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Background: Vaspin is an adipokine that regulates glucose and lipid metabolism. Plasma vaspin level is increased in chronic kidney disease but decreased in hemodialysis patients. However, plasma vaspin level in peritoneal dialysis (PD) patients, as well as its prognostic role, has not been studied., Methods: We recruited 146 incident PD patients. Their baseline plasma vaspin levels, body anthropometry, the profile of insulin resistance, bioimpedance spectroscopy parameters, dialysis adequacy, and nutritional indices were measured. They were followed for up to 5 years for survival analysis., Results: The average age was 58.4 ± 11.8 years; 96 patients (65.8%) were men, and 90 (61.6%) had diabetes. The median vaspin level was 0.18 ng/dL (interquartile range [IQR] 0.11 to 0.30 ng/dL). Plasma vaspin level did not have a significant correlation with adipose tissue mass or baseline insulin level. However, plasma vaspin level had a modest correlation with the change in insulin resistance, as represented by the HOMA-IR index, in non-diabetic patients (r = -0.358, p = 0.048). Although the plasma vaspin level quartile did not have a significant association with patient survival in the entire cohort, it had a significant interaction with diabetic status (p < 0.001). In nondiabetic patients, plasma vaspin level quartile was an independent predictor of patient survival after adjusting for confounding clinical factors (adjusted hazard ratio 2.038, 95% confidence interval 1.191-3.487, p = 0.009), while the result for diabetic patients was not significant., Conclusions: Plasma vaspin level quartile had a significant association with patient survival in non-diabetic PD patients. Baseline plasma vaspin level also had a modest inverse correlation with the subsequent change in the severity of insulin resistance, but the exact biological role of vaspin deserves further studies., (© 2023. The Author(s).)

Background: Cross-sectional studies showed that fluid overload (FO) measured by bioimpedance spectroscopy (BIS) predicted adverse outcomes in patients on peritoneal dialysis (PD). We aimed to describe the longitudinal change in volume status in Chinese PD patients and determine its relation with clinical outcomes., Methods: We performed a single-centre, retrospective analysis of all PD patients who underwent repeated BIS from 2010 to 2015. FO was defined by relative hydration index (RHI; volume of overhydration adjusted by extracellular water >7%). Variability of volume status (VVS) was denoted by the standard deviation of all RHI. The association of time-averaged RHI and VVS on patient and technique survival was explored by a competing risk model., Results: A total of 269 patients were followed for a median of 47.1 months. Mean time-averaged RHI was 17.6 ± 10.2%. Multivariable mixed linear regression revealed that RHI was significantly associated with diabetes, time-varying systolic blood pressure, and inversely with time-varying albumin level, lean tissue index and fat tissue index ( p <0.0001 for all). Time-averaged RHI independently predicted patient survival (subdistribution hazard ratio (SHR) 1.05, 95% CI 1.03-1.07, p <0.0001) and technique survival (SHR 1.04, 95% CI 1.02-1.06, p <0.0001), whereas VVS did not. The mortality risk for patients with persistent FO was consistently higher than the corresponding risk estimated from baseline FO of the same extent., Conclusions: Persistent FO was a strong predictor of patient and technique failure. Repeated bioimpedance measurements to monitor volume status may provide additional prognostic information in PD patients.

Rationale & Objective: Omentin-1 is an adipokine with anti-inflammatory and cardioprotective properties. The objective of this study was to determine the prognostic role of plasma omentin-1 levels in incident peritoneal dialysis (PD) patients., Study Design: Retrospective analysis of prospective cohort., Setting & Participants: 152 incident PD patients., Predictors: Plasma omentin-1 level, adipose tissue omentin-1 messenger RNA (mRNA) expression., Outcomes: Patient survival, technique survival, hospital admission, and duration of stay., Analytical Approach: Time-to-event survival analyses; linear regression for hospitalization., Results: The mean age was 58.4 ± 11.7 years; 102 were men, and 92 had diabetes. There was no significant correlation between plasma omentin-1 level and its adipose tissue mRNA expression. A higher plasma omentin-1 level quartile was not associated with patient survival ( P  = 0.92) or technique survival ( P  = 0.83) but had a modest correlation with a lower number of hospital admissions ( P  = 0.07) and shorter duration of hospital stay ( P  = 0.04). In adjusted models using multivariable linear regression, a higher plasma omentin-1 level quartile remained significantly associated with fewer hospital admissions (β, -0.13; 95% CI, -0.26 to -0.002; P  = 0.05) and shorter hospitalization duration (β, -0.20; 95% CI, -0.38 to -0.02; P  = 0.03)., Limitations: Observational study with baseline measures only., Conclusions: Plasma omentin-1 level was not associated with patient survival, technique survival, or peritonitis, but higher plasma omentin-1 levels were associated with fewer hospital admissions and shorter duration of hospitalization among incident PD patients., (© 2023 The Authors.)

Rationale & Objective: Cardiovascular disease is the major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Adiponectin, a key adipokine, is related to obesity and insulin resistance. We determined the clinical and prognostic value of plasma adiponectin level and its adipose tissue messenger RNA (mRNA) expression in new PD patients., Study Design: Retrospective analysis of a prospective observational study., Setting & Participants: 152 new PD patients from a single center; 6 adults undergoing abdominal surgeries without kidney disease served as controls., Predictors: Plasma adiponectin level and its adipose tissue mRNA expression., Outcomes: Body build and composition, patient and technique survival., Analytical Approach: Adiponectin level and mRNA expression were grouped in quartiles for correlation analysis for body build and Cox regression for survival analysis., Results: The median plasma adiponectin level was 31.98 μg/mL (IQR, 16.81-49.49 μg/mL), and adiponectin mRNA expression in adipose tissue was 1.65 times higher than in controls (IQR, 0.98-2.63). There was a modest but statistically significant correlation between plasma adiponectin and its adipose tissue mRNA expression ( r   =  0.40, P  < 0.001). Plasma adiponectin level inversely correlated with body mass index, waist-hip ratio, mid-arm circumference, adipose tissue mass, plasma triglyceride ( r  = -0.39, -0.38, -0.41, -0.38, and -0.30, respectively; P  < 0.001 for all), as well as serum insulin level ( r  = -0.24, P  = 0.005). Similar correlations were present but less marked with adipose tissue adiponectin mRNA level. Neither plasma adiponectin level nor adipose tissue adiponectin mRNA level predicted patient or technique survival., Limitations: Observational study, single center, single baseline measurement., Conclusions: Plasma adiponectin level correlated with the degree of adiposity in new PD patients. However, neither plasma adiponectin level nor its adipose tissue mRNA expression was an independent prognostic indicator in kidney failure patients newly started on PD., (© 2022 The Authors.)

Background: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD., Methods: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD., Results: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57-3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08-2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80-13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13-12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006-0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02-0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35-50.5, p = 0.02)., Conclusion: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.

