDH before its onset, than in those without symptomatic IDH, whereas changes in cerebral oxygenation did not differ. Evaluating changes in hepatic oxygenation during HD might help to predict symptomatic IDH.

Abstract In hemodialysis (HD) patients with arteriovenous fistula (AVF), changes in systemic or peripheral tissue circulation occur non-physiologically via the presence of AVF; however, associations between blood flow and tissue oxygenation in the brain and access hand are uncertain. In this study, 85 HD patients with AVF were included and evaluated for changes in flow volume (FV) and regional oxygen saturation (rSO2) in the brain and hands with AVF before and after percutaneous transluminal angioplasty (PTA). Furthermore, we evaluated the factors that determine access hand rSO2 without stenosis after PTA. Brachial arterial FV increased after PTA (p

Only a few cases of renal vein thrombosis (RVT) occurring in patients with vasculitis have been reported. RVT associated with vasculitis and hemolytic anemia has not been reported yet. We describe here a patient with RVT complicated by pulmonary embolism, autoimmune hemolytic anemia, and eosinophilic granulomatous polyangiitis. A 69-year-old Japanese man who had been treated with corticosteroids was referred to our department for severe proteinuria (4.32 g/gCr). Abdominal ultrasonography showed bilateral RVT, and contrast-enhanced computed tomography showed bilateral pulmonary embolism. Therefore, the patient was diagnosed with RVT complicated by pulmonary embolism. Anticoagulation therapy with heparin followed by apixaban was started. Thereafter, the D-dimer concentration decreased from 8.3 to 1.2 μg/mL, and urinary protein excretion improved to 0.62 g/gCr. Renal function was unchanged with an estimated glomerular filtration rate of 68.8 mL/minute/1.73 m 2 . The thrombi in both renal veins and pulmonary arteries gradually regressed. Clinicians should be aware of this complication when worsening proteinuria is observed during steroid therapy in patients with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

A 68-year-old man received hemodialysis (HD) for the treatment of end-stage renal failure for 6 years. Five years prior to carotid artery stenting (CAS), a neck ultrasound performed to screen for carotid atherosclerosis revealed an asymptomatic right internal carotid artery stenosis. One month prior, the stenotic lesion progressed to 74% by cerebral angiography; therefore, CAS was performed. To evaluate the influence of right internal carotid artery stenosis on the intradialytic cerebral circulation and oxygenation, cerebral regional oxygen saturation (rSO2) at bilateral forehead was measured using the INVOS 5100c oxygen saturation monitor (Covidien Japan, Japan) during HD before and after CAS. Before CAS, right cerebral rSO2 was maintained during HD, whereas left cerebral rSO2 gradually increased from the initiation to end of HD. However, the differences of intradialytic cerebral rSO2 changes between bilateral sides disappeared after CAS. In the present case, before CAS, the intradialytic increase in left cerebral rSO2 might reflect the increase in the left cerebral blood flow to compensate for the ultrafiltration-associated decreases in the right cerebral blood flow and perfusion pressure. Furthermore, the preserved right cerebral rSO2 before CAS might reflect the mechanism maintaining the right cerebral blood flow from the collateralized circle of Willis during HD. Throughout our experience, cerebral oxygenation monitoring during HD might disclose intradialytic changes in cerebral blood flow distribution between the ipsilateral and contralateral side in HD patients with carotid artery stenosis.

In general populations, age-dependent renal impairment contributes to the progression of renal dysfunction. It has not been known which molecules are involved in age-dependent renal impairment. Messenger RNA (mRNA) has been reported to modulate various renal diseases, and we therefore investigated mRNA signatures in age-dependent renal impairment. We performed an initial microarray-profiling analysis to screen mRNAs, the expression levels of which changed in the kidneys of 50-week-old senescence-accelerated prone (SAMP1) mice (which have accelerated age-dependent renal impairments) compared with those of 50 wk old senescence-accelerated-resistant (SAMR1) mice (which have normal aged kidneys) and with younger (10 wk old) SAMP1 and SAMR1 mice. We next assessed the expressions of mRNAs that were differentially expressed in the kidneys of SAMP1-50wk mice by conducting a quantitative real-time polymerase chain reaction (qRT-PCR) and compared the expressions among the SAMP1-10wk, SAMR1-10wk, and SAMR1-50wk mice. The results of the microarray together with the qRT-PCR analysis revealed five mRNAs whose expression levels were significantly altered in SAMP1-50wk mouse kidneys versus the control mice. The expression levels of the five mRNAs were increased in the kidneys of the mice with age-dependent renal impairment. Our findings indicate that the five mRNAs might be related and could become therapeutic targets for age-dependent renal impairment.

