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.

AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.

BACKGROUND: Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability. METHODS: We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether AQP1 variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an AQP1 variant and investigate mitigation strategies. RESULTS: The common AQP1 promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (±SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506±237 ml vs. 626±283 ml, P = 0.007) and in the validation phase (368±603 ml vs. 563±641 ml, P = 0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P = 0.001), as well as a higher risk of death from any cause (24% vs. 15%, P = 0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in AQP1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant. CONCLUSIONS: A common variant in AQP1 was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.).

Gene polymorphisms of VEGF and KDR are associated with initial fast peritoneal solute transfer rate in peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is an effective and successful renal replacement therapy. The baseline peritoneal solute transfer rate (PSTR) is related to local membrane inflammation and may be partially genetically determined. Herein, we focused on vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR). METHODS: This study recruited 200 PD patients from Renji Hospital in Shanghai, China. We analysed the association between the polymorphisms of VEGF and KDR and the 4-hour dialysate-to-plasma ratio for creatinine (4 h D/P Cr), which was measured between one and three months after initiating PD. RESULTS: The CC genotype in VEGF rs3025039 and the AA genotype in KDR rs2071559 were both positively associated with a fast baseline PSTR (VEGF rs3025039 CC vs. TT + TC: 0.65 ± 0.12 vs. 0.61 ± 0.11; P = 0.029; KDR rs2071559 AA vs. GA + GG: 0.65 ± 0.12 vs. 0.62 ± 0.12; P = 0.039). CONCLUSION: Baseline PSTR was partly determined by VEGF and KDR gene polymorphisms.

Understand the difference between clinical measured ultrafiltrationand real ultrafiltration in peritoneal dialysis.

BACKGROUND: It has been noticed for years that ultrafiltration (UF) is important for survival in peritoneal dialysis. On the other hand, precise and convenient UF measurement suitable for patient daily practice is not as straight forward as it is to measure UF in the lab. Both overfill and flush before fill used to be source of measurement error for clinical practice. However, controversy finding around UF in peritoneal dialysis still exists in some situation. The current study was to understand the difference between clinical measured UF and real UF. The effect of evaporation and specific gravity in clinical UF measurement were tested in the study. METHODS: Four different brands of dialysate were purchased from the market. The freshest dialysate available in the market were intentionally picked. The bags were all 2 L, 2.5% dextrose and traditional lactate buffered PD solution. They were stored in four different conditions with controlled temperature and humidity. The bags were weighted at baseline, 6 months and 12 months of storage. Specific gravity was measured in mixed 24 h drainage dialysate from 261 CAPD patients when they come for their routine solute clearance test. RESULTS: There was significant difference in dialysate bag weight at baseline between brands. The weight declined significantly after 12 month's storage. The weight loss was greater in higher temperature and lower humidity. The dialysate in non-PVC package lose less weight than PVC package. The specific gravity of dialysate drainage was significantly higher than pure water and it was related to dialysate protein concentration. CONCLUSION: Storage condition and duration, as well as the type of dialysate package have significant impact in dialysate bag weight before use. Evaporation is likely to be the reason behind. The fact that specific gravity of dialysate drainage is higher than 1 g/ml overestimates UF in manual exchanges, which contributes to systemic measurement error of ultrafiltration in CAPD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03864120 (March 8, 2019) (Understand the Difference Between Clinical Measured Ultrafiltration and Real Ultrafiltration).

B-type natriuretic peptide levels and volume status in twice-weekly hemodialysis patients.

