Yu-Jen Su

Mitochondrial DNA copy number correlates with oxidative stress and predicts mortality in nondiabetic hemodialysis patients

BACKGROUND Oxidative stress is highly prevalent in hemodialysis patients and may contribute to atherosclerosis and mortality. The copy number of mitochondrial DNA (mtDNA) is affected by oxidative stress in blood circulation. This study aimed to test whether mtDNA copy number correlates with oxidative stress and predicts all-cause mortality in nondiabetic hemodialysis patients. METHODS Ninety-five nondiabetic hemodialysis patients and 95 healthy subjects were enrolled. Plasma thiobarbituric acid-reactive substances (TBARS) and plasma free thiol were used as indicators of oxidative stress and antioxidant defense, respectively. Mitochondrial DNA copy number in peripheral blood leukocytes was measured by determining relative amounts of mtDNA to nuclear DNA by quantitative real-time PCR. All-cause mortality of hemodialysis patient was recorded during a follow-up of 3 years. RESULTS Nondiabetic hemodialysis patients showed higher TBARS levels, lower free thiol levels and higher mtDNA copy numbers compared with normal control subjects. The plasma TBARS level was a significant factor correlating positively to the mtDNA copy number (p=0.024). Patients with a mtDNA copy number higher than the median had a higher all-cause mortality than patients with a lower mtDNA copy number (17.0% vs. 4.2%; log-rank test: p=0.038). A 1-log increase in mtDNA copy number was independently related to an increase in the risk for mortality (hazard ratio 21.360; 95% confidence interval, 1.298-351.572). CONCLUSIONS Nondiabetic hemodialysis patients had higher oxidative stress and mtDNA copy numbers than healthy subjects. The mtDNA copy number correlates with oxidative stress and predicts mortality in nondiabetic hemodialysis patients.

Relationship between Kt/V urea-based dialysis adequacy and nutritional status and their effect on the components of the quality of life in incident peritoneal dialysis patients

BackgroundIt is well known that the quality of life of patients with chronic kidney disease can be improved by dialysis. While previous studies have used retrospective designs and adhered to a standard target prescribed by clinical guidelines, our study prospectively investigates the association between the adequacy of peritoneal dialysis (PD) and measures of nutritional status on quality-of-life domains in a cohort of incident PD patients.MethodsIt was a prospective 6-month observational study. Eighty incident PD participants who were treated in a hospital-based PD center were enrolled. The period of enrollment was January 2009–June 2010; follow-up continued until December 2010. PD adequacy indices, including Kt/V urea, weekly Ccr (WCcr), measures of nutritional status (albumin, BMI), and nPCR were measured at 1 month and 6 months after PD initiation. SF-36 health survey questionnaires were used to measure the quality of life. The outcomes were used to measure the changes in the domains of the SF-36 after 6 months of PD therapy.ResultsSeventy-seven incident patients who underwent PD for 6 months were included in the study. The mean age was 47.3 years, and the male-to-female ratio was 38:39. A peritoneal Kt/V urea value of 1.2, which was also the baseline cutoff value, was found to have the highest influence on SF-36 domains. Patients with baseline peritoneal Kt/V urea value of <1.2 showed improvement in the physical functioning and role limitation of physical functioning components after 6 months of PD. In contrast, patients with baseline peritoneal Kt/V urea values of ≥1.2 showed remarkable improvement in the general health, physical functioning, role limitation caused by physical problems, and bodily pain components. However, the trend of improvement decreased in patients with baseline nPCR of <1.2. Baseline renal WCcr did not influence the improvement in the SF-36 domains.LimitationsA small cohort and a short observation period.ConclusionsThe baseline level of peritoneal Kt/V urea affected the components of the quality of life after PD initiation. In contrast, a lower baseline nPCR level was associated with deterioration in the quality of life after PD therapy.

