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Abstract Background Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still’s disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing. Case presentation A 42 years old man was admitted with suspected adult-onset Still’s disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still’s disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml). Conclusion Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.

Abstract 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.

Rationale & Objective: Staphylococcus lugdunensis (S lugdunensis) is a coagulase-negative staphylococcus species that has been increasingly recognized to cause serious infections with virulence resembling Staphylococcus aureus (S aureus). No studies have evaluated the characteristics and outcomes of patients with S lugdunensis peritoneal dialysis-related peritonitis compared with those with S aureus peritonitis. We aim to evaluate the clinical course of peritonitis as caused by these organisms. Study Design: A retrospective matched comparative analysis involving a single tertiary center from July 2000 to July 2020. Setting & Participants: Forty-eight episodes of S aureus peritonitis were matched to 19 cases of S lugdunensis peritonitis. Analytical Approach: The cases were individually matched for year of peritonitis, sex, age (±10 years), and Charlson Comorbidity Index (±3). A comparative analysis was performed between the 2 organisms. The outcome includes responses at day 5 of peritonitis and the rate of complete response. Results: There is a higher predilection of diabetes in those with S aureus peritonitis than in those with S lugdunensis (64.6% vs 31.6%; P = 0.03). Patients with S aureus peritonitis also have a much higher total cell count at presentation (4,463.9 ± 5,479.5 vs 1,807.9 ± 3,322.7; P = 0.05); a higher prevalence of poor response at day 5 (50.0% vs 15.8%; P = 0.03); a lower rate of complete response (64.6% vs 94.7%; P = 0.01) and are more prone to relapse with the same organism (29.2% vs 0%, respectively; P = 0.01) as compared to those with S lugdunensis. Limitations: The result of this small retrospective study involving a single center may not be generalizable to other centers. There is also no data for comparative analysis on other coagulase-negative staphylococci such as Staphylococcus epidermidis, which belongs to the same family as S lugdunensis. Conclusions: Although S aureus peritonitis is more virulent with significant morbidity, S lugdunensis can cause similarly serious peritonitis. This largest case series of S lugdunensis peritonitis enabled better characterization of clinical features and outcomes of patients with S lugdunensis peritonitis. Plain Language Summary: Staphylococcus lugdunensis is a coagulase-negative staphylococcus species that has been increasingly recognized to cause serious infections with virulence resembling Staphylococcus aureus. No studies have evaluated the characteristics and outcomes of patients with S lugdunensis peritoneal dialysis-related peritonitis compared those with S aureus peritonitis. This largest retrospective matched comparative analysis of S lugdunensis peritonitis enabled better characterization of clinical features and outcomes of patients with S lugdunensis. Our result suggested that although S. aureus peritonitis is more virulent with significant morbidity, S lugdunensis can cause similarly serious peritonitis. Regardless, S lugdunensis remains susceptible to most antibiotics and penicillin group, penicillin G in particular, can be considered as the first line antibiotic.

Abstract 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

Background: Recombinant human erythropoietin (rHuEPO) is an effective treatment for renal anemia. Recently, there is evidence to suggest that rHuEPO may reduce podocyte injury in diabetic kidney disease (DKD). However, there is no published study on the change in podocyte injury marker levels before and after rHuEPO treatment in DKD. Methods: We measured serum nephrin and podocalyxin level, and their corresponding plasma mRNA levels, in 49 DKD patients before rHuEPO treatment, and then 12 and 36 weeks afterward. Results: There were reductions in serum nephrin (p = 0.002) and podocalyxin levels (p = 0.09), as well as their corresponding plasma mRNA levels (p

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.

Abstract 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

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.

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

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%, to 4.0 ± 10.3% for each 5-year period, respectively (p for linearity 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 multi-variable 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 the 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 two 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 a worse patient survival subsequently.

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

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.

