Tenapanor in Chinese ESRD patients with hyperphosphatemia on haemodialysis: a randomised, phase 3 trial.

Background: The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD). Methods: This was a randomised, double blind, phase 3 trial conducted at 26 dialysis facilities in China (https://www.chictr.org.cn/index.aspx; CTR20202588). After a 3-week washout, adults with ESRD on HD with hyperphosphatemia were randomised (1:1) using an interactive web response system to oral tenapanor 30 mg twice a day or placebo for 4 weeks. The primary endpoint was the change in mean serum phosphorous level from baseline to the endpoint visit (day 29 or last serum phosphorus measurement). Efficacy was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug. Results: Between 5 March 2021 and 8 June 2022, 77 patients received tenapanor and 73 received placebo. Tenapanor treatment (n = 75) resulted in a significantly greater least squares (LS) mean reduction in serum phosphate at the endpoint visit versus placebo (n = 72): LS mean difference -1.17 mg/dl (95% CI -1.694 to -0.654, P < .001). More patients receiving tenapanor achieved a serum phosphorous level <5.5 mg/dl at the endpoint visit (44.6% versus 10.1%). The most common treatment-related adverse event was diarrhoea [tenapanor 28.6% (22/77), placebo 2.7% (2/73)], which was mostly mild and led to treatment discontinuation in two patients receiving tenapanor. Conclusions: Tenapanor significantly reduced the serum phosphorous level versus placebo in Chinese ESRD patients on HD and was generally well tolerated.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Independent risk factors for depression in older adult patients receiving peritoneal dialysis for chronic kidney disease.

BACKGROUND: According to the trend of global population aging, the proportion of elderly patients with chronic kidney disease (CKD) is expected to increase. However, there are more than 20 million people in China with decompensated kidney function, of which 19.25% are elderly people. Therefore, special attention should be paid to the education years, sleep quality, anxiety status, comorbidities with diabetes, cardiovascular disease (CVD), and anemia as independent risk factors for depression in elderly CKD patients. This study explores the clinical mana-gement of elderly CKD patients that should address these risk factors to prevent depression and improve their prognosis. AIM: To investigate depression risk factors in older patients receiving peritoneal dialysis, aiding future prevention of depression in these patients. METHODS: This retrospective study included a primary study population of 170 patients with CKD who received peritoneal dialysis from January 2020 to December 2022. We assessed the patients' mental status using the Beck Depression Inventory Score-II (BDI-II), Self-Rating Anxiety Scale (SAS), Anxiety Inventory Score, and the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was employed to identify depression independent risk factors among these patients. RESULTS: The non-depressed group had a significantly longer education period than the depressed group (P < 0.05). The depressed group exhibited significantly higher mental status scores than the non-depressed group (P < 0.001). Patients with diabetes mellitus (DM) or CVD had a higher probability of developing dep-ression. Patients with depression had significantly lower hemoglobin and albumin levels than patients without depression (P < 0.05). Spearman correlation analysis of BDI-II scale scores, measuring depression, indicated positive correlations with BDI-II and SAS scores as risk factors for depression in patients with CKD. In contrast, years of education, hemoglobin levels, and peritoneal Kt/V were negatively correlated, serving as protective factors against depression. An analysis of variance for influences with significant differences in the univariate analysis revealed that years of schooling, BDI-II, SAS, PSQI, DM, CVD, and hemoglobin levels independently influenced depression in older patients with CKD. CONCLUSION: Education, BDI-II, SAS, PSQI, DM, and CVD are independent risk factors for depression in older patients with CKD; therefore, post-treatment psychological monitoring of high-risk patients is crucial to prevent depression.

Effects of paricalcitol combined with hemodiafiltration on bone-metabolism-related indexes in patients with diabetic nephropathy and chronic renal failure.