Increasing high-sensitive C-reactive protein level predicts peritonitis risk in chronic peritoneal dialysis patients

BackgroundThe aim of this study was to evaluate whether a high baseline level of high-sensitivity C-reactive protein (hs-CRP) or changes in the level predicts the risk of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD).MethodsA prospective, cross-sectional, case–control study was conducted in a single hospital-based PD unit. A total of 327 patients were included in the study. Serum hs-CRP was measured annually for 2 years. Patients were divided into 4 groups according to the changes in annual hs-CRP levels (at baseline and at 1 year intervals): group 1 (from <5 mg/L to <5 mg/L, n = 171), group 2 (from <5 mg/L to ≥5 mg/L, n = 45), group 3 (from ≥5 mg/L to <5 mg/L, n = 45), and group 4 (from ≥5 mg/L to ≥5 mg/L, n = 80). Demographics, biochemistry results, PD adequacy indices, and peritonitis risk were compared between the groups.ResultsThe initial serum albumin level was similar in the 4 groups (p = 0.12). There was a negative linear correlation between the serial albumin change (∆alb) and serial hs-CRP change (∆hs-CRP; r = −0.154, p = 0.005). The hazard ratio (HR) for peritonitis was significantly higher in group 2 (HR = 1, reference) than in group 4 (HR = 0.401, 95% CI 0.209 − 0.769). Group 2 had a greater serum albumin decline rate (∆alb: –3% ± 9%) and hs-CRP elevation rate (∆hs-CRP: 835% ± 1232%) compared to those for the other groups.ConclusionsA progressive increase in the hs-CRP level was associated with a corresponding decline in the serum albumin level. Progressive rather than persistently high levels of serum hs-CRP predicted peritonitis risk in CAPD patients.

Clinical Safety and Anticoagulation Efficacy of Low-Molecular-Weight Heparins in Chronic Hemodialysis Patients: A Single Medical Center Experience

Background: In many countries low-molecular-weight heparins (LMWHs) are increasingly used for hemodialysis (HD). Low-range activated clotting time (ACT-LR) values and anti-Xa activity had been used to monitor the degree of anticoagulation caused by LMWH. However, the facilities are not easily available at most hospitals. Such data are limited in Taiwan. Methods: A total of 76 patients receiving maintenance HD were prospectively enrolled. The HD patients were randomized to receive either nadroparin or enoxaparin and checked the ACT-LR values and anti-Xa activity. We aimed to analyze ACT-LR values and anti-Xa activity along with the clotting of the dialyzer or bleeding events associated with two LMWHs after they were administered. We also aimed to determine the dose necessary to reach maximum safety and efficacy. Results: We found no significant differences in LMWH dosage, ACT-LR values, and anti-Xa activity between the two groups. There were no significant differences in bleeding/adverse events and extracorporeal circuit thrombosis between the two groups. Most of the bleeding and adverse events were subcutaneous minor bleeding. No major bleeding or mortality was found. We found significant differences in mean dosage, cost, bleeding/adverse effect, and extracorporeal circuit thrombosis between excessive and reduced nadroparin dosage groups. Conclusion: LMWH is not still routinely used due to its high cost in Taiwan. In our clinical experience, nadroparin and enoxaparin exhibited high levels of safety and efficacy in chronic HD patients. Reduced LMWHs dosage could promote patient’s safety and decreased HD cost in HD patients with excessive dosage of LMWHs. Feng-Rong Chuang and Te-Chuan Chen contributed equally to the article.

Study protocol for a single-blind, placebo-controlled randomised trial of Tianjiu effects in patients with intradialytic hypotension.

