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Background: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on calcium phosphate homeostasis in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remain uncertain., Methods: A retrospective observational cohort study of patients with T2DM at CKD stage G3b-5ND who received SGLT2i as compared to control from 1 January 2015 through 31 December 2021 was recruited. Propensity score assignment at 1:3 ratio by logistic regression was done. All patients were followed for 12 months. Outcomes were changes in phosphate level., Results: We analyzed 1,450 SGLT2i users and 4,350 control subjects. At the 12 th month, SGLT2i users had a slower increase in phosphate levels (absolute change: -0.01 ± 0.28 vs + 0.14 ± 0.34 mmol/L; percentage change: -0.74 % ± 25.56 vs + 10.88 ± 28.15 %, P for both < 0.001). The proportion of patients with high phosphate was lower with SGLT2i (8.2 % vs 24.6 % increase). In the generalized estimating equation, SGLT2i was linked to a longitudinal reduction in phosphate (B -0.039, P<0.001)., Conclusions: SGLT2i can effectively slow down the progression of phosphate retention in advanced CKD with T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Sarcopenia is common in peritoneal dialysis (PD) patients. Modified creatinine index (MCrI) by the Canaud's formula and single-pool Kt/V value is an accurate surrogate marker for muscle mass in hemodialysis patients. However, the method of calculation and validity of MCrI has not been tested in PD., Methods: In the exploratory cohort, we studied 138 consecutive patients converted from PD to hemodialysis. Their MCrI during PD, calculated by the Canaud's formula with total weekly Kt/V, and the conventional MCrI after conversion to HD, were compared by the Bland-Altman method. Their correlation with muscle mass as determined by bioimpedance spectroscopy and creatinine kinetic methods was explored. The result was then validated in a second cohort of 605 incident PD patients., Results: In the exploratory cohort, the average bias of computing MCrI during PD and hemodialysis was 0.758 mg/kg/day (95%CI -4.356 to 5.873 mg/kg/day). The MCrI during PD significantly correlated with the muscle mass by creatinine kinetics ( r  = .684, P  < .0001) and by bioimpedance spectroscopy ( r  = .641, P  < .0001), but not with protein nitrogen appearance, overhydration, or adipose tissue mass, and the result was similar in the validation cohort. For incident PD patients, MCrI quartile was significantly associated with the risk of death from all cause in 12 months (Gray's test, P  = .013) but not conversion to chronic hemodialysis ( P  = .14)., Conclusion: In PD patients, MCrI computed by the Canaud's formula and total weekly Kt/V is a simple and reliable marker of skeletal muscle mass and may serve as a short-term prognostic indicator., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Limited data exist on the association between gut permeability, circulating bacterial fragment and volume overload in peritoneal dialysis (PD) patients. We measured circulating bacterial fragments, N-terminal pro B-type natriuretic peptide (NT-proBNP), calprotectin and zonulin levels, and evaluate their association with the clinical outcomes in PD patients., Methods: This was a single-center prospective study on 108 consecutive incident PD patients. Plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels were measured. Primary outcomes were technique and patient survival, secondary outcomes were hospitalization data., Results: There was no significant correlation between plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels. The Homeostatic Model Assessment for Insulin Resistance (HOMA)-2β index, which represents insulin resistance, positively correlated with plasma bacterial DNA (r = 0.421, P  < .001) and calprotectin levels (r = 0.362, P  = .003), while serum NT-proBNP level correlated with the severity of volume overload and residual renal function. Serum NT-proBNP level was associated with technique survival even after adjusting for confounding factors [adjusted hazard ratio (aHR) 1.030, 95% confidence interval 1.009-1.051]. NT-proBNP level was also associated with patient survival by univariate analysis, but the association became insignificant after adjusting for confounding factors (aHR 1.010, P  = .073). Similarly, NT-proBNP correlated with the number of hospitalizations and duration of hospitalization by univariate analysis, but the association became insignificant after adjusting for confounding factors., Conclusion: There was no correlation between markers of gut permeability, circulating bacterial fragments and measures of congestion in PD patients. Bacterial fragments levels and gut permeability are both associated with insulin resistance. Serum NT-proBNP level is associated with the severity of volume overload and technique survival. Further studies are required to delineate the mechanism of high circulating bacterial fragment levels in PD patients., Competing Interests: C.-C.S. is member of the CKJ Editorial Board. The other authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Diabetic kidney diseases (DKD) is a the most common cause of end-stage kidney disease (ESKD) around the world. Previous studies suggest that urinary podocyte stress biomarker, e.g. podocin:nephrin mRNA ratio, is a surrogate marker of podocyte injury in non-diabetic kidney diseases., Method: We studied 118 patients with biopsy-proved DKD and 13 non-diabetic controls. Their urinary mRNA levels of nephrin, podocin, and aquaporin-2 (AQP2) were quantified. Renal events, defined as death, dialysis, or 40% reduction in glomerular filtration rate, were determined at 12 months., Results: Urinary podocin:nephrin mRNA ratio of DKD was significantly higher than the control group (p = 0.0019), while urinary nephrin:AQP2 or podocin:AQP2 ratios were not different between groups. In DKD, urinary podocin:nephrin mRNA ratio correlated with the severity of tubulointerstitial fibrosis (r = 0.254, p = 0.006). and was associated with the renal event-free survival in 12 months (unadjusted hazard ratio [HR], 1.523; 95% confidence interval [CI] 1.157-2.006; p = 0.003). After adjusting for clinical and pathological factors, urinary podocin:nephrin mRNA ratio have a trend to predict renal event-free survival (adjusted HR, 1.327; 95%CI 0.980-1.797; p = 0.067), but the result did not reach statistical significance., Conclusion: Urinary podocin:nephrin mRNA ratio has a marginal prognostic value in biopsy-proven DKD. Further validation is required for DKD patients without kidney biopsy., (© 2024. The Author(s).)

