Shao-Yu Yang

Sleep Disturbance in Chronic Hemodialysis Patients: The Impact of Depression and Anemia

Background. Many patients with end-stage renal disease who are undergoing chronic hemodialysis suffer from sleep disturbance. This paper was designed to study the severity and prevalence of sleep disorders and the factors affecting the syndromes in this unique patient group. Methods. We conducted this study by the use of questionnaires. Included in this study were a total of 245 patients at our center who had end-stage renal disease (ESRD) and who received hemodialysis thrice weekly for more than three months. Their demographic data and biochemical and hematologic parameters were analyzed. All patients were asked to complete two questionnaires (in a Chinese version) of the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory second edition (BDI-II), either by themselves or with assistance from the medical staff. Results. One hundred and sixty-four patients completed both questionnaires with a response rate of 70.4%. Their mean age was 57.9 ± 11.8 (ranging from 23.1 to 83.7) years old. They had been receiving hemodialysis for an average of 49.1 ± 50.9 months before the study. The male to female ratio was 77:87. Seventy six (46.3%) patients had diabetes mellitus. The prevalence of sleep disturbance was 74.4% (122/164), defined as PSQI scores >5. The poor sleepers had higher BDI scores and a higher ratio of females comparing to the good sleepers. By a multivariate analysis, the BDI scores and female sex were the independent predictors of the patients being poor sleepers. In analyzing the poor sleepers, the BDI scores, durations of hemodialysis and hemoglobin levels were the independent factors for predicting the global PSQI scores. Conclusion. The questionnaire showed a high prevalence of insomnia in the dialytic population. The study also attributes a predictive role in sleep quality to gender, depression, dialytic duration, and hemoglobin levels. The data indicate that in the management of insomnia in this patient group, anemia and depression, both of which are potentially correctable, should be assessed.

Kidney impairment in primary aldosteronism

BACKGROUND Kidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration. METHODS A prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment. RESULTS The diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR<60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p=0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p=0.018) was correlated with kidney impairment (p=0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p<0.001). Pre-operative hypokalemia (p=0.013) and the long latency of hypertension (p=0.016) could enhance the significant decrease of eGFR after adrenalectomy. CONCLUSIONS Patients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.

Primary Aldosteronism: Diagnostic Accuracy of the Losartan and Captopril Tests

BACKGROUND To assess whether angiotensin-II receptor blockers (ARBs) offer any additional advantage in confirming the diagnosis of primary aldosteronism (PA) and their use in the differentiation of PA subtypes. METHODS A prospective, cohort, head-to-head study was conducted between July 2003 and July 2006. A total of 135 patients received captopril and losartan tests to confirm the diagnosis of PA in the TAIPAI (Taiwan Primary Aldosteronism Investigation) intervention. RESULTS In total, 71 patients were diagnosed with PA. The area under the receiver-operating characteristic (ROC) curve of the postcaptopril plasma aldosterone concentration (PAC) was significantly less than that of the postlosartan PAC (0.744 vs. 0.829, P = 0.038). Using an aldosterone-renin ratio (ARR, ng/dl per ng/ml/h) >35 with a PAC >10 ng/dl, the specificity was 89.1% vs. 93.8% and the sensitivity was 66.2% vs. 84.5 % for the captopril test vs. the losartan test, respectively. With respect to the losartan test, the accuracy was 88.9%, the agreement was good (k = 0.778), and there was no disagreement with the McNemar test (P = 0.118). Losartan had the advantage of a better negative predictive value to exclude PA when patients were referred with a serum potassium (SK) level <3.8 mmol/l. When a postlosartan ARR >60 was the cutoff value, the positive predictive value was 82% with a negative predictive value of 57% in distinguishing aldosterone-producing adