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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Serum hepatocyte growth factor is associated with truncal fat mass and increased mortality in chronic kidney disease stage 5 patients with protein-energy wasting.

BACKGROUND: Obese sarcopenia characterized by increased fat mass and protein-energy wasting (PEW) is not uncommon in chronic kidney disease (CKD) stage 5 patients in whom it is associated with worse outcomes. Serum hepatocyte growth factor (HGF) is associated with obesity in the general population and is increased in CKD patients in whom its association with body composition is not known. We studied the associations between HGF, PEW and body composition, and between HGF and mortality, in CKD stage 5 patients starting dialysis. METHODS: In 224 CKD stage 5 patients (139 males, mean age 52 years, mean glomerular filtration rate (GFR) 6.6 mL/min), blood samples were obtained for analyses of HGF, high-sensitivity C-reactive protein (hsCRP), glucose, insulin and lipids. Total fat mass index (FMI), truncal fat mass index (TFMI) and lean body mass index (LBMI) assessed by dual-energy X-ray absorptiometry and PEW assessed by subjective global assessment (SGA) were recorded at baseline. Patients were followed up for 5 years. RESULTS: Serum HGF levels were higher in patients with high TFMI versus low TFMI [3.1 (IQR: 2.4-4.5) versus 2.7 (IQR: 1.9-3.8) ng/mL; P = 0.01] and in those with PEW versus non-PEW [3.4 (IQR: 2.4-3.6) versus 2.8 (IQR: 2.1-3.8) ng/mL; P = 0.03]. Patients with both high TFMI and presence of PEW had significantly (P < 0.001) higher HGF concentration [4.4 (IQR: 3.3-6.6) ng/mL] than other patient groups (high TFMI and non-PEW, low TFMI and PEW or low TFMI and non-PEW). Multivariate linear regression showed that TFMI was an independent predictor of HGF (R(2) = 0.21, P = 0.048). In Cox analysis, patients with high HGF and presence of PEW had worse all-cause mortality after adjusting for age, gender and hsCRP (HR: 3.59, 95% CI: 1.19-5.35). CONCLUSIONS: Increased TFMI was an independent predictor of HGF in CKD stage 5 patients. Moreover, an elevated HGF level increased the mortality risk in the presence of PEW. These results suggest a central role of HGF in the metabolic and nutritional alterations in CKD stage 5 patients.

Dietary phosphorus intake and distribution in Chinese peritoneal dialysis patients with and without hyperphosphatemia.

BACKGROUND: The present study was conducted to analyze the dietary phosphorus intake and distribution in different food categories in peritoneal dialysis (PD) patients, to evaluate the relationship between dietary phosphorus intake and hyperphosphatemia. METHODS: It was a cross-sectional study, in which prevalent Chinese PD patients were instructed by dietitians to record 3-day diet diary. Dietary phosphorus and other nutrient contents were calculated using a food composition computer program. Renal and peritoneal phosphorus clearance (CPh) was estimated, and serum phosphorus, as well as other serological parameters, were measured at the same time. RESULTS: 93 PD patients [age 52.9 ± 13.0 years, PD duration 30.1 (8.0, 71.0) months] finished the 3-day diet diary. Hyperphosphatemic patients (serum phosphorus level 1.97 ± 0.28 mmol/l, n = 48) showed higher dietary phosphorus intake (771.6 ± 195.1 versus 620.8 ± 155.3 mg/day, p = 0.040) than those with normal serum phosphorus level (1.37 ± 0.21 mmol/l, n = 45), due to greater phosphorus intake from meat, snacks, beverage, food condiments and additives. Significantly lower dietary phosphorus intake (605.6 ± 122.5 mg/day) and phosphorus to protein ratio (12.7 ± 1.4 mg/g) were observed in patients with anuria who maintained serum phosphorus within normal range. Multivariate linear regression analysis indicated normalized phosphorus intake, renal CPh and dietary protein intake were independently associated with serum phosphorus level. CONCLUSION: High dietary phosphorus intake is associated with elevated serum phosphorus level in PD patients. The study suggests that PD patients, particularly those with anuria, shall limit the intake of meat, snacks, beverage, food condiments and additives to reduce dietary phosphorus ingestion.

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.

Circulating vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sVEGFR-1) are associated with inflammation and mortality in incident dialysis patients.