BACKGROUND: Twice-weekly hemodialysis (HD) could be regarded as an important part of incremental hemodialysis, volume status of this treatment model remains to be elucidated. METHODS: Patients undergoing regular twice-weekly or thrice-weekly hemodialysis in our unit on June 2015 were enrolled into the cohort study with an average of 2.02 years follow-up. Volume status of the subjects was evaluated by clinical characteristics, plasma B-type natriuretic peptide (BNP) levels and bioimpedance assessments with body composition monitor (BCM). Cox proportional hazards models and Kaplan-Meier analysis were used to compare patient survival between the two groups. RESULTS: Compared with patients on thrice-weekly HD, twice-weekly HD patients had significantly higher log-transformed BNP levels (2.54 ± 0.41 vs. 2.33 ± 0.49 pg/ml, p = 0.010). Overhydration (OH) and the ratio of overhydration to extracellular water (OH/ECW) in twice-weekly HD group were significantly higher than that of thrice-weekly HD (OH, 2.54 ± 1.42 vs. 1.88 ± 1.46, p = 0.033; OH/ECW, 0.17 ± 0.07 vs. 0.12 ± 0.08, p = 0.015). However, subgroup analysis of patients within 6 years HD vintage indicated that the two groups had similar hydration status. Multivariate Cox regression analysis showed that log-transformed BNP levels, serum albumin and diabetes status were predictors of mortality in hemodialysis patients. Kaplan-Meier survival analysis indicated that patients with BNP levels higher than 500 pg/ml had significantly worse survival compared with those with lower BNP levels (p = 0.014). CONCLUSIONS: Twice-weekly hemodialysis patients had worse volume status than that of thrice-weekly HD patients especially for those with long-term dialysis vintage, BNP level was a powerful predictor of mortality in HD patients.

Leflunomide plus low-dose prednisone in patients with progressive IgA nephropathy: a multicenter, prospective, randomized, open-labeled, and controlled trial.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge. METHODS: We did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. RESULTS: One hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p < 0.01) and increase in sALB (p < 0.01), with stable Scr and eGFR throughout the 12-month treatment period. What's more, these effects were sustained through the 12-month follow-up period. However, there was no difference in 24-h UPE, sALB, Scr, and eGFR between the two groups (p > 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant. CONCLUSIONS: The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.

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.

Abdominal aortic calcification score as a predictor of clinical outcome in peritoneal dialysis patients: a prospective cohort study.

BACKGROUND: Abdominal aortic calcification assessed by X-ray is recommended to evaluate vascular calcification in dialysis patients. It has been shown that abdominal aortic calcification score (AACS) is a predictor of adverse outcomes in hemodialysis patients, but evidence regarding its prognostic value in peritoneal dialysis (PD) patients is still insufficient. We aimed to examine the predictive role of AACS for major adverse cardiac and cerebrovascular events (MACCE) and mortality in PD patients. METHODS: Eligible patients undergoing PD between July 2011 and July 2014 were recruited. AACS was quantified using lateral lumbar radiography at recruitment. Patients were prospectively followed up until death, PD cessation, or to the end of the study (August 31, 2018). Both subdistribution hazards and cause-specific hazards models were used to evaluate the association between AACS and MACCE as well as mortality. RESULTS: 292 patients were enrolled, including 160 males (54.8%) with mean age 57.1 ± 15.2 years and median PD duration 28.4 (IQR 12.0, 57.8) months. Among them, 75 (25.7%) patients were comorbid with diabetes, and 94 (32.2%) patients had cardiovascular disease (CVD). The average AACS was 2.0 (0.0, 6.0). Patients were categorized on the tertiles of AACS (Low AACS group, AACS = 0, n = 125; Medium AACS group, AACS 1-4, n = 72; and High AACS group, AACS> 4, n = 95). AACS was associated with age (OR = 1.081, P < 0.001), PD duration (OR = 1.012, P = 0.003), CVD (OR = 1.919, P = 0.020) and diabetes (OR = 2.554, P = 0.002). During the follow-up period of 43.6 (24.6, 50.7) months, there were 65 MACCEs and 84 deaths. Significantly higher cumulative incidences of all-cause mortality (Log-rank = 35.992, P<0.001; Gray = 38.662, P < 0.001) and MACCE (Log-rank = 26.146, P<0.001; Gray = 27.810, P < 0.001) were observed in the upper AACS tertile. AACS was an independent predictor of all-cause mortality (HR = 2.438, 95% CI 1.246-4.772, P = 0.009; SHR = 2.323, 95%CI 1.229-4.389, P = 0.009) and MACCE (HR = 3.455, 95% CI 1.734-6.884, P < 0.001; SHR = 3.063, 95%CI 1.460-6.430, P = 0.003) in this study. CONCLUSIONS: AACS was associated with age, PD duration, CVD and diabetes in PD patients. AACS could predict MACCE and all-cause mortality in this population. It thus might be a safe and feasible method to identify PD patients with adverse outcomes.

