Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.

Association between sarcopenic obesity and mortality in patients on peritoneal dialysis: a prospective cohort study.

Background: Whether sarcopenic obesity had unfavorable effect on survival of peritoneal dialysis (PD) patients is unknown. We aimed to investigate the association between sarcopenic obesity and survival in PD patients. Methods: This was a prospective observational study. Eligible PD patients from November 2016 to December 2017 were enrolled and followed until August 31, 2023. Sarcopenia was defined following the recommendations of the Asian Working Group for Sarcopenia (AWGS) as low appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Obesity was defined using the percentage of body fat (PBF). Survival analysis was conducted using the Kaplan-Meier and log-rank test. The Cox regression and the cumulative incidence competing risk (CICR) analyzes were used to investigate the association between sarcopenic obesity and all-cause mortality. Results: A total of 223 patients were enrolled with 133 (59.6%) males, a median age of 57.5 (44.6, 65.7) years, a median dialysis vintage of 20.3 (6.4, 57.7) months and 48 (21.5%) who had comorbid diabetes mellitus. Among them, 46 (20.6%) patients were sarcopenic, and 25 (11.2%) patients were diagnosed with sarcopenic obesity. After followed up for 51.6 (25.6, 73.9) months, the Kaplan-Meier curve showed the sarcopenic obesity (log-rank = 13.527, p < 0.001) group had significant lower survival rate compared to the nonsarcopenic non-obesity group. For multivariate analysis, the CICR method showed patients with sarcopenic obesity had significantly higher mortality rate (HR: 2.190, 95% CI: 1.011-4.743, p = 0.047) compared to those with nonsarcopenic non-obesity. Conclusion: Sarcopenia is not uncommon in PD patients, with a considerable proportion having sarcopenic obesity. There is a significant association between sarcopenic obesity and an increased risk of mortality in PD patients.

Sarcopenia predicts cardiovascular disease in chronic kidney disease at advanced stage and associated risks.

Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD), and sarcopenia is a new risk factor for CKD. However, whether sarcopenia predicts CVD in CKD remains to be determined. Sarcopenia would predict CVD in CKD at advanced stage. This analysis included 101 patients with CKD at stage 3 or over to determine the prevalence of sarcopenia and cardiovascular disease in patients with CKD at stage 3 or over in our center. The patients were further categorized into sarcopenia group (N = 19) and non-sarcopenia group (N = 82) according to the diagnostic criteria for sarcopenia. Data on demographics, laboratory tests, and measurements of extracardiac adipose tissue thickness (EAT) was collected. The prevalence of sarcopenia in patients with CKD at stage ≥ 3 was 19%. Compared with non-sarcopenia group, patients from the sarcopenia group were older (P = .005), and presented longer disease durations (P = .002). The serum level of albumin was significantly decreased, (P = .047), and high-sensitivity C-reactive protein level (CRP) was significantly increased (P = .003) in sarcopenia group. In addition, the EAT was thicker in the sarcopenia group compared with non-sarcopenia group (P = .032). Furthermore, the le-stratified atherosclerotic cardiovascular disease (ASCVD) risk scores were positively correlated with inflammation, nutrition, body mass index (BMI) and disease duration of CKD in sarcopenia group (P < .001). Patients with CKD are prone to have sacropenia, which is associated with inflammation and malnutrition. Presence of sarcopenia in CKD patients predicts the risk of ASCVD.

Clinical risk factors for peritoneal dialysis withdrawal at different dialysis duration.

