Hepatic Oxygenation Changes and Symptomatic Intradialytic Hypotension.

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.

Factors Affecting Psoas Muscle Mass Index in Patients Undergoing Peritoneal Dialysis.

INTRODUCTION: Many patients with chronic kidney disease (CKD), including peritoneal dialysis (PD), have sarcopenia. It is important to evaluate muscle mass to prevent sarcopenia in the field of CKD management. Recently, muscle mass assessment using psoas muscle evaluated by computed tomography (CT) has been reported in patients undergoing hemodialysis. However, few clinical studies have investigated the clinical factors associated with the evaluation of psoas muscle in patients undergoing PD. METHODS: Psoas muscle mass index (PMI) was measured in cross-sectional areas of the bilateral psoas muscles at the third lumbar spine level to evaluate psoas muscle status. The associations between PMI and possible clinical factors were investigated in 68 patients undergoing PD. RESULTS: The mean PMI was 6.3 ± 2.0 cm2/m2, and the PMI was higher in men than in women (p < 0.001). In a multivariable linear regression analysis of the factors associated with PMI, male gender (standardized coefficient: 0.331), body mass index (standardized coefficient: 0.283), serum creatinine concentration (standardized coefficient: 0.289), serum albumin concentration (standardized coefficient: 0.235), and the use of vitamin D (standardized coefficient: 0.195) were independently identified. CONCLUSION: PMI was independently and significantly associated with gender, BMI, serum creatinine concentration, serum albumin concentration and the use of vitamin D. Further prospective studies are needed to clarify whether the maintenance of nutritional status or vitamin D administration could affect muscle mass in patients undergoing PD.

Steroid-resistant minimal change nephrotic syndrome associated with thymoma treated effectively with rituximab following thymectomy and cyclosporine: a case report.

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.

The Efficacy and Safety of Dotinurad on Uric Acid and Renal Function in Patients with Hyperuricemia and Advanced Chronic Kidney Disease: A Single Center, Retrospective Analysis.

Objective: We investigated the efficacy and safety of dotinurad, a selective urate reabsorption inhibitor, in hyperuricemic patients with advanced chronic kidney disease (CKD) (stage G3-5). Patients and Methods: We retrospectively analyzed the cases of 34 patients (mean age, 68.6 ± 13.3 years; 17 men and 17 women) after 12 months of dotinurad treatment based on the changes in uric acid (UA) and the urine protein-to-creatinine ratio (UPCR) plus the annual change in estimated glomerular filtration rate (eGFR). Hyperuricemia (UA ≥6.0 mg/dL) and advanced CKD (mean eGFR: 32.0 ± 13.3 mL/min/1.73m2; stage G3, n=17; G4, n=13; G5, n=4) were present in all of the patients. The cases of 34 matched individuals with similar propensity scores (who were not taking dotinurad) were analyzed as a control group. Results: UA values decreased significantly in the dotinurad group (7.1 ± 0.8 mg/dL to 5.9 ± 1.0 mg/dL, p<0.05) but those did not change in the control group. UPCR did not change in either group. Low-density lipoprotein cholesterol also decreased significantly in the dotinurad group (98.8 ± 43.4 mg/dL to 82.9 ± 33.1 mg/dL, p<0.05). With the 12-month dotinurad treatment, the annual change in the patients' eGFR was significantly improved from -6.0 ± 12.9 mL/min/1.73 m2/year to -0.9 ± 4.6 mL/min/1.73 m2/year (p<0.05), but there was no change in the control group. Conclusion: Dotinurad can decrease UA levels and might attenuate renal function decline in individuals with hyperuricemia and advanced CKD.

Short-term memory impairment following recovery from systemic inflammation induced by lipopolysaccharide in mice.