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.

The Incidence Prognosis and Risk Factors of Cognitive Impairment in Maintenance Haemodialysis Patients.

OBJECTIVE: To investigate the incidence and the prognosis of cognitive impairment (CI) and to find out the risk factors associated with the outcome in maintenance haemodialysis (MHD) patients. METHODS: Enrolled the patients who met the criteria as below: MHD (≥3 months) patients before July 2014, ≥18 years old and could carry on the cognitive function test (Montreal Cognitive Assessment [MoCA]). All enrolled patients were divided into 2 groups: CI group (MoCA < 26) and non-CI group (MoCA ≥26). All patients were followed up for 36 months. The incidence, demography data, medical history, haemodialysis data, laboratory examination and prognosis of CI in haemodialysis patients were prospectively compared and analyzed. Multivariate logistic regression analysis was used to investigate the risk factors of CI. Kaplan-Meier survival curve was used for survival analysis. RESULTS: In the present study, 219 patients were enrolled. The ratio of male to female was 1.46: 1. Age was 60.07 ± 12.44 and dialysis vintage was 100.79 ± 70.23 months. One hundred thirteen patients' MoCA scores were lower than 26 were divided into CI group. Education status (OR 3.428), post-dialysis diastolic pressure (OR 2.234) and spKt/V (OR 1.982) were independent risk factors for CI in MHD patients. During the follow-up period, 15 patients died (13.2%) in the CI group and 5 died (4.72%) in the non-CI group (p < 0.05). The Kaplan-Meier survival curve analysis showed that the survival rate of patients with CI was lower than that of non-CI group in MHD patients during 3 years follow-up (p = 0.046). CONCLUSION: CI is one of the most common complications in MHD patients. The mortality is high in patients who had CI. Education status, post-dialysis diastolic pressure and spKt/V are independent risk factors for CI in MHD patients.

Association of serum angiopoietin-2 with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients: a prospective cohort study.

BACKGROUND: To examine serum angiopoietin-2 (Angpt-2) in relation to malnutrition, inflammation, atherosclerosis and cardiac valvular calcification, so-called MIAC syndrome and its predictive role in outcomes of peritoneal dialysis (PD) patients. METHODS: A prospective observational study was conducted in 324 chronic PD patients. Biochemical analysis was performed at baseline for serum angiopoietins, albumin and high sensitive C-reactive protein (hs-CRP) and echocardiography was done to detect cardiac valvular calcification. Primary study end points were fatal or nonfatal cardiovascular events and mortality. RESULTS: The median of serum Angpt-2 levels was 5.44 ng/mL (interquartile range, 3.41-7.85). Across the three tertiles of serum Angpt-2, a significant trend effect was observed for body mass index, normalized protein catabolic rate, calcium × phosphorus product, hs-CRP, brain natriuretic peptide, lower-density lipoprotein cholesterol, left ventricular ejection fraction, total weekly urea clearance and residual renal function (all p < 0.05). Serum Angpt-2 showed a significant increase across the four groups of patients with increasing components of MIAC syndrome (p < 0.001). There were 77 deaths and 57 cardiovascular events. High serum Angpt-2 was an independent predictor of fatal and nonfatal cardiovascular events in PD patients (p = 0.02), however serum Angpt-2 was not an independent predictor of all-cause mortality (p = 0.3). CONCLUSIONS: Serum Angpt-2 showed close association with valvular calcification, atherosclerosis, inflammation and malnutrition, having significant independent prognostic value and is useful for cardiovascular event stratification in chronic PD patients. Angpt-2 might be a potential mediator of increased cardiovascular risk in patients undergoing PD treatment.

Clinical Outcome of Twice-Weekly Hemodialysis Patients with Long-Term Dialysis Vintage.