Abstract In chronic kidney disease (CKD) patients, the prevalence of cognitive impairment increases with CKD progression; however, longitudinal changes in cognitive performance remain controversial. Few reports have examined the association of cerebral oxygenation with cognitive function in longitudinal studies. In this study, 68 CKD patients were included. Cerebral regional oxygen saturation (rSO2) was monitored. Cognitive function was evaluated using mini-mental state examination (MMSE) score. Clinical assessments were performed at study initiation and 1 year later. MMSE score was higher at second measurement than at study initiation (p = 0.022). Multivariable linear regression analysis showed that changes in MMSE were independently associated with changes in body mass index (BMI, standardized coefficient: 0.260) and cerebral rSO2 (standardized coefficient: 0.345). This was based on clinical factors with p

Abstract Background Hypokalemia is common in patients with malnutrition undergoing hemodialysis and is often involved in the development of lethal arrhythmia. Moreover, hemodialysis therapy decreases the serum potassium concentration due to potassium removal to the dialysate. However, it is difficult to adjust the dialysate potassium concentration owing to the use of the central dialysate delivery system in Japan. Here, we have presented a case undergoing hemodialysis with dialysate potassium concentration adjustment to prevent ventricular arrhythmia. Case presentation A 56-year-old man with Emery-Dreifuss muscular dystrophy and chronic heart failure was admitted to our hospital and needed subsequent hemodialysis therapy due to renal dysfunction. During hemodialysis, the cardiac resynchronization therapy defibrillator was activated to the treatment of his lethal ventricular arrhythmia. Decreases in serum potassium concentration after hemodialysis and changes in serum potassium concentration during HD were considered the causes of lethal ventricular arrythmia. Therefore, along with using anti-arrhythmic agents, the dialysate potassium concentration was increased from 2.0 to 3.5 mEq/L to minimize changes in the serum potassium concentration during hemodialysis. Post-dialysis hypokalemia disappeared and these changes during hemodialysis were minimized, and no lethal ventricular arrhythmia occurred thereafter. Conclusions In this case, we prevented lethal arrhythmia by maintaining the serum potassium concentration by increasing the dialysate potassium concentration, in addition to the use of anti-arrhythmic agents. In the acute phase of patients with frequent lethal arrhythmia undergoing hemodialysis, an increase in dialysate potassium concentration may be an effective method for preventing arrhythmogenic complications.

BackgroundWe determined the effects of roxadustat on the values of anemia, iron metabolism, renal function, proteinuria, and lipid metabolism and identified the associated factors of the change in hemoglobin levels after roxadustat administration in non-dialysis chronic kidney disease (CKD) patients who were receiving an erythropoietin-stimulating agent (ESA).MethodsWe conducted retrospective analysis of the changes in hemoglobin, serum ferritin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels; transferrin saturation; the estimated glomerular filtration rate; and the urinary protein/creatinine ratio over 24 weeks after the change from an ESA to roxadustat in 50 patients with non-dialysis CKD and anemia (roxadustat group). Seventy-two patients with non-dialysis CKD and anemia who proceeded ESA therapy were used as the control (ESA) group.ResultsWe observed no significant between-group differences in clinical parameters at baseline except for the significantly lower hemoglobin concentration and lower proportion of diabetes mellitus in the roxadustat group. The hemoglobin concentration was significantly higher in the roxadustat group after 24 weeks (11.3 ± 1.2 versus 10.3 ± 1.0 g/dL; value of p

An arteriovenous fistula (AVF) can fail for different reasons at each stage after its creation. The study aimed to analyze the associations of the clinical and laboratory parameters, including the intraoperative AVF blood flow, with AVF failure at different periods (3 weeks and 3, 6, 9, 12, 24, and 36 months) after the AVF's creation and to evaluate the usefulness of the intraoperative AVF blood flow as a surrogate marker of AVF failure in patients with end-stage renal disease (ESRD). This was a single-center, retrospective cohort study that included 130 patients with ESRD who underwent the creation of new radiocephalic AVFs. The associations of the preoperative clinical and laboratory parameters and intraoperative flow with AVF failure in the different observation periods were investigated. Intraoperative AVF blood flow was significantly associated with AVF failure from 3 weeks to 24 months (P 225 mL/min is crucial for long-term AVF patency. The intraoperative AVF blood flow level could be a surrogate marker of AVF failure in ESRD patients.

Early diagnosis and therapeutic intervention improve the quality of life and prognosis of patients with sarcopenia. The natural polyamines spermine and spermidine are involved in many physiological activities. Therefore, we investigated blood polyamine levels as a potential biomarker for sarcopenia. Subjects were Japanese patients >70 years of age who visited outpatient clinics or resided in nursing homes. Sarcopenia was determined based on muscle mass, muscle strength, and physical performance according to the criteria of the Asian Working Group for Sarcopenia (2019). The analysis included 182 patients (male: 38%, age: 83 [76–90] years). Spermidine levels were higher (p = 0.002) and the spermine/spermidine ratio was lower (p < 0.001) in the sarcopenia group than in the non-sarcopenia group. Polyamine concentration analysis showed that the odds ratios for age and spermidine changed in parallel with sarcopenia progression, and the odds ratio for the spermine/spermidine ratio changed inversely with the degree of sarcopenia progression. Additionally, when the odds ratio was analyzed with spermine/spermidine instead of polyamine concentrations, only for spermine/spermidine, the odds ratio values varied in parallel with the progression of sarcopenia. Based on the present data, we believe that the blood spermine/spermidine ratio may be a diagnostic indicator of risk for sarcopenia.