BACKGROUND: The duration of patients maintained on peritoneal dialysis (PD) varied. This study investigated the clinical risk factors for PD withdrawal at different dialysis duration. METHODS: Patients who initiated PD from 1994 to 2011 were recruited and followed for at least 10 years until 2021. Patients were grouped into four groups according to dialysis duration or time on treatment (TOT) when withdrew PD. RESULTS: A cohort of 586 patients were enrolled (mean age of 54.9 years, median dialysis duration or TOT of 47.9 months). Patients who maintained PD for longer than 10 years were younger, with lower prevalence of diabetes, lower serum C-reactive protein (CRP) level and white blood cell (WBC) count, higher serum albumin and pre-albumin level, higher normalized protein catabolic rate (nPCR) and residual kidney function, and more common use of renin-angiotensin system inhibitors (RASi) at baseline (p < 0.05 for all). Peritonitis related death and ultrafiltration failure related HD transferring increased along with time on PD (p < 0.001). Old age, diabetes, low serum albumin, high WBC count, hypertensive nephropathy, and nonuse of RASi were associated with increased risk of non-transplantation related PD withdrawal (p < 0.05 for all). Low baseline CRP and use of RASi were independent predictors for long-term PD maintenance (p < 0.05 for all). CONCLUSIONS: Long-term PD patients demonstrated young age, low prevalence of diabetes, better nutrition status, absence of inflammation, better residual kidney function, and higher proportion of RASi usage at baseline. Absence of inflammation and use of RASi were independently associated with long-term PD maintenance.

Low Blood Glucose Index Associated with Cardiovascular Events in Diabetic Hemodialysis Patients.

INTRODUCTION: Blood glucose monitoring was vitally important in diabetic kidney disease (DKD) patients for preventing complications and improving survival rates. The associations between glycemic variability and blood biochemical indicators were underestimated in patients with DKD undergoing hemodialysis. Therefore, we primarily aimed to investigate the glycemic variability and 1-year risk of cardiovascular disease events in diabetic hemodialysis patients. And we secondarily aimed to explore the association between glycemic variability and blood biochemical indicators. METHODS: In total, 27 patients were included in the final analysis. Continuous glucose monitoring (CGM) was used to evaluate glucose variability for 14 days. Patients were divided into two groups by the cutoff level of time in range (TIR; >70% or ≤70%). The three-point major adverse cardiovascular event (3P MACE) was recorded within 1 year. RESULTS: After 1 year of follow-up, 4 patients in the high-TIR group and 3 patients in the low-TIR group had 3p MACE. Higher low blood glucose index (LBGI) level in diabetic hemodialysis patients increased the risk of 3p MACE outcomes (HR = 2.37, p = 0.018). And the level of albumin was positively associated with LBGI (ß = 0.51, p = 0.036). The plasma levels of albumin, glycosylated hemoglobin, and hemoglobin were positively associated with other CGM parameters. CONCLUSION: LBGI during 14 days was positively associated with the risk of cardiovascular events in diabetic hemodialysis patients.

CVD risk in non-albuminuric chronic kidney disease in hypertensive, non-diabetic subjects: A post-hoc analysis from SPRINT.

Introduction: The risks associated with non-albuminuric chronic kidney disease (CKD) have been investigated in diabetes mellitus but not in hypertensive patients. The objective of this study was to investigate the risks associated with non-albuminuric CKD in treated hypertensive patients in the Systolic Blood Pressure Intervention Trial (SPRINT) population. Methods: Based on baseline albuminuria status (urine albumin/creatinine ratio [UACR], ≥30 or <30 mg/g) and the levels of estimated glomerular filtration rate ([eGFR], ≥60, 45-59, or <45 mL/min/1.73 m2), participants were classified into six subgroups to assess the risks associated with the primary outcome and mortality. The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or mortality from cardiovascular causes. Results: During a median follow-up of 3.26 years in 8,866 hypertensive patients, there were 352 deaths and 547 participants with the primary outcome. In adjusted Cox regression analysis using non-CKD and non-albuminuria (eGFR ≥60 mL/min/1.73 m2 combined with UACR <30 mg/g) as reference, albuminuria whether combined with CKD or not, showed significantly higher risk of both primary outcome and all-cause mortality in the total population. Whereas, non-albuminuria only combined with eGFR <45 mL/min/1.73 m2 showed significantly higher risk of both primary outcome and all-cause mortality in the intensive-therapy group. Discussion: Non-albuminuric CKD did have higher risk of all-cause and CVD mortality only if the eGFR <45 mL/min/1.73 m2. Increased albuminuria conferred higher risk of primary outcome and all-cause mortality irrespective the levels of eGFR. Clinical trial registration: ClinicalTrials.gov, number: NCT01206062.

