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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.

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Background: Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis but complications and side-effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but it is inconsistently and infrequently measured in trials. We convened a consensus workshop on establishing a core outcome measure for life participation for use in all trials in kidney transplantation. Methods: Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from eight countries participated in six facilitated breakout group discussions. Transcripts were analyzed thematically. Results: Four themes were identified. Returning to normality conveyed the patients’ goals to fulfill their given roles (i.e. in their family, work, and community) and re-establish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of ‘life’ explicitly acknowledged life participation as a subjective concept that could refer to different activities (e.g. employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations post-transplant (e.g. due to complications and side-effects) distinguished between experiences in the first year post-transplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation. Conclusions: A feasible and validated core outcome measure for life participation is needed so critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision-making and care of recipients.

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

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

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

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.

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 Inflammation and fibrosis play important roles in the progression of diabetic nephropathy. We determine the urinary mRNA levels of ELR-CXC chemokine ligand and extracellular matrix in diabetic nephropathy. Methods We studied 26 patients with biopsy-proven diabetic nephropathy, 15 with hypertensive nephrosclerosis and 10 healthy controls. Urinary mRNA levels of CXCL9, CXCL10, CXCL11, collagen I A1 chain, collagen IV A3 chain and fibronectin were measured. Patients were followed for 36.9 ± 7.4 months to determine the rate of glomerular filtration rate (GFR) decline. Results Urinary mRNA levels of CXCL10 and CXCL11 are decreased, and those of collagen I A1 chain and fibronectin are increased in diabetic nephropathy. Baseline estimated GFR correlates with urinary mRNA level of CXCL9 (r = 0.583, p = 0.002) and CXCL11 (r = 0.703, p

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

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. .

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.

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

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

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

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

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

Aim Although calcimimetics cinacalcet can reduce parathyroid hormone level and control secondary hyperparathyroidism in end-stage renal disease patients, risk of vascular calcification remains high. Whether cinacalcet can further reduce vascular damage or arterial stiffness is unknown. Methods We studied the effect of cinacalcet in 33 peritoneal dialysis patients with inadequately controlled secondary hyperparathyroidism despite standard treatment. The primary outcome was the aortic pulse wave velocity at 26 and 52 months after cinacalcet treatment. The pulse wave velocity was compared with that of a matched control cohort of 37 peritoneal dialysis patients with secondary hyperparathyroidism. Results Thirty-three patients completed the cinacalcet treatment, after median dialysis duration of 1.0 year. Significant improvement of parathyroid hormone level was achieved after 52 weeks, from 87.5 ± 28.7 pmol/L to 34.5 ± 45.5 pmol/L (P

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.

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

Summary Background andobjectivesRelapsing andrecurrentperitonitisepisodesareimportantcausesoftreatmentfailure in patients undergoing peritoneal dialysis (PD). This study explored whether the level of bacteria-derived DNA fragment in PD effluent predicts the development of relapsing or recurrent peritonitis. Design, setting, participants, & measurements The study included 143 patients with PD peritonitis in a dialysis unit between September 2010 and December 2011. Every 5 days until antibiotic treatment ended, PD effluent was collected to determine bacteria-derived DNA fragment level, which is represented by the number of PCR cycles at which bacterial DNA could be detected. Patients were followed for the development of relapsing or recurrent peritonitis. Results Thirty-nine patients were excluded because of immediate treatment failure or incorrect diagnosis. Of the other 104patients, 15 (14.4%) developed relapsingperitonitis, 3(2.9%) had recurrent peritonitis,and 5(4.8%) had repeat episodes. Patients with relapsing or recurrent peritonitis episodes had significantly higher levels of bacterial DNA fragment in PD effluent than those without relapsing or recurrence, both 5 days before (31.963.4 versus 34.363.0 cycles; P=0.002) and on the day of (32.362.6 versus 34.161.7 cycles; P,0.001) completion of antibiotics.WhenbacterialDNAfragmentdetectableby34PCRcycles5daysbeforethecompletionofantibiotics isusedasthecutoff,ithasasensitivityof88.9%andspecificityof60.5%forthepredictionofrelapsingorrecurrent peritonitis. Conclusions Bacterial DNA fragment levels in PD effluent are significantly higher, both 5 days before and on the date of completion of antibiotics, among patients who subsequently develop relapsing or recurrent peritonitis than among those cured by antibiotics. Further studies are needed to validate these results and confirm the clinical utility of dialysate bacterial DNA fragment level. Clin J Am Soc Nephrol 8: ccc–ccc, 2013. doi: 10.2215/CJN.02360213