The relationship between neuroinflammation and mental disorders has been recognized and investigated for over 30 years. Diseases of systemic or peripheral inflammation, such as sepsis, peritonitis, and infection, are associated with increased risk of mental disorders with neuroinflammation. To elucidate the pathogenesis, systemic administration of lipopolysaccharide (LPS) in mice is often used. LPS-injected mice exhibit behavioral abnormalities with glial activation. However, these studies are unlikely to recapitulate the clinical pathophysiology of human patients, as most studies focus on the acute inflammatory response with systemic symptoms occurring within 24 h of LPS injection. In this study, we focus on the effects of LPS on behavioral abnormalities following recovery from systemic symptoms and investigate the mechanisms of pathogenesis. Several behavioral tests were performed in LPS-injected mice, and to assess neuroinflammation, the time course of the morphological change and expression of inflammatory factors in neurons, astrocytes, and microglia were investigated. At 7 days post-LPS injection, mice exhibited short-term memory impairment accompanied by the suppression of neuronal activity and increases in morphologically immature spines. Glial cells were transiently activated in the hippocampus concomitant with upregulation of the microglial phagocytosis marker CD68 3 days after injection. Here we show that transient glial cell activation in the acute response phase affects neuronal activity and behavior following recovery from systemic symptoms. These findings provide novel insights for studies using the LPS-induced inflammation model and that will contribute to the development of treatments for mental disorders of this etiology.

A case of renal vein thrombosis associated with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

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.

Acupuncture Treatment Improves Transport Stress in Microminipigs Through the Acupoint in Ears.

BACKGROUND/AIM: This study aimed to investigate the effects of acupuncture treatment through the ear acupoints on transport stress in experimental microminipigs. MATERIALS AND METHODS: Experiment 1: Six animals were equally divided into two groups (Control and Treatment). In the treatment group, before transportation (6 h; vehicle and plane), short, ultrathin circular transdermal needles were applied to locations corresponding to the acupoints on the apical area of both ears. Peripheral blood samples were collected from the cranial vena cava 2 days before and immediately after transportation. Blood stress markers, biochemistry indicators, and oxidative stress levels were examined. Experiment 2 (follow-up study: diarrhea incidence after transportation): Diarrhea incidence after transportation in the control and treatment groups was investigated. RESULTS: Experiment 1: Transport stress induced an increase in blood cortisol, serum amyloid A (SAA), glucose, non-esterified fatty acid, and derivatives of reactive oxygen metabolites (d-ROMs) and decreased the biological antioxidant potential (BAP)/d-ROMs ratio yet did not affect BAP. Acupuncture suppressed the increases in SAA and d-ROMs values and the decrease in BAP/d-ROMs ratio. Experiment 2: The total diarrhea incidence was 25% in the control group, whereas diarrhea was not observed in the treatment group. CONCLUSION: Acupuncture treatment suppresses hypothalamic-pituitary-adrenal function and, as a result, reduces transport stress without affecting the suppression of the central catecholaminergic system. Acupuncture treatment for transport stress can improve animal welfare.

Factors affecting intradialytic hepatic oxygenation: Associations between ultrafiltration rate and changes in systemic blood pressure.

INTRODUCTION: Hepato-splanchnic circulation influences the oxygenation of abdominal organs and is important in preventing a reduction in intradialytic blood volume. However, the association between changes in intradialytic hepato-splanchnic circulation and clinical factors remain unknown. METHODS: We enrolled 91 hemodialysis (HD) patients (20 with intradialytic hypotension (IDH) and 71 without IDH). During HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting hepato-splanchnic circulation and oxygenation, was monitored. Changes in hepatic rSO2 at the lowest systolic blood pressure (BP) during HD were analyzed to identify associations with clinical factors. RESULTS: Hepatic rSO2 levels were 55.8 ± 15.3% before HD and 53.8 ± 14.9% at the lowest systolic BP; therefore, % changes in hepatic rSO2 were -2.7 ± 11.3%. These values were significantly lower in patients with IDH than in those without IDH (-13.8 ± 9.3% vs 0.4 ± 9.8%, p < 0.001). Multivariable regression analysis showed that % changes in hepatic rSO2 were independently associated with % changes in systolic BP (standardized coefficient: 0.416) and ultrafiltration rate (-0.206). Furthermore, % changes in mean BP (0.304) were identified as affecting % changes in hepatic rSO2 instead of those in systolic BP. CONCLUSIONS: Changes in intradialytic hepatic oxygenation is associated with ultrafiltration rate and changes in systemic BP. Further studies are required to clarify the directionality of the association between changes in hepatic oxygenation and changes in systemic BP during HD.