Self-care or assisted PD: development of a new approach to evaluate manual peritoneal dialysis practice ability.

BACKGROUND: Peritoneal dialysis (PD) is a home-based therapy which requires the patients or their caregivers to perform the practice. We aimed to develop a practical approach to evaluate PD practice ability of the patients and to identify berries to self-care PD. METHODS: A structural form was designed comprising measures of physical, cognitive, and operational abilities which were required to perform manual PD independently. The evaluation was jointly conducted by a PD nurse, a nephrologist and a close family member of the patient. Patients who met all the requirements were deemed as capable of performing PD independently (self-care PD) and others were deemed as needing an assistant (assisted PD). RESULTS: The evaluation form was applied in 280 prevalent PD patients and 33.9% of them were assessed as needing assisted PD, mainly due to physical (62.1%) or operational (66.3%) disabilities. The evaluation result was consistent with current dialysis status in 79.3% patients and it matched better in patients who performed PD with the help of an assistant (93.0 vs. 76.8%, p = 0.014). Patients who were evaluated as having barriers to self-care PD but still performed PD without an assistant were older and demonstrated higher prevalence of diabetic nephropathy and PD-related infection, lower education level, and lower serum albumin (p < 0.05). CONCLUSIONS: The PD practice ability assessment form is useful to identify patients with barriers to self-care PD. It provides objective information to the patients and their family to choose feasible PD practice modality, self-care, or assisted PD.

High intraperitoneal interleukin-6 levels predict ultrafiltration (UF) insufficiency in peritoneal dialysis patients: A prospective cohort study.

Introduction: UF insufficiency is a major limitation in PD efficiency and sustainability. Our study object to investigate the efficacy of intraperitoneal inflammation marker, IL-6 level as a predictor of UF insufficiency in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: Stable prevalent CAPD patients were enrolled in this prospective study. IL-6 concentration in the overnight effluent was determined and expressed as the IL-6 appearance rate (IL-6 AR). Patients were divided into two groups according to the median of IL-6 AR and prospectively followed up until death, transfer to permanent HD, recovery of renal function, kidney transplantation, transfer to other centers, lost to follow-up or to the end of study (January 31, 2021). Factors associated with UF capacity as well as dialysate IL-6 AR were assessed by multivariable linear regression. Cox proportional hazards model was used to examine the association between dialysate IL-6 AR and UF insufficiency. Results: A total of 291 PD patients were enrolled, including 148 males (51%) with a mean age of 56.6 ± 14.1 years and a median PD duration of 33.4 (12.7-57.5) months. No correlation was found between dialysate IL-6 AR and UF capacity at baseline. PD duration was found positively correlated with baseline dialysate IL-6 AR, while 24h urine volume was negatively correlated with baseline dialysate IL-6 AR (P < 0.05). By the end of study, UF insufficiency was observed in 56 (19.2%) patients. Patients in the high IL-6 AR group showed a significantly inferior UF insufficiency-free survival when compared with their counterparts in the low IL-6 AR group (P = 0.001). In the multivariate Cox regression analysis, after adjusting for DM, previous peritonitis episode and 24h urine volume, higher baseline dialysate IL-6 AR (HR 3.639, 95% CI 1.776-7.456, P = 0.002) were associated with an increased risk of UF insufficiency. The area under the ROC curve (AUC) for baseline IL-6 AR to predict UF insufficiency was 0.663 (95% CI, 0.580-0.746; P < 0.001). Conclusion: Our study suggested that the dialysate IL-6 AR could be a potential predictor of UF insufficiency in patients undergoing PD.

sPD-1 and sPD-L1 Levels in Serum and Urine of Patients with Primary Nephrotic Syndrome and their Clinical Significance.

