平井 啓之

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 was 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 cutoff 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 cutoff 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.

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 m2. 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.

BACKGROUND: We investigated factors associated with the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody titer after the second dose of the BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine in Japanese patients undergoing hemodialysis. METHODS: Overall, 75 patients (41 men, 34 women; mean age 71.4 ± 12.2 years) with a hemodialysis duration of 5.7 ± 6.1 [interquartile range, 1.0-8.5] years were enrolled in this single-center, prospective, cross-sectional study. We used multiple linear regression analysis to determine the relationships of the anti-SARS-CoV-2 spike antibody titer with patient demographic and clinical parameters. We also compared the anti-SARS-CoV-2 spike antibody titer between hemodialysis patients and 22 healthcare workers (10 men, 12 women; mean age 48.5 ± 14.4 years). RESULTS: Autoimmune disease presence (standard coefficient [β] =  - 0.290, p = 0.018), lymphocyte counts (β = 0.261, p = 0.015), hemoglobin levels (β = 0.290, p = 0.009), and blood urea nitrogen concentrations (β = 0.254, p = 0.033) were significantly and independently correlated with the log-anti-SARS-CoV-2 spike antibody titer. The anti-SARS-CoV-2 spike antibody titer was significantly lower in hemodialysis patients than in healthcare workers (3589 ± 3921 [813-4468] vs. 12,634 ± 18,804 [3472-10,257] AU/mL; p < 0.002). CONCLUSIONS: Autoimmune disease presence, lymphocyte counts, hemoglobin levels, and blood urea nitrogen concentrations were associated with the anti-SARS-CoV-2 spike antibody titer after the second dose of the BNT162b2 messenger RNA COVID-19 vaccine in Japanese patients undergoing hemodialysis.

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.

PURPOSE: We compared the efficacy of teneligliptin versus linagliptin for glycemic control and renoprotection in patients with advanced-stage diabetic kidney disease. PATIENTS AND METHODS: Changes in the glycated hemoglobin (HbA1c), fasting blood glucose concentration, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) during a 12-month period were retrospectively analyzed after switching from linagliptin to teneligliptin in 13 patients with advanced-stage diabetic kidney disease (teneligliptin group). Thirteen propensity score-matched patients who were treated with linagliptin alone served as controls (linagliptin group). RESULTS: The HbA1c, fasting blood glucose concentration, and UACR did not change during the 12-month study period in either group. The annual change rate in the eGFR did not differ between before and after baseline in either group. CONCLUSION: Switching from linagliptin to teneligliptin may not improve glycemic control, reduce urinary protein excretion, or ameliorate the rate of renal function decline in patients with advanced-stage diabetic kidney disease. These results suggest that teneligliptin may not be more advantageous for glycemic control and renoprotection compared with linagliptin in patients with advanced-stage diabetic kidney disease.

Background Few studies have assessed the relationship between serum total carbon dioxide (CO2) and bicarbonate ion (HCO3 -) concentration in patients undergoing peritoneal dialysis. We determined the agreement between serum total CO2 and HCO3 - concentration 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 patients on peritoneal dialysis. Methods We collected 245 samples of venous blood from 51 patients on peritoneal dialysis. Independent factors that correlated with the HCO3 - concentration were analyzed using multiple linear regression analysis. The diagnostic accuracy of serum total CO2 was evaluated by receiver operating characteristic (ROC) curve analysis and a 2×2 table. Agreement between serum total CO2 and HCO3 - concentration was assessed by Bland-Altman analysis. Results Serum total CO2 was independently correlated with HCO3 - concentration (β = 0.354, p < 0.001). The area under the curve of serum total CO2 for the identification of low and high bicarbonate concentrations was 0.909. The diagnostic accuracy of serum total CO2 for the prediction of low and high bicarbonate concentrations was: sensitivity, 91.5%; specificity, 74.7%; positive predictive value, 53.5%; negative predictive value, 96.5%; and accuracy, 78.8%. Bland-Altman analysis showed a moderate agreement between serum total CO2 and HCO3 - concentration. Conclusion Serum total CO2 correlated closely with the HCO3 - concentration in patients undergoing peritoneal dialysis. Serum total CO2 might be useful for predicting low and high bicarbonate in peritoneal dialysis patients.

INTRODUCTION: The prevalence of cognitive impairment in patients undergoing hemodialysis (HD) is higher than that in healthy controls. To date, studies on the association between cognitive function and cerebral oxygenation in these patients are limited. Therefore, in this study, we aimed to cross-sectionally investigate the association between cognitive assessment scores and clinical factors, including cerebral oxygenation, in patients undergoing HD. METHODS: In this observational study, 193 HD patients were included. Cerebral regional oxygen saturation (rSO2) was monitored using an INVOS 5,100c oxygen saturation monitor. Poor cognition was defined as a Mini-Mental State Examination (MMSE) score ≤23. We analyzed the association between MMSE score and clinical factors, including cerebral rSO2. RESULTS: MMSE score in HD patients included in this study was 26.8 ± 3.3. There were 164 patients (85%) with MMSE score ≥24 and 29 patients (15%) with an MMSE score ≤23. In the patients with MMSE score ≥24, cerebral rSO2 (53.8% ± 8.3%) was significantly higher than that in patients with MMSE score ≤23 (49.5% ± 9.8%; p = 0.013). Multivariable linear regression analysis was performed using the following confounding factors: age, mean blood pressure, cerebral rSO2, HD duration, ultrafiltration rate, hemoglobin, serum Cr, serum calcium, serum phosphate, total cholesterol, high-density lipoprotein cholesterol levels, serum albumin, presence of diabetes mellitus or chronic glomerulonephritis, history of comorbid cardiovascular or cerebrovascular disease, and use of renin-angiotensin-aldosterone system inhibitors or vitamin D analogs. MMSE score was independently and significantly associated with age (standardized coefficient: -0.244) and cerebral rSO2 (standardized coefficient: 0.180). CONCLUSIONS: MMSE score was independently associated with age (negative effect) and cerebral rSO2 (positive effect) in this cross-sectional study. Further prospective studies are needed to clarify whether maintaining cerebral oxygenation prevents the deterioration of cognitive function in patients undergoing HD.

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: 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.

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.