Jack Kit-Chung Ng

Circulating bacterial-derived DNA fragment level is a strong predictor of cardiovascular disease in peritoneal dialysis patients.

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

Urinary Mitochondrial DNA Level as a Biomarker of Acute Kidney Injury Severity

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

Inflammation and Peritoneal Dialysis.

Inflammation is one of the well-recognized nontraditional risk factors that contributes to the excessive cardiovascular mortality in peritoneal dialysis (PD) patients. Serum C-reactive protein and interleukin-6 levels are common surrogate markers used to measure inflammatory burden and predict adverse clinical outcomes in PD patients. Causes of inflammation are complex and can be categorized into factors related to a decrease in renal function and factors related to dialysis. They interact with each other and finally result in systemic and intraperitoneal inflammation. This review discusses the various causes and clinical implications of inflammation in PD patients. More importantly, potential therapeutic options that target the underlying pathogenic mechanisms are explored.

Frailty in Chinese Peritoneal Dialysis Patients: Prevalence and Prognostic Significance.

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 Charlsons comorbidity score (r = 0.40, p < 0.0001), Malnutrition Inflammation Score (r = 0.59, p < 0.0001), and inversely with Subjective Global Assessment score (r = -0.44, p < 0.0001). Frailty was closely associated with the need of hospitalization. Patients with nil, mild, moderate, and severe frailty required 2.4 ± 6.0, 1.6 ± 1.6, 2.7 ± 2.5, 5.2 ± 4.8 hospital admissions per year, respectively (p < 0.0001), and they stayed in hospital for 6.4 ± 9.2, 5.3 ± 6.2, 10.0 ± 10.4, 12.9 ± 20.1 days per hospital admission, respectively (p < 0.0001). However, Frailty Score was not an independent predictor of patient or technique survival. Conclusions: Frailty is prevalent among Chinese PD patients. Frail PD patients have a high risk of requiring hospitalization and their hospital stay tends to be prolonged. Early identification may allow timely intervention to prevent adverse health outcomes in this group of patients.

Relatives in silent kidney disease screening (RISKS) study: A Chinese cohort study

Family members of patients with end‐stage renal disease (ESRD) have higher risk for chronic kidney disease (CKD). Limited study has examined the risk of developing CKD in relatives of patients in earlier stages of CKD.

Causes of nephrotic syndrome and nephrotic-range proteinuria are different in adult Chinese patients: a single centre study over 33 years.

The reported causes of nephrotic syndrome (NS) varies between different countries. Less is known about the causes of nephrotic‐range proteinuria (NPU). We aimed to evaluate the underlying causes of NS and NPU.

Peritoneal dialysis effluent miR-21 and miR-589 levels correlate with longitudinal change in peritoneal transport characteristics.

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

Asymptomatic fluid overload predicts survival and cardiovascular event in incident Chinese peritoneal dialysis 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.

Peritoneal Dialysis Catheter Revision and Replacement by Nephrologist for Peritoneal Dialysis Catheter Malfunction

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

Depression and Physical Frailty Have Additive Effect on the Nutritional Status and Clinical Outcome of Chinese Peritoneal Dialysis

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.