BACKGROUND/AIMS: Twice-weekly hemodialysis(HD) is prevalent in the developing countries, scarce data are available for this treatment in patients with long-term dialysis vintage. METHODS: 106 patients with more than 5 years HD vintage undergoing twice-weekly HD or thrice-weekly HD in a hemodialysis center in Shanghai between December 1, 2013 and December 31, 2013 were enrolled into the cohort study with 3 years follow-up. Kaplan-Meier analysis and Cox proportional hazards models were used to compare patient survival between the two groups. Subgroup analysis of 62 patients more than 10 years HD vintage was also performed according to their different dialysis frequency. RESULTS: Compared with patients on thrice-weekly HD, twice-weekly HD patients had significantly longer HD session time and higher single-pool Kt/V (spKt/V) (session time, 4.59±0.45 vs 4.14±0.31 hours/per session, P< 0.001; spKt/V, 2.12±0.31 vs 1.83±0.30, P< 0.001). Kaplan-Meier survival analysis indicated that the two groups had similar survival (P=0.983). Multivariate Cox regression analysis showed that age and time-dependent serum albumin were predictors of patient mortality. Subgroup analysis of 62 patients more than 10 years HD vintage also indicated that the two groups had similar survival. During the follow-up, 4 patients dropped out from the twice-weekly HD group and transferred to thrice-weekly HD. CONCLUSION: The similar survival between twice-weekly HD and thrice-weekly HD in patients with long-term dialysis vintage is likely relating to patient selection, individualized treatment for dialysis patients based on clinical features and socioeconomic factors remains a tough task for the clinicians.

Six-minute walk test predicts all-cause mortality and technique failure in ambulatory peritoneal dialysis patients.

AIM: This study investigated the associated factors of 6-min walk test (6MWT) and its predictive value of outcome in patients undergoing peritoneal dialysis (PD). METHODS: This is a single centre prospective observational cohort study. Stable ambulatory PD patients in our centre between 1 May 2010 and 30 April 2011 were enrolled in this study. All included subjects performed 6MWT, and 6-min walk distances (6MWDs) were recorded. Patients were divided into two groups according to 6MWD and prospectively followed up until death, cessation of PD or to the end of the study (30 September 2012). RESULTS: A total of 145 patients were enrolled, including 63 (43%) males. Multiple stepwise regression showed that age (ß = -0.295, P = 0.001), diastolic blood pressure (DBP) (ß = 0.292, P = 0.001), left ventricular ejection fraction (LVEF) (ß = 0.198, P = 0.019) were independently associated with lower 6MWD. By the end of the study, six (8%) patients died in long 6MWD group while 15 (20%) died in the short 6MWD group, a significantly lower patient survival was observed in short 6MWD group (Log-rank = 4.983, P = 0.026). Patients with short 6MWD also showed inferior technique survival (Log-rank = 4.838, P = 0.028). There was no significant difference in peritonitis-free survival between the two groups (Log-rank = 0.801, P = 0.371). However, more patients in short 6MWD group had been transferred to hemodialysis due to peritonitis (25% vs 4.2%, P = 0.013). CONCLUSION: Age, diastolic blood pressure, LVEF are independent associated factors of 6MWD in patients undergoing PD. Having the advantages of easy applicability and safety, 6MWT may be proposed as an important predictor of outcome in ambulatory PD patients.

Longitudinal bioimpedance vector plots add little value to fluid management of peritoneal dialysis patients.

Bioimpedance (BI) has the potential to enable better management of fluid balance, which can worsen over time on peritoneal dialysis (PD) due to loss of residual kidney function and progressive muscle wasting. We undertook a prospective, randomized, open-label, blinded end-point controlled trial to determine whether availability of longitudinal BI measures as vector plots helped clinicians maintain stable fluid status over 12 months in 308 peritoneal dialysis patients from the United Kingdom and Shanghai, China. Patients were recruited into 4 groups nested within a single trial design according to country and residual kidney function. Nonanuric subjects from both countries demonstrated stable fluid volumes irrespective of randomization. Hydration worsened in control anuric patients in Shanghai with increased extracellular/total body water (ECW/TBW) ratio (0.04; 95% CI: 0.01, 0.06) and reduced TBW (-1.76 L 95% CI: -2.70, -0.82), but was stable in the BI intervention group whose dialysate glucose prescription was increased. However, multilevel analysis incorporating data from both countries showed worsening ECW/TBW in active and control anuric patients. Clinicians in the United Kingdom reduced target weight in the nonanuric BI intervention group causing a reduction in TBW without beneficial effects on ECW or blood pressure. Thus, routine use of longitudinal BI vector plots to improve clinical management of fluid status is not supported.