Bioelectrical impedance analysis (BIA) has been extensively applied in nutritional assessments on the general population, and it is recommended in establishing the diagnosis of malnutrition and sarcopenia. The bioimpedance technique has become a promising modality through which to measure the whole-body composition in dialysis patients, where the presence of subclinical volume overload and sarcopenic obesity may be overlooked by assessing body weight alone. In the past two decades, bioimpedance devices have evolved from applying a single frequency to a range of frequencies (bioimpedance spectroscopy, BIS), in which the latter is incorporated with a three-compartment model that allows for the simultaneous measurement of the volume of overhydration, adipose tissue mass (ATM), and lean tissue mass (LTM). However, clinicians should be aware of common potential limitations, such as the adoption of population-specific prediction equations in some BIA devices. Inherent prediction error does exist in the bioimpedance technique, but the extent to which this error becomes clinically significant remains to be determined. Importantly, reduction in LTM has been associated with increased risk of frailty, hospitalization, and mortality in dialysis patients, whereas the prognostic value of ATM remains debatable. Further studies are needed to determine whether modifications of bioimpedance-derived body composition parameters through nutrition intervention can result in clinical benefits.

Background: The relationship between dietary patterns and the malnutrition-inflammation-frailty complex in patients undergoing peritoneal dialysis (PD) is currently unknown. Our objective was to measure dietary nutrient intake and evaluate its association with malnutrition, inflammation, and frailty., Methods: We prospectively recruited adult PD patients. We assessed their dietary nutrient intake using a food frequency questionnaire. Frailty, malnutrition, and inflammation were evaluated by validated Frailty Score (FQ), Subjective Global Assessment (SGA), and Malnutrition-Inflammation Score (MIS)., Results: A total of 209 patients were recruited for the study. Among them, 89 patients (42.6%) had an insufficient protein intake, and 104 patients (49.8%) had an insufficient energy intake. Additionally, 127 subjects were identified as frail, characterized by being older (61.9 ± 9.5 vs. 55.6 ± 12.8, p < 0.001), malnourished (SGA: 21.0 ± 2.7 vs. 22.7 ± 3.1, p < 0.001), and having a high inflammation burden (MIS: 10.55 ± 3.72 vs. 7.18 ± 3.61, p < 0.001). There was a significant correlation between dietary zinc intake and body mass index (r = 0.31, p < 0.001), SGA (r = 0.22, p = 0.01), and MIS (r = -0.22, p = 0.01). In the multivariate model, a higher dietary zinc intake predicted a higher SGA (beta 0.03, p = 0.003) and lower FQ (beta -0.38, p < 0.001) and MIS (beta -0.14, p < 0.001), indicating a better nutrition, less frail and inflamed state. A higher dietary zinc intake was also associated with a lower odds of being frail (adjusted odds ratio 0.96, p = 0.009)., Conclusion: Dietary inadequacy and micronutrient deficiency are common among the PD population. Dietary zinc intake is independently associated with an improved nutrition, physical condition, and reduced inflammatory state.

Background: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2., Methods: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded., Results: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic., Conclusions: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis., Method: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions., Results: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = -0.423, p = 0.018) and ANRIL levels (r = -0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = -0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis ( p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = -0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy ( p = 0.003) and minimal change nephropathy ( p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01)., Conclusions: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis.

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).)

Rationale & Objective: The efficacy and safety profile of apixaban remains uncertain in patients receiving peritoneal dialysis (PD) despite increasing use in this population. Accordingly, we assessed the pharmacokinetics of apixaban among patients receiving PD., Study Design: A pharmacokinetics study in a single center. Patients recruited received 1 week of apixaban at 2.5 mg twice a day to reach steady state. Serial blood samples were then taken before and after the last dose for pharmacokinetics analysis of apixaban., Setting & Participants: Ten stable PD patients with atrial fibrillation in an outpatient setting., Analytical Approach/outcomes: Pharmacokinetic parameters including the area under the concentration-time curve from time 0 to 12 hours after the last dose of apixaban (AUC0-12), peak concentration, trough level, time to peak apixaban concentration, half-life, and drug clearance were analyzed., Results: There was a wide variation in the range of apixaban concentration across the 10 patients. The AUC 0-12 for the PD group was significantly higher than those reported previously for hemodialysis patients or healthy individuals. Three patients had a supratherapeutic peak concentration whereas 2 patients had a supratherapeutic trough level as compared with the pharmacokinetic parameter in healthy individuals taking equivalent therapeutic dosage., Limitations: Small sample size with short study duration limits the ability to ascertain the true bleeding risk and to detect any clinical outcomes. Results may be limited to Asian populations only., Conclusions: A proportion of PD patients had supratherapeutic levels even when the reduced dosage 2.5 mg twice a day was used. Given the large interindividual variation in the drug level, therapeutic drug monitoring should be done if available. Otherwise, one should start the drug at reduced doses with caution and with more frequent clinical monitoring for any signs of bleeding., (© 2023 The Authors.)