BACKGROUND: Diabetic nephropathy (DN) is frequently seen in the development of diabetes mellitus, and its pathogenic factors are complicated. Its current treatment is controversial, and there is a lack of a relevant efficacy prediction model. AIM: To determine the effects of paricalcitol combined with hemodiafiltration on bone-metabolism-related indexes in patients with DN and chronic renal failure (CRF), and to construct an efficacy prediction model. METHODS: We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022. We selected 94 patients who met the inclusion and exclusion criteria. Patients were assigned to a dialysis group (n = 45) and a joint group (n = 49) in relation to therapeutic regimen. The clinical efficacy of the two groups was compared after treatment. The changes in laboratory indexes after treatment were evaluated, and the two groups were compared for the incidence of adverse reactions. The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed. RESULTS: The dialysis group showed a notably worse improvement in clinical efficacy than the joint group (P = 0.017). After treatment, the joint group showed notably lower serum levels of serum creatinine, uric acid (UA) and blood urea nitrogen (BUN) than the dialysis group (P < 0.05). After treatment, the joint group had lower serum levels of phosphorus, procollagen type I amino-terminal propeptide (PINP) and intact parathyroid hormone than the dialysis group, but a higher calcium level (P < 0.001). Both groups had a similar incidence of adverse reactions (P > 0.05). According to least absolute shrinkage and selection operator regression analysis, UA, BUN, phosphorus and PINP were related to treatment efficacy. According to further comparison, the non-improvement group had higher risk scores than the improvement group (P < 0.0001), and the area under the curve of the risk score in efficacy prediction was 0.945. CONCLUSION: For treatment of CRF and DN, combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients, with good safety.

Study on the Efficacy of Sacubitril/Valsartan in Patients with Heart Failure with Preserved Ejection Fraction Undergoing Peritoneal Dialysis.

INTRODUCTION: Cardiovascular disease is the most common cause of death and morbidity in patients with end-stage renal disease. Sacubitril/valsartan (SAC/VAL) can reduce the risk of cardiovascular mortality among patients with heart failure (HF). The present study set out to evaluate the efficacy of SAC/VAL in the treatment of patients with HF with preserved ejection fraction (HFpEF) undergoing peritoneal dialysis (PD) (HFpEF&PD). METHODS: A total of 160 patients with HFpEF&PD were enrolled and randomly divided into the control group (N = 80) and SAC/VAL group (N = 80). The cardiac function efficacy, HF scoring efficacy, echocardiographic parameters, serological indicators, and 6-minute walking test were compared before and after treatment. RESULTS: After 6 months of treatment, the total number of patients who responded to treatment in the SAC/VAL group was higher than that of the control group in terms of cardiac function and HF scoring efficacy. After treatment, levels of early diastolic/late diastolic filling velocity and left ventricular ejection fraction were increased in both groups, while the levels of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, inter-ventricular septal diameter, and left ventricular posterior wall diameter were decreased; the NT-proBNP levels were diminished in both groups, while hemoglobin levels and the 6-minute walk distance were increased; the systolic blood pressure, diastolic blood pressure, and 24-h ultrafiltration volume were lowered in all patients. The changes in these indexes in the SAC/VAL group were more obvious than those in the controls. CONCLUSION: SAC/VAL can significantly improve cardiac function in patients with HFpEF&PD.

Expression profiles of miR-129 and miR-29a-5p in vascular calcification of patients with end-stage renal disease and the underlying correlation.