BACKGROUND: Endotoxemia is common in peritoneal dialysis (PD) patients, and circulating lipopolysaccharide (LPS) level is related to the degree of systemic inflammation and atherosclerosis. We hypothesize that circulating bacterial DNA, another microbial component, correlates with the degree of systemic inflammation and predicts the survival of new PD patients. METHODS: We measured the plasma bacterial DNA level in the archive blood samples of 300 consecutive new PD patients. The result was compared with serum C-reactive protein (CRP) level, patient survival and peritonitis-free survival. RESULTS: The average age was 57.8 ± 12.1 years, average plasma bacterial DNA level 34.3 ± 1.3 cycles and average follow-up 37.9 ± 22.2 months. The plasma bacterial DNA level correlated with serum CRP (r = 0.565, P < 0.001) and LPS levels (r = 0.224, P = 0.029). At 36 months, the patient survival were 77.5, 78.3, 74.6 and 65.2% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (log-rank test, P = 0.034). By multivariate analysis with the Cox proportional hazard model to adjust for confounders, the plasma bacterial DNA level had no independent effect. Similarly, peritonitis-free survival were 60.6, 59.8, 60.3 and 50.4% for plasma bacterial DNA level quartiles I, II, III and IV, respectively, at 36 months (P = 0.020), and the difference was not significant after adjusting for confounding factors. CONCLUSION: We found that the plasma bacterial DNA level correlated with the degree of systemic inflammatory state in PD patients. Although plasma bacterial DNA level seems to predict patient survival and peritonitis-free survival, the association disappears after adjusting for confounding factors. Further prospective studies are needed to delineate the role of plasma bacterial DNA as a prognostic marker of renal failure patients.

Aim To compare the clinical outcome between continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) in specific subgroups of patients. Methods We reviewed the clinical outcome of 90 consecutive incident APD patients and 180 CAPD patients in our centre. Results The median follow up was 21.9 months (inter-quartile range, 9.5 to 46.5 months). The APD group was younger and had a lower Charlson's score than the CAPD group. Furthermore, the APD group had a highly skewed distribution of the Charlson's score, indicating the possibility of two different groups of patients. Multivariate analysis showed that in addition to the treatment mode (APD vs CAPD) and Charlson's score, there was a significant interaction between the two (P = 0.043) on patient survival. For patients with Charlson's score ≤6, the APD group had a significantly better patient survival than the CAPD group (78.3% vs 65.4% at 5 years, P = 0.039), while for patients with Charlson's score ≥7, the APD group had a worse patient survival than the CAPD group (16.3% vs 48.4% at 5 years, P = 0.028). Similarly, Charlson's score and its interaction with treatment mode, but not the APD group per se, were independent predictors of technique survival (P = 0.013). For patients with Charlson's score ≥7, the APD group had a significantly lower technique survival than the CAPD group (8.8% vs 34.3%, P = 0.001), while for patients with Charlson's score ≤6, the technique survival was similar (44.4% vs 42.5%, P = 0.15). Peritonitis-free survival was 35.2% and 32.2% for APD and CAPD groups, respectively (P = 0.021), and the difference was not affected by Charlson's score. Conclusions Comorbid diseases had a significant interaction with the mode of PD on patient and technique survival of incident PD patients. Our result suggests that APD may offer benefit in, and only in, young patients with minimal comorbid diseases.

Background MicroRNAs are a group of non-coding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigate the urinary sediment miRNA levels of adult patients with nephrotic syndrome. Methods We study 20 patients with diabetic glomerulosclerosis (DGS), 21 with minimal change nephropathy (MCN) or focal glomerulosclerosis (FGS), 23 with membranous nephropathy (MGN), and 10 healthy controls. Urinary sediment miRNA levels are quantified. Results Urinary sediment miR-29a, miR-192, and miR-200c levels were significantly different between diagnosis groups. Post hoc analysis showed that urinary miR-638 level was significantly lower in all causes of nephrotic syndrome than healthy controls, while the DGS group had lower urinary miR-192 level than other diagnosis groups. In contrast, the MCN/FGS group had higher urinary miR-200c level than other diagnosis groups. For each specific pathology group, urinary level of several miRNA targets significantly correlated with kidney function and histological scarring. Conclusions Urinary miR-29a, miR-192 and miR-200c levels have characteristic alterations among patients with different causes of nephrotic syndrome. Our results suggest that urinary miRNA levels have the potential of being developed as the diagnosis tool and marker of disease severity in adult nephrotic syndrome.