Effects of roxadustat on anemia, iron metabolism, and lipid metabolism in patients with non-dialysis chronic kidney disease.

Background: We 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). Methods: We 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. Results: We 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 < 0.05), whereas the transferrin saturation, ferritin concentration, estimated glomerular filtration rate, and urinary protein/creatinine ratio were not different between the two groups. TC (135.9 ± 40.0 versus 165.3 ± 38.4 mg/dL; value of p < 0.05), LDL-C (69.1 ± 28.3 versus 87.2 ± 31.5 mg/dL; value of p < 0.05), HDL-C (41.4 ± 13.5 versus 47.2 ± 15.3 mg/dL; value of p < 0.05), and triglyceride concentrations (101.5 ± 52.7 versus 141.6 ± 91.4 mg/dL, value of p < 0.05) were significantly lower in the roxadustat group compared with the ESA group at 24 weeks. Multiple linear regression analysis showed that the roxadustat dose at baseline (standard coefficient [ß] = 0.280, value of p = 0.043) was correlated with the change in the hemoglobin levels during the first 4 weeks of roxadustat treatment, whereas age (ß = 0.319, value of p = 0.017) and the roxadustat dose at 24 weeks (ß = -0.347, value of p = 0.010) were correlated with the hemoglobin concentration after 24 weeks of roxadustat administration. Conclusion: Roxadustat can improve anemia and reduce serum cholesterol and triglyceride levels in non-dialysis CKD patients after the patients' treatment was switched from an ESA without affecting renal function or proteinuria. These results indicate that roxadustat has superior effects to ESAs regarding anemia and lipid metabolism at the dose selected for the comparison in patients with non-dialysis CKD.

A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats.

Mammary tumors are the most prevalent type of tumors in female dogs. Breast cancer 2, early onset (BRCA2) malignant mutations are associated with tumorigenesis in humans and dogs. BRCA2 plays a pivotal role in homologous recombination repair by recruiting RAD51 recombinase to DNA damage sites to maintain genome stability. To recruit RAD51, BRCA2 must interact with RAD51 via BRC repeats, but the regulation of this interaction has been unclear. In this study, we focused on a highly conserved region (HCR) near BRC repeats. Using co-immunoprecipitation and mammalian two-hybrid assay, we found that HCR suppressed the RAD51-interaction activity of BRC repeats and that substitutions of HCR phosphorylation sites affected it. In canine tumor samples, we found ten mutations, including a novel HCR mutation (I1110M) from canine tumor samples. The effect of four HCR mutations, including I1110M, on the RAD51-interaction activity of BRC repeats was tested. One of the HCR mutations found in canine mammary tumors increased the interaction, but the two mutations found in human breast cancers decreased it. This study suggested that the HCR regulated the RAD51-interacting activity of BRC repeats through HCR phosphorylation and that mutations in HCR may be related to tumorigenesis in both dogs and humans.

Plasmodium berghei Brca2 is required for normal development and differentiation in mice and mosquitoes.