Air and surface contamination of the SARS-CoV-2 have been reported by multiple studies. However, the evidence is limited for the change of environmental contamination of this virus in the surrounding of patients with COVID-19 at different time points during the course of disease and under different conditions of the patients. Therefore, this study aims to understand the risk factors associated with the appearance of SARS-CoV-2 through the period when the patients were staying in the isolation wards. In this study, COVID-19 patients admitted to the isolation wards were followed up for up to 10 days for daily collection of air and surface samples in their surroundings. The positivity rate of the environmental samples at different locations was plotted, and multiple multi-level mixed-effect logistic regressions were used to examine the association between the positivity of environmental samples and their daily health conditions and environmental factors. It found 6.6 % of surface samples (133/2031 samples) and 2.1 % of air samples (22/1075 samples) were positive, and the positivity rate reached to peak during 2–3 days after admission to the ward. The virus was more likely to present at bedrail, patients’ personal items and medical equipment, while less likely to be detected in the air outside the range of 2 m from the patients. It also revealed that higher positivity rate is associated with lower environmental temperature, fever and cough at the day of sampling, lower Ct values of latest test for respiratory tract samples, and pre-existing respiratory or cardiovascular conditions. The finding can be used to guide the hospital infection control strategies by identifying high-risk areas and patients. Extra personal hygiene precautions and equipment for continuously environmental disinfection can be used for these high-risk areas and patients to reduce the risk of hospital infection.

Background It is believed that the excessive cardiovascular (CV) burden of patients on peritoneal dialysis (PD) is closely associated with chronic inflammation. Neutrophil-lymphocyte ratio (NLR) is an inflammatory marker that was shown to correlate with CV outcomes. However, little is known about the significance of serial monitoring of serum NLR. We aimed to determine the prognostic value of serial NLR on all-cause mortality and CV mortality in PD patients. Methods Serial measurement of NLR was obtained from 225 incident PD patients in a single center, with each measurement one year apart. Patients were divided into two groups (‘high’ versus ‘low’) by the median value of NLR. The primary and secondary outcome measure was all-cause and CV mortality respectively. Results After a median of follow up for 43.9 months, patients with lower baseline NLR demonstrated a higher survival rate (p=0.01). Patients with persistently high NLR values on serial measurement had the lowest survival rate (p=0.03). Multivariate Cox regression showed that this group of patients had significantly higher all-cause mortality (HR 1.74, 95%CI 1.09 to 2.79, p=0.02). However, the NLR failed to demonstrate a statistically significant relationship with CV mortality. Conclusions While baseline NLR was an independent predictor of all-cause mortality in PD patients, persistent elevation in NLR appeared to further amplify the risk. Regular monitoring of serial serum NLR may enable early identification of patients who are at risk of adverse outcome.

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.

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 < 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.

Abstract 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: 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.

Abstract 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.

Rationale & Objective: Previous studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN). Study Design: Prospective cohort study. Setting & Participants: 40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls. Predictors: miR-21 levels in kidney biopsy specimen and urinary sediment, quantified as ratio to the housekeeping gene. Outcomes: Kidney event–free survival and rate of kidney function decline. Analytic Approach: Time-to-event and correlation analysis. Results: The IgAN group had significantly higher intrarenal miR-21 expression compared with the hypertensive nephrosclerosis group (1.71 [IQR, 0.99-2.77] vs 0.31 [IQR, 0.25-1.32]; P

BackgroundFrailty and obesity contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients, but the interaction between frailty and obesity remains uncertain.ObjectiveTo examine the interaction between frailty and obesity on the clinical outcome of PD patients.DesignSingle centre prospective observational cohort study.Patients267 prevalent Chinese PD patients were recruited.MeasurementsFrailty 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.ResultsOf 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.ConclusionThere 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.

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.

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 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.