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.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Two decades ago, the common co-existence of malnutrition and systemic inflammation PD patients with atherosclerosis and CVD led to the proposed terminology of 'malnutrition-inflammation-atherosclerosis (MIA) syndrome'. Although the importance of malnutrition is well accepted, frailty represents a more comprehensive assessment of the physical and functional capability of the patient and encompasses the contributions of sarcopenia (a key component of malnutrition), obesity, cardiopulmonary as well as neuropsychiatric impairment. In recent years, it is also increasingly recognized that fluid overload is not only the consequence but also play an important role in the pathogenesis of CVD. Moreover, fluid overload is closely linked with the systemic inflammatory status, presumably by gut oedema, gastrointestinal epithelial barrier dysfunction and leakage of bacterial fragments to the systemic circulation. There are now a wealth of published evidence to show intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on PD, a phenomenon that we propose the term 'FIFA complex'. In this system, frailty and atherosclerotic disease may be regarded as two patient-oriented outcomes, while inflammation and fluid overload are two inter-connected pathogenic processes. However, there remain limited data on how the treatment of one component affect the others. It is also important to define how treatment of fluid overload affect the systemic inflammatory status and to develop effective anti-inflammatory strategies that could alleviate atherosclerotic disease and frailty., (© 2023 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Background: Dysnatraemias are commonly reported in COVID-19. However, the clinical epidemiology of hypernatraemia and its impact on clinical outcomes in relation to different variants of SARS-CoV-2, especially the prevailing Omicron variant, remain unclear., Methods: This was a territory-wide retrospective study to investigate the clinical epidemiology and outcomes of COVID-19 patients with hypernatraemia at presentation during the period from 1 January 2020 to 31 March 2022. The primary outcome was 30-day mortality. Key secondary outcomes included rates of hospitalization and ICU admission, and costs of hospitalization., Results: In this study, 53,415 adult COVID-19 patients were included for analysis. Hypernatraemia was observed in 2688 (5.0%) patients at presentation, of which most cases (99.2%) occurred during the local "5th wave" dominated by the Omicron BA.2 variant. Risk factors for hypernatraemia at presentation included age, institutionalization, congestive heart failure, dementia, higher SARS-CoV-2 Ct value, white cell count, C-reactive protein and lower eGFR and albumin levels ( p < 0.001 for all). Patients with hypernatraemia showed significantly higher 30-day mortality (32.0% vs. 5.7%, p < 0.001) and longer lengths of stay (12.9 ± 10.9 vs. 11.5 ± 12.1 days, p < 0.001) compared with those with normonatraemia. Multivariate analysis revealed hypernatraemia at presentation as an independent predictor for 30-day mortality (aHR 1.32, 95% CI 1.14-1.53, p < 0.001) and prolonged hospital stays (OR 1.55, 95% CI 1.17-2.05, p = 0.002)., Conclusions: Hypernatraemia is common among COVID-19 patients, especially among institutionalized older adults with cognitive impairment and other comorbidities during large-scale outbreaks during the Omicron era. Hypernatraemia is associated with unfavourable outcomes and increased healthcare utilization.

Introduction: Obesity at the initiation of dialysis was reported to adversely affect the clinical outcome of peritoneal dialysis (PD) patients, and weight gain is common after started on PD. However, there are few studies on the prognostic implications of weight gain after PD., Methods: We reviewed the change in body weight of 954 consecutive patients during the first 2 years of PD in a single Hong Kong center. Their subsequent clinical outcomes, including patient and technique survival rates, hospitalization, and peritonitis rates, were analyzed., Results: The mean age was 60.3 ± 12.2 years; 535 patients (56.1%) were men, and 504 (52.8%) had diabetes. From 1995-1999 to 2015-2019, the percentage of body weight gain during the first 2 years of PD was 1.0 ± 7.9%, 1.6 ± 7.1%, 1.6 ± 7.2%, 3.9 ± 9.5%, and 4.0 ± 10.3% for each 5-year period, respectively ( p for linearity <0.0001). The subsequent 5-year patient survival rates were 29.9%, 43.3%, 40.5%, 43.6%, and 43.3% for patients with weight loss >5%, weight loss 2-5%, weight change with ±2%, weight gain 2-5%, and weight gain >5% during the first 2 years on PD, respectively (log-rank test, p = 0.035). With multivariable Cox regression model to adjust for clinical confounders, weight loss >5% during the first 2 years of PD was associated with a worse patient survival rate subsequently (adjusted hazard ratio 4.118, 95% confidence interval 1.040-16.313, p = 0.044), while weight gain was not associated with subsequent patient survival. Weight change during the first 2 years of PD does not appear to affect subsequent technique survival, hospitalization, decline in residual renal function, or peritonitis rate., Discussion and Conclusions: Weight gain is common during the first 2 years of PD, but weight gain does not appear to have any significant impact on the subsequent outcome. In contrast, weight loss >5% was significantly associated with worse patient survival subsequently., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Hyponatremia is common in COVID-19, but its epidemiology and impact on clinical outcomes in relation to different variants, especially the Omicron variant, requires further clarification., Methods: This was a territory-wide retrospective study to investigate the epidemiology and outcomes of COVID-19 patients with hyponatremia from January 1, 2020 to March 31, 2022 in Hong Kong. The primary outcome was 30-day mortality of patients with COVID-19 and hyponatremia at presentation. Secondary outcomes included rate of hospitalization, intensive care unit (ICU) hospitalization, overall duration of hospitalization, and duration of ICU hospitalization., Results: A total of 53,415 COVID-19 patients were included for analysis, of which 14,545 (27.2%) had hyponatremia at presentation. 9813 (67.5%), 2821 (19.4%), and 1911 (13.1%) had mild (130 to <135 mmol/L), moderate (125 to <130 mmol/L), and severe hyponatremia (<125 mmol/L) at presentation respectively. Age, male sex, diabetes, active malignancy, white cell count, serum creatinine, hypoalbuminemia, C-reactive protein, and viral loads were independent predictors for hyponatremia in COVID-19 patients ( P < 0.001, for all). Hyponatremic patients had increased 30-day mortality (9.7 vs. 5.7%, P < 0.001), prolonged hospitalization (11.9 ± 15.1 days vs. 11.5 ± 12.1 days, P < 0.001), and more ICU admissions (7.0% vs. 3.3%, P < 0.001). Patients diagnosed during the "fifth wave" Omicron BA.2 outbreak had 2.29-fold risk (95% CI 2.02-2.59, P < 0.001) of presenting with hyponatremia compared to other waves., Conclusion: Hyponatremia is common among COVID-19 patients, and may serve as a prognostic indicator for unfavorable outcomes and increased healthcare utilization in the evolving COVID-19 outbreak., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chan, Wong, So, Ng, Lui, Szeto, Hung, Tse, Tang, Chan, Chow and Yap.)