Background: There are limited data on the association of adipose microRNA expression with body composition and adverse clinical outcomes in patients with advanced chronic kidney disease (CKD). We aimed to evaluate the association of adipose miR-130b and miR-17-5p expressions with body composition, functional state, cardiovascular outcome and mortality in incident dialysis patients., Methods: We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. miR-130b and miR-17-5p expressions were measured from subcutaneous and pre-peritoneal fat tissue obtained during peritoneal dialysis catheter insertion. Body composition and physical function were assessed by bioimpedance spectroscopy and Clinical Frailty Scale. Primary outcome was 2-year survival. Secondary outcomes were 2-year technique survival and major adverse cardiovascular event (MACE) rate., Results: Adipose expression of miR-130b and miR-17-5p correlated with parameters of muscle mass including intracellular water (miR-130b: r = 0.191, P = 0.02; miR-17-5p: r = 0.211, P = 0.013) and lean tissue mass (miR-17-5p: r = 0.176, P = 0.04; miR-17-5p: r = 0.176, P = 0.004). miR-130b expression predicted frailty significantly (P = 0.017). Adipose miR-17-5p expression predicted 2-year all-cause survival (P = 0.020) and technique survival (P = 0.036), while miR-130b expression predicted incidence of MACE (P = 0.015)., Conclusions: Adipose miR-130b and miR-17-5p expressions correlated with body composition parameters, frailty, and predicted cardiovascular events and mortality in advanced CKD patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

There were limited data on adipose and serum zinc alpha-2-glycoprotein (ZAG) expression and its association with body composition in patients with advanced chronic kidney disease (CKD). This study aimed to quantify adipose and serum ZAG expression and evaluate their association with body composition and its longitudinal change, together with mortality in incident dialysis patients. We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. ZAG levels were measured from serum sample, subcutaneous and pre-peritoneal fat tissue obtained during peritoneal dialysis catheter insertion. Body composition and functional state were evaluated by bioimpedance spectroscopy and Clinical Frailty Scale respectively at baseline and were repeated 1 year later. Primary outcome was 2-year survival. Secondary outcomes were longitudinal changes of body composition. At baseline, the average adipose and serum ZAG expression was 13.4 ± 130.0-fold and 74.7 ± 20.9 µg/ml respectively. Both adipose and serum ZAG expressions independently predicted adipose tissue mass (ATM) (p = 0.001, p = 0.008, respectively). At 1 year, ATM increased by 3.3 ± 7.4 kg (p < 0.001) while lean tissue mass (LTM) remained similar (p = 0.5). Adipose but not serum ZAG level predicted change in ATM (p = 0.007) and LTM (p = 0.01). Serum ZAG level predicted overall survival (p = 0.005) and risk of infection-related death (p = 0.045) after adjusting for confounders. In conclusion, adipose and serum ZAG levels negatively correlated with adiposity and predicted its longitudinal change of fat and lean tissue mass, whilst serum ZAG predicted survival independent of body mass in advanced CKD patient., (© 2022. The Author(s).)

Background: Depression and frailty contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients. However, the interaction between depression and frailty in PD patients remains uncertain. We determined the prevalence of depression and frailty in prevalent Chinese PD patients, dissected the internal relationship between depression and frailty, and determined their relative contribution to the adverse clinical outcome in PD patients., Methods: In a prospective observational study, we recruited 267 prevalent PD patients. Depression was identified by Patient Health Questionnaire (PHQ-9). Frailty was identified by a validated Frailty Score. All cases were followed for one year. Outcome measures included number and duration of hospitalization, peritonitis rate, and all-cause mortality., Results: Of the 267 patients, 197 patients (73.8%) were depressed, and 157 (58.8%) were frail. There was a substantial overlap between depression and frailty. Although depression and frailty were associated the number and duration of hospitalization by univariate analysis, the association became insignificant after adjusting for confounding factors by multivariate analysis. Both depression and frailty were associated with one-year mortality by univariate analysis. One-year patient survival was 95.9, 86.5, 82.4 and 71.0% for patients with nil, mild, moderate and severe frailty, respectively (p = 0.001). Frailty was an independent predictor of patient survival by multivariate analysis (adjusted hazard ratio 1.424, 95% confidence interval 1.011-2.005. p = 0.043), while the prognostic effect of depression disappears after adjusting for frailty score., Conclusion: Depression and frailty were common among Chinese PD patients. Frailty, but not depression, was an independent predictor of one-year mortality.

The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.

Background: Extracellular volume overload is a common problem in peritoneal dialysis (PD) patients and is associated with excessive mortality. We determine the effectiveness of treating PD patients with extracellular volume overload by a structured nurse-led intervention program., Methods: The hydration status of PD patients was screened by bioimpedance spectroscopy (BIS). Fluid overload was defined as overhydration volume ≥ 2 L. Patients were classified into Symptomatic and Asymptomatic Groups and were managed by a structured nurse-led intervention protocol that focused on education and motivation. Hypertonic cycles were given for short term symptom relief for the Symptomatic group. Patients were followed for 12 weeks for the change in volume status, blood pressure, knowledge and adherence as determined by standard questionnaires., Results: We recruited 103 patients (53 Symptomatic, 50 Asymptomatic Group. There was a significant reduction in overhydration volume 4 weeks after intervention, which was sustained by week 12; the overall reduction in overhydration volume was 0.96 ± 1.43 L at 4 weeks, and 1.06 ± 1.70 L at 12 weeks (p < 0.001 for both). The improvement was significant for both Symptomatic and Asymptomatic Groups. There was a concomitant reduction in systolic blood pressure in the Asymptomatic (146.9 ± 20.7 to 136.9 ± 19.5 mmHg, p = 0.037) but not Symptomatic group. The scores of knowledge, adherence to dietary control and advices on daily habit at week 4 were all significantly increased, and the improvement was sustained at week 12., Conclusions: The structured nurse-led intervention protocol has a lasting benefit on the volume status of PD patients with extracellular volume overload. BIS screening allows prompt identification of volume overload in asymptomatic patients, and facilitates a focused effort on this high risk group.

Background: Peritoneal protein clearance has been suggested to be a marker of peritoneal inflammation and systemic endothelial dysfunction., Methods: We enrolled 711 consecutive incident PD patients. Baseline peritoneal protein clearance and other clinical information were reviewed. All patients were followed for at least 1 year for all-cause and cardiovascular mortality., Results: The average PD effluent protein loss was 6.41 ± 2.16 g/day; peritoneal protein clearance was 97.15 ± 41.55 mL/day. The average duration of follow-up was 50.8 ± 36.2 months. Multivariate linear regression analysis showed that serum albumin, C-reactive protein, and mass transfer area coefficients of creatinine were independently associated with peritoneal protein clearance. By multivariate Cox regression analysis, age, Charlson comorbidity score, volume of overhydration and peritoneal protein clearance were independent predictors of all-cause mortality. Every 10 mL/day increase in peritoneal protein clearance confers 10.4% increase in risk of all-cause mortality (95% confidence interval 2.6-18.7%, p = 0.008). Peritoneal protein clearance was also associated with cardiovascular mortality by univariate analysis, but the association became insignificant after adjusting for confounding factors Cox regression analysis., Conclusions: Baseline peritoneal protein clearance is an independent predictor of all-cause mortality in incident PD patients. Routine measurement of peritoneal protein clearance may facilitate patient risk stratification.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Urinary micro-RNA (miRNA) level is increasingly reported to as non-invasive markers of various kidney diseases. We aim to identify urinary miRNA targets for the diagnosis of IgAN., Methods: In the development cohort, we performed complete miRNA profiling of urinary sediment in 22 patients with IgAN and 11 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 33 IgAN patients and 9 healthy controls., Results: In the development cohort, we identified 39 miRNA targets that have significantly different expression between IgAN and CTL (14 up-regulated, and 25 down-regulated). Among the 8 miRNA targets chosen for validation study, urinary miR-204, miR-431 and miR-555 remained significantly reduced, and urinary miR-150 level was significantly increased in the IgAN as compared to CTL. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-204 level for the diagnosis of IgAN was 0.976, and the diagnostic performance of combining additional miRNA targets was not further improved. At the cut-off 1.70 unit, the sensitivity and specificity of urinary miR-204 was 100 and 55.5%, respectively, for diagnosing IgAN., Conclusions: Urinary miR-150, miR-204, miR-431 and miR-555 levels are significantly different between IgAN and healthy controls; urinary miR-204 level alone has the best diagnostic accuracy.