To analyze the changes and correlation of Mir-129 and Mir-29A-5p in vascular calcification in end-stage renal disease. A total of 97 patients with end-stage renal disease admitted to our hospital from August 2021 to August 2020 were selected as the research objects, and another 97 healthy people who underwent physical examination in our hospital during the same period were selected as the control study. According to X-ray examination, 97 subjects were divided into the vascular calcification group (39 cases) and the non-vascular calcification group (58 cases). Blood samples were extracted from each group, and the expressions of serum Mir-129 and Mir-29A-5p were detected by RT-PCR after centrifugation. The expressions of Mir-129 and Mir-29A-5p in healthy people with end-stage renal disease and vascular calcification were analyzed. To analyze the correlation of Mir-129 and Mir-29A-5p in vascular calcification of end-stage renal disease and its correlation with vascular calcification of end-stage renal disease. Compared with healthy people, the expression of Mir-129 and Mir-29A-5p in patients with the end-stage renal disease was abnormally increased, and there was a difference between the two groups (P<0.05). The expression levels of Mir-129 and Mir-29A-5p in patients with end-stage renal disease without vascular calcification were lower than those in the vascular calcification group, and there were differences between the two groups (P<0.05). Compared with mild vascular calcification, mir-129 and Mir-29A-5p expressions were higher in moderate and severe vascular calcification patients. In addition, compared with moderate patients, the expressions of Mir-129 and Mir-29a-5p were lower in mild patients and higher in severe patients. The expressions of Mir-129 and Mir-29A-5p in patients with mild and moderate vascular calcification were lower than those in patients with severe vascular calcification, and there were differences among the three groups (P < 0.05). Mir-129 and Mir-29A-5p were positively correlated with vascular calcification in end-stage renal disease (R =5.426, P=0.001). Mir-129 was positively correlated with vascular calcification in end-stage renal disease (r=0.649, P=0.001). Mir-29a-5p was positively correlated with vascular calcification in end-stage renal disease (r=0.529, P=0.001). Mir-129 and Mir-29a-5p showed high expression in the patients with end-stage renal disease, and they also increased with the occurrence of vascular calcification, and they showed a positive correlation in the vascular calcification of end-stage renal disease.

Expression of mir-29a-5p, sclerostin and fetuin-A in patients with chronic kidney disease and their correlation with vascular calcification.

The objective of the current study was to analyze the expression of mir-29a-5p, osteosclerotin and fetuin-A in patients with chronic kidney disease and their correlation with vascular calcification. For this purpose, 162 patients with chronic kidney disease treated in our hospital from January 2020 to January 2022 were selected retrospectively, and then 162 healthy people who underwent physical examination with our hospital in the same period were selected. The expressions of serum mir-29a-5p, sclerostin and fetuin-A were analyzed after fasting venous blood was drawn from the two groups. According to the coronary artery calcification score (CACS), patients with chronic kidney disease were divided into the calcification group (69 cases) and the non-calcification group (93 cases). The expressions of mir-29a-5p, sclerostin and fetuin-A in the two groups were analyzed, and the correlation between the three in chronic kidney disease and vascular calcification was analyzed. Results showed that compared with the control group, the expression of mir-29a-5p and sclerostin in the study group was higher, and the expression of fetuin-A was lower, the difference was statistically significant (P < 0.05); The expression of mir-29a-5p, sclerostin and fetuin-A in calcified group was higher than that in non-calcified group, and the expression of fetuin-A was lower (P < 0.05); Mir-29a-5p and sclerostin showed positive correlation (r=6.776, P=0.011); The expression of mir-29a-5p and fetuin-A showed negative correlation (r=-5.326, P=0.001); The expression of mir-29a-5p and sclerostin showed negative correlation (r=-9.677, P=0.001); Mir-29a-5p and sclerostin were positively correlated with vascular calcification (r=0.695, P=0.001; r=0.715, P=0.001), and fetuin-A was positively correlated with vascular calcification (r = -0.953, P = 0.001). Then, Mir-29a-5p, sclerostin and fetuin-A are abnormally expressed in chronic kidney disease. There is an abnormal correlation among them in chronic kidney disease, and they are correlated with vascular calcification.

Characteristics and prognostic outcome factors between young and elderly peritoneal dialysis patients: a prospective cohort study.