BackgroundAge-dependent renal impairment contributes to renal dysfunction in both the general population and young and middle-aged patients with renal diseases. Pathological changes in age-dependent renal impairment include glomerulosclerosis and tubulointerstitial fibrosis. The molecules involved in age-dependent renal impairment are not fully elucidated. MicroRNA (miRNA) species were reported to modulate various renal diseases, but the miRNA species involved in age-dependent renal impairment are unclear. Here, we investigated miRNAs in age-dependent renal impairment, and we evaluated their potential as biomarkers and therapeutic targets.MethodsWe conducted an initial microarray profiling analysis to screen miRNAs whose expression levels changed in kidneys of senescence-accelerated resistant (SAMR1)-10-week-old (wk) mice and SAMR1-50wk mice and senescence-accelerated prone (SAMP1)-10wk mice and SAMP1-50wk mice. We then evaluated the expressions of differentially expressed miRNAs in serum from 13 older patients (>65 years old) with age-dependent renal impairment (estimated glomerular filtration ratio

Several mechanisms strictly regulate polyamine concentration, and blood polyamines are excreted in urine. This indicates polyamine accumulation in renal dysfunction, and studies have shown increased blood polyamine concentrations in patients with renal failure. Hemodialysis (HD) may compensate for polyamine excretion; however, little is known about polyamine excretion. We measured whole-blood polyamine levels in patients on HD and examined the relationship between polyamine concentrations and indicators associated with health status. Study participants were 59 hemodialysis patients (median age: 70.0 years) at Minami-Uonuma City Hospital and 26 healthy volunteers (median age: 44.5 years). Whole-blood spermidine levels were higher and spermine/spermidine ratio (SPM/SPD) was lower in hemodialysis patients. Hemodialysis showed SPD efflux into the dialysate; however, blood polyamine levels were not altered by hemodialysis and appeared to be minimally excreted. The skeletal muscle mass index (SMI), which was positively correlated with hand grip strength and serum albumin level, was positively correlated with SPM/SPD. Given that sarcopenia and low serum albumin levels are reported risk factors for poor prognosis in HD patients, whole blood SPM/SPD in hemodialysis patients may be a new indicator of the prognosis and health status of HD patients.

Background : Few studies have investigated the relationship between serum total carbon dioxide (CO2) concentration and bicarbonate ion (HCO3-) concentration in patients undergoing hemodialysis. We determined the agreement and discrepancy between serum total CO2 and HCO3- concentrations and the diagnostic accuracy of serum total CO2 for the prediction of low (HCO3- < 24 mEq/L) and high (HCO3- ≥ 24 mEq/L) bicarbonate concentrations in hemodialysis patients. Methods : One hundred forty-nine arteriovenous blood samples from 84 hemodialysis patients were studied. Multiple linear regression analysis was used to determine factors correlated with HCO3- concentration. Diagnostic accuracy of serum total CO2 was evaluated using receiver operating characteristic curve analysis and a 2 × 2 table. Agreement between serum total CO2 and HCO3- concentrations was assessed using Bland-Altman analysis. Results : Serum total CO2 concentration was closely correlated with HCO3- concentration (β = 0.858, P < 0.001). Area under the curve of serum total CO2 for the identification of low and high bicarbonate concentrations was 0.989. Use of serum total CO2 to predict low and high bicarbonate concentrations had a sensitivity of 100%, specificity of 50.0%, positive predictive value of 96.5%, negative predictive value of 100%, and accuracy of 96.6%. Bland-Altman analysis showed moderate agreement between serum total CO2 and HCO3- concentrations. Discrepancies between HCO3- and serum total CO2 concentrations (serum total CO2 - HCO3- ≤ -1) were observed in 89 samples. Conclusion : Serum total CO2 concentration is closely correlated with HCO3- concentration in hemodialysis patients. However, there is a non-negligible discrepancy between serum total CO2 and HCO3- concentrations.

Abstract Background It has been difficult to sufficiently achieve body-fluid management using blood volume (BV) monitor during hemodialysis (HD) with constant ultrafiltration (UF) rate. Recently, a relative BV change-guided UF control (BV-UFC) system was developed by combining the concepts of an automatic feedback system that could control the UF rate and profile with real- time monitoring of relative changes in BV (%ΔBV). However, this system has limited application in the clinical setting. Therefore, in this study, we aimed to perform the crossover study on HD with BV-UFC compared to standard HD in terms of hemodynamic stability during HD. Methods Forty-eight patients entered an 8-week crossover period of standard HD or HD with BV-UFC. Prevalence of intradialytic hypotension (IDH) as a primary outcome and changes in blood pressure (BP), differences in %ΔBV, and achievement of the target ultrafiltration volume as secondary outcomes were compared. IDH was defined as a reduction in systolic BP ≥20 mmHg from the baseline value at 10 min after HD initiation. Results No significant differences were found in the prevalence of IDH, frequency of intervention for symptomatic IDH, and achievement of the target ultrafiltration volume between the groups. The %ΔBV was significantly fewer (-12.1 ± 4.8% vs. -14.4 ± 5.2%, p

Background We report a unique case of renal cholesterol crystal embolism (CCE) induced by carotid artery stenting that was successfully treated with evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9). Case presentation A 77-year-old man with hypertension, hyperlipidemia, and chronic kidney disease was referred to our department for decreased estimated glomerular filtration rate (eGFR)—from 32.0 to 13.9 mL/min/1.73 m2—5 weeks after carotid artery stenting. Further examination revealed livedo reticularis in the bilateral toes and eosinophilia (723/μL). Skin biopsy from livedo reticularis tissue in the bilateral toes showed cholesterol clefts in the small arteries. The patient was therefore diagnosed with CCE. After 25 weeks’ administration of evolocumab at a dose of 140 mg subcutaneously administered every 2 weeks, his eGFR had improved from 10.7 to 18.1 mL/min/1.73 m2. Conclusion Evolocumab may have a beneficial effect on renal involvement in patients with CCE.