Background: Endocan is associated with endothelial dysfunction. In peritoneal dialysis (PD) patients, cardiovascular disease is a common cause of mortality. We examined the relationship between serum endocan level and clinical outcome of PD patients., Methods: We recruited 193 new PD patients (118 males, mean age 58.8 ± 11.6 years). Serum endocan levels were determined and stratified into tertile 1 (lowest) to 3 (highest). Nutritional status, arterial pulse wave velocity (PWV) and serum C-reactive protein (CRP) levels were measured. The patients were followed for at least 4 years for clinical outcomes., Results: For the whole cohort, patients with higher serum endocan levels had lower serum albumin and subjective global assessment score, higher carotid-femoral PWV, and higher serum CRP. For patients with suboptimal blood pressure (BP) control, cardiovascular event-free survival was 95.0, 95.5, and 78.5% for tertiles 1, 2, and 3 at 60 months respectively (p = 0.019). Multivariate Cox regression analysis showed that serum endocan level was an independent predictor of cardiovascular event-free survival. No association with cardiovascular event-free survival was found for patients with adequate BP control (95.0, 92.3, and 100% for tertile 1, 2, and 3 at 60 months, respectively, p = 0.6)., Conclusions: Higher serum endocan level is associated with unfavourable nutritional, arterial and inflammatory conditions in PD patients. In patients with suboptimal BP control, higher serum endocan is also associated with worse cardiovascular outcome., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD., Methods: We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3 ± 31.8 months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR])., Results: The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81-3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r = 0.429, p < 0.001), proteinuria (r = 0.368, p < 0.001), severity of glomerulosclerosis (r = - 0.537, p < 0.001), and tubulointerstitial fibrosis (r = - 0.374, p = 0.014). The overall rate of eGFR decline was - 2.18 ± 5.94 ml/min/1.73m 2 per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors., Conclusion: Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.

Background: Mitochondrial dysfunction plays an important role in the pathogenesis and progression of chronic kidney disease (CKD). We study the relation between urinary mitochondrial DNA (mtDNA) levels and renal dysfunction in non-diabetic CKD., Methods: We recruited 32 CKD patients (20 had hypertensive nephrosclerosis, 12 had IgA nephropathy). Urinary supernatant mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 57.8 ± 30.5 months for renal function decline., Results: The average urinary supernatant mtDNA level was 222.0 ± 210.3 copy/μL. There was a modest but significant correlation between urinary mtDNA level and proteinuria (Spearman's r = 0.387, p = 0.035), but not any other baseline clinical or pathological parameter. Urinary mtDNA level had a significant inverse correlation with the slope of GFR decline (r = -0.402, p = 0.023). Urinary mtDNA level is a predictor of renal survival even after adjusting for baseline proteinuria with multivariate Cox analysis. In this model, every increase in urinary mtDNA by 100 copy/μL confers a 25.0% increase in risk of doubling of serum creatinine or need of dialysis (95%CI, 0.7% to 55.1%)., Conclusion: Mitochondrial DNA is readily detectable in the urinary supernatant of non-diabetic CKD, and its level correlates with the rate of renal function decline and predicts the risk of doubling of serum creatinine or need of dialysis. Further studies are needed to determine the value of urinary supernatant mtDNA level as a prognostic indicator of non-diabetic CKD., (Copyright © 2018. Published by Elsevier B.V.)

Background: Fluid overload is common among asymptomatic peritoneal dialysis (PD) patients. We aim to determine the prevalence and prognostic significance of fluid overload, as measured by bioimpedance spectroscopy, in asymptomatic incident PD patients., Methods: We performed a single-center study on 311 incident PD patients. Volume status was represented by the volume of overhydration (OH), OH/extracellular water (ECW) ratio, ECW/total body water (TBW) ratio, and ECW to intracellular water (ICW) ratio (E:I ratio). Patient survival, technique survival and cardiovascular event-free survival were determined., Results: The median period of follow up was 27.3 months. Fluid overload was present in 272 patients (87.5%) when defined as OH volume over 1.1L. All hydration parameters significantly correlated with Charlson Comorbidity Index, and inversely with total Kt/V, and serum albumin. Multivariate cause-specific Cox analysis showed that volume status independently predicted patient survival; every 0.1 unit increase in E:I ratio was associated with 24.5% increase in all-cause mortality (adjusted cause-specific hazard ratio [ACSHR] 1.245, p = 0.002). Hydration status was also an independent predictor of cardiovascular event-free survival after excluding hospital admission for congestive heart failure; each 0.1 unit increase in E:I ratio was associated with 18.7% decrease in cardiovascular event-free survival (ACSHR 1.187, p = 0.011). In contrast, hydration parameters were not associated with technique survival., Conclusions: Fluid overload is common in asymptomatic incident PD patients and is a strong predictor of patient survival and cardiovascular event. The impact of bioimpedance spectroscopy-guided fluid management on the outcome of PD patients deserves further study., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests. Dr. CC Szeto receives research grant and consultancy from Baxter Healthcare. The authors declare no other conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aim: The reported causes of nephrotic syndrome (NS) varies between different countries. Less is known about the causes of nephrotic-range proteinuria (NPU). We aimed to evaluate the underlying causes of NS and NPU., Methods: This was a single-centre, retrospective study of adult patients who underwent renal biopsy between 1983 and 2015 in a tertiary referral hospital in Hong Kong. We determined the distribution of histopathological diagnoses with regard to the age subgroups and time periods., Results: Among 7456 patients who underwent renal biopsy, 982 and 838 patients had NS and NPU, respectively. The most common diagnosis in NS was minimal change disease (MCD) (33.3%), followed by membranous nephropathy (MN) (23.6%) and lupus nephritis (LN) (12.8%); whereas the most common diagnosis in NPU was LN (27.4%), followed by immunoglobulin A nephropathy (IgAN) (21.4%) and diabetic nephropathy (DN) (9.3%). In the NS group, MCD was the most common diagnosis in young adults while MN was the leading cause in the elderly. On the other hand, LN was the most common pathology in the NPU group until the age of 60. Over the past three decades, there was a trend of decrease in the proportion of IgAN in both NS and NPU group, while a combined pathology of hypertensive nephrosclerosis and diabetic nephropathy (HTNS and DN) increased significantly., Conclusions: The causes of NS and NPU in Chinese adults were different and may represent two distinct pathological identities. The spectrum of renal histopathology among these two groups changed significantly over time., (© 2017 Asian Pacific Society of Nephrology.)

Background: Pseudomonas peritonitis is a serious complication of peritoneal dialysis (PD). However, the clinical course of Pseudomonas peritonitis following the adoption of international guidelines remains unclear., Methods: We reviewed the clinical course and treatment response of 153 consecutive episodes of PD peritonitis caused by Pseudomonas species from 2001 to 2015., Results: Pseudomonas peritonitis accounted for 8.3% of all peritonitis episodes. The bacteria isolated were resistant to ceftazidime in 32 cases (20.9%), and to gentamycin in 18 cases (11.8%). In 20 episodes (13.1%), there was a concomitant exit site infection (ESI); in another 24 episodes (15.7%), there was a history of Pseudomonas ESI in the past. The overall primary response rate was 53.6%, and complete cure rate 42.4%. There was no significant difference in the complete cure rate between patients who treated with regimens of 3 and 2 antibiotics. Amongst 76 episodes (46.4%) that failed to respond to antibiotics by day 4, 37 had immediate catheter removal; the other 24 received salvage antibiotics, but only 6 achieved complete cure., Conclusions: Antibiotic resistance is common amongst Pseudomonas species causing peritonitis. Adoption of the treatment guideline leads to a reasonable complete cure rate of Pseudomonas peritonitis. Treatment with three antibiotics is not superior than the conventional two antibiotics regimen. When there is no clinical response after 4 days of antibiotic treatment, early catheter removal should be preferred over an attempt of salvage antibiotic therapy.