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.

An observational study on the effect of seasonal variation on peritoneal dialysis patients.

Background: Seasonal variation has an impact on plants, wild animals, and also human beings. Data have shown seasonal variation has a significant impact on patients' fluid status, biochemistry results, and outcomes in hemodialysis populations. The relevant data on peritoneal dialysis is scant. Methods: This was a cross sectional study. All patients followed up in our center had a peritoneal equilibration test and PD adequacy test every 6 months. All the peritoneal equilibration test and PD adequacy test data were collected during December 2019 to November 2020. The monthly delivery information of the whole center was collected from 2015 to 2019. Results: There were 366 patients and 604 sets of peritoneal equilibration test and PD adequacy test results in the study. Plasma albumin and phosphate levels were higher in summer. The monthly average outdoor temperature was positively correlated with plasma albumin. There was no seasonal difference in peritoneal dialysis ultrafiltration or urine volume. The percentage of low glucose concentration (1.5%) usage was higher in summer and lower in winter. Conclusion: Plasma albumin and phosphate levels were higher in summer in PD patients. Weaker glucose peritoneal dialysis dialysate was more widely used in summer. Understanding the seasonal variation of peritoneal dialysis is helpful in individualized treatment.

Olmesartan alleviates SARS-CoV-2 envelope protein induced renal fibrosis by regulating HMGB1 release and autophagic degradation of TGF-ß1.

Background and aims: Renal damage in severe coronavirus disease 2019 (COVID-19) is highly associated with mortality. Finding relevant therapeutic candidates that can alleviate it is crucial. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have been shown to be harmless to COVID-19 patients, but it remains elusive whether ACEIs/ARBs have protective benefits to them. We wished to determine if ACEIs/ARBs had a protective effect on the renal damage associated with COVID-19, and to investigate the mechanism. Methods: We used the envelope (E) protein of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) to induce COVID-19-like multiple organ damage and observed renal fibrosis. We induced the epithelial-mesenchymal transformation of HK-2 cells with E protein, and found that olmesartan could alleviate it significantly. The protective effects of olmesartan on E protein-induced renal fibrosis were evaluated by renal-function assessment, pathologic alterations, inflammation, and the TGF-ß1/Smad2/3 signaling pathway. The distribution of high-mobility group box (HMGB)1 was examined after stimulation with E protein and olmesartan administration. Results: E protein stimulated HMGB1 release, which triggered the immune response and promoted activation of TGF-ß1/Smad2/3 signaling: both could lead to renal fibrosis. Olmesartan regulated the distribution of HMGB1 under E protein stimulation. Olmesartan inhibited the release of HMGB1, and reduced the inflammatory response and activation of TGF-ß1/Smad2/3 signaling. Olmesartan increased the cytoplasmic level of HMGB1 to promote the autophagic degradation of TGF-ß1, thereby alleviating fibrosis further. Conclusion: Olmesartan alleviates E protein-induced renal fibrosis by regulating the release of HMGB1 and its mediated autophagic degradation of TGF-ß1.

Automated peritoneal dialysis in urgent-start dialysis ESRD patients: Safety and dialysis adequacy.

BACKGROUND: Recent evidence suggests that automated peritoneal dialysis (APD) might be a feasible alternative to hemodialysis (HD) in urgent-start peritoneal dialysis. METHODS: This prospective study enrolled end-stage renal disease (ESRD) patients who had started APD as an urgent-start dialysis modality at a single center. Dialysis-related complications were recorded. Dialysis adequacy and electrolytes imbalance were compared between baseline, 14 and 42 days after catheter insertion. Technique survival and patient survival were also recorded. RESULTS: A total of 36 patients were included in the study. Mean follow-up duration was 22 months. During the follow-up, 11 PD patients (30.6%) developed dialysis-related complications. Only two patients (5.6%) required re-insertion and one patients (2.8%) transfer to HD. The 2-year technique survival rate and patient survival rate were 94.4% and 97.2%, respectively. CONCLUSION: In considering safety and dialysis adequacy, APD could be a feasible dialysis modality for urgent-start dialysis in ESRD patients, using a standard procedure.