Introduction Intradialytic hypotension (IDH) is the most frequent complication of haemodialysis (HD) and may contribute to cardiovascular events and high mortality. The aetiology of IDH is multifactorial; therefore, it remains a challenging problem in the management of patients with HD. Since the application of Tianjiu at specific points can influence haemodynamics, we hypothesise that Tianjiu therapy at the traditionally used meridian points will reduce the severity of hypotension in patients who undergo HD. Methods/analysis In this clinical trial, eligible patients with IDH will be divided randomly and equally into a Tianjiu group and a control group for 4 weeks. In the Tianjiu group, the patients will have Tianjiu applied at three points (conception vessel 4, and bilateral kidney 1) during each HD session. In the control group, patients will have clay patches applied in the same way as those in the Tianjiu treatment group. Both groups will be followed up for 2 weeks. The primary outcome measure will be the percentage of target ultrafiltration achieved, defined as the actual ultrafiltration volume divided by the target ultrafiltration volume. Secondary outcome measures, including frequency of IDH episodes and number of nursing interventions during HD sessions, predialysis and postdialysis blood pressure (BP), patients participative assessment of the degree of fatigue after dialysis (scale from 0, not at all, to 10, extremely), and recovery time from fatigue after dialysis will be recorded at the 0th and 4th weeks. Ethics/dissemination This trial has undergone ethical scrutiny and been approved by the ethics review board of Chang Gung Memorial Hospital (Permission number: 102-4749A3 and 104-3156C). The pre-results of this trial will help to determine whether Tianjiu is an effective and safe treatment for IDH, and, if so, whether it is a therapeutic effect rather than a placebo effect. Trial registration number NCT02210377; Pre-results.

Renal Outcome of Patients with Chronic Kidney Disease Stage 3-5 under a Multidisciplinary Care Program

BACKGROUND: A variety of factors are well-recognized as active being active in mediating the progression of chronic kidney disease (CKD). Multidisciplinary care programs (MDCPs) have been shown to be effective in retarding the progression of CKD. However, little is known regarding the progression of CKD in a cohort receiving MDCP. The objectives of this study were to identify factors associated with rapid decline of renal function among a CKD cohort and analyze their outcome. METHODS: CKD patients (stage 3-5) who had been receiving MDCP for at least 24 months were analyzed retrospectively. Their demographic data, co-morbidities and biochemical data were reviewed and collected. Glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease Study (MDRD) equation. RESULTS: Of the total 343 patients, 32.1% were CKD stage 3, 23.0% were stage 4 and 44.9% were stage 5. Their mean age was 63.5 years and 36.7% were diabetic. Their baseline GFR was 24.5 mL/min/ 1.73 m^2 and biennial GFR change was -3.0 ± 6.4 mL/min/1.73 m^2. We further divided the patients into two groups according to the rate of GFR decline. Patients with biennial GFR change of more than -4 mL/min/1.73 m2 were considered to have rapid progression. 133 patients with rapid progression were then compared with 210 patients with non-rapid progression. Patients with diabetes, hypertension, proteinuria, higher baseline systolic and diastolic blood pressure, and lower albumin level progressed more rapidly. During the follow-up, 30 patients (8.8%) reached the combined endpoint of the study. Logistic regression analysis disclosed that systolic blood pressure and serum albumin level were the independent factors of rapid renal progression. Patients with stage 4 or 5 experienced more rapid progression (stage 4: -3.4 ± 6.8; stage 5: -4.8 ± 5.0 mL/min/1.73 m^2) than those with stage 3 (0.1 ± 6.9 mL/ min/1.73 m^2, P ＜ 0.001). CONCLUSION: The average annual rate of renal function decline in our MDCP cohort was slightly higher than the aging process. Baseline systolic blood pressure and serum albumin level were independent factors of rapid progression among moderate CKD patients under the MDCP.

Treatment of intradialytic hypotension with an herbal acupoint therapy in hemodialysis patients: A randomized pilot study