Background: Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic nephropathy (DN). We study the relation between urinary and intra-renal mitochondrial deoxyribonucleic acid (mtDNA) levels and renal dysfunction in DN., Methods: We recruited 92 patients with biopsy-proven DN. Urinary sediment, urinary supernatant and intra-renal mtDNA levels were measured and compared with baseline renal biopsy, kidney scarring and renal function decline in the subsequent 24 months., Results: mtDNA could be detected in all urine supernatant, urine sediment and renal biopsy specimens. There was a modest but statistically significant inverse correlation between urinary supernatant and intra-renal mtDNA levels (r = -0.453, P = 0.012). Urinary supernatant mtDNA level had modest but statistically significant correlations, inversely with estimated glomerular filtration rate (r = -0.214, P = 0.04), and positively with interstitial fibrosis (r = 0.300, P = 0.005). Intra-renal mtDNA had significant inverse correlation with interstitial fibrosis (r = -0.537, P = 0.003). However, there was no significant relation between renal function decline and urinary supernatant, urinary sediment or intra-renal mtDNA levels., Conclusions: mtDNA is readily detectable in urinary supernatant and kidney tissue, and their levels correlate with renal function and scarring in DN. Further studies are needed to determine the accuracy of urinary supernatant mtDNA level as a prognostic indicator of DN, as well as its role in other kidney diseases.

Background: Several comorbidity scoring systems have been developed and validated, mostly in western hemodialysis patients with a high risk of cardiovascular disease. The performance of comorbidity scoring, however, depends on the patient population. In this study, we determine the optimal comorbidity scoring system for predicting survival of incident Chinese PD patients., Methods: We studied 461 incident PD patients. The performance of Charlson Comorbidity Index (CCI), Hemmelgarn score, and Liu score as the survival predictor was compared., Results: The mean age was 57.7 ± 13.7 years. The median CCI, Hemmelgarn, and Liu scores were 4 [inter-quartile range (IQR) 2-5], 1 (IQR 0-2), and 4 (IQR 2-5), respectively. Patients were followed for 45.5 ± 33.0 months. All 3 comorbidity scores were predictors of patient survival by univariate analysis. After adjusting for confounding factors, CCI was the best predictor of patient survival among the 3 indices, with each point increase in CCI conferring 31% excess in mortality risk [95% confidence interval (CI) 21-41%, p < 0.001]. In contrast, each point increase in Liu score confers 20% excess in mortality risk (95% CI 13-27%, p < 0.001). Although the Hemmelgarn score is an independent predictor of patient survival, over 70% of patients score 0 or 1 by this system, limiting its role as a prognostic marker., Conclusion: CCI should be the preferred method for quantifying comorbidity load in incident Chinese PD patients, and it is a good predictor of survival in this group of patients.

Background: Catheter malfunction is an important cause of technique failure for peritoneal dialysis (PD) patients, and is commonly managed by surgeons or intervention radiologists. We reviewed our experience in catheter revision or replacement by nephrologists., Method: We reviewed the clinical outcome and complication rate of 95 consecutive patients who had PD catheter malfunction, with catheter revision or replacement by nephrologist., Result: Amongst the 95 patients, 32 had catheter revision, 24 catheter replacement via the original wound, and 39 catheter replacement via a new mini-laparotomy wound. Catheter survival was 71.6% at 1 month and 48.4% at 6 months; technique survival was 88.4% at 1 month and 77.4% at 6 months. When the 3 types of procedure were analyzed separately, technique survival at 1 month was 96.8, 75.0, and 89.7%, respectively, for patients who received catheter revision, catheter replacement via the original wound, and catheter replacement via a new mini-laparotomy wound (p = 0.0002), although their catheter survival rates were not significantly different. Also, 2 patients had bleeding that required urgent surgical exploration, 2 had wound infection, and 8 had peritonitis within 4 weeks after the surgery., Conclusion: PD catheter revision and replacement by nephrologist has an acceptable catheter survival and a reasonable complication rate. Given that prompt intervention is an important consideration, catheter revision and replacement by nephrologist is a suitable method for the management of catheter malfunction., (© 2017 S. Karger AG, Basel.)

Background/aims: Frailty and depression both contribute to malnutrition and adverse clinical outcome of peritoneal dialysis (PD) patients. However, their interaction is incompletely defined., Methods: We studied 178 adult Chinese PD patients. Physical frailty was assessed by a validated in-house questionnaire; depressive symptoms was screened by the Geriatric Depression Scale; nutritional status was determined by subjective global assessment (SGA) and malnutrition inflammation score (MIS). All patients were followed for up to 24 months for survival and hospitalization analysis., Results: There were 111 patients (62.4%) physically frail, amongst those 48 (43.2%) had depressive symptoms. Only 1 patient had depressive symptoms without frailty. There was an additive effect of depressive symptoms and physical frailty on nutritional status. For the groups with no frailty, frail but no depressive symptoms, and frail with depressive symptoms, serum albumin decreased in a stepwise manner (35.8 ± 5.6, 34.9 ± 4.4, and 32.9 ± 5.3 g/L, respectively, p=0.025); overall SGA score was 5.75 ± 0.61, 5.41 ± 0.59, and 5.04 ± 0.77, respectively (p< 0.0001), and MIS was 5.12 ± 2.30, 7.13 ± 3.22, and 9.48 ± 3.97, respectively (p< 0.0001). At 24 months, patient survival was 86.6%, 71.4%, and 62.5% for patients with no frailty, frail but no depressive symptoms, and frail with depressive symptoms, respective (p=0.001). The median number of hospital stay was 8.04 (inter-quartile range [IQR] 0.91 - 19.42), 14.05 (IQR 3.57 - 37.27), and 26.62 (IQR 10.65 - 61.18) days per year of follow up, respectively (p< 0.0001)., Conclusion: Physical frailty and depressive symptoms are both common in Chinese PD patients, and they have additive adverse effect on the nutritional status and clinical outcome., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: Mitochondrial dysfunction contributes to the pathogenesis of acute kidney injury (AKI). The urinary mitochondrial DNA (mtDNA) level was previously shown to predict renal function recovery in AKI following cardiac surgery. Herein, we determine whether urinary mtDNA is a marker of severity and predictor of recovery in AKI due to other etiologies., Methods: We recruited 107 AKI patients. The urinary mtDNA level was measured, the severity of AKI was quantified, and patients were followed for 90 days., Results: The urinary mtDNA level had modest but statistically significant correlations with the peak serum creatinine level (Spearman's r = -0.248, p = 0.010) and the duration of hospital stay ( r = -0.217, p = 0.025). Patients who required temporary dialysis also tended to have higher urinary mtDNA levels than those without dialysis (22.6 ± 4.5 vs. 24.9 ± 5.7 cycles, p = 0.06). There was no definite relation between the urinary mtDNA level and renal function recovery., Conclusion: The urinary mtDNA level is a marker of AKI severity, as reflected by its significant correlation with the peak serum creatinine level, duration of hospital stay, and probably the need for temporary dialysis. Our result suggests that urinary mtDNA has the potential to serve as a biomarker of AKI.