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

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 4 h (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.

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

Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count.

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

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

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline published by the expert panel addresses the treatment approach to IgA nephropathy. The KDIGO Work Group commissioned a systematic review of randomized trial evidence, evaluated the evidence, made recommendations, indicated the level of evidence supporting those recommendations, used GRADE methodology, and reported conflicts of interest. This provides important guidance for the care of patients with IgA nephropathy, with emphasis on treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers to decrease proteinuria. The treatment goal of blood pressure depends on the level of proteinuria ( 1 g/day and

Aim: We aimed to gain an understanding of patient concerns while on a transplantation waiting list in areas with long transplant waiting time. Methods: The study population comprised patients with organ failure on the transplant waiting list in Hong Kong. They were invited to complete a questionnaire survey. Demographic data and waiting time were collected. Respondents rated their chance of getting transplanted, their subjective concerns and feelings, level of happiness and support received. Results: A total of 442 patients on the waiting list for kidney, liver, lung and heart-lung transplants completed the questionnaire survey. The majority of patients (93.0%) were waiting for kidney transplantation. More than half of the respondents (63.3%) had been waiting for more than 3 years. Patients with longer transplant waiting times had lower self-estimated chance of receiving a transplant (P = 0.004). Self-estimated chance of getting transplanted was positively associated with the happiness score (P

Aim: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can counteract inflammation and atherosclerosis, both common causes of morbidity in peritoneal dialysis (PD) patients. We examined the relation between serum soluble TRAIL (sTRAIL) levels and the outcome of Chinese PD patients. Methods: We studied 116 new PD patients (67 males, age 56.7 ± 13.4 years). Baseline serum sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest). All patients were followed for 20.9 ± 7.0 months. Results: Patient survival was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months (P = 0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was an independent predictor of patient survival after adjusting for confounding factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935–0.991, P = 0.010). Conclusion: A higher baseline serum sTRAIL level was associated with a better survival of PD patients. The detailed mechanism deserves further investigation.

Aim: MicroRNAs (miRNAs) play important roles in the pathogenesis of autoimmune diseases. We studied the intra-renal expression of miRNA targets that were reported to be differentially expressed in peripheral blood or urine between lupus nephritis (LN) patients and normal controls. Methods: We quantified the expression of in glomerulus and tubulointerstitium of miR-146a, miR-155, miR-198 miR-638 and miR-663 in 42 patients with LN and 10 healthy controls. Results: As compared with controls, LN patients had lower glomerular expression of miR-638 (P