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.)

Background: There were limited data on the efficacy and safety profile on use of sodium-glucose co-transporter 2 receptor (SGLT2) inhibitors in diabetic patients with advanced chronic kidney disease (CKD). We aimed to evaluate the efficacy, in terms of improvement in glycemic profile, kidney function, prevention of adverse kidney and cardiovascular events, and the safety profile of SGLT2 inhibitors in a group of diabetic patients at CKD stage 3B-5 from a real-world population-based cohort., Methods: We performed a retrospective observational cohort study of type 2 diabetic patients at CKD stage 3B-5 who received SGLT2 inhibitors as compared to control from 1 January 2015 through 31 December 2021. Propensity score assignment by logistic regression and matching with control by the nearest score at 1:3 ratio was done. All patients were followed for 1 year. Outcomes were kidney-related adverse events and major adverse cardiovascular events (MACE), change in estimated glomerular filtration rate (eGFR), glycemic control, and side effects profiling., Results: We analyzed 1,450 SGLT2 inhibitor users. They had significantly lower rates of kidney-related adverse events (7.7 % versus 24.1 %, p < 0.001) and MACE (9.6 % versus 15.1 %, p < 0.001) as compared to control group. Their eGFR also significantly improved (0.4 ± 9.3 versus -5.5 ± 10.6 ml/min/1.73 m 2 , p < 0.001). These patients also had a greater reduction in HbA1c (-0.40 ± 1.13 versus -0.04 ± 1.47 %, p < 0.001), and insulin requirement (-8.8 ± 35.2 versus 4.1 ± 19.4 units/day, p < 0.001). After adjusting for confounders, SGLT2 inhibitors protected against kidney-related adverse events (odds ratio [OR] 0.48, 95 % confidence interval [CI] 0.33 - 0.71, p < 0.001) and MACE (OR 0.47, 95 % CI 0.37 - 0.60, p < 0.001). Apart from a marginally higher rate of fungal urinary tract infection (0.08 ± 0.66 versus 0.03 ± 0.23 episodes per year, p < 0.001), SGLT2 inhibitor use was not associated with other side effects., Conclusions: SGLT2 inhibitor improved kidney function, glycemic profile, and reduced adverse kidney-related and cardiovascular events in diabetic patients with advanced CKD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Renal glycogen synthase kinase-3 beta (GSK3β) overactivity has been associated with a diverse range of kidney diseases. GSK3β activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intrarenal GSK3β levels in DKD and nondiabetic chronic kidney disease (CKD)., Methods: We recruited 118 consecutive biopsy-proved DKD patients and 115 nondiabetic CKD patients. Their urinary and intrarenal GSK3β levels were measured. They were then followed for dialysis-free survival and rate of renal function decline., Results: DKD group had higher intrarenal and urinary GSK3β levels than nondiabetic CKD (p &lt; 0.0001 for both), but their urinary GSK3β mRNA levels were similar. Urinary p-GSK3β level is statistically significantly correlated with the baseline estimated glomerular filtration rate (eGFR), but urinary GSK3β level by ELISA, its mRNA level, the p-GSK3β level, or the p-GSK3β/GSK3β ratio had no association with dialysis-free survival or the slope of eGFR decline. In contrast, the intrarenal pY216-GSK3β/total GSK3β ratio significantly correlated with the slope of eGFR decline (r = -0.335, p = 0.006) and remained an independent predictor after adjusting for other clinical factors., Conclusion: Intrarenal and urinary GSK3β levels were increased in DKD. The intrarenal pY216-GSK3β/total GSK3β ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3β in kidney diseases deserve further studies., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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.

Rationale & Objective: Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD., Study Design: Observational cohort., Setting & Participants: 118 consecutive patients with biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls., Predictors: Urinary podocalyxin and podocin levels were obtained by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) and the corresponding intrarenal levels by western blotting., Outcomes: Dialysis-free survival; kidney event-free survival; rate of kidney function decline in 12 months., Analytical Approach: Correlation and time to event analysis., Results: Urinary podocalyxin level was closely correlated with its messenger RNA (mRNA) level ( r  = 0.562, P  < 0.001), but this did not predict the progression of DKD. Intrarenal podocalyxin level had only modest correlation with its urinary mRNA and ELISA levels, was an independent predictor of dialysis-free survival (adjusted HR, 1.85; 95% CI, 1.21-2.82; P  = 0.005), and showed an insignificant trend of predicting kidney event-free survival (adjusted HR, 1.36; 95% CI, 0.94-1.95; P  = 0.10). Urinary podocin level by ELISA had a modest correlation with the rate of kidney function decline ( r  = 0.238, P  = 0.01) but did not predict dialysis-free survival., Limitations: Small sample size; lack of serial measurement., Conclusions: Intrarenal podocalyxin level, but not its urinary level, was an independent predictor of dialysis-free survival, whereas urinary podocin level by ELISA correlated with the rate of kidney function decline. Although intrarenal podocalyxin level has prognostic value, it may not be suitable for routine clinical use., (© 2022 The Authors.)