Aim: Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent commonly used for the prevention and treatment of bleeding disorders. The aim of this study is to describe the clinical manifestation of TXA toxicity in chronic kidney disease (CKD) patients., Methods: From 2005 to 2014, we encountered four CKD patients who experienced severe complications related to TXA. Clinical manifestations and outcome of these patients were recorded. We then performed a qualitative literature review of published cases of TXA toxicity in CKD patients in the PubMed database from 1 January 1972 to 31 December 2015., Results: In our centre, two peritoneal dialysis (PD) patients developed neurotoxicity after intravenous TXA use for surgical bleeding and one PD patient developed neurotoxicity after oral TXA use for post-polypectomy colonic bleeding. One kidney transplant recipient developed acute obstructive uropathy due to retention of blood clot at the pelvi-ureteric junction of graft kidney after taking oral TXA for menorrhagia. Dosage of TXA was not adjusted according to renal function in all cases. All of them recovered without permanent disability after TXA was stopped. From our literature search, we identified two cases of neurotoxicity (one PD, one stage 4 CKD patient), one case of retinal toxicity in a haemolysis (HD) patient, one case of ligneous conjunctivitis in a CKD patient, and one case of toxic epidermal necrolysis in a CKD patient., Conclusion: Neurotoxicity is a very common clinical manifestation of TXA toxicity in CKD patients. Thrombotic complication is rare. Dosage adjustment of TXA is essential in CKD patients., (© 2016 Asian Pacific Society of Nephrology.)

Aim: C-reactive protein (CRP) is a mediator of systemic inflammation. Peritoneal dialysis (PD) is known to cause peritoneal inflammation and fibrosis. We compare the degree of peritoneal inflammation and fibrosis in wild-type (WT) and CRP-transgenic (Tg) mice after PD treatment., Methods: WT (n = 7) and CRP-Tg (n = 10) C57BL/6 J mice (all male, 10-12 weeks old) were injected intra-peritoneally with 4.25% dextrose PD solution (3 mL/mouse) daily for 28 days, followed by a 2-h peritoneal equilibration test (PET). The mice were then killed. Parietal peritoneal and omental tissues were collected for the assessment of inflammation and fibrosis., Results: After 28 days of PD treatment, CRP-Tg mice had higher dialysate-to-plasma (D/P) creatinine ratio than that of WT mice. Parietal peritoneum of the CRP-Tg mice was more cellular and thicker than that of the WT mice. CRP-Tg mice also had higher connective tissue growth factor (CTGF), intercellular adhesion molecule 1 (ICAM1) and tumor necrosis factor α (TNFα) RNA expressions as well as immunohistochemical staining in the parietal peritoneum than that of the WT mice., Conclusions: CRP-Tg mice have significantly more inflammation and fibrosis than WT mice after PD treatment. Our results suggest that CRP play a role in inflammation and fibrosis induced by PD. The implication of our results to human PD therapy needs further investigations., (© 2016 Asian Pacific Society of Nephrology.)

Background: The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain., Methods: We studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients., Results: Baseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated with dialysate-to-plasma creatinine concentration at 4h (D/P4) at baseline (r=0.377, p=0.001 and r=0.237, p=0.037, respectively) and after one year of PD (r=0.362, p=0.014 and r=0.402, p=0.007). The change in PD effluent -21 and miR-589 levels over one year correlated with the corresponding change in D/P4 (r=0.470, p=0.001 and r=0.479, p=0.002). The number of peritonitis episodes during follow up significantly correlated with the change in PD effluent miR-21 (r=0.387, p=0.009) and miR-589 (r=0.336, p=0.027) levels. There was no significant correlation between PD effluent miRNA level and ultrafiltration volume., Conclusion: Amongst the 10 miRNA targets tested, miR-21 and miR-589 showed consistently significant relation with peritoneal transport. Further studies are needed to delineate their mechanisms of regulating peritoneal transport., (Copyright © 2016. Published by Elsevier B.V.)

Background/aims: Enterococcal peritonitis in peritoneal dialysis (PD) patients is associated with a high complication rate. The optimal treatment regimen of PD-related enterococcal peritonitis is controversial. The latest international guideline recommends intra-peritoneal (IP) vancomycin. Although ampicillin is often effective for systemic enterococcal infections, they have little in vitro activity when added to common PD solutions. Since oral amoxicillin achieves therapeutic drug level in the peritoneal cavity, we explore the efficacy of oral amoxicillin for enterococcal peritonitis., Methods: We studied 105 episodes of enterococcal peritonitis over 20 years in our unit; 43 (41.0%) were treated with oral amoxicillin, and 62 (59.0%) with IP vancomycin. Their clinical outcome was reviewed., Result: The overall primary response rate to oral amoxicillin and IP vancomycin was 76.4% and 85.5%, respectively (p = 0.3). The complete cure rate of oral amoxicillin and IP vancomycin was 55.8% and 54.8%, respectively (p = 0.8). When the 5 episodes of ampicillin-resistant Enterococcus episodes were excluded, the primary response rate and complete cure rate of oral amoxicillin were 86.8% and 63.2%, respectively., Conclusion: Oral amoxicillin has an excellent primary response rate and complete cure rate for PD-related peritonitis episodes caused by Enterococcus species, indicating that oral amoxicillin is a valid and convenient therapeutic option for enterococcal peritonitis episodes., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count., (© 2016 Asian Pacific Society of Nephrology.)

Peritonitis is a debilitating infectious complication of peritoneal dialysis (PD). Drug-resistant bacterial peritonitis typically has a lower response rate to antibiotics. In the past 15 years, newer antibiotics with activities against drug-resistant Gram-positive bacteria have been developed. In most circumstances, peritonitis due to methicillin-resistant staphylococci responds to vancomycin. If vancomycin cannot be used due to allergy and/or non-susceptibility, there is increasing evidence that linezolid and daptomycin are the drugs of choice. It is reasonable to start linezolid orally or intravenously, but subsequent dose reduction may be necessary in case of myelosuppression. Daptomycin can be given intravenously or intraperitoneally and has excellent anti-biofilm activity. Other treatment options for drug-resistant Gram-positive bacterial peritonitis include teicoplanin, tigecycline and quinupristin/dalfopristin. Teicoplanin is not available in some countries (e.g. the USA). Tigecycline can only be given intravenously. Quinupristin/dalfopristin is ineffective against Enterococcus faecalis and there is only low-quality evidence to support its efficacy in the treatment of peritonitis. Effective newer antibiotics against drug-resistant Gram-negative bacteria are lacking. Polymyxins can be considered, but evidence on its efficacy is limited. In this review, we will discuss the potential use of newer antibiotics in the treatment of drug-resistant bacterial peritonitis in PD patients.

Background and Objectives: Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP., Design, Setting, Participants, & Measurements: In this single-center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls., Results: Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3-62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0-65.8 days versus 27.5; IQR, 23.0-35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8-60.5 months versus 55.8; IQR, 40.4-71.2 months; P=0.02). Technique failure occurred in 11.5% and 10.6% of patients in the PTP and control groups, respectively., Conclusions: S. aureus is the most common causative organism of PTP. Nutritional interventions in patients who are hypoalbuminemic before catheter insertion deserve additional study., (Copyright © 2016 by the American Society of Nephrology.)