BACKGROUND: Primary nephrotic syndrome (PNS), a clinically prevalent glomerular disease, mostly results in a large loss of plasma albumin, and its predominant clinical manifestations are proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Research has uncovered [9] that sPD-L1 and sPD-1 modulate the PD and PD-L1 pathway in the development of various autoimmune diseases. METHODS: We randomly selected 80 PNS patients treated for PNS in our institution from October 2017 to October 2018 as the case group and 78 healthy volunteers examined in our hospital during the same period as the control group. Not only sPD-1 but also sPD-L1 level in serum and urine was assayed via ELISA. We compared the distribution of T lymphocyte subsets in peripheral blood and mALB and NAG levels in urine. Pearson's correlation analysis was adopted for assessing the relationship of serum and urine sPD-1, sPD-L1 with T lymphocyte subsets and mALB. RESULTS: (1) In contrast to the control group, the case group harbored higher pretreatment serum and urine sPD-1 and sPD-L1 contents (p < 0.05). (2) Before treatment, sPD-1 in the serum and urine held a positive relationship with sPD-L1 level (r was 0.683 and 0.235, respectively, p < 0.05); serum sPD-1 harbored a positive link with urine sPD-1 (r = 0.287, p < 0.01), whereas no relationship was discovered in serum sPD-L1 and urine sPD-L1. (3) In contrast to the control group, the CD4+ level in the case group abated, CD8+ increased, the CD4+/CD8+ ratio assuaged, and mALB level in urine increased (all p < 0.05), whereas NAG harbored no statistical difference (p > 0.05). (4) In the case group, the CD4+/CD8+ ratio possessed positive association with serum sPD-1 (r = 0.384, p < 0.001), and the mALB had a positive relationship with urine sPD-1 (r = 0.704, p < 0.001). (5) After treatment, in comparison with the remission group, the serum sPD-1 level of the non-remission group was increased (p < 0.05), whereas sPD-L1 value was not statistically different (p > 0.05); the sPD-1 level in urine was not statistically significant (p > 0.05), while sPD-L1 content was elevated (p < 0.05). CONCLUSIONS: Serum and urine sPD-1/sPD-L1 levels of PNS patients change dynamically. Detecting sPD-L1 and sPD-1 has certain clinical value for the prognosis of PNS.

Assisted peritoneal dialysis: a feasible KRT modality for frail older patients with end-stage kidney disease (ESKD).

Assisted PD is used as an alternative option for the growing group of frail, older ESKD patients unable to perform their own PD. This study was undertaken to investigate the outcomes of assisted PD in older patients by comparing assisted PD patients with self-care PD patients. This study included all patients aged 70 and above who started on PD in our hospital from 2009 to 2018. Patients were followed up until death, PD cessation or to the end of the study (December 31, 2019). Risk factors associated with mortality, peritonitis and technique failure were evaluated using both cause-specific hazards and subdistribution hazards models. 180 patients were enrolled, including 106 (58.9%) males with a median age of 77.5 (77.2-81.2) years. Among the 180 patients, 62 patients (34.4%) were assisted. Patients on assisted PD group were older, more likely to be female, more prevalent in DM and CVD, with a higher Charlson score than patients undergoing self-care PD (P all < 0.05). In the multivariable analysis, assisted patients had a comparable patient survival and peritonitis-free survival compared to self-care PD patients either in the Cox or in the FG models. According to a Cox model, the use of assisted PD was associated with a lower risk of technique failure (cs-HR 0.20, 95% CI 0.04-0.76), but the association lost its statistical significance in the Fine and Gray model. Our results suggest that assisted PD could be a safe and effective KRT modality for older ESKD patients who need assistance.