BACKGROUND: Peritoneal dialysis (PD) is the main renal replacement therapy in elderly patients account for hemodynamic stability. The clinical characteristics and prognosis of elderly PD patients are varies in different dialysis centers. We analyzed the characteristics, outcomes and prognosis factors of survival in elderly PD patients in China, to better understand their status and improve their quality of life. METHODS: This prospective, observational study categorized 202 PD patients by age: elderly group ≥65 years, younger group <65 years. The inclusion criteria were: age >18 years, first PD treatment and dialysis time >3 months, and complete data. Clinical characteristics including demographic data, hemodynamic variables were compared between groups. After a median follow-up of 44 months, prognosis outcomes between young and elderly groups were measured. Multivariate Cox regression analysis were used to establish the models for predicting outcomes. Then the nomogram of the model was generated. RESULTS: A total of 202 PD patients were enrolled: 61 in the elderly group and 141 in the younger group. The comparison of baseline data revealed decreased serum albumin, normalized protein catabolic rate and higher incidence of previous cardiovascular, cerebrovascular diseases, Charlson Comorbidity Index (CCI) in the elderly group. The mortality rate was substantially higher in the elderly group. Cardiovascular disease was the main cause of death in elderly PD patients. High body mass index (BMI) [hazard ratio (HR) =1.0, 95% confidence interval (CI): 1.0-1.1, P=0.005], high CCI (HR =1.1, 95% CI: 1.0-1.2, P=0.022), and ischemic heart disease (ISD) (HR =2.5, 95% CI: 1.0-6.1, P=0.042) were risk factors for the long-term survival of elderly PD patients. CONCLUSIONS: High BMI, high CCI and ISD were important factors for evaluating the adverse outcomes of elderly PD patients. Larger studied are needed to identify risk factors in elderly PD patients and to improve their outcomes.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

Bile Acid Detection Techniques and Bile Acid-Related Diseases.

Bile acid is a derivative of cholinergic acid (steroidal parent nucleus) that plays an important role in digestion, absorption, and metabolism. In recent years, bile acids have been identified as signaling molecules that regulate self-metabolism, lipid metabolism, energy balance, and glucose metabolism. The detection of fine changes in bile acids caused by metabolism, disease, or individual differences has become a research hotspot. At present, there are many related techniques, such as enzyme analysis, immunoassays, and chromatography, that are used for bile acid detection. These methods have been applied in clinical practice and laboratory research to varying degrees. However, mainstream detection technology is constantly updated and replaced with the passage of time, proffering new detection technologies. Previously, gas chromatography (GS) and gas chromatography-mass spectrometry (GC-MS) were the most commonly used for bile acid detection. In recent years, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has developed rapidly and has gradually become the mainstream bile acid sample separation and detection technology. In this review, the basic principles, development and progress of technology, applicability, advantages, and disadvantages of various detection techniques are discussed and the changes in bile acids caused by related diseases are summarized.

Insights into coloration enhancement of mercerized cotton fabric on reactive dye digital inkjet printing.

Mercerization can improve the utilization rate of dyes in the dyeing process, and reduce the discharge of washing wastewater. However, the effect and mechanism of mercerization is not clear on digital inkjet printing of cotton fabric. In this work, two kinds of cotton fabrics (original and mercerized) were used for reactive dye digital inkjet printing, and the color improvement mechanism of caustic soda mercerization was investigated. It was found that the crystallinity of cotton fibre was adjusted from 73.9% to 58.5% by caustic mercerization, and the breaking strength did not decrease compared with original cotton fibre. Thus, the accessible reactive hydroxyl groups and the wettability were enhanced for treated cotton fibres, which promoted the inks' wick into the fibres. Interestingly, the penetration of ink droplets between the yarns and fibres after caustic mercerization was decreased, thus the dyes mainly gathered on the surface of cotton fabric. The cotton fibres' cross section structure changed from flat oval to round, which increased the contact area between reactive dyes and fibres. At a certain amount of ink, the optimal K/S value of 23.47 was achieved for treated cotton fabrics, which was higher than that of untreated cotton fabrics (17.15). Meanwhile, the printed fabrics displayed good washing fastness, rubbing fastness and glossiness. This work has important theoretical guiding significance for producing high quality mercerized cotton fabric digital printing products and reducing printing wastewater discharge.

The Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study: Design and methods.

OBJECTIVES: The primary objective of the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study is to explore potential predictors and their effects on patient survival, technique survival, and the occurrence of infectious and noninfectious complications. DESIGN: The PDTAP study is a national-level cohort study in China. A newly developed PD telemedicine application provided a unique and convenient way to collect multicenter, structured data across units. SETTING: The PDTAP study was underway in 27 hospitals from 14 provinces located at 7 geographical regions (northwest, northeast, north, central, southwest, southeast, and south) in China. PARTICIPANTS: Our study aims to enroll at least 7000 adult patients with end-stage renal disease receiving PD. METHODS: Approval has been obtained through the ethics committees of all hospitals. All participants signed the informed consent form after the center had received ethics board approval in accordance with the Declaration of Helsinki. MAIN OUTCOME MEASURES: Patient survival, technique survival, hospitalization, and the occurrence of infectious and noninfectious complications. CONCLUSIONS: The PDTAP study aims to explore potential predictors and their effects on patient survival, technique survival, and infectious and noninfectious complications using a newly developed PD telemedicine system to collect multicenter, structured data in real-world practice. Substantial and transformable findings in relation to PD practices were expected. This study also developed a national-level infrastructure for further collaboration and ancillary investigation.

Controlling the Spreading of Nanoliter-Scale Droplets on the Fibers of Fabrics for Enhancing Image Quality and Ink Utilization.

Electronic and traditional textiles have been widely manufactured through inkjet printing. However, nanoliter-scale ink droplets tend to excessively spread along the fiber direction, which results in poor image quality and low ink utilization. Here, hydroxyethyl cellulose (HEC) and hydroxypropyl methyl cellulose (HPMC) were introduced to control the spreading of nanoliter-scale droplets on cotton fabrics. The results showed that both HEC and HPMC could reduce the spreading of nanoliter droplets along the fibers through increasing the hydrophobicity of the fabric. However, the effect of HPMC was much better than that of HEC due to its higher surface activity. The flow of nanoliter droplets along the fibers was well consistent with the Washburn function. After HPMC treatment, the depositing length of one droplet reduced from beyond 200 µm to about 50 µm. The imaging quality was greatly improved. In addition, the dye utilization increased by 33-78% due to the decrease in the diffusion of dye solution to the back of the fabric. This study is of great significance for improving the quality of inkjet printing and the utilization of depositing materials, particularly expensive materials.

WITHDRAWN: Exosome-derived long non-coding RNA ZFAS1 controls cardiac fibrosis in chronic kidney disease.

This paper was originally published in Aging Advance Online Publications on February 26, 2021. In compliance with Aging's withdrawal policy, the paper was withdrawn in its entirety. It will not appear in Aging internal or any external indexes or archives.

CdSe/ZnS quantum dots exhibited nephrotoxicity through mediating oxidative damage and inflammatory response.

OBJECTIVE: This study aimed to the evaluate the nephrotoxicity of CdSe/ZnS QDs in vitro and vivo, as well as investigate the underlying toxicity mechanisms. RESULTS: In vitro experiments showed that compared with control cells, CdSe/ZnS QDs treatment significantly inhibited cell viability and promoted cell apoptosis in dose-dependent manner in NRK cells. Notably, CdSe/ZnS QDs treatment increased the contents of MDA and ROS, and decreased the activities of SOD, CAT and GSH-Px; however, the co-treatment of NAC and QDs relieved the oxidative damage of NRK cells. Moreover, in vivo experiments also revealed that CdSe/ZnS QDs treatment obviously increased kidney weight coefficient, damaged the kidney function, as well as induced inflammatory response and inhibited the activation of NRF2/Keap1 pathway in kidney tissues of mice. CONCLUSIONS: CdSe/ZnS QDs exhibited obvious nephrotoxicity by mediating oxidative damage and inflammatory response in vitro and in vivo via NRF2/Keap1 pathway. METHODS: The characterization of CdSe/ZnS QDs was analyzed by transmission electron microscope, emission spectrum scanning, and dynamic light scattering. Rat kidney cells (NRK) were exposed to different doses of CdSe/ZnS QDs with or without N-acetylcysteine (NAC, antioxidant). Then, cellular uptake of CdSe/ZnS QDs was detected, and in vitro cytotoxicity was evaluated by MTT assay and TUNEL assay.