Carnitine deficiency contributes to developing various pathological conditions, such as cardiac dysfunction, muscle weakness, and erythropoietin-resistant anemia in patients undergoing hemodialysis. However, a conclusion has not been reached concerning the prevalence and the effect of carnitine deficiency in patients undergoing peritoneal dialysis (PD). In this study, the prevalence of carnitine deficiency and the clinical factors associated with carnitine deficiency were investigated in 60 patients undergoing PD. The median age of the patients was 62.5 years (52.5–72.5 years), the proportion of male sex was 44/60 (73.3%), and the median PD period was 24 months (12–45 months). Carnitine deficiency (acyl carnitine/free carnitine ratio >0.4) was detected in 56/60 (93%) patients. Multiple regression analysis showed that the erythropoietin resistance index was independently associated with carnitine deficiency (β = 0.283, p = 0.04). These results suggest that carnitine plays pivotal roles in hematogenesis in patients undergoing PD.

A 60-year-old woman with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome and intractable ascites presented with acute renal failure and received hemodialysis (HD) therapy. Due to frequent intradialytic hypotension, ultrafiltration with cell-free and concentrated ascites reinfusion therapy (CART) was performed to adequately manage the body fluid status and massive ascites. During HD with CART, her blood pressure was maintained compared with that during HD without CART, and an ultrafiltration volume of 3.7 L was achieved after HD with CART. In HD patients with intradialytic hypotension and massive ascites, the combination of CART and ultrafiltration during HD may be an effective therapeutic option for body-fluid management.

Objective:The aim of this study was to investigate the effects of elobixibat on constipation and lipid metabolism; and determine the factors associated with the effect of elobixibat on constipation in patients with moderate to end-stage chronic kidney disease (CKD).Methods:Stool frequency and serum lipid parameters were retrospectively analyzed before and after 4 weeks of elobixibat administration in 42 patients (CKD stage G3, 6; stage G4, 9; stage G5, 9; stage G5D, 18). Relationships between the change in stool frequency after initiation of elobixibat and various clinical parameters were analyzed by using linear regression analysis.Results:Elobixibat increased stool frequency from 0.5 ± 0.4 per day to 1.1 ± 0.6 per day (p < 0.001) regardless of whether patients were undergoing dialysis, on concomitant laxatives, or were administered elobixibat before or after breakfast. Elobixibat reduced low-density lipoprotein cholesterol concentration (from 90.9 ± 37.2 mg/dL to 77.5 ± 34.8 mg/dL, p < 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p < 0.05), but did not change triglyceride concentration. Adverse effects were observed in two patients (nausea and diarrhea). Only phosphate concentration was correlated with the change in stool frequency after initiation of elobixibat (standard coefficient = 0.321, p = 0.043).Conclusions:Elobixibat improved constipation and lipid metabolism in patients with moderate to end-stage CKD, without serious adverse events.

Abstract Background Proteinase 3-antineutrophil cytoplasmic antibody has been reported to be positive in 5–10% of cases of renal injury complicated by infective endocarditis; however, histological findings have rarely been reported for these cases. Case presentation A 71-year-old Japanese man with a history of aortic valve replacement developed rapidly progressive renal dysfunction with gross hematuria and proteinuria. Blood analysis showed a high proteinase 3-antineutrophil cytoplasmic antibody (163 IU/ml) titer. Streptococcus species was detected from two separate blood culture bottles. Transesophageal echocardiography detected mitral valve vegetation. Histological evaluation of renal biopsy specimens showed necrosis and cellular crescents in glomeruli without immune complex deposition. The patient met the modified Duke criteria for definitive infective endocarditis. On the basis of these findings, the patient was diagnosed with proteinase 3-antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis complicated by Streptococcus infective endocarditis. His renal disease improved, and his proteinase 3-antineutrophil cytoplasmic antibody titer normalized with antibiotic monotherapy. Conclusion Few case reports have described histological findings of proteinase 3-antineutrophil cytoplasmic antibody-positive renal injury complicated with infective endocarditis. We believe that an accumulation of histological findings and treatments is mandatory for establishment of optimal management for proteinase 3-antineutrophil cytoplasmic antibody-positive renal injury complicated with infective endocarditis.

Background: Carnitine supplementation improves various dialysis-related symptoms including erythropoietin-resistant anemia in patients who are undergoing hemodialysis. However, the utility of carnitine supplementation in patients who are undergoing peritoneal dialysis (PD) is not fully understood.Methods: Thirteen patients undergoing PD [mean age: 54.2 ± 14.8 years, males: 9/13 (69%)] administered oral carnitine supplementation (mean dose: 9.1 ± 3.3 mg/kg/day) for 4–6 months were retrospectively investigated. Changes in serum carnitine levels and other clinical variables including the erythropoietin resistance index (ERI) were analyzed after carnitine supplementation.Results: Carnitine supplementation increased serum total carnitine (48.5 ± 10.2 vs. 130.1 ± 37.2 μmol/L, P < 0.01), free carnitine (31.1 ± 8.3 vs. 83.1 ± 24.6 μmol/L, P < 0.01), and acyl carnitine (17.4 ± 2.8 vs. 46.9 ± 13.8, P < 0.01) levels. The acyl carnitine/free carnitine ratio was not affected (0.6 ± 0.1 vs. 0.6 ± 0.1, P = 0.75). Although the mean ERI was not affected by carnitine supplementation [13.7 ± 4.7 vs. 11.6 ± 3.4 IU/kg/(g/dL)/week, P = 0.28], the ERI change rate was significantly decreased (1.00 ± 0.00 vs. 0.87 ± 0.11, P < 0.01).Conclusion: Carnitine supplementation may improve erythropoietin resistance in patients who are undergoing PD.