Clinical characteristics associated with the properties of gut microbiota in peritoneal dialysis patients.

BACKGROUND: Gut microbiota alters in patients with end-stage renal disease, which contributes to inflammation, atherosclerosis, and results in increased incidence of cardiovascular diseases. The present study investigated the potential clinical factors, which influence the gut microbial structure and function in patients undergoing peritoneal dialysis (PD). METHODS: This is a cross-sectional study performed in 81 prevalent PD patients. Gut microbiota was assessed by high throughput sequencing of 16S ribosomal ribonucleic acid gene in fecal samples. Gas chromatography was conducted to measure stool short-chain fat acid (SCFA) concentrations. Demographic parameters and clinical characteristics, including dialysis regimen, residual renal function, nutrition, and inflammation, were retrieved and related to the properties of gut microbiota. RESULTS: PD duration, peritoneal glucose exposure, and estimated glomerulus filtration rate (eGFR) were identified to be associated with microbial variations. Significant separation of microbial composition was shown between patients with short or long PD duration (p = 0.015) and marginal differences were found between patients grouped by different levels of peritoneal glucose exposure (p = 0.056) or residual renal function (p = 0.063). A couple of gut bacteria showed different abundance at amplicon sequencing variant level between these patient groups (p < 0.05). In addition, stool isobutyric and isovaleric acid concentrations were significantly reduced in patients with longer dialysis duration, higher peritoneal glucose exposure, or declined eGFR (p < 0.05). CONCLUSIONS: This pilot study demonstrated that long dialysis duration, high peritoneal glucose exposure, and loss of residual renal function were associated with gut microbiota alteration and reduced branched-chain SCFA production in PD patients.

Visceral adipogenesis inhibited by Pref-1 is associated with peritoneal angiogenesis.

AIM: Studies showed an increased visceral adipose tissue and peritoneal angiogenesis in peritoneal dialysis (PD) patients. However, the relationship between the visceral adipose expands and peritoneal angiogenesis remains unclear. METHODS: Pref-1 (preadipocyte factor-1) recombinant adeno-associated virus (AAV) and control AAV were constructed. Mice were divided into four groups, mice in control and PD group were injected intraperitoneally with PBS, mice in control-AAV-PD were injected intraperitoneally with plaque-forming unit (PFU) control AAV and mice in pref-1-AAV-PD group were injected with PFU recombinant AAV. Two weeks later, control group was injected intraperitoneally with normal saline while other groups were injected intraperitoneally with 4.25% peritoneal dialysis fluid (PDF). Thirty days later, viscerall adipose tissue was collected and weighed. Pref-1 protein expression was measured by Western blot, and peritoneal permeability was measured by Evans blue. Cluster of differentiation 31(CD31) immunohistochemical staining was used to detect mesenteric blood vessel number, and vascular endothelial growth factor (VEGF) in serum were measured by enzyme-linked immunosorbent assay. RESULTS: Pref-1 protein expression increased in pref-1-AAV-PD group. Visceral adipose expanded in PD and control-AAV-PD group while decreased in pref-1-AAV-PD group, which approves PD fluid enhance visceral adipogensis, and the process could be inhibited by Pref-1 recombinant AAV. The reduction of peritoneal vessel number and the decrease of vascular permeability as well as down-regulation of serum vascular endothelial growth factor observed in pref-1-AAV-PD group suggested peritoneal angiogenesis could be inhibited following visceral adipose tissue reduction. CONCLUSION: Visceral adipose expands is associated with peritoneal angiogenesis in PD treatment, and prevention of visceral adipogenesis may be an alternative way to protect the validity of peritoneum. Copyright © 2019 John Wiley & Sons, Ltd.

IL-6 trans-signaling drives a STAT3-dependent pathway that leads to structural alterations of the peritoneal membrane.