BACKGROUND: Malaria is a major global parasitic disease caused by species of the genus Plasmodium. Zygotes of Plasmodium spp. undergo meiosis and develop into tetraploid ookinetes, which differentiate into oocysts that undergo sporogony. Homologous recombination (HR) occurs during meiosis and introduces genetic variation. However, the mechanisms of HR in Plasmodium are unclear. In humans, the recombinases DNA repair protein Rad51 homolog 1 (Rad51) and DNA meiotic recombinase 1 (Dmc1) are required for HR and are regulated by breast cancer susceptibility protein 2 (BRCA2). Most eukaryotes harbor BRCA2 homologs. Nevertheless, these have not been reported for Plasmodium. METHODS: A Brca2 candidate was salvaged from a database to identify Brca2 homologs in Plasmodium. To confirm that the candidate protein was Brca2, interaction activity between Plasmodium berghei (Pb) Brca2 (PbBrca2) and Rad51 (PbRad51) was investigated using a mammalian two-hybrid assay. To elucidate the functions of PbBrca2, PbBrca2 was knocked out and parasite proliferation and differentiation were assessed in mice and mosquitoes. Transmission electron microscopy was used to identify sporogony. RESULTS: The candidate protein was conserved among Plasmodium species, and it was indicated that it harbors critical BRCA2 domains including BRC repeats, tower, and oligonucleotide/oligosaccharide-binding-fold domains. The P. berghei BRC repeats interacted with PbRad51. Hence, the candidate was considered a Brca2 homolog. PbBrca2 knockout parasites were associated with reduced parasitemia with increased ring stage and decreased trophozoite stage counts, gametocytemia, female gametocyte ratio, oocyst number, and ookinete development in both mice and mosquitoes. Nevertheless, the morphology of the blood stages in mice and the ookinete stage was comparable to those of the wild type parasites. Transmission electron microscopy results showed that sporogony never progressed in Brca2-knockout parasites. CONCLUSIONS: Brca2 is implicated in nearly all Plasmodium life cycle stages, and especially in sporogony. PbBrca2 contributes to HR during meiosis.

Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors.

Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 µM) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 µM) were inhibited by a ß-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 µM) promoted process formation, which was inhibited by a ß-antagonist and enhanced by both an α-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and ß-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and ß-adrenoceptors. Furthermore, bidirectional regulation exists; namely, the effects of D1-like receptors and ß-adrenoceptors were negatively regulated by D2-like receptors and α2-adrenoceptors.

BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents.

Breast cancer type 2 susceptibility (BRCA2) protein is crucial for initiating DNA damage repair after chemotherapy with DNA interstrand crosslinking agents or X-ray irradiation, which induces DNA double-strand breaks. BRCA2 contains a C-terminal RAD51-binding domain (CTRBD) that interacts with RAD51 oligomer-containing nucleofilaments. In this study, we investigated CTRBD expression in cells exposed to X-ray irradiation and mitomycin C treatment. Surprisingly, BRCA2 CTRBD expression in HeLa cells increased their resistance to X-ray irradiation and mitomycin C. Under endogenous BRCA2 depletion using shRNA, the sensitivities of the BRCA2-depleted cells with and without the CTRBD did not significantly differ. Thus, the resistance to X-ray irradiation conferred by an exogenous CTRBD required endogenous BRCA2 expression. BRCA2 CTRBD-expressing cells demonstrated effective RAD51 foci formation and increased homologous recombination efficiency, but not nonhomologous end-joining efficiency. To the best of our knowledge, our study is the first to report the ability of the BRCA2 functional domain to confer resistance to X-ray irradiation and mitomycin C treatment by increased homologous recombination efficiency. Thus, this peptide may be useful for protecting cells against X-ray irradiation or chemotherapeutic agents.

Risk Factors and Utility of Intraoperative Arteriovenous Fistula Blood Flow Level as a Surrogate Marker of Arteriovenous Fistula Failure in Patients with End-stage Renal Disease.

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 <0.05). Hemoglobin level and the size of the anastomosis were significantly associated with AVF failure at 6 months (P <0.05). In the analysis of the receiver operating characteristic curve, intraoperative AVF blood flow was significant from 3 weeks to 24 months (P <0.05). The intraoperative blood flow with the greatest sensitivity and specificity was 205-225 mL/min. Intraoperative blood flow was independently associated with AVF failure from 3 weeks to 24 months after the AVF's creation. An intraoperative AVF blood flow of >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.

Change in Anemia by Carnitine Supplementation in Patients Undergoing Peritoneal Dialysis: A Retrospective Observational Study.

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.