OBJECTIVE Hypotension during hemodialysis (HD) is the most common complication that negatively affects the quality of life of patients. The objective of the current study was to evaluate the preliminary efficacy and safety of herbal acupoint therapy (HAT) for intradialytic hypotension (IDH). METHODS A randomized, placebo-controlled trial was performed in 32 HD patients to determine whether HAT was more effective than a sham treatment for the treatment of IDH. The outcomes were frequency of IDH episodes and number of nursing interventions during HD sessions, pre- and post-dialysis BP, subjective change in fatigue as measured by the Visual Analogue Scale (VAS), and recovery time from fatigue after dialysis at the 0th and 4th week. Data analyses were performed using per-protocol population. RESULTS In all, 27 patients (84%) completed the entire study. At the end of the intervention, the patients in the HAT group were found to have a significantly lower frequency of IDH episodes, fewer nursing interventions, a lower intervention failure rate, and earlier discontinuation of dialysis than those in the sham group (p < .05). The improvement in degree of fatigue (p = .001) was greater and recovery time from fatigue after dialysis (p = .03) was shorter in the group treated with HAT than in the sham group. HAT was safe, with 2 withdrawal cases due to local erythema caused by the patch. CONCLUSIONS HAT appears to be safe and efficacious for improving IDH-related symptoms and intervention in HD patients. Larger studies are needed to confirm the benefit of this technique for IDH.

Relationship between Kt/V Urea Values, Comorbidity Index and Components of Quality of Life in Incident Peritoneal Dialysis Patients

BACKGROUND: It is well known that the quality of life (QoL) of patients with chronic kidney disease (CKD) can be improved by initiation of dialysis. The purpose of this study is to investigate the association between dialysis adequacy, comorbidity indices, and QoL domains in a cohort of incident peritoneal dialysis (PD) patients.METHODS: This was a prospective 6-month observational study. Seventy-seven incident PD patients who were treated in a hospital-facilitated PD center for 6 consecutive months were enrolled. The mean patient age was 47.3 ± 13.4 years, and 38 patients were male. The effects of baseline PD adequacy indices, Charlson comorbidity index (CCI) on QoL were investigated in a 6-month period. The Short-form- 36 (SF-36) health survey questionnaire was employed to assess the QoL of the patients. The outcomes were measured as changes in scores of the various domains of SF-36 after the 6-month PD therapy. Multivariate analysis was performed to assess the effects of the abovementioned indices on QoL.RESULTS: The cutoff level of 1.2 for baseline peritoneal Kt/V urea level was found to have the greatest effect on scores of the SF-36 domains after the 6-month PD period. Patients with baseline peritoneal Kt/V urea levels of ≥ 1.2 had improvement in the components of general health, physical functioning, role limitation caused by physical problems, and bodily pain. However, patients with baseline peritoneal Kt/V urea level of ＜ 1.2 had improvement only in components of physical functioning and role limitation due to physical problems. Multivariate analysis revealed that a CCI score of ≥ 5 did not have any significant influence in any of the SF-36 domains, while CCI scores of 3-5 were associated with an improvement in the domains of role limitation due to physical problems (P=0.001) and role limitation due to emotional problems (P=0.025).CONCLUSIONS: The baseline level of peritoneal Kt/V urea correlates significantly with the scores of various components of QoL after PD initiation. PD patients with moderate comorbidities had significant improvement in QoL when PD was initiated.

Quiz Page November 2010

H LINICAL PRESENTATION 28-year-old woman with a 10-year history of recurrent yspnea was evaluated for 4 days of worsening shortess of breath and anorexia. One month before admision, fasting hyperglycemia was diagnosed and she was rescribed a low-carbohydrate high-protein diet. On examination, blood pressure was 112/71 mm Hg nd heart rate was 141 beats/min. She weighed 42 kg nd was 162 cm tall; body mass index was 16 kg/m. he was alert, but afebrile and emaciated and had dry kin. Initial laboratory findings showed metabolic acidois and ketosis. Intravenous hydration with normal saline olution was started, and nutritional supplements with rotein and amino acids were given. Despite these meaures, the patient developed blurred vision and confusion n hospital day 4. Neurologic examination showed noral cranial nerves, including no ophthalmoparesis or acial diplegia, but decreased visual acuity. Computed omography (Fig 1) of the brain showed an area of ecreased attenuation (arrow) within the bilateral basal anglia. Serial blood biochemistry and arterial blood gas esults are listed inTable 1. Of note is the development of rofound hyperammonemia with an ammonia level of 27 g/dL (192 mol/L).