IL-6 is a vital inflammatory factor in the peritoneal cavity of patients undergoing peritoneal dialysis (PD). The present study examined the effect of IL-6 trans-signaling on structural alterations of the peritoneal membrane. We investigated whether the epithelial-to-mesenchymal transition (EMT) process of human peritoneal mesothelial cells (HPMCs) and the production of proangiogenic factors were controlled by IL-6 trans-signaling. Its role in the peritoneal alterations was detected in a mouse model. The morphology of HPMCs and levels of cytokines in PD effluent were also explored. Stimulation of HPMCs with the IL-6 and soluble IL-6 receptor complex (IL-6/S) promoted the EMT process of HPMCs depending on the STAT3 pathway. In a coculture system of HPMCs and human umbilical vein endothelial cells, IL-6/S mediated the production of VEGF and angiopoietins so as to downregulate the expression of endothelial junction molecules and finally affect vascular permeability. Daily intraperitoneal injection of high glucose-based dialysis fluid induced peritoneal fibrosis, angiogenesis, and macrophage infiltration in a mouse model, accompanied by phosphorylation of STAT3. Blockade of IL-6 trans-signaling prevented these peritoneum alterations. The fibroblast-like appearance of HPMCs ex vivo was upregulated in patients undergoing prevalent PD accompanied by increasing levels of IL-6, VEGF, and angiopoietin-2 in the PD effluent. Taken together, these findings identified a critical link between IL-6 trans-signaling and structural alterations of the peritoneal membrane, and it might be a potential target for the treatment of patients undergoing PD who have developed peritoneal alterations.

Protective effect of COMP-angiopoietin-1 on peritoneal vascular permeability and peritoneal transport function in uremic peritoneal dialysis rats.

The angiopoietin-1 (Ang-1)/Tie-2 signaling pathway plays a crucial role in the maintenance of vascular stabilization and permeability. In this study, we evaluated the protective effect of a designed Ang-1 variant (COMP-Ang-1) on peritoneal vascular permeability and peritoneal transport function in a uremic peritoneal dialysis (PD) model. Compared to the sham controls, uremic rats were characterized by decreased pericyte coverage and downregulated endothelial junction expression. The permeability of the peritoneal vasculature to FITC-BSA and FITC-dextran in uremic rats was also higher than that in the sham controls, as well as increased levels of proinflammatory adhesion molecules and cytokines, increased D/Pcr and decreased ultrafiltration. Such changes were more marked in uremia+PD rats after exposure to glucose-based peritoneal dialysis fluid (PDF) for 4 weeks. Peritoneal Ang-1 protein expression and Tie-2 phosphorylation were significantly lower in uremic rats than in control rats and were further significantly reduced in uremia+PD rats. After COMP-Ang-1 administration, phosphorylation of the Tie-2 receptor was significantly increased. Treatment with COMP-Ang-1 also significantly enhanced pericyte coverage, upregulated endothelial junction protein expression and inhibited leakage of FITC-BSA and FITC-dextran from the peritoneal vasculature induced during PD therapy; these changes were accompanied by reduced peritoneal tissue levels of proinflammatory adhesion molecules and cytokines, decreased D/Pcr and increased ultrafiltration. These findings suggest that COMP-Ang-1 may exert a protective effect against glucose-based PDF-induced peritoneal vascular permeability and inflammation, at least in part, by enhancing pericyte coverage and endothelial junction protein expression, which subsequently significantly improves peritoneal transport function.

Efficacy and safety of tacrolimus-based treatment for nephrotic idiopathic membranous nephropathy in young adults: A retrospective study.