Background: Glomerular and tubulointerstitial fibrosis play important roles in the progression of chronic kidney disease. We determine whether urinary mRNA levels of extracellular matrix proteins reflect the degree of kidney fibrosis and predict renal function decline in adult nephrotic patients., Methods: We studied 56 adult nephrotic patients and 20 controls. Urinary mRNA levels of collagen I A1 chain (COL1A1), collagen IV A3 chain (COL4A3), and fibronectin were measured., Results: Urinary sediment mRNA levels of COL1A1 and fibronectin were significantly higher in nephrotic patients as compared to the control, irrespective to the pathological diagnosis. Urinary COL1A1 mRNA level correlates with proteinuria, glomerular and interstitial fibrosis, and inversely with estimated glomerular filtration rate (GFR); urinary fibronectin mRNA level significantly correlates with glomerular and interstitial fibrosis, and inversely with estimated GFR. After 42.4 ± 12.6 months follow-up, the rate of GFR decline inversely correlates with urinary mRNA level of COL1A1 (r = -0.273, p = 0.044). Multivariate analysis confirmed that urinary COL1A1 mRNA level is an independent predictor of serum creatinine doubling or progressing to end stage renal disease; for each 10-fold increase in urinary COL1A1 mRNA level, there is 15.1% excess in risk (95% confidence interval, 1.9% to 30.4%, p=0.022)., Conclusions: Urinary COL1A1 mRNA level is elevated in nephrotic patients irrespective to the pathological diagnosis, and it correlates with proteinuria, histological scarring, and inversely with renal function. Furthermore, urinary COL1A1 mRNA level predicts renal function loss during follow-up. Our results suggest that urinary COL1A1 mRNA level may be used for risk stratification of adult nephrotic syndrome., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background/aims: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients., Methods: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival., Results: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 ± 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p < 0.0001). At 24 months, the event-free survival was 67.4%, 66.4%, 63.4% and 44.2% for plasma mitochondrial DNA level quartiles I, II, III and IV, respectively (p = 0.049). After adjusting for confounders, plasma mitochondrial DNA level, malnutrition-inflammation score, and baseline arterial pulse wave velocity were independent predictors of composite cardiovascular end-point; each doubling in plasma mitochondrial DNA level confers 16.0% (95% confidence interval, 2.5 - 31.3%, p = 0.001) excess in risk. Plasma mitochondrial DNA also correlated with the number of hospital admission (r = -0.218, p = 0.002) and duration of hospitalization for cardiovascular reasons (r = -0.232, p = 0.001)., Conclusion: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background/aims: Previous studies showed that frailty is prevalent in both pre-dialysis and dialysis patients. However, the prevalence and prognostic implication of frailty in Chinese peritoneal dialysis (PD) patients remain unknown., Methods: We used a validated questionnaire to determine the Frailty Score of 193 unselected prevalent PD patients. All patients were then followed for 2 years for their need of hospitalization and mortality., Results: Amongst the 193 patients, 134 (69.4%) met the criteria of being frail. Frailty Score significantly correlated with Charlson's comorbidity score (r = 0.40, p < 0.0001), Malnutrition Inflammation Score (r = 0.59, p < 0.0001), and inversely with Subjective Global Assessment score (r = -0.44, p < 0.0001). Frailty was closely associated with the need of hospitalization. Patients with nil, mild, moderate, and severe frailty required 2.4 ± 6.0, 1.6 ± 1.6, 2.7 ± 2.5, 5.2 ± 4.8 hospital admissions per year, respectively (p < 0.0001), and they stayed in hospital for 6.4 ± 9.2, 5.3 ± 6.2, 10.0 ± 10.4, 12.9 ± 20.1 days per hospital admission, respectively (p < 0.0001). However, Frailty Score was not an independent predictor of patient or technique survival., Conclusions: Frailty is prevalent among Chinese PD patients. Frail PD patients have a high risk of requiring hospitalization and their hospital stay tends to be prolonged. Early identification may allow timely intervention to prevent adverse health outcomes in this group of patients., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Podocyte depletion is a characteristic feature of progressive renal failure. We hypothesize that studying the podocyte mRNA level in urinary sediment may provide diagnostic and prognostic information in adult nephrotic syndrome., Methods: We studied 25 patients with minimal change nephropathy (MCN), 25 with focal segmental glomerulosclerosis (FSGS), and 17 healthy controls. The mRNA levels of nephrin, podocin, and synaptopodin in urinary sediment were quantified., Results: There were significant differences in the urinary sediment nephrin and podocin, but not synaptopodin, mRNA levels between diagnosis groups. Post-hoc analysis further showed that urinary nephrin mRNA levels of the MCN group were lower than those in the control and FSGS groups, although the difference between MCN and FSGS groups did not reach statistical significance. The degree of proteinuria inversely correlated with urinary nephrin mRNA levels in the MCN (r = -0.526, p = 0.007) as well as in the FSGS group (r = -0.521, p = 0.008). For the FSGS group, the rate of renal function decline significantly correlated with baseline urinary synaptopodin mRNA levels (r = -0.496, p = 0.012)., Conclusions: Urinary nephrin and podocin mRNA levels were reduced in patients with MCN and probably FSGS, and the magnitude of reduction correlated with the degree of proteinuria. Urinary synaptopodin mRNA levels correlated with the subsequent rate of renal function decline in patients with FSGS. Our result indicates that urine sediment podocyte mRNA levels provide novel insights in the pathophysiology of nephrotic syndrome and could be useful for risk stratification.

Background: Inflammation and fibrosis play important roles in the progression of diabetic nephropathy. We determine the urinary mRNA levels of ELR-CXC chemokine ligand and extracellular matrix in diabetic nephropathy., Methods: We studied 26 patients with biopsy-proven diabetic nephropathy, 15 with hypertensive nephrosclerosis and 10 healthy controls. Urinary mRNA levels of CXCL9, CXCL10, CXCL11, collagen I A1 chain, collagen IV A3 chain and fibronectin were measured. Patients were followed for 36.9 ± 7.4 months to determine the rate of glomerular filtration rate (GFR) decline., Results: Urinary mRNA levels of CXCL10 and CXCL11 are decreased, and those of collagen I A1 chain and fibronectin are increased in diabetic nephropathy. Baseline estimated GFR correlates with urinary mRNA level of CXCL9 (r = 0.583, p = 0.002) and CXCL11 (r = 0.703, p < 0.0001), respectively. The rate of GFR decline significantly correlates with urinary CXCL9 (r = -0.618, p = 0.0008) and CXCL11 mRNA levels (r = -0.726, p < 0.0001). Multivariate linear regression analysis confirms that urinary CXCL9 mRNA level is independently associated with the rate of GFR decline, while the correlation with urinary CXCL11 mRNA level has borderline significance., Conclusion: Urinary CXCL9 and CXCL11 mRNA levels correlate with baseline renal function. The rate of renal function decline correlates with urinary CXCL9 mRNA level. Our results suggest that urinary CXCL9 mRNA levels may be used for risk stratification of diabetic nephropathy., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: We studied the urinary sediment mRNA level of Th9- and Th22-related cytokines in patients with systemic lupus erythematosus (SLE)., Methods: We quantified urinary mRNA levels of interleukin (IL) 9, IL-10, IL-22, and their corresponding transcription factors in 73 patients with active lupus nephritis, 13 patients with hypertensive nephrosclerosis (HTN), and 25 healthy subjects., Results: There was no detectable IL-9 mRNA in all samples. Patients with proliferative lupus nephritis had significantly lower urinary IL-22 mRNA levels than those with nonproliferative nephritis (2.2 ± 5.4 vs 8.6 ± 20.0 copies, p = 0.019), and urinary IL-22 mRNA level inversely correlated with the histological activity index (r = -0.427, p < 0.0001). In contrast, patients with lupus nephritis had significantly higher urinary IL-10 mRNA levels than patients with HTN (7.8 ± 18.5 vs 1.9 ± 4.0 copies, p = 0.012), and urinary IL-10 mRNA levels correlated with its intrarenal mRNA levels (r = 0.337, p = 0.004) and SLE disease activity index (r = 0.277, p = 0.018). Urinary IL-10 mRNA level was significantly lower among patients who achieved complete remission than those with partial remission or no response (4.1 ± 6.5 vs 14.1 ± 28.0 copies, p = 0.036)., Conclusion: Urinary IL-22 mRNA level is decreased in patients with SLE with proliferative nephritis, while urinary IL-10 mRNA levels correlates with its intrarenal mRNA level and disease activity. Urinary IL-10 mRNA levels may also predict treatment response. These results suggest that urinary mRNA levels of IL-10 and IL-22 might be used as biomarkers for assessing disease activity and risk stratification in lupus nephritis.