The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR−122−5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR−122−5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR−122−5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR−122−5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR−122−5p mimic, and the expression level of FOXO3, an anti−fibrotic mRNA, was upregulated by the miR−122−5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR−122−5p inhibitor. These results suggest that miR−122−5p has critical roles in renal fibrosis.

Background: We investigated the effects of roxadustat on the anemia, iron metabolism, peritoneal membrane function, and residual renal function; and determined the factors associated with the administration of roxadustat in patients who were undergoing peritoneal dialysis.Methods: We retrospectively analyzed the changes in hemoglobin, serum ferritin, transferrin saturation (TSAT), 4-h dialysate/plasma creatinine, and renal weekly urea clearance over the 24 weeks following the change from an erythropoiesis-stimulating agent (ESA) to roxadustat in 16 patients who were undergoing peritoneal dialysis and had anemia (Roxadustat group). Twenty-three peritoneal dialysis patients who had anemia and continued ESA served as a control group (ESA group).Results: There were no significant differences in hemoglobin, serum ferritin, TSAT, 4-h dialysate/plasma creatinine, or renal weekly urea clearance between the two groups at baseline. The hemoglobin concentration was significantly higher in the Roxadustat group than in the ESA group after 24 weeks (11.6 ± 1.0 g/dL vs. 10.3 ± 1.1 g/dL, p < 0.05), whereas the ferritin concentration and TSAT were significantly lower (139.5 ± 102.0 ng/mL vs. 209.2 ± 113.1 ng/mL, p < 0.05; and 28.1 ± 11.5% vs. 44.8 ± 10.4%, p < 0.05, respectively). The changes in 4-h dialysate/plasma creatinine and renal weekly urea clearance did not differ between the two groups. Linear regression analysis revealed that the serum potassium concentration correlated with the dose of roxadustat at 24 weeks (standard coefficient = 0.580, p = 0.019).Conclusion: Roxadustat may improve the anemia and reduce the serum ferritin and TSAT of the peritoneal dialysis patients after they were switched from an ESA, without association with peritoneal membrane function or residual renal function.

A 79-year-old woman who was on chronic hemodialysis due to diabetic nephropathy and had previously undergo surgery for radiocephalic arteriovenous fistula (AVF) in her right wrist needed percutaneous transluminal angioplasty (PTA) for stenosis at the juxta-anastomotic access site. After successful PTA, the systemic blood pressure decreased from 144/93 mm Hg to 117/67 mm Hg in response to the increase in AVF blood flow. Furthermore, the regional oxygen saturation (rSO2) value in her dorsal hand decreased from 67.9% to 64.9% and, simultaneously, the cerebral rSO2 decreased from 63.6% to 60.1%. Our experience indicates that the PTA procedure may affect the rapid deterioration of systemic oxygenation, including that in the hand and brain, in association with the increase in the AVF blood flow and change in systemic circulation.

Background : We investigated the relationship between serum total carbon dioxide (CO2) and bicarbonate ion (HCO3−) concentrations in pre-dialysis chronic kidney disease (CKD) patients and devised a formula for predicting low bicarbonate (HCO3−< 24 mmol/L) and high bicarbonate (HCO3− ≥ 24 mmol/L) using clinical parameters. Methods : In total, 305 samples of venous blood collected from 207 pre-dialysis patients assessed by CKD stage (G1 + G2, 46; G3, 50; G4, 51; G5, 60) were investigated. The relationship between serum total CO2 and HCO3− concentrations was analyzed using Pearson's correlation coefficient. An approximation formula was developed using clinical parameters correlated independently with HCO3− concentration. Diagnostic accuracy of serum total CO2 and the approximation formula was evaluated by receiver operating characteristic curve analysis and a 2 × 2 table. Results : Serum total CO2 correlated strongly with HCO3− concentration (r = 0.91; P < 0.001). The following approximation formula was obtained by a multiple linear regression analysis: HCO3− (mmol/L) = total CO2 − 0.5 × albumin − 0.1 × chloride − 0.01 × (estimated glomerular filtration rate + blood glucose) + 15. The areas under the curves of serum total CO2 and the approximation formula for detection of low bicarbonate and high bicarbonate were 0.981, 0.996, 0.993, and 1.000, respectively. This formula had superior diagnostic accuracy compared with that of serum total CO2 (86.6% vs. 81.3%). Conclusion : Serum total CO2 correlated strongly with HCO3− concentration in pre-dialysis CKD patients. An approximation formula including serum total CO2 showed superior diagnostic accuracy for low and high bicarbonate compared with serum total CO2.