BACKGROUND: Vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sVEGFR-1) predict mortality in nondialyzed chronic kidney disease (CKD) stage 3-5 patients and prevalent hemodialysis (HD) patients. We investigated determinants of VEGF and sVEGFR-1 as well as their relationship with all-cause mortality in incident dialysis patients. METHODS: In this longitudinal cohort study of 211 CKD 5 patients [64% males, mean age of 54 ± 12 years and median glomerular filtration rate (GFR) 5.9 [interquartile range (IQR), 4.6-7.2 mL/min/1.73 m2] who were enrolled at initiation of renal replacement therapy, demographics, clinical characteristics, including comorbidities and laboratory data were obtained at the beginning of the study. After 12 months, blood was again drawn from 95 dialysis patients [42 HD patients and 53 peritoneal dialysis (PD) patients]. The 211 patients were followed up for a median of 29 (IQR, 15-37) months for survival analysis. Plasma was also obtained from 47 healthy controls. RESULTS: VEGF and sVEGFR-1 levels did not change significantly after 12 months on HD or PD. The sVEGFR-1, but not VEGF levels, differed between the patients and the healthy controls. VEGF and sVEGFR-1 correlated with high-sensitivity C-reactive protein (hsCRP; rho = 0.19, P = 0.01 and rho = 0.16, P = 0.03; respectively), leukocyte count (rho = 0.22; P < 0.01 and rho = 0.23; P < 0.01; respectively) and sVEGFR-1 correlated also with interleukin-6 (IL-6) (rho = 0.21, P < 0.01). In Kaplan-Meier analysis, a high VEGF level was associated with increased all-cause mortality (Chi-square = 5.8, P = 0.02) which remained after adjustments for age, gender, body mass index (BMI), IL-6, GFR and comorbidities [hazard ratio, HR: 3.08, 95% confidence intervals (CI) 1.48-6.42]. Whereas sVEGFR-1 per se did not predict mortality, a high sVEGFR-1 level in patients with concomitant high IL-6 was associated with increased all-cause mortality (HR 2.83, 95% CI 1.32-6.06) which remained significant after adjustments for age, gender, BMI and comorbidities (HR 2.33, 95% CI 1.06-5.14) but not after adjusting also for GFR. CONCLUSIONS: The circulating levels of VEGF and sVEGFR-1 are associated with biomarkers of inflammation. VEGF predicts all-cause mortality, independent of inflammation, while an elevated sVEGFR-1 level increased the mortality risk in inflamed patients.

Antibiotic-induced neurotoxicity in dialysis patients: a retrospective study.

OBJECTIVE: The study was to evaluate neurotoxicity caused by antibiotics in dialysis patients, including incidence, clinical features, treatments and prognosis. METHODS: In this retrospective study, we reviewed the medical records of 1066 dialysis patients (254 peritoneal dialysis [PD] cases and 812 hemodialysis [HD] cases) who also received intravenous antibiotics in our hospital during July 2006 - April 2012. Naranjo scale was used for estimating the probability of an adverse drug reaction. RESULTS: The incidence of antibiotic-induced neurotoxicity was 5.66% in patients receiving HD, and 7.87% in patients receiving PD. There was no significant difference between the two dialysis modalities about the incidence of antibiotic-induced neurotoxicity (p > 0.05). The risk factors included extremely old age, history of central nervous system disorder, low residual renal function, hypoalbuminemia, and the use of multiple antibiotics that share one mechanism. The neurotoxic antibiotics included cephalosporins, penicillins, carbapenems and quinolones in our study. Most patients could be properly diagnosed early according to their medical history, symptoms, signs, electroencephalography (EEG), other related auxiliary examination, and with the help of experienced neurologists. Most neurotoxic patients showed clinical improvement after the discontinuation of antibiotics and active treatment. CONCLUSIONS: The adverse neurotoxic effects of antibiotics were common in dialysis patients due to wide and incorrect usage. Neurotoxicity could be prevented in high-risk cases with dosage adjustments. Better prognosis can be achieved with early and proper diagnosis, decisive withdrawal, and aggressive treatment including enhanced HD.

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.

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.

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.

Treatment of nephrotic idiopathic membranous nephropathy with monthly i.v. pulse cyclophosphamide and oral steroids: a single centre's retrospective study.

AIM: While the best treatment of nephrosis-inducing idiopathic membranous nephropathy (IMN) is controversial, some trials have suggested positive outcomes following treatment with oral cyclophosphamide used in combination with steroids. However, data on i.v. cyclophosphamide plus steroids in treatment of nephrotic IMN are few. METHODS: The charts of every patient diagnosed with membranous nephropathy in the Renal Division of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, from January 2003 to December 2009 (n = 189) were retrospectively analyzed. Patients with nephrotic IMN (n = 32) were treated with monthly i.v. cyclophosphamide (500-750 mg/m(2)) and oral prednisone for at least 6 months. Efficacy as well as safety and tolerability of this regimen were evaluated. RESULT: Thirty-two patients with nephrotic IMN (56% male, age 51.5 ± 12.6 years, estimated glomerular filtration rate 73.7 ± 20.0 mL/min per 1.73 m(2)) were included in our study. During the median follow-up duration of 30.0 (12.5-42.8) months, 40.6% of patients achieved complete remission, while 40.6% achieved partial remission. Relapse occurred in five patients in a median of 16 (11.5-26) months after cessation of immunosuppressive treatment. No patients developed renal insufficiency during the follow up, while 16 side-effects were noted in 10 patients. Complete remission rates at 3, 6 and 15 months were 0%, 12.5% and 40.6% and remission rates were 21.9%, 68.8% and 81.2%, respectively. Complement 3 deposition was significantly associated with the probability of non-remission. CONCLUSION: Monthly i.v. pulse cyclophosphamide plus oral steroids may be an alternative treatment option in Chinese patients with nephrotic IMN.

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.