Patients treated with peritoneal dialysis (PD) experience complex body composition changes that are not adequately reflected by traditional anthropometric parameters. While lean and adipose tissue mass can be readily assessed by bioimpedance spectroscopy (BIS), there is concern about the potential confounding effect of volume overload on these measurements. This study aimed to assess the influence of fluid status (by echocardiography) on body composition parameters measured by BIS and to describe the longitudinal changes in adipose and lean tissue mass. We conducted a prospective observational study in a tertiary hospital. Incident Chinese PD patients underwent baseline echocardiography and repeated BIS measurements at baseline and 12 months later. Among 101 PD patients, lean tissue index (LTI) or fat tissue index (FTI) was not associated with echocardiographic parameters that reflected left ventricular filling pressure (surrogate of volume status). Sixty-eight patients with repeated BIS had a significant increase in body weight and FTI, while LTI remained similar. Gains in fat mass were significantly associated with muscle wasting (beta = −0.71, p < 0.0001). Moreover, progressive fluid accumulation independently predicted decrease in FTI (beta = −0.35, p < 0.0001) but not LTI. Body composition assessments by BIS were not affected by fluid status and should be considered as part of comprehensive nutrition assessment in PD patients., Competing Interests: Philip Li received speaker honoraria from FibroGen, AstraZeneca and Baxter Healthcare. All other authors declare no conflicts of interest.

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.)

Background: Peritoneal dialysis (PD) is a home-based renal replacement therapy. Since hospital staff are not often familiar with PD and its complications, PD patients may have an excess risk of developing PD-related peritonitis during hospital admission for unrelated reasons, and the outcome may be affected., Methods: We reviewed 371 episodes of hospital-acquired PD peritonitis in our center from 2000 to 2019. Their clinical characteristics and outcomes were compared with 825 episodes that required hospital admission and 1964 episodes that were treated as outpatient., Results: Hospitalized PD patients had a significantly higher risk of developing peritonitis than outpatients [incident rate ratio 4.41 (95% confidence interval 3.95-4.91]. Hospital-acquired peritonitis episodes were more commonly culture negative. Bacterial isolates from the hospital-acquired episodes were more likely resistant to ceftazidime ( P < .0001) than the other groups. The primary response rate, complete cure rate and overall mortality of the hospital-acquired episodes were 66.6%, 62.0%, and 23.2%, respectively, all worse than episodes that developed outside the hospital ( P < .0001 for all)., Conclusion: PD patients admitted to the hospital had a 4-fold increase in the risk of developing peritonitis. Hospital-acquired peritonitis episodes were more likely culture negative and resistant to antibiotics. They also had a lower primary response rate, a lower complete cure rate and higher mortality than episodes that developed outside the hospital., (© The Author(s) 2022. 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: Urinary micro-RNA (miRNA) level may serve as non-invasive disease markers for immunoglobulin A nephropathy (IgAN), but urinary miRNA targets identified in previous studies may represent kidney scarring rather than being specific for IgAN. We aim to identify urinary miRNA targets for the diagnosis of IgAN by including hypertensive nephrosclerosis (HTN) as a control group. Methods In the development cohort, we performed complete miRNA profiling of urinary sediment in 33 patients with IgAN, 9 with HTN, and 9 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 72 IgAN, 34 HTN, and 20 healthy controls. Results In the development cohort, we identified 6 miRNA targets with urinary levels significantly increased in IgAN as compared to both HTN and CTL. In the validation study, all 6 miRNA targets remained increased than the other groups, although the result of miR-345 did not reach statistical significance. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-106a level for the diagnosis of IgAN was 0.742 (p < 0.0001), and the diagnostic performance was not further improved by having additional miRNA targets. At the cut-off ≥ 800 copy per 1000 copies of housekeeping gene, urinary miR-106a has 100% sensitivity and 14.8% specificity in detecting IgA nephropathy. Conclusions We identified 6 miRNA targets whose urinary levels are significantly elevated in IgAN, and urinary miR-106a level has an excellent sensitivity for the identification of IgAN. Further validation studies are needed to confirm its role in disease screening., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Distinguishing Mycobacterium tuberculosis (TB) and nontuberculous Mycobacterium (NTM) from bacterial peritoneal dialysis (PD)-related peritonitis (peritonitis) is often very challenging and can lead to a significant delay in diagnosis and treatment. The neutrophil-to-lymphocyte ratio (NLR) is readily calculable and has been shown to be useful in differentiating pulmonary TB from bacterial pneumonia. We are the first group to demonstrate the predictive efficacy of peritoneal dialysate (PDE) NLR in distinguishing TB/NTM peritonitis from bacterial causes in the PD population., Methods: We retrospectively reviewed the clinical and laboratory characteristics of all patients with TB/NTM peritonitis, methicillin-sensitive Staphylococcus aureus (MSSA) peritonitis, and culture-negative peritonitis in our tertiary center between July 2000 and July 2020. The diagnostic ability of the blood and PDE NLR for differential diagnosis was evaluated., Results: In total, 258 episodes, 38 episodes, and 27 episodes were caused by MSSA, TB, and NTM species, respectively; 364 episodes were culture negative. The PDE NLR level taken at presentation were lowest in the TB peritonitis, followed by the NTM, culture-negative, and MSSA groups, (9.44±13.01, 16.99±23.96, 36.63±32.33, 48.51±36.01; P <0.001, respectively). The area under the receiver operating characteristic curve for the NLR taken at presentation was 0.83 (95% confidence interval, 0.77 to 0.89; P <0.001). A PDE NLR <15 was an optimal cut-off value with sensitivity, specificity, positive predictive value, and negative predictive values of 81%, 70%, 97%, and 22%, respectively., Conclusions: The PDE NLR obtained at presentation is a useful and easily accessible marker to discriminate TB/NTM peritonitis from bacterial peritonitis, especially in areas with intermediate TB/NTM burden. The NLR may enable early prompting of TB/NTM peritonitis, allowing specific investigation and treatment to be instigated earlier., Competing Interests: C. Szeto reports having consultancy agreements with Baxter Healthcare and Gilead Science; reports receiving research funding from Baxter Healthcare, Fibrogen Inc., Fresnius, and Gilead; reports receiving honoraria from Baxter Healthcare; reports having an advisory or leadership role with Baxter Healthcare and Gilead Science; and reports having other interests or relationships with AstraZeneca and Pfizer. P. Li reports having consultancy agreement with (2019) Fibrogen; reports being the Co-Chair of the advisory board for Treatment of Anemia in Peritoneal Dialysis Patients: What is the Asia Pacific Experience?; reports receiving honoraria from AstraZeneca for being a moderator for a symposium during the Asian Pacific Congress of Nephrology October 2020 and from Baxter on Modern PD Symposium May 2021; reports having an advisory or leadership role with Kidney International and Peritoneal Dialysis International; reports being Co-Chair for Fibrogen Advisory Board Meeting on Anemia in PD Patients (2019); and reports other interests or relationships as Immediate Past President, Asian Pacific Society of Nephrology, President, International Association of Chinese Nephrologists, and President, Hong Kong College of Physicians. The remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Background: Peritonitis is a common and serious complication of peritoneal dialysis (PD). Translocation of gut bacteria to peritoneum is an important mechanism, which may be enhanced by gastrointestinal endoscopy., Methods: In this retrospective observational cohort study, we identified 450 gastroscopies performed in PD patients within a single centre between 2014 and 2019. Gastroscopy-related peritonitis was defined by peritonitis within 1 week after endoscopy., Results: A total of 408 endoscopic episodes in 216 patients were analysed after excluding 42 cases with either pre-existing peritonitis before endoscopy, or concomitant biliary, small bowel or large bowel endoscopy. There were 16 episodes of peritonitis within 1 week of endoscopy (3.9%). One-quarter of cases were polymicrobial (four episodes, 25.0%). Logistic regression model showed that patient's age, number of endoscopic biopsies, and histamine-2 receptor blocker use were independently associated with peritonitis, while prior antibiotics exposure was associated with lower risk of peritonitis, odds ratio 0.23 (95% confidence interval 0.06-0.95; p = 0.04)., Conclusion: Peritonitis can complicate gastroscopy in PD patients and occurs more often in elderly or after repeated biopsy procedures.