In China, the prevalence of idiopathic membranous nephropathy (IMN) is increasing with a younger age of onset. From January 2012 to October 2018, biopsy-proven nephrotic IMN patients aged between 15 and 40 in Taian City Central Hospital treated with tacrolimus (TAC) were retrospectively analyzed. Twelve-month follow-up data were collected. A total of 86 patients were enrolled in this study. Forty patients in the TAC group received TAC monotherapy with an initial dose of 0.05 to 0.1 mg/kg/day. Forty-six patients in the TAC + Pred group received TAC combined with oral prednisone (0.5 mg/kg/day initially). Remission rate, relapse rate, and adverse events in the two groups were assessed. Total remission (TR) rates at the end of the 3rd, 6th, and 12th month were 15%, 35%, and 77.5% (TAC group) and 28.3%, 56.5%, and 80.4% (TAC + Pred group), respectively. Compared with the TAC group, the TAC + Pred group had higher complete remission rates at the end of the 6th and 12th month, and TR rate at the 6th month was significantly higher. Twenty-four-hour urinary protein excretion, serum albumin and estimated glomerular filtration rate between the two groups were comparable during the follow-up. Decrease in proteinuria was significantly greater in the TAC + Pred group. No significant difference of relapse rate was found between the two groups. Adverse effects in the two groups were mild and controllable. Both TAC monotherapy and TAC combined with medium-dose prednisone are effective and safe for young adults with nephrotic IMN, while TAC + Pred regimen brings more benefits.

Peritoneal Dialysis as an Option for Unplanned Dialysis Initiation in Patients with End-Stage Renal Disease and Diabetes Mellitus.

AIMS: This study aimed to compare the short-term complications and long-term prognosis between urgent-start peritoneal dialysis (PD) and hemodialysis (HD), and explore the safety and feasibility of PD in end-stage renal disease (ESRD) patients with diabetes. METHODS: This retrospective study enrolled ESRD patients with diabetes who required urgent-start dialysis at a single center from January 2011 to December 2014. Short-term (30-day) dialysis-related complications and patient survival trends were compared between patients receiving PD and HD. RESULTS: Eighty patients were included in the study, including 50 (62.5%) who underwent PD. The incidence of dialysis-related complications and complications requiring reinsertion during the first 30 days was significantly lower in PD patients. Logistic regression identified urgent-start HD as an independent risk factor for dialysis-related complications compared with urgent-start PD. The patient survival rate was higher in the PD compared to that in the HD group. CONCLUSIONS: PD may be acceptable, safe, and feasible for urgent-start dialysis in ESRD patients with diabetes.

Different patterns of inflammatory and angiogenic factors are associated with peritoneal small solute transport and peritoneal protein clearance in peritoneal dialysis patients.

BACKGROUND: Both peritoneal small solute transport and peritoneal protein clearance are closely linked to outcomes in peritoneal dialysis (PD) patients. However, the associated factors of these two components are not fully understood so far. This study aimed to investigate the association between a panel of systemic and peritoneal inflammatory and angiogenic factors and peritoneal solute transport properties. METHODS: Stable PD patients in PD center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled in present study. Serum and overnight effluent markers including angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), sTie-2, VEGF, IL-6 and IL-10 were determined. Mass transfer area coefficient of creatinine (MTACcr) and peritoneal protein clearance (Prcl) were calculated. Multivariable linear regression was used to examine the association between these markers and MTACcr as well as Prcl. RESULTS: A total of 320 patients were enrolled in present study, which consisted of 166 (51.9%) males with a mean age of 56.8 ± 14.2 years and a median PD duration of 32.5 (9.0-56.3) months. Multiple regression analyses showed that BSA, history glucose exposure, dialysate IL-6 AR and dialysate Ang-1 AR were independent associated factors of MTACcr, while BSA and serum Ang-1 were independent associated factors of Prcl. CONCLUSIONS: MTACcr representing peritoneal small-solute transport and Prcl representing peritoneal large molecular transport are associated with slightly different panels of inflammatory and angiogenic factors.

Elevated levels of serum sclerostin are linked to adverse cardiovascular outcomes in peritoneal dialysis patients.