No Significant Changes of Glycemic Control and Renal Function in Patients with Advanced-Stage Diabetic Kidney Disease by Switching from Linagliptin to Teneligliptin.

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.

A case report of PR-3-ANCA-positive glomerulonephritis with histological features of GPA associated with infectious endocarditis.

RATIONALE: Several renal diseases are associated with infectious endocarditis. However, there are few reports on patients with granulomatosis with polyangiitis (GPA) associated with infectious endocarditis, and there is no consensus for appropriate treatment. PATIENTS CONCERNS: A 35 -years-old man with congenital ventricular septal defect presented severe anemia, hematuria and proteinuria. The blood and urine examinations showed elevated white blood cells (12,900 cells/µL), C-reactive protein level (13.1 mg/dL) and proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level (11.0 IU/mL), severe anemia (hemoglobin: 6.1 g/dL) and renal dysfunction [estimated glomerular filtration rate (eGFR): 12.7 ml/min.1.78 m2 with hematuria and proteinuria]. DIAGNOSES: The patient was diagnosed with crescentic glomerulonephritis with histological features of GPA associated with infectious endocarditis by renal biopsy and transthoracic echocardiography. INTERVENTIONS: Antibacterial drugs (ampicillin-sulbactam) were administrated. No immunomodulating agents were used because immunosuppressive drugs may worsen infectious endocarditis. Subsequently, renal function and urinary findings improved. However, infectious endocarditis was not improved. Therefore, valve replacements and ventricular septal closure surgery were conducted. OUTCOMES: Thereafter, his postoperative course was uneventful, renal function improved (eGFR: 64.3 ml/min.1.78 m2), and PR3-ANCA level normalized. LESSONS: We reported a case report of PR3-ANCA positive glomerulonephritis with histological features of GPA associated with infectious endocarditis. Physicians might note this renal complication when they manage infectious endocarditis.

Effects of Roxadustat on the Anemia and Iron Metabolism of Patients Undergoing Peritoneal Dialysis.

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.

Clinical factors affecting cerebral oxygenation in patients undergoing peritoneal dialysis.

BACKGROUND: Although cerebral regional oxygen saturation (rSO2) is significantly lower in hemodialysis (HD) patients than that in healthy controls, investigations on cerebral oxygenation in peritoneal dialysis (PD) patients are limited. We aimed to confirm the cerebral oxygenation status and identify the factors affecting cerebral rSO2 in PD patients. METHODS: Thirty-six PD patients (21 men and 15 women; mean age, 62.8 ± 12.7 years) were recruited. In addition, 27 healthy volunteers (17 men and 10 women; mean age, 43.5 ± 18.8 years) were recruited as a control group. Cerebral rSO2 was monitored at the forehead using an INVOS 5100c oxygen saturation monitor. RESULTS: Cerebral rSO2 was significantly lower in PD patients than that in healthy controls (57.0 ± 7.3% vs 68.9 ± 8.6%, p < 0.001); moreover, cerebral rSO2 was significantly correlated with natural logarithm (Ln)-PD duration (r = -0.389, p = 0.019) and serum albumin concentration (r = 0.370, p = 0.026) in a simple linear regression analysis. Multivariable linear regression analysis was performed using variables that showed a significant correlation and p < 0.20 (serum creatinine, serum sodium, Ln-C-reactive protein, and dosage of erythropoiesis-stimulating agent) with the cerebral rSO2. Cerebral rSO2 was independently associated with Ln-PD duration (standardized coefficient: -0.339) and serum albumin concentration (standardized coefficient: 0.316). CONCLUSIONS: Cerebral rSO2 was significantly affected by the PD duration and serum albumin concentration. Further prospective studies are needed to clarify whether preventing a decrease in serum albumin concentration leads to the maintenance of cerebral oxygenation in patients undergoing PD.

Relationship Between Serum Total Carbon Dioxide Concentration and Bicarbonate Concentration in Patients Undergoing Peritoneal Dialysis.

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 (ß = 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.