Background & Aims: Frailty and body composition contribute to adverse pre-transplant outcomes including hospitalization and waitlist mortality, but the interaction between frailty and body composition remains uncertain., Methods: Frailty was diagnosed by Clinical Frailty Scale (CFS) and a standard Frailty Questionnaire (FQ). Nutrition was evaluated by serum albumin level, subjective global assessment (SGA) and comprehensive malnutrition-inflammation score (MIS). Body composition was assessed by bioimpedance spectroscopy. All patients were followed up for three years. Primary outcome measure was a composite of death and permanent removal from waitlist. Secondary outcomes were emergency room attendance and hospitalization., Results: 432 prevalent peritoneal dialysis (PD) patients were recruited. 148 (34.3%) were listed on transplant waitlist. Frailty, age and comorbidity load predicted waitlisting. With time, 47 patients were delisted. Frailty by FQ (p = 0.028), serum albumin level (p = 0.005) and waist circumference (p = 0.010) predicted delisting after adjustment for confounders. Frailty significantly interacted with lean tissue wasting (FQ: p = 0.002, CFS: p = 0.048), and MIS (FQ: p = 0.004; CFS: p = 0.014) on delisting. Lean tissue wasting caused 2.56 times risk of delisting among frail individuals identified by FQ (p = 0.016), while serum albumin and the presence of diabetes mellitus predicted the risk of delisting among non-frail individuals. Lean tissue wasted and frail subjects had a higher all-cause and infection-related hospitalization., Conclusion: Frailty predicted both kidney transplant waitlisting and subsequent delisting. Frailty interacted with body composition on transplant waitlist delisting. Lean tissue wasting and malnutrition independently predicted delisting in frail and non-frail listed subjects respectively., Competing Interests: Conflict of interest Dr. CC Szeto receives research grant and consultancy from Baxter Healthcare. The authors declare no conflict of interest. The results of this article have not been published previously in whole or in part, except in abstract format., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Mitochondrial DNA (mtDNA) resembles bacterial DNA and potentially triggers local and systemic inflammation. We evaluate the prognostic implications of PD effluent mtDNA level in peritoneal dialysis (PD) patients., Methods: We measured mtDNA in the PD effluent (PDE) sediment and supernatant of 168 incident PD patients. All patients were followed for hospitalization, technique and overall survival., Results: The median PD effluent supernatant and sediment mtDNA levels were 255.4 unit (interquartile range [IQR] 157.5-451.3) and 201.6 unit (IQR 147.8-267.3), respectively. Serum C-reactive protein level closely with PDE sediment mtDNA level (r = 0.471, p < 0.001) and less with supernatant mtDNA level (r = 0.156, p = 0.044). PDE supernatant mtDNA level correlates with dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.361, p < 0.001) but not with any clinical outcome. PDE sediment mtDNA was an independent predictor of technique survival (p = 0.011) and the duration of hospitalization (p = 0.044) after adjusting for clinical confounding factors., Conclusions: PDE sediment mtDNA level significantly correlated with systemic inflammation, while PDE supernatant mtDNA level correlated with peritoneal transport. PDE sediment mtDNA level also independently predicted technique survival and duration of hospitalization. The mechanism of the different implications between PDE sediment and supernatant mtDNA levels deserves further investigations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The global prevalence of both obesity and end-stage kidney diseases (ESKDs) has increased in recent decades. Given the complicated interaction between obesity and ESKD, we examined the change in the prevalence of obesity in incident Chinese peritoneal dialysis (PD) patients over the past 25 years., Methods: We reviewed the anthropometric measures of incident PD patients in a single Hong Kong center from 1995 to 2019. The results are reported in five 5-year periods. Patients with and without diabetes were analyzed separately, and the incidence of new-onset diabetes after PD was explored., Results: We reviewed 1681 patients. Their mean age was 58.4 ± 12.5 years; 931 patients (55.4%) had pre-existing diabetes. From 1995-99 to 2015-19, the prevalence of obesity or overweight at the initiation of PD increased progressively for every 5-year period (from 21.9% to 26.2, 37.9, 42.7 and 47.3%, P < 0.001 for linearity). The increase in the prevalence of obesity or overweight was more pronounced in diabetic patients (from 33.7% to 59.6%) than non-diabetic ones (from 13.2% to 32.3%). Among nondiabetics patients, the incidence of new-onset diabetes after started on PD showed an insignificant rising trend during that period (from 18.0, 19.7, 17.8 and 22.4% to 23.3%, P = 0.106). The incidence of new-onset impaired fasting glucose or diabetes was significantly higher in obese or overweight patients than the others (56.9% versus 51.4%, P < 0.001)., Conclusions: The prevalence of obesity has increased substantially in both diabetic and nondiabetic new PD patients in Hong Kong over the past 25 years. The incidence of new-onset diabetes was significantly higher in new PD patients with pre-existing obesity or overweight than those without obesity. The prognostic implication and impacts on the healthcare system deserve further studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