Summary Background/Purpose Human oxoguanine-DNA glycosylase 1 (hOGG1) is the enzyme that has DNA repairing capacity. C1245 G substitution of the hOGG1 gene results in reduced enzyme activity. Peritoneal dialysis (PD) is known to cause oxidative DNA damage. We investigated the effect of hOGG1 polymorphism on the clinical outcomes of PD patients. Methods We studied the hOGG1 polymorphism in 441 new PD patients (232 men, age 56.6 ± 13.5 years). The patients were followed for 41.4 ± 18.2 months for cardiovascular events. Results For the entire cohort, there was no significant difference in the 5-year event-free survival between the CC and CG/GG groups (42.9% vs. 33.2%; p = 0.1). However, for patients with baseline serum C-reactive protein (CRP) levels ≤ 5.0 mg/L, 5-year event-free survival of the CC group was significantly better than that of CG/GG group (50.3% vs. 31.9%, p = 0.046). Multivariate analysis showed that hOGG1 polymorphism was an independent predictor of the survival (p = 0.008). In contrast, for patients with baseline CRP > 5.0 mg/L, there was no significant difference in 5-year event-free survival between the CC and CG/GG groups (26.7% vs. 30.2%, p = 0.9). Conclusion In PD patients with no systemic inflammation, hOGG1 1245CC genotype confers a survival benefit as compared to CG or GG genotype, but the protective effect disappears in patients with systemic inflammation. Our results suggest a complex interaction between hOGG1 and inflammation in the pathogenesis of cardiovascular disease in PD patients. 背景 人類oxoguanine-DNA glycosylase 1 (hOGG1)是一種具DNA修復能力的酵素，其酵素活動在hOGG1基因的C1245G替換後會有所下降。此外，腹膜透析(PD)已知會導致DNA的氧化性損害。本研究調查了hOGG1多態性對PD患者的影響。 方法 研究人員對441位剛開始接受PD的病人(男232人, 年齡56.6 ± 13.5歲)，作出hOGG1多態性的調查，並對心血管事件的發生進行共41.4 ± 18.2個月的追蹤。 結果 在整體病人中，CC與CG/GG組別之間在5年無事件存活率上無明顯差異(42.9% vs. 33.2%, p = 0.1)；然而，在基線血清C-反應蛋白(CRP)水平 ≤ 5.0 mg/L的病人中，CC組的5年無事件存活率明顯高於CG/GG組(50.3% vs. 31.9%, p = 0.046)。多變數分析顯示，hOGG1多態性是存活的獨立預測因子(p = 0.008)。相反，在基線CRP > 5.0 mg/L的病人中， CC與CG/GG組別之間在5年無事件存活率上並無明顯差異(26.7% vs. 30.2%, p = 0.9)。 結論 在不具系統性發炎的PD患者間，相比於CG或GG基因型，hOGG1 1245CC基因型具備若干的存活效益，但其效益並未出現於系統性發炎患者間。這些結果意味著，在PD患者的心血管致病過程中，hOGG1與發炎之間存在著複雜的交互關係。

Background Systemic lupus erythematosus (SLE) is characterized by disease flares and remission. We hypothesize that in clinically quiescent SLE patients, the mRNA level of target genes in the urinary sediment is an early indicator of disease flare. Methods From a cohort of 134 adult SLE patients prospectively followed for 56 weeks, we identified 19 patients with a single disease flare. The mRNA level of eight pre-defined target genes in their urinary sediment before disease flare was compared to 19 matched controls with no disease flare during the same period. Results Urinary mRNA level remained static in the control group during the study period. Before disease flare, there was a significant increase in the mRNA level of monocyte chemotactic protein (MCP)-1and forkhead box P3 (FOXP3), and decrease in interleukin (IL)-17 and GATA-3, in the urinary sediment. The mRNA level of FOXP3 in urinary sediment increases 8 weeks prior to a flare, which precedes the corresponding change in serum complement and anti-DNA antibody titer, while that of MCP-1, IL-17, and GATA3 began to change 4 weeks prior to a flare. The same pattern of change in urinary mRNA level was observed in patients with mild-to-moderate or severe flare, and those with renal or non-renal flare. The SLE Disease Activity Index (SLEDAI) score at the time of flare significantly correlated with the change in urinary level of IL-17 (r = − 0.462, p = 0.046) and GATA-3 (r = − 0.455, p = 0.05), but not MCP-1 or FOXP3, prior to the flare. Conclusion Monitoring of MCP-1, IL-17, GATA-3 and FOXP3 mRNA level in urinary sediment may provide an early clue for detecting disease flare in SLE patients.

Objective: In 2009, 1659 patients with end-stage renal failure in Hong Kong were waiting for a renal transplant. The overall number of renal transplants carried out locally remains low, with an even lower number being live donor donations. Yet, live donor kidney transplantation yields results that are consistently superior to those of deceased donor kidney transplantation, and laparoscopic donor nephrectomy (LDN) is increasingly accepted worldwide as a safe and preferred surgical option. We aim to evaluate the outcome of LDN in our setting, and to compare with that of deceased donors in this retrospective review. Patients and Methods: A total of 12 patients received LDN over the study period of 2006–2009. Standard left transperitoneal LDN was carried out. Grafts including three with double vessels were prepared using the bench technique. The postoperative outcomes up to 1 year for both the donors and the recipients were studied. Contemporary results for the 47 deceased donor kidneys were studied and compared. Results: All donors had an eventful recovery. The operating time was 225.0 ± 67.4 min. The hospital stay was 5.6 ± 2.3 days. The recipient outcomes including hospital stay and creatinine levels at discharge and 1 year were 11 days, 121 umol/L and 116 umol/L, respectively. Specifically, no ureteric stricture or graft loss was noted at the 1-year follow up. Recipient complications included haematoma (1 patient), renal artery stenosis (1 patient) and redo of vascular anastomosis (1 patient). In contrast, the deceased donor graft recipients had a hospital stay of 11 days, and creatinine levels of 205 umol/L on discharge and 205 umol/L at 1 year, respectively. The delayed graft function rates for the live donor and deceased donors group were 0% and 14.9%, whereas the 1-year graft survival rates were 100% and 87.2% respectively. Conclusion: The results showed that the donor morbidity rate was low, as reflected by the short hospital stay. Also, the overall parameters of recipients were good. In particular, no ureteric stricture was noted, and graft survival was 100% at 1 year. Living donor kidney transplant program using the laparoscopic technique is a viable option to improve the pool of kidneys for transplantation.