Background: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients., Methods: We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival., Results: The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 - 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005)., Conclusions: Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients.

Background: We tested the strategy of mTOR inhibitors with calcineurin inhibitor minimization in renal transplant recipients with known chronic allograft dysfunction., Methods: In this open-label, single-arm study, renal transplant patients were recruited after biopsy-confirmed chronic allograft dysfunction in the absence of acute rejection episode within 2 months, with proteinuria <0.8 g/day, and serum creatinine <220 μmol/L or estimated glomerular filtration rate >40 mL/min/1.73 m(2). They were converted to everolimus (aiming for trough everolimus level 3-8 ng/mL) with cyclosporine minimization, to assess the effect on renal function, rate of glomerular filtration rate decline, and longitudinal transplant biopsy at 12 months., Results: Seventeen Chinese patients (median transplant duration, 4.2 years) were recruited; no patients discontinued study medication. The mean slope of the glomerular filtration rate over time was -4.31±6.65 mL/min/1.73 m(2) per year in the year before everolimus, as compared with 1.29±5.84 mL/min/1.73 m(2) per year in the 12 months of everolimus therapy, a difference of 5.61 mL/min/1.73 m(2) per year (95% confidence interval [CI], 0.40-10.8) favoring everolimus therapy (P=0.036). Serial renal biopsy histology showed significant decrease of tubular atrophy (15.7%±11.3% versus 7.1%±7.3%, P=0.005) and interstitial fibrosis (14.8%±11.5% versus 7.2%±8.2%, P=0.013). Intrarenal expression of TGF-β1 mRNA showed a nonsignificant decrease after everolimus treatment., Conclusion: In renal transplant recipients with biopsy-confirmed chronic allograft dysfunction, we found a significant beneficial effect of everolimus rescue therapy and calcineurin inhibitor minimization strategy on the improvement of glomerular filtration rate decline rate. In secondary analysis, everolimus was shown to slow down the disease progression by reducing the tubular atrophy and interstitial fibrosis scoring.

Background: Minimal change nephropathy is a common cause of primary nephrotic syndrome in adults. However, there are few studies of its clinical course, response to treatment, and long-term outcome., Study Design: Retrospective cohort study., Setting & Participants: 340 consecutive adult patients with nephrotic syndrome and biopsy-proven minimal change nephropathy treated in a university hospital from 1984 until 2004., Factors: Treatment response groups: primary steroid resistance, frequent relapse (≥4 relapses within 1 year), infrequent relapse (≥1 relapse but not frequent relapse), and no relapse (reference group); disease pattern., Outcome: Medical problems after diagnosis; patient survival; renal survival., Results: Median time to remission was 10 (IQR, 8-12) weeks; 179 (52.6%) had no relapse, 42 (12.4%) had infrequent relapses, 86 (25.3%) were frequent relapsers or steroid dependent, and 33 (9.7%) had primary steroid resistance. After a median follow-up of 174.7 (IQR, 119.7-235.0) months, 32 patients developed end-stage renal disease and 62 died (25 after progression to end-stage renal disease). Cox regression analysis showed that age and treatment response groups were the independent predictors of patient survival. Compared to the no-relapse group, the infrequent-relapse group had significantly better patient survival (adjusted HR, 0.19; 95% CI, 0.08-0.44; P<0.001), whereas the primary-steroid-resistance group had significantly worse patient survival (adjusted HR, 5.87; 95% CI, 1.83-18.85; P<0.001). Renal survival was excellent except in the primary-steroid-resistance group., Limitations: Retrospective study., Conclusions: A substantial proportion of adult patients with minimal change nephropathy continue to have disease flares more than 10 years after the initial presentation, and medical problems after diagnosis are common., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Residual renal function (RRF) is an important prognostic indicator in continuous ambulatory peritoneal dialysis (CAPD) patients. We determined the predictors of RRF loss in a cohort of incident CAPD patients., Methods: We reviewed the record of 645 incident CAPD patients. RRF loss is represented by the slope of decline of residual glomerular filtration rate (GFR) as well as the time to anuria., Results: The average rate of residual GFR decline was -0.083 ± 0.094 mL/min/month. The rate of residual GFR decline was faster with a higher proteinuria (r = -0.506, p < 0.0001) and baseline residual GFR (r = -0.560, p < 0.0001). Multivariate analysis showed that proteinuria, baseline residual GFR, and the use of diuretics were independent predictors of residual GFR decline. Cox proportional hazard model showed that proteinuria, glucose exposure, and the number of peritonitis episodes were independent predictors of progression to anuria, while a higher baseline GFR was protective. Each 1 g/day of proteinuria is associated with a 13.2% increase in the risk of progressing to anuria, each 10 g/day higher glucose exposure is associated with a 2.5% increase in risk, while each peritonitis episode confers a 3.8% increase in risk., Conclusions: Our study shows that factors predicting the loss of residual solute clearance and urine output are different. Proteinuria, baseline residual GFR, and the use of diuretics are independently related to the rate of RRF decline in CAPD patients, while proteinuria, glucose exposure, and the number of peritonitis episodes are independent predictors for the development of anuria. The role of anti-proteinuric therapy and measures to prevent peritonitis episodes in the preservation of RRF should be tested in future studies., (Copyright © 2015 International Society for Peritoneal Dialysis.)

Macrolide antibiotics, erythromycin, clarithromycin and azithromycin are commonly prescribed for upper respiratory infection, and their use has recently been further linked to immunomodulatory effects. With the widespread and expanded use of macrolides, special attention should be paid to their potential adverse effects. We reported two cases of end-stage renal disease (ESRD) patients who developed hallucinations such as vivid images of worms after taking clarithromycin. Similar to previous case reports of clarithromycin neurotoxicity, the visual hallucination resolved upon cessation of clarithromycin. Furthermore, we discussed the pharmacokinetic properties and other toxicities of macrolide antibiotics in patients with chronic kidney disease and ESRD.

Aim: To investigate the clinical course and outcome of peritoneal dialysis-associated peritonitis secondary to Gordonia species., Method: We reviewed all Gordonia peritonitis episodes occurring in a single dialysis unit from 1994 to 2013., Results: During the study period, four episodes of Gordonia peritonitis were recorded. All were male patients. One patient responded to vancomycin therapy. One patient had refractory peritonitis despite vancomycin, but responded to imipenem and amikacin combination therapy. One patient had relapsing peritonitis and required catheter removal. The fourth patient had an elective Tenckhoff catheter exchange. No patient died of peritonitis. Causative organism was not fully identified until 7 to 18 days of peritonitis., Conclusion: Gordonia species is increasingly recognized to cause serious infections. In patients undergoing peritoneal dialysis, Gordonia peritonitis should be considered in case of refractory Gram-positive bacilli peritonitis, especially when the exact organism could not be identified one week after the onset of peritonitis. A close liaison with a microbiologist is needed for a timely diagnosis., (© 2014 Asian Pacific Society of Nephrology.)