Abstract Background Sleep apnea syndrome (SAS) is a sleep disturbance, which is frequently comorbid in dialysis patients. SAS induces hypoxia, and therefore, systemic and cerebral oxygenation would be low. Near-infrared spectroscopy (NIRS) has recently been used to measure regional saturation of oxygen (rSO2), as a marker of tissue oxygenation. Although cerebral rSO2 was measured in patients in various clinical settings, few reports have previously shown the associations of changes in cerebral rSO2 and systemic oxygenation using measurement of peripheral arterial oxygen saturation (SpO2) in patients undergoing hemodialysis (HD) with SAS. We herein report a first HD case with SAS-induced reduction in cerebral oxygenation during sleep. Case presentation A 74-year-old woman underwent HD therapy for 1 month, because of advanced CKD caused by hypertension and obesity. In addition, she was diagnosed with obstructive sleep apnea with polysomnography about 4 years prior. Her apnea-hypopnea index (AHI) was 77.5 per hour, and therefore, continuous positive airway pressure (CPAP) was started. Thereafter, her AHI was improved to 3 to 6 per hour. However, she discontinued CPAP therapy at HD initiation. Since her oxygenation without CPAP would deteriorate, we evaluated her SpO2 and cerebral rSO2 by NIRS monitoring during sleep. We confirmed the deterioration in cerebral rSO2 according to the SpO2 decrease, and furthermore, the improvement in cerebral rSO2 was apparently delayed even after the improvement in her SpO2. The patient’s cerebral oxygenation under CPAP therapy could not be evaluated because she refused to receive CPAP therapy after HD initiation. Therefore, as a comparison, we evaluated a 69-year-old male HD patient without SAS and found that in contrast to a patient with SAS, his SpO2 and cerebral rSO2 were maintained throughout sleep. Conclusion We observed deterioration in cerebral oxygenation during sleep in addition to a decrease in systemic oxygenation in a patient with SAS undergoing HD. Real-time cerebral NIRS monitoring during sleep might be a useful method for detection of SAS.

The hepato-splanchnic circulation directly influences oxygenation of the abdominal organs and plays an important role in compensating for the blood volume reduction that occurs in the central circulation during hemodialysis (HD) with ultrafiltration. However, the hepato-splanchnic circulation and oxygenation cannot be easily evaluated in the clinical setting of HD therapy. We included 185 HD patients and 15 healthy volunteers as the control group in this study. Before HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting the hepato-splanchnic circulation and oxygenation, was monitored using an INVOS 5100c oxygen saturation monitor. Hepatic rSO2 was significantly lower in patients undergoing HD than in healthy controls (56.4 ± 14.9% vs. 76.2 ± 9.6%, p < 0.001). Multivariable regression analysis showed that hepatic rSO2 was independently associated with body mass index (BMI; standardized coefficient: 0.294), hemoglobin (Hb) level (standardized coefficient: 0.294), a history of cardiovascular disease (standardized coefficient: -0.157), mean blood pressure (BP; standardized coefficient: 0.154), and serum albumin concentration (standardized coefficient: 0.150) in Model 1 via a simple linear regression analysis. In Model 2 using the colloid osmotic pressure (COP) in place of serum albumin concentration, the COP (standardized coefficient: 0.134) was also identified as affecting hepatic rSO2. Basal hepatic oxygenation before HD might be affected by BMI, Hb levels, a history of cardiovascular disease, mean BP, serum albumin concentration, and the COP. Further prospective studies are needed to clarify whether changes in these parameters, including during HD, affect the hepato-splanchnic circulation and oxygenation in HD patients.

Background: Zinc deficiency is common and is associated with erythropoietin resistant anemia, dysgeusia, and hypogonadism in patients undergoing hemodialysis. However, the prevalence and clinical effects of zinc deficiency in patients undergoing peritoneal dialysis (PD) have not been determined.Methods: This was a retrospective, cross-sectional study. The prevalence of serum zinc deficiency and the clinical factors related to serum zinc concentration were determined in 49 patients undergoing PD [mean age 59.5 years (±14.8 years), 38/49 were men (78.6%), median PD period 24.0 months (12.5–45.0 months)]. A serum zinc concentration

Diabetic nephropathy is one of the major complications of diabetes mellitus and is the leading cause of end-stage renal disease worldwide. Podocyte injury contributes to the development of diabetic nephropathy. However, the molecules that regulate podocyte injury in diabetic nephropathy have not been fully clarified. MicroRNAs (miRNAs) are small non-coding RNAs that can inhibit the translation of target messenger RNAs. Previous reports have described alteration of the expression levels of many miRNAs in cultured podocyte cells stimulated with a high glucose concentration and podocytes in rodent models of diabetic nephropathy. The associations between podocyte injury and miRNA expression levels in blood, urine, and kidney in patients with diabetic nephropathy have also been reported. Moreover, modulation of the expression of several miRNAs has been shown to have protective effects against podocyte injury in diabetic nephropathy in cultured podocyte cells in vitro and in rodent models of diabetic nephropathy in vivo. Therefore, this review focuses on miRNAs in podocyte injury in diabetic nephropathy, with regard to their potential as biomarkers and miRNA modulation as a therapeutic option.