Background: In addition to the control of gene translation intra-cellularly, microRNAs (miRNAs) have been found to exist extracellularly. However, extracellular miRNA identified in previous studies were largely confined to microvesicles. It remains uncertain whether free extracellular miRNA exists. Methods: We quantify a panel of miRNAs (miRNA 200 family, miR-205, and miR-192) in spent culture medium of renal tubular epithelial cells, as well as serum and urine from patients with systemic lupus erythematosus and healthy controls. Microvesicle bound and free miRNA were separated by ultracentrifugation. Results: In spent cell culture medium, we found substantial amount of miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-205, and miR-192 in microvesicles, as well as the presence of miR-200a, miR-200b, miR-429, miR-205 and miR-192, but not miR-200c or miR-141 as nonvesicle bound free form. In healthy individuals, we found substantial amount of miR-200a, miR-200b, miR-200c, miR-141 and miR-192 in microvesicles from serum and urine, while only miR-141 exists as free form in both serum and urine. There was no significant difference in serum or urinary free miR-141 levels between SLE patients and healthy controls. In SLE patients, urinary free miR-141 level was significantly higher than serum. Neither serum nor urinary free miR-141 levels correlated with lupus disease activity. Conclusion: We found miRNA is present extracellularly, both within microvesicles and as free form, in spent cell culture medium, serum and urine. The biological role of extracellular miRNA requires further study.

Background: Cell-free microRNAs (miRNAs) exist in body fluid. Previous studies showed that cell-free mi-RNAs are partly bound in microvesicles, and could transfer between cells via fusion with cell membrane. Methods: We quantified the amount of a panel of mi-RNA targets in and outside microvesicles in human proximal tubular epithelial cell (HK2) medium by microarray and real-time quantitative polymerase chain reaction (RT-QPCR). Intercellular miRNA transfer was explored by medium transfer experiments. Results: We identified a portion of cell-free miRNAs that exists as non-vesicle bound, truly naked form. More importantly, these non-vesicle bound free miRNA could transfer between cells and exert biological effects. By miRNA microarray, we showed that the expression of many miRNA targets in HK-2 cells were altered, either up- or down-regulated, after exposure to extrinsic free miRNAs. The miRNA-200 family was the most affected in our model, with a corresponding alteration in the messenger RNA expression of down-stream targets including ZEB1 and vimentin. Conclusion: Our results suggest that free miRNA may serve as an intercellular messenger, a phenomenon that needs further exploration.

Background: Myeloid-related protein 8/14 (MRP8/14) is released by cells of myeloid lineage upon inflammatory challenges. Experimental data suggested that MRP8/14 is important in the initiation and progression of inflammation and cardiovascular diseases. We examined the relation between serum MRP8/14 level and cardiovascular disease in Chinese peritoneal dialysis (PD) patients. Methods: We studied 102 new PD patients (58 males, mean age 57.3 ± 11.9 years). Baseline serum MRP8/14 was determined and grouped to quartiles for analysis. All patients were then followed for an average of 23.9 ± 6.9 months. Results: There was a trend of lower 3-year cardiovascular event-free survival for patient quartiles with high serum MRP8/14 levels (log-rank test, p = 0.064). The 3-year actuarial survival was significantly lower for quartile groups with higher MRP8/14 levels (96.0, 94.7, 72.9, and 62.5% for quartiles 1–4, respectively, p = 0.003). Cox regression analysis showed that serum MRP8/14 level and Kt/V were independent predictors of actuarial survival; in this model, every 1 µg/ml increase in serum MRP8/14 level confers a 25.1% increase in risk of death (95% confidence interval, 1.3–54.4%, p = 0.037). There was no significant difference in technique survival between the MRP8/14 quartile groups. Conclusion: A high baseline serum MRP8/14 level was associated with a lower actuarial survival in Chinese PD patients. The pathogenic role of MRP8/14 in the cardiovascular disease of PD patients needs further investigation.