CKD is a global problem that causes significant burden to the healthcare system and the economy in addition to its impact on morbidity and mortality of patients. Around the world, in both developing and developed economies, the nephrologists and governments face the challenges of the need to provide a quality and cost-effective kidney replacement therapy for CKD patients when their kidneys fail. In December 2019, the 3rd International Congress of Chinese Nephrologists was held in Nanjing, China, and in the meeting, a symposium and roundtable discussion on how to deal with this CKD burden was held with opinion leaders from countries and regions around the world, including Australia, Canada, China, Hong Kong, Singapore, Taiwan, the UK, and the USA. The participants concluded that an integrated approach with early detection of CKD, prompt treatment to slow down progression, promotion of home-based dialysis therapy like peritoneal dialysis and home HD, together with promotion of kidney transplantation, are possible effective ways to combat this ongoing worldwide challenge., Competing Interests: P.K.T.L. received speaker honorarium from FibroGen and AstraZeneca. W.H.L. received speaker honorarium from Alexion and Astellas and an education grant from Novartis. B.W.T. received honoraria, consulting or speaker fees, or travel support from Böhringer Ingelheim, Novartis, Astellas, Sanofi, Servier, M.S.D., Astra-Zeneca, and Otsuka. X.Q.Y. received research study supports from Baxter Healthcare Corporation, Wanbang company, Kyowa-Kirin, and AstraZeneca. G.S.K. and X.Q.Y. also acted as consultants for Fresenius Kabi, Baxter Healthcare Corporation, and AstraZe­neca. Z.H.L. and J.C.H. are working as editor-in-chief and associate editor, respectively, for Kidney Diseases, and P.K.T.L., J.H.C., and X.Q.Y. are editorial board members for Kidney Diseases., (Copyright © 2021 by S. Karger AG, Basel.)