Hypoalbuminaemia, systemic albumin leak and endothelial dysfunction in peritoneal dialysis patients.

BACKGROUND: Inflammation, hypoalbuminaemia and peritoneal protein clearance are important predictors of survival in patients treated with peritoneal dialysis (PD). We hypothesized that the common link is abnormal endothelial barrier function. To test this, we explored associations between hypoalbuminaemia, systemic albumin leak and soluble markers of systemic inflammation and endothelial injury. METHODS: This was a cross-sectional study of 41 prevalent PD patients. Endothelial barrier function was measured as transcapillary escape rate of (125)I albumin [transcapillary escape rate of albumin (TER(alb))]. Seventeen plasma biomarkers including pro-inflammatory cytokines, endothelial biomarkers and metalloproteinases were measured. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) were used to explore the hypothesis. RESULTS: The mean TER(alb) was 13.7 ± 8.9 (%/h), higher than in non-uraemic subjects 8.22 ± 5.8 (%/h). Three patient clusters were defined from HCA according to their biomarker patterns. Cluster 1 was characterized by inflammation, hypoalbuminaemia, overhydration and intermediate TER(alb). Cluster 2 was non-inflamed, preserved muscle mass and more normal TER(alb). Cluster 3 had highest TER(alb), platelet activation, preserved plasma albumin and intermediate high-sensitivity C-reactive protein levels. Two principal components (PCs) were identified from the biomarker matrix, PC1, indicating platelet activation and PC2, pro-inflammatory. TER(alb) was positively related to PC1 but not PC2. Diabetes and ischaemic heart disease were associated with PC1 and PC2, respectively. CONCLUSIONS: This exploratory analysis indicates that endothelial barrier function is decreased in PD patients and is associated with diabetic status and markers of platelet activation more than inflammation. In contrast, hypoalbuminaemia is associated more with inflammation and atherosclerotic disease indicating a more complex relationship between systemic endothelial barrier function, inflammation and hypoalbuminaemia which requires further validation.

Peritoneal Protein Clearance Is Associated With Cardiovascular Events but Not Mortality in Peritoneal Dialysis Patients.

Introduction: Association of peritoneal protein clearance (Pcl) with outcomes in patients with peritoneal dialysis (PD) is uncertain. Thus, we aimed to investigate its impact on cardiovascular events and all-cause mortality in patients with PD and factors associated with Pcl. Methods: Prevalent patients with PD from January 2014 to April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters and Angiopoietin-2-Tie2 system cytokines. Mass transfer area coefficient of creatinine (MTACcr) and Pcl were calculated. Patients were dichotomized into two groups by the median Pcl level (68.5 ml/day) and were followed up prospectively until the end of the study (1 October 2018). Results: A total of 318 patients with PD [51.2% men, mean age 56.7 ± 14.3 y, median PD duration 31.5 (12.1-57.2) months] were enrolled. Among them, 25.7% were comorbid with diabetes and 28.6% had a history of cardiovascular disease (CVD). After being followed up for up to 43.9 (24.2-50.3) months, 63 had developed cardiovascular events, and 81 patients were died. Among them, the high Pcl group had occurred 39 cardiovascular events and 51 deaths, and the low Pcl group had 24 cardiovascular events and 30 deaths. Kaplan-Meier analysis showed that both the occurrence of cardiovascular events and all-cause mortality were increased in patients with high Pcl. However, after adjusting for important confounders and serum Angiopoietin-2 (Angpt-2) level, Pcl was still an independent risk factor for cardiovascular events [hazard ratio (HR) = 1.006 (1.000-1.012), p = 0.038] but not mortality. On multivariate regression analysis, serum albumin, MTACcr, and body mass index (BMI) were found to be independently associated with Pcl. Conclusion: High Pcl is an independent risk factor for cardiovascular events but not all-cause mortality. The prediction of cardiovascular events by Pcl was independent of serum Angpt-2.