Background: The clinical benefits of using icodextrin during acute peritonitis in peritoneal dialysis are uncertain. On the premise that high glucose concentration might jeopardize the peritoneal defense during peritonitis, icodextrin administration during acute peritonitis could have the potential to improve the peritonitis outcome whilst improving ultrafiltration., Methods: We conducted a single-center, open-label, randomized controlled trial in which 53 adult continuous ambulatory peritoneal dialysis patients underwent randomization to receive either icodextrin or original glucose-based dialysis solution. The primary outcome measure was the peritoneal dialyzate white cell count on Day 3. Secondary outcome measures comprised the need of additional hypertonic exchanges, fluid control as denoted by changes in body weight, and the clinical outcome of peritonitis including 30-day and 120-day all-cause mortality., Results: Between icodextrin and control treatment groups, there were no statistically significant differences in the peritoneal dialyzate white cell count on day (1829 versus 987/mm(3), P = 0.13). There was neither improvement in primary cure rate (31.8 versus 32.3%, P = 1.00), nor was there any change in 120-day mortality after icodextrin use (13.6 versus 12.9%, P = 1.00). However, requirement of hypertonic dialysis exchange was much more frequent in the control group than in those randomized to icodextrin (35.5 versus 0%, P = 0.001). Body weight did not change significantly in the icodextrin group, but body weight in the control group increased from 63.3 ± 14.5 kg at baseline to 64.2 ± 14.2 kg at Day 5 (P = 0.0002) and 65.2 ± 14.1 kg at Day 10 (P < 0.0001)., Conclusions: As compared with glucose-based peritoneal dialysis solution, use of icodextrin achieved better ultrafiltration and fluid control during acute peritonitis complicating continuous ambulatory peritoneal dialysis, although we found no evidence of a worthwhile clinical benefit on peritonitis resolution. (ClinicalTrial.gov number, NCT0104446 [ClinicalTrial.gov].)., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Aim: Although calcimimetics cinacalcet can reduce parathyroid hormone level and control secondary hyperparathyroidism in end-stage renal disease patients, risk of vascular calcification remains high. Whether cinacalcet can further reduce vascular damage or arterial stiffness is unknown., Methods: We studied the effect of cinacalcet in 33 peritoneal dialysis patients with inadequately controlled secondary hyperparathyroidism despite standard treatment. The primary outcome was the aortic pulse wave velocity at 26 and 52 months after cinacalcet treatment. The pulse wave velocity was compared with that of a matched control cohort of 37 peritoneal dialysis patients with secondary hyperparathyroidism., Results: Thirty-three patients completed the cinacalcet treatment, after median dialysis duration of 1.0 year. Significant improvement of parathyroid hormone level was achieved after 52 weeks, from 87.5 ± 28.7 pmol/L to 34.5 ± 45.5 pmol/L (P < 0.0001). Serial carotid-femoral pulse wave velocity did not differ between cinacalcet treatment group and control group (general linear model with repeated measures, P = 0.19). Among patients receiving cinacalcet, the average carotid-femoral pulse wave velocity increased from 10.46 ± 2.12 m/s at baseline to 11.41 ± 2.79 m/s at 52 weeks (P = 0.001). The change in carotid-femoral pulse wave velocity over 1 year had no significant correlation with the final parathyroid hormone level or change in parathyroid hormone level., Conclusions: Among prevalent patients receiving peritoneal dialysis and with hyperparathyroidism, a reduction of 60.6% parathyroid hormone level after cinacalcet treatment for one year did not reduce the carotid-femoral pulse wave velocity., (© 2014 Asian Pacific Society of Nephrology.)

Background: Fluid overload probably contributes to the cardiovascular risk of peritoneal dialysis (PD) patients. We studied the relationship between over-hydration as determined by bioimpedance spectroscopy and dialysis adequacy, nutritional status, and arterial stiffness in Chinese PD patients., Methods: We studied 122 asymptomatic prevalent PD patients: bioimpedance spectroscopy, arterial pulse wave velocity, dialysis adequacy and nutritional status were determined., Results: Of the 122 patients, 88 (72.1%) had over-hydration of ≥ 1 L, while 25 (20.5%) were ≥ 5 L. Over-hydration significantly correlated with total body water (r = 0.474, p < 0.001) and extracellular water (r = 0.755, p < 0.001). Over-hydration was more severe in male and diabetic patients, and significantly correlated with Charlson's comorbidity score, blood pressure, body mass index, body weight, peritoneal transport characteristics, and carotid-femoral pulse wave velocity. Over-hydration significantly correlated with Kt/V (r = -0.287, p = 0.016), serum albumin level (r = -0.465, p < 0.001) and malnutrition inflammation score (r = 0.410, p = 0.006), but not residual renal function., Conclusion: Over-hydration is common in asymptomatic Chinese PD patients. The degree of over-hydration is particularly pronounced in patients who are inadequately dialyzed, have multiple comorbid conditions and low serum albumin levels. Over-hydration is associated with high blood pressure and arterial stiffness, and may contribute to the excessive risk of cardiovascular disease in this group of patients., (Copyright © 2014 International Society for Peritoneal Dialysis.)

Background and Objective: In the general population, metabolic syndrome (MES) is associated with cardiovascular risk. However, the definition of MES and its prognostic implication among patients undergoing peritoneal dialysis (PD) remain controversial., Design, Setting, Participants, & Measurements: We studied 329 prevalent PD patients from April 2008 to April 2011 and compared four sets of diagnostic criteria: the original World Health Organization (WHO) criteria, the International Diabetes Federation (IDF) criteria, the original National Cholesterol Education Program (NCEP) criteria, and the modified NCEP criteria. Nutritional status, body composition, and arterial pulse-wave velocity were measured. Patients were followed for 31.7 ± 15.5 months., Results: Among the 329 patients, 175 (53.2%) fulfilled the WHO criteria, 177 (53.8%) the IDF criteria, 199 (60.5%) the original NCEP criteria, and 218 (66.3%) the modified NCEP criteria. The agreement among the four sets of criteria was fair to moderate (Cohen κ=0.35-0.58). Patients with MES defined by all four criteria had higher adipose tissue mass than the others, although the difference in adipose tissue mass was most pronounced with the IDF criteria (MES versus no MES, 18.2 ± 7.9 versus 10.7 ± 5.9 kg; P<0.001). Patients with MES, as defined by the IDF criteria, were hospitalized longer than those without MES (3.82 [interquartile range, 0.00-12.61] versus 1.07 [interquartile range, 0.00-6.43]) days per year of follow-up; P=0.01). Overall survival, cardiovascular survival, or technique survival did not differ between patients with and without MES, irrespective of the diagnostic criteria after adjustment for diabetic status., Conclusion: In patients undergoing PD, overall survival, cardiovascular survival, and technique survival did not differ between patients with and without MES, irrespective of diabetic status and diagnostic criteria. Further studies are needed to establish a new definition or clinical scoring system for risk stratification of PD patients.

Background: Heat shock proteins (HSPs) are expressed by cells in response to various environmental stresses. A single-nucleotide polymorphism A+1267G of the HSPA1B gene affects the expression of HSP70-2, with the A allele being protective against inflammatory conditions. We investigated the relation between the HSP A+1267G polymorphism and the clinical outcomes of Chinese peritoneal dialysis (PD) patients., Methods: We studied 347 new PD cases (181 males, age 56.6 ± 13.7 years). Genotyping was done by standard methods. Patients were followed for 40.5 ± 20.7 months for survival analysis., Results: For the entire cohort, there was no difference in the 5-year survival between genotype groups. However, there was a significant interaction between HSP polymorphism and diabetic status on the cardiovascular event-free survival. In patients without pre-existing diabetes, 5-year cardiovascular event-free survival of the GG/AG genotype group was significantly better than that of the AA genotype group (57.2 vs. 32.1%, p = 0.011)., Conclusion: The G allele of the HSP70-2 A+1267G polymorphism confers survival advantages in non-diabetic PD patients. The role of HSP in the pathogenesis of cardiovascular disease in renal failure patients needs further investigation., (© 2014 S. Karger AG, Basel.)