PURPOSE: To investigate the correlation between elevated serum sclerostin levels and chronic kidney disease outcomes for patients receiving peritoneal dialysis (PD). METHODS: We performed a prospective observational study in stable PD patients. Serum sclerostin levels were determined via enzyme immunoassay, and median levels of sclerostin were used to divide patients into high and low sclerostin groups. New-onset cardiovascular events (CVEs) and cardiovascular mortality were evaluated during a 6-year follow-up period. RESULTS: Ninety-eight patients [mean age 52.5 ± 10.9 years, 49% males, 21.4% diabetic, median dialysis vintage 40.7 (range 17.9-72.2) months] were recruited. Compared with those in the low sclerostin group, patients in the high sclerostin group demonstrated higher levels of total-cholesterol, NT-proBNP, and osteoprotegerin (all P < 0.05). During the 6-year study period, 25 CVEs and 17 cardiovascular deaths occurred in the high sclerostin group, whereas 11 CVEs and four cardiovascular deaths occurred in the low sclerostin group. A Cox regression analysis determined that high sclerostin levels significantly increased the risk for CVEs (HR 2.475, 95% CI 1.116-5.489, P = 0.026) and cardiovascular death (HR 3.484, 95% CI1.134-10.706, P = 0.029), after multiple adjustments were made. CONCLUSIONS: Our data suggest that high sclerostin levels may predict the onset of CVEs and cardiovascular mortality among PD patients.

Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model.

BACKGROUND: Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model. METHODS: 32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal® for 4 weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot. RESULTS: Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p < 0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001). CONCLUSION: PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.

Calcium dobesilate may alleviate diabetes­induced endothelial dysfunction and inflammation.

Diabetic kidney disease (DKD) is a leading cause of end­stage renal disease. However, the pathogenesis of DKD remains unclear, and no effective treatments for the disease are available. Thus, there is an urgent need to elucidate the pathogenic mechanisms of DKD and to develop more effective therapies for this disease. Human umbilical vein endothelial cells (HUVECs) were cultured using different D­glucose concentrations to determine the effect of high glucose (HG) on the cells. Alternatively, HUVECs were incubated with 100 µmol/l calcium dobesilate (CaD) to detect its effects. The authors subsequently measured HUVEC proliferation via cell counting kit­8 assays. In addition, HUVEC angiogenesis was investigated via migration assays and fluorescein isothiocyanate (FITC)­labelled bovine serum albumin (BSA) permeability assays. The content or distribution of markers of endothelial dysfunction [vascular endothelial growth factor (VEGF), VEGF receptor (R) and endocan) or inflammation [intercellular adhesion molecule (ICAM)­1, monocyte chemotactic protein (MCP)­1 and pentraxin­related protein (PTX3)] was evaluated via reverse transcription­quantitative polymerase chain reaction and western blotting. HG treatment induced increased in VEGF, VEGFR, endocan, ICAM­1, MCP­1 and PTX3 mRNA and protein expression in HUVECs. HG treatment for 24 to 48 h increased cell proliferation in a time­dependent manner, but the cell proliferation rate was decreased at 72 h of HG treatment. Conversely, CaD inhibited abnormal cell proliferation. HG treatment also significantly enhanced HVUEC migration compared to the control treatment. In contrast, CaD treatment partially inhibited HUVEC migration compared to HG exposure. HG­treated HUVECs exhibited increased FITC­BSA permeability compared to control cells cultured in medium alone; however, CaD application prevented the HG­induced increase in FITC­BSA permeability and suppressed HG­induced overexpression of endothelial markers (VEGF, VEGFR­2, endocan) and inflammation markers (ICAM­1, MCP­1, PTX3) in HUVECs. CaD has angioprotective properties and protects endothelial cells partly by ameliorating HG­induced inflammation. The current results demonstrated the potential applicability of CaD to the treatment of diabetic nephropathy, particularly during the early stages of this disease.