Idiopathic membranous nephropathy in a patient diagnosed with IgG4-related disease: A case report.

RATIONALE: Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a newly recognized, systemic disease. Membranous nephropathy is the most common glomerular lesion in IgG4- related kidney disease. However, the lack of relationship with IgG4-related kidney disease and monoclonal gammopathy of undetermined significance (MGUS) warrants investigation of the potential mechanisms. PATIENT CONCERNS: A 62-year-old patient was diagnosed with IgG4-RD, tubulointerstitial nephritis, retroperitoneal fibrosis. After 2 years, she was presented with proteinuria, hypoproteinemia, facial, and bilateral lower limb edema. Furthermore, this patient exhibited deposits of IgG k of monoclonal hyperplasia, and bone marrow plasma cell count was 2.5%. DIAGNOSIS: The patient was diagnosed with nephrotic syndrome, acute kidney injury, and MGUS. The pathological diagnosis was IgG4-related tubulointerstitial nephritis, IgG4-related membranous nephropathy. INTERVENTIONS: The patient was treated with intravenous methylprednisolone (40 mg daily), which was changed to oral prednisone 50 mg/d after 2 months. OUTCOMES: After 1 month, the patient exhibited a rapid response only with corticosteroid, and experienced partial remission of serum albumin and proteinuria. LESSONS: This case may suggest a possible relationship between IgG4-RD and MGUS, provide some guidance for investigating the mechanism between them.

The mitochondrial-targeted peptide SBT-20 ameliorates inflammation and oxidative stress in chronic renal failure.

Chronic renal failure (CRF) is the final outcome of the development of chronic kidney disease with different causes. Although CRF is a common clinical disease, its pathogenesis remains to be improved. SBT-20 belongs to a class of cell-permeable peptides that target the inner mitochondrial membrane, reduce reactive oxygen species (ROS), normalize electron transport chain function, and ATP generation. Our experiment was to evaluate whether SBT-20 affected the oxidative stress and inflammatory process of CRF. The levels of ROS production, mitochondrial membrane potential, NF- κB-p65, TNF-α, Drp1, and mfn2 were measured before and after SBT-20 treatment. We observed that SBT-20 treatment inhibited H2O2-induced mitochondrial ROS production. SBT-20 could also restore the mitochondrial membrane potential and reduce the elevated levels of NF-κB-p65 and TNF-α in HK-2 cells. In vivo, the renal function of CRF mice recovered after treating with SBT-20, the levels of necrotic cells and inflammation decreased, and the morphology of mitochondria recovered. The results showed that SBT-20 had a protective effect on CRF by reducing oxidative stress, inflammation progression via down-regulating of NF-κB-p65, TNF-α, and Drp1 and upregulating of Mfn2. These data support SBT-20 could be used as a potential preparation for CRF.

Effect of Sleeve Gastrectomy on Glycometabolism via Forkhead Box O1 (FoxO1)/Lipocalin-2 (LCN2) Pathway.