Background: MicroRNAs (miRNAs) play important roles in the progression of renal fibrosis. We studied the urinary levels of miR-21, miR-29 family and miR-93, which are downstream mediators of the transforming growth factor-β1 (TGF-β1), in patients with immunoglobulin A (IgA) nephropathy. Methods: We studied the urinary miRNA levels of 43 IgA nephropathy patients and 13 healthy controls. Results: The IgA nephropathy group had significantly lower urinary miR-29b and miR-29c, but higher miR-93 levels than controls. Proteinuria significantly correlated with urinary levels of miR-29b (r = –0.388, p = 0.003) and miR-29c (r = –0.409, p = 0.002). Glomerular filtration rate significantly correlated with urinary levels of miR-21 (r = 0.338, p = 0.028), miR-29b (r = 0.333, p = 0.031) and miR-29c (r = 0.304, p = 0.050). Urinary miR-93 level significantly correlated with glomerular scarring (r = –0.392, p = 0.010). Urinary miRNA level of SMAD3, but not TGF-β1, correlated with urinary miR-21 (r = 0.624, p < 0.001), miR-29b (r = 0.566, p < 0.001), miR-29c (r = 0.619, p < 0.001) and miR-93 (r = 0.332, p = 0.032). Conclusions: Urinary miR-29b and miR-29c levels correlated with proteinuria and renal function, while urinary miR-93 level correlated with glomerular scarring. More importantly, urinary levels of these miRNA targets significantly correlated with urinary SMAD3 level. Our results suggest that these miRNA targets are regulated by the TGF-β1/SMAD3 pathway and they may play important roles in the development of progressive renal fibrosis in IgA nephropathy.

This Review focuses on the changing epidemiology of infections among patients with end-stage renal disease who are undergoing dialysis. In particular, bloodstream infections related to vascular access in patients undergoing hemodialysis, and peritonitis in patients undergoing peritoneal dialysis, are highlighted. Gram-positive (staphylococcal and enterococcal) bloodstream infections and Gram-negative peritonitis (especially extended-spectrum β-lactamase-producing organisms) contribute substantially to excess health-care use owing to infection caused by dialysis access. Although the management of peritoneal-dialysis-related peritonitis has been hampered by a dearth of randomized, controlled studies, epidemiological data have provided useful information. To overcome the problem of differing methods used to monitor infections within various dialysis centers, uniform reporting systems for vascular-access-related infection and peritoneal-dialysis-related peritonitis, as recommended by the Centers for Disease Control and Prevention and the International Society for Peritoneal Dialysis, respectively, are discussed. Infections unrelated to the port of entry for dialysis are also examined, namely hepatitis and respiratory infection. To address the disease burden, we examine the infection-related mortality as well as the implications for subsequent cardiovascular mortality.

Aim: Long term dialysis is life-saving for patients with end stage renal disease (ESRD). However, in ESRD patients with multiple comorbid conditions, dialysis may actually be futile, and conservative management is advisable. We studied the life expectancy of Chinese ESRD patients treated conservatively. Methods: We reviewed 63 consecutive ESRD patients who were treated conservatively in our centre. Duration of survival was calculated from the date of initial assessment for dialysis, as well as the expected date of needing dialysis based on previous trend of renal function decline. Results: At the end of the observation period, 55 patients died. Twelve patients died before the expected date of needing dialysis because of unrelated reasons, while 36 deaths were directly attributed to uraemia. The median overall survival after initial assessment for dialysis was 41.3 months (95% confidence interval (CI), 33.2 to 49.4 months). The median overall survival was 6.58 months (inter-quartile range, 0.92 to 9.33 months) from the theoretical date of needing dialysis. The survival from the theoretical date of needing dialysis did not correlate with patient age, sex, diabetic status, or baseline renal function. Conclusions: In Chinese ESRD patients treated conservatively, the median survival is around 6 months after the theoretical date of needing dialysis. Our result provides an important piece of information for the decision of dialysis and patient counselling.