Background: Chronic kidney disease (CKD) continues to be a significant global public health issue. The escalating burden of CKD is probably driven by the aging population and the rising prevalence of diabetes. CKD not only adversely impacts an individual’s health and well-being, but also poses significant challenge on the economy of the society. Summary: Experts from ten countries and regions around the world (Australia, Canada, China, Hong Kong, Malaysia, New Zealand, Singapore, Taiwan, United Kingdom, and United States) convened in the 4th International Congress of Chinese Nephrologists on December 1, 2023 to discuss the global dialysis burden. Although the cost of kidney replacement therapy (KRT) accounts for 2–3% of total healthcare expenditure in developed countries, patients with end stage kidney disease (ESKD) only represent a small percentage (

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 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.

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.

Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied.We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV.After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001).Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study.ClinicalTrials.gov NCT00966615.

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.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.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).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.

Laboratory research and previous study suggest that aliskiren, a direct renin inhibitor, has anti-proteinuric effects. We conducted a randomized crossover study to evaluate the anti-proteinuric effect of aliskiren in patients with immunoglobulin A (IgA) nephropathy.We studied 22 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to either oral aliskiren 300 mg/day or placebo for 16 weeks and then crossed over to the other treatment arm after a washout period. Proteinuria, estimated glomerular filtration rate (eGFR), blood pressure, and serum potassium were monitored.After aliskiren treatment, there was a significant reduction in proteinuria in 4 weeks (1.76±0.95 to 1.03±0.69 g:g-Cr, p

The scarcity of donor organs for transplant results in long waiting times for kidney transplantation and low transplant rate worldwide. Utilization of kidneys from donors with acute kidney injury (AKI) is one of the strategies that has attracted attention recently. This article reviewed the outcomes of transplanted renal allografts from donors with acute kidney injury. Key findings about the transplant outcomes included a higher incidence of delayed graft function and primary non function, but respectable outcomes in the context of similar acute rejection rates, and graft function and graft survival. Against this background and with evidence of high mortality for patients remaining on waiting list of transplant, we advocate consideration of AKI donors for kidney transplantation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 m2. 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 m2 per year in the year before everolimus, as compared with 1.29±5.84 mL/min/1.73 m2 per year in the 12 months of everolimus therapy, a difference of 5.61 mL/min/1.73 m2 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. [ABSTRACT FROM AUTHOR]

Background A territory-wide diabetes management program (Risk Assessment Management Program - RAMP) was recently established, providing comprehensive management for all diabetics, helping to delineate current level of control and complications prevalence among primary care diabetic patients in Hong Kong. Method This cross-sectional study captured anonymous clinical data from RAMP patients. Data obtained include sociodemographic details, type of diabetes, illness duration, family history, drug usage, coexisting illnesses, diabetic complications and other clinical parameters. Results Data from 15,856 type 2 diabetic patients were analyzed. 57.1% were above 60 years old, with mean disease duration of 7.3 years. Hypertension was the commonest coexisting chronic illness (57.6%). 30.2% and 61.8% have their systolic and diastolic pressure controlled to below 130 mmHg and 80 mmHg respectively. Over half (51.5%) had an HbA1c level of less than 7.0%. 88.4% did not achieve target lipid level. 15% were on diet control alone . Only 22.2% were on statins. In patients with microalbuminuria and macroalbuminuria, 40.7% and 54.5% were on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) respectively. 12.9%, 38.8% and 2.4% had diabetic retinopathy, nephropathy and neuropathy respectively. Overall, 37.9%, 7.3% and 0.4% had single, two and three concurrent microvascular complications respectively. Conclusion The level of diabetic control is comparable with other developed countries. We demonstrated a high prevalence of microvascular complications among Chinese primary care patients despite achieving adequate HbA1c levels, highlighting the importance of managing all aspects of diabetes including weight, lipid and blood pressure. Efforts to improve holistic management must be tailored according to the needs of our population, with the challenges that the majority have low educational background and in the older age group. [ABSTRACT FROM AUTHOR]