Background: Patients with chronic kidney disease (CKD) are at risk for bone loss and sarcopenia because of associated mineral and bone disorders (MBD), malnutrition, and chronic inflammation. Both osteoporosis and sarcopenia are associated with a poor prognosis; however, few studies have evaluated the relationship between muscle mass and bone mineral density (BMD) in hemodialysis (HD) patients. The present study examined the association between skeletal muscle mass index (SMI) and BMD in the lumbar spine and femoral neck in HD patients.Methods: Fifty HD patients (mean age, 69 ± 10 years; mean HD duration, 9.0 ± 8.8 years) in Minami-Uonuma City Hospital were evaluated. BMD was measured by dual-energy X-ray absorptiometry, and SMI was measured by bioelectrical impedance analysis (InBodyTM) after HD. The factors affecting lumbar spine and femoral neck BMD were investigated, and multivariate analysis was performed.Results: In simple linear regression analysis, the factors that significantly affected the lumbar spine BMD were sex, presence of hypertension, presence of diabetes mellitus, body mass index, triglyceride level, grip strength, and SMI; the factors that significantly affected the femoral neck BMD were sex, HD duration, serum creatinine level, tartrate-resistant acid phosphatase 5b level, undercarboxylated osteocalcin (ucOC) level, N-terminal propeptide of type I procollagen level, grip strength, and SMI. In multivariate analysis, SMI (standardized coefficient: 0.578) was the only independent factor that affected the lumbar spine BMD; the independent factors that affected the femoral neck BMD were SMI (standardized coefficient: 0.468), ucOC (standardized coefficient: −0.366) and sex (standardized coefficient: 0.231).Conclusion: SMI was independently associated with the BMD in the lumbar spine and femoral neck in HD patients. The preservation of skeletal muscle mass could be important to prevent BMD decrease in HD patients, in addition to the management of CKD-MBD.

Sarcopenia, which is characterized by the loss of skeletal muscle, has been reported to contribute to development of physical disabilities, various illnesses, and increasing mortality. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit translation of target messenger RNAs. Previous studies have shown that miRNAs play pivotal roles in the development of sarcopenia. Therefore, this systematic review focuses on miRNAs that regulate sarcopenia.

Hemoglobin (Hb) is associated with cerebral oxygenation status owing to its important role of carrying oxygen to systemic tissues. However, data concerning the associations between Hb levels and cerebral regional oxygen saturation (rSO2) of hemodialysis (HD) patients is limited. We aimed to identify these associations to consider a target Hb level for renal anemia management. This study included 375 HD patients. Cerebral rSO2 before HD was monitored using the INVOS 5100c oxygen saturation monitor. Multivariable linear regression analysis showed that cerebral rSO2 was independently associated with natural logarithm (Ln)-HD duration (standardized coefficient: -0.36), mean blood pressure (standardized coefficient: 0.13), pH (standardized coefficient: -0.10), serum albumin (standardized coefficient: 0.14), presence of diabetes mellitus (standardized coefficient: -0.20), and Hb level (standardized coefficient: 0.29). Furthermore, a generalized linear model with restricted cubic spline function was used to investigate the non-linear association between cerebral rSO2 and Hb levels. In the multivariable analysis for the adjustment with Ln-HD duration, mean blood pressure, pH, serum albumin, and presence of diabetes mellitus, a linear relationship was demonstrated between the two variables (p for linearity = 0.79). Hb levels revealed the positive and significant association with cerebral rSO2 in this study. Moreover, the relationship between cerebral rSO2 and Hb level was proven to be linear. Therefore, the target Hb level in renal anemia management would be considered to be the upper limits for the appropriate management of renal anemia by previous guidelines and position statement from the viewpoint of maintaining cerebral oxygenation in HD patients.

Background: Mizoribine (MZR) is an immunosuppressive drug used in Japan for treating patients with lupus nephritis and nephrotic syndrome and has been also reportedly effective in patients with immunoglobulin A (IgA) nephropathy. However, to date, few randomized control studies of MZR are performed in patients with IgA nephropathy. Therefore, this prospective, open-label, randomized, controlled trial aimed to investigate the efficacy and safety of adding MZR to standard treatment in these patients, and was conducted between April 1, 2009, and March 31, 2016, as a multicenter study. Methods: Patients were randomly assigned (1:1) to receiving standard treatment plus MZR (MZR group) or standard treatment (control group). MZR was administered orally at a dose of 150 mg once daily for 12 months. Results: Primary outcomes were the percentage reduction in urinary protein excretion from baseline and the rate of patients with hematuria disappearance 36 months after study initiation. Secondary outcomes were the rate of patients with proteinuria disappearance, clinical remission rate, absolute changes in estimated glomerular filtration rate from baseline, and the change in daily dose of prednisolone. Forty-two patients were randomly assigned to MZR (n = 21) and control groups (n = 21). Nine patients in MZR group and 15 patients in the control group completed the study. No significant differences were observed between the two groups with respect to primary and secondary outcomes. Conclusion: The addition of MZR to standard treatment has no beneficial effect on reducing urinary protein excretion and hematuria when treating patients with IgA nephropathy.

BackgroundDietary management is highly important for the maintenance of renal function in patients with chronic kidney disease (CKD). Cerebral oxygen saturation (rSO2) was reportedly associated with the estimated glomerular filtration rate (eGFR) and cognitive function. However, data concerning the association between cerebral rSO2 and dietary intake of CKD patients is limited.MethodsThis was a single-center observational study. We recruited 67 CKD patients not undergoing dialysis. Cerebral rSO2 was monitored using the INVOS 5100c oxygen saturation monitor. Energy intake was evaluated by dietitians based on 3-day meal records. Daily protein and salt intakes were calculated from 24-h urine collection.ResultsMultivariable regression analysis showed that cerebral rSO2 was independently associated with energy intake (standardized coefficient: 0.370) and serum albumin concentration (standardized coefficient: 0.236) in Model 1 using parameters with p < 0.10 in simple linear regression analysis (body mass index, Hb level, serum albumin concentration, salt and energy intake) and confounding factors (eGFR, serum sodium concentration, protein intake), and the energy/salt index (standardized coefficient: 0.343) and Hb level (standardized coefficient: 0.284) in Model 2 using energy/protein index as indicated by energy intake/protein intake and energy/salt index by energy intake/salt intake in place of salt, protein and energy intake.ConclusionsCerebral rSO2 is affected by energy intake, energy/salt index, serum albumin concentration and Hb level. Sufficient energy intake and adequate salt restriction is important to prevent deterioration of cerebral oxygenation, which might contribute to the maintenance of cognitive function in addition to the prevention of renal dysfunction in CKD patients.