Background: Relapsing and recurrent peritonitis episodes are major causes of technique failure in peritoneal dialysis (PD). We examined the efficacy of extended antibiotic therapy for the prevention of relapsing and recurrent peritonitis., Methods: From February 2016 to November 2018 we recruited 254 PD patients who fulfilled the diagnostic criteria for PD peritonitis. They were randomized to a standard group, with the duration of intraperitoneal (IP) antibiotic treatment following the International Society for Peritoneal Dialysis (ISPD) guideline according to the causative microorganisms, and an extended group, with 1 extra week of IP antibiotics. The primary endpoint was relapsing, recurrent or repeat peritonitis episodes within 6 months., Results: The primary endpoint developed in 36 and 29 patients of the extended and standard groups, respectively (28.3% versus 22.8%; P = 0.34). The rate of complete cure, without relapsing, recurrent or repeat peritonitis within 6 months, was 63.8 and 69.3% for the extended and standard groups, respectively (P = 0.35). Repeat peritonitis episodes were more common in the extended than the standard group (15.0% versus 5.5%; P = 0.013)., Conclusions: In patients with PD-related peritonitis, extending the antibiotic therapy for 1 extra week beyond the ISPD protocol should not be recommended. Extending the treatment does not reduce the risk of relapsing or recurrent peritonitis episodes but rather is associated with a higher risk of repeat peritonitis episodes., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Physical frailty contributes to adverse clinical outcomes in peritoneal dialysis (PD) patients. Little has been reported about frailty transitions in this population. We aimed to describe the transitions of frailty in PD patients and identify factors that predicted changes in frailty state., Methods: In a prospective observational study, we recruited 267 PD patients. Frailty was assessed by a validated frailty score. Depression was graded by PHQ-9 score, and nutritional status was evaluated by serum albumin, Subjective Global Assessment (SGA), and comprehensive Malnutrition Inflammation Score (MIS). The primary outcome was the change in frailty score at follow-up compared to baseline., Results: At baseline, 194 (72.7%) patients were classified as frail. With time, their frailty scores significantly increased (p < 0.001), and 93 of the surviving subjects (78.2%) were classified as frail. There was a modest significant correlation between change in MIS (p < 0.001), change in SGA score (p < 0.001), and change in PHQ-9 score (p < 0.001) with change in frailty score. An increase in PHQ-9 score (p < 0.001) and MIS (p = 0.001), as well as longer duration of hospitalization (p = 0.001), was independently associated with a greater change in frailty score after adjustment for confounding factors. Frailty score was also improved in patients who were converted to hemodialysis (p = 0.048) and received renal transplantation (p = 0.005)., Conclusion: Our findings suggested that frailty transitions were common in PD patients. Worsening in nutrition and depression, together with a longer duration of hospitalization, were associated with worsening in frailty., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: Frailty and obesity contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients, but the interaction between frailty and obesity remains uncertain., Objective: To examine the interaction between frailty and obesity on the clinical outcome of PD patients., Design: Single centre prospective observational cohort study., Patients: 267 prevalent Chinese PD patients were recruited., Measurements: Frailty was identified by a standard score. General and central obesity were determined by body mass index (BMI) and waist-hip ratio (WHR), respectively. Body composition was assessed by bioimpedance spectroscopy. All patients were followed for two years. Outcome measures included all-cause as well as cardiovascular mortality and hospitalization., Results: Of the 267 patients, 120 (44.9%) were frail. Frail individuals were more likely to have central obesity (p < 0.001) but not general obesity. Although WHR did not predict patient survival, there was a significant interaction between WHR and frailty on patient survival and cardiovascular survival (p = 0.002 and p = 0.038, respectively). For patients without frailty, the two-year cardiovascular survival was 91.3% and 74.4% for those with and without central obesity, respectively (p = 0.002). For patients with frailty, however, the two-year cardiovascular survival was 64.6% and 66.7% for those with and without central obesity, respectively (p = 0.6). For patients without frailty, the number of hospital admission for cardiovascular disease over 2 years were 0.12 ± 0.37 and 0.34 ± 0.72 for those with and without central obesity, respectively (p = 0.03). For frail patients, however, the number of hospital admission was similar between those with and without central obesity., Conclusion: There is a significant interaction between frailty and central obesity on the outcome of PD patients. The protective role of central obesity is only apparent in PD patients without frailty but not the frail ones, and there is a little prognostic value of general (non-central) obesity., Competing Interests: The authors declare no conflict of interest.

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.

Background: There is an increasing number of elderly patients on continuous ambulatory peritoneal dialysis (CAPD) who could not perform dialysis exchange themselves and require assistance. We examine the outcome of Chinese CAPD patients who required helper-assisted dialysis and compare the outcome between different types of helper., Methods: We reviewed 133 incident patients on helper-assisted CAPD and 266 incident patients who performed self-CAPD exchanges (self-peritoneal dialysis (PD) group). Outcome measures included patient survival, peritonitis-free survival, and overall peritonitis rate., Results: At 24 months, patient survival of the helper-assisted and self-PD groups were 56.0% and 80.6%, respectively ( p < 0.0001). Within the helper-assisted group, patient survival at 24 months was 55.5%, 63.2%, and 27.2% for the patients with domestic helper, family member, and nursing home staff as their helpers, respectively ( p = 0.037). Peritonitis-free survival of the helper-assisted and self-PD groups were 54.2% and 64.9%, respectively ( p = 0.039). Within the helper-assisted group, peritonitis-free survival at 24 months was 59.4%, 55.4%, and 37.2% for the patients with domestic helper, family member, and nursing home staff as their helpers, respectively ( p = 0.06). There was no significant difference in peritonitis rate between patients with domestic helper, family member, and nursing home staff as their helpers (0.54, 0.57, and 0.94 episodes per patient-year, respectively, p = 0.2)., Conclusions: Helper-assisted CAPD patients had worse patient survival and peritonitis-free survival than the self-PD group. Assistance by nursing home staff was associated with worse patients' survival and peritonitis-free survival than assistance by family members or domestic maids.

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.)

Traditionally, ingestion of alcohol-based hand rub solution results in isopropanol poisoning, which has a low toxicity. We describe a case of combined methanol and isopropanol intoxication by ingestion of alcohol-based hand rub solution. Metabolic acidosis was absent in our patient, presumably because formic acid production is blocked by isopropanol, which inhibits alcohol dehydrogenase. Our case highlights the importance of considering methanol intoxication in patients who ingested alcohol-based hand rub solution, even when there is no metabolic acidosis, and timely removal of the toxic alcohols by dialysis in these patients would prevent permanent retinal damage.
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