BACKGROUND The mechanism by which sleeve gastrectomy (SG) improves glycometabolism has remained unclear so far. Increasing evidence has demonstrated that bone is a regulator of glucose metabolism, and osteoblast-derived forkhead box O1 (FoxO1) and lipocalin-2 (LCN2) are regulators of energy metabolism. The aim of this study was to investigate whether the FOXO1/LCN2 signaling pathway is involved in the anti-diabetic effect of SG. MATERIAL AND METHODS Insulin resistance was induced in Wistar rats, which were then intraperitoneally injected with streptozotocin to induce a type 2 diabetic state. Levels of fasting blood glucose, serum insulin, HbA1c, and LCN2 were analyzed at corresponding time points after SG and sham surgeries. The expressions of FOXO1, LCN2, and the melanocortin 4 receptor (MC4R) in bone and hypothalamus were detected by immunofluorescence. FOXO1 siRNA was applied to downregulate FOXO1 expression in osteoblasts of rats. The influence of FOXO1 gene on expression of LCN2 was investigated in cultured osteoblasts by western blot and PCR. RESULTS Glucose metabolism in the SG group was significantly improved. The LCN2 expression in bone in the SG group was higher than that in the sham group, whereas FOXO1 expression in the SG group was lower than that in the sham group. The binding rate of LCN2 and MC4R in the hypothalamus was also higher in the SG group compared with that in the sham group. The downregulation of FOXO1 expression in osteoblasts was accompanied by upregulation of LCN2 expression. CONCLUSIONS These results suggest that the FOXO1/LCN2 signaling pathway participates in the anti-diabetic effect of SG.

Effect of Sleeve Gastrectomy on Bone Metabolism and Serum 5-Hydroxytryptamine in Obese Rats.

BACKGROUND Studies have shown that bariatric surgery, such as sleeve gastrectomy (SG), has an adverse effect on bone, including decreased bone mineral density (BMD) and bone metabolism. Peripheral 5-hydroxytryptamine (5-HT) has an adverse regulatory effect on bone formation. Here, we assessed changes in bone metabolism and whether 5-HT is involved in the effect of SG on bone metabolism. MATERIAL AND METHODS A rat model of obesity was established using Wistar rats. After successful modeling, rats were randomly assigned to 2 groups - the SG group and the Sham group - with 10 rats in each group. We then performed sleeve gastrectomy or sham operation. Bone metabolic markers and BMD of rats were measured at 2 and 16 weeks after the operation and the level of 5-HT in serum was determined. Rats were killed at 16 weeks after the operation, and bones of the hind limbs were harvested to measure 5-HT by immunofluorescence. RESULTS BMD was decreased and bone metabolism demonstrated a trend of bone destruction in the rats after SG. A significantly increasing trend in the level of serum 5-HT was found, and bone immunofluorescence showed increased expression of 5-HT. CONCLUSIONS BMD was decrease and bone metabolism demonstrated a trend of bone destruction after SG. SG can affect the level of 5-HT in serum or bone tissue and the 5-HT may be involved in the process through which SG affects bone metabolism.

Pramipexole in peritoneal dialysis patients with restless legs syndrome (RLS): a protocol for a multicentre double-blind randomised controlled trial.

INTRODUCTION: Restless legs syndrome (RLS) is a common neurological sensorimotor disorder among patients with end stage renal disease. This clinical trial aimed to provide evidence on the efficacy and safety of pramipexole in patients with uremic RLS receiving peritoneal dialysis (PD). METHODS AND ANALYSIS: This is a 12-week, multicentre, randomised, double-blind, placebo-controlled clinical trial. In total, 104 patients with uremic RLS receiving PD will be enrolled from four hospitals and randomly assigned in a 1:1 ratio to either placebo or pramipexole. We will determine the efficacy of pramipexole in the improvement of International RLS Study Group Rating Scale as the primary outcome, while responder rates for other RLS scales at week 12, change from baseline to week 12 for psychological status, sleep disorder and quality of life and blood pressure represent the secondary outcomes. ETHICS AND DISSEMINATION: The study was approved by the ethics committees of Peking University First Hospital, Xinqiao hospital of Army Medical University, Cangzhou Center Hospital and Peking University Shenzhen Hospital. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03817554.