Background: Hyperkalemia is one of the more serious complications of chronic kidney disease (CKD), and the cause of potassium retention is a reduction in urinary potassium excretion. However, few studies have examined the extent of the decrease of urinary potassium excretion in detail with respect to decreased renal function. Methods: Nine hundred eighty-nine patients with CKD (CKD stages G1 and G2 combined: 135; G3a: 107; G3b: 170; G4: 289; and G5: 288) were evaluated retrospectively. Values for urinary potassium excretion were compared between CKD stages, and the associations between urinary potassium excretion and clinical parameters, including diabetes mellitus status and use of renin–angiotensin–aldosterone system inhibitors, were analyzed using a multivariable linear regression analysis. Results: Urinary potassium excretion gradually decreased with worsening of CKD (G5: 24.8 ± 0.8 mEq/d, P

We detected an increase in small arterioles around glomeruli, particularly adjacent to tuft adhesive lesions in immunoglobulin A nephropathy (IgAN), for the 1 st time, as far as we know. We labeled these as periglomerular microarterioles (PGMAs). This study aimed to clarify the pathological significance of PGMAs. Sixty-two patients with IgAN and 19 controls with minor glomerular abnormalities without proteinuria were evaluated in this study. The number of PGMAs located between the Bowman′s capsule and the adjoining tubules was counted for each glomerulus. The mean number of PGMAs per glomerulus in cases of IgAN was significantly higher than those of the controls (0.530 ± 0.477 vs. 0.240 ± 0.182, P

We herein report a case of ureter rupture with severe oliguric acute renal injury due to benign prostatic hypertrophy. After insertion of an indwelling urinary catheter, the patient’s urine output immediately increased. His symptoms and renal function also rapidly improved to the normal range without a surgical operation. Clinicians should note this complication in patients with oliguria.

BACKGROUND:A decline in estimated glomerular filtration rate (eGFR) is reportedly associated with increased prevalence rates of cognitive impairment. However, data concerning the association between the cerebral saturation of oxygen (rSO2) and cognitive function of patients with chronic kidney disease (CKD) is limited. This study aimed to (i) elucidate the clinical factors associating with cerebral rSO2 and (ii) investigate the association between cerebral rSO2 and cognitive assessment in CKD patients. METHODS:A total of 40 CKD patients not requiring dialysis (26 men and 14 women; mean age, 61.0 ± 2.7 years) were recruited. The numbers of patients at each CKD stage were as follows: G1, 5; G2, 8; G3a, 6; G3b, 5; G4, 11; and G5, 5. Cerebral rSO2 was monitored at the forehead using the oxygen saturation monitor INVOS 5100C. The cognitive function of each patient was confirmed using the Mini-Mental State Examination (MMSE). RESULTS:Cerebral rSO2 levels were significantly higher in CKD patients than in hemodialysis patients (63.8 ± 1.5% vs. 44.9 ± 2.2%, p < 0.001). Multiple regression analysis showed that cerebral rSO2 was independently associated with eGFR (standardized coefficient: 0.530), serum albumin concentration (standardized coefficient: 0.365), and serum sodium concentration (standardized coefficient: 0.224). Furthermore, MMSE showed a significantly positive correlation with cerebral rSO2 (r = 0.624, p < 0.001). CONCLUSIONS:Cerebral rSO2 was affected by eGFR and serum albumin and sodium concentrations in CKD patients. Furthermore, cerebral rSO2 monitoring, which reflected MMSE scores, might be a useful method for assessing cognitive function in CKD patients.

A 54-year-old Japanese man noticed painful swelling and redness of his left leg. He was admitted for treatment of cellulitis, which was accompanied with increased anti-streptolysin O and anti-streptokinase titers in his clinical course. After Piperacillin/Tazobactam administration, the skin lesion resolved. However, the patient then developed arthritis, palpable purpura, and intermittent abdominal pain, later found to be secondary to a severe duodenal ulcer. He was diagnosed with cellulitis-associated anaphylactoid purpura and was given prednisolone, which dramatically improved his symptoms. The anaphylactoid purpura was likely caused by Streptococcus-induced cellulitis, which was successfully treated with prednisolone. Association between these diseases is rare.

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Patients undergoing hemodialysis (HD) often develop cerebral disease complications. Furthermore, cerebral regional saturation of oxygen (rSO2) was previously reported to be significantly lower in HD patients than in healthy subjects. We aimed to identify the factors affecting the cerebral rSO2 in HD patients.Fifty-four HD patients (38 men and 16 women; mean age, 67.7 ± 1.2 years, HD duration, 6.5 ± 1.9 years) were recruited. Cerebral rSO2 was monitored at the forehead before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan).The rSO2 levels were significantly lower in HD patients compared with healthy controls (49.5 ± 1.7% vs. 68.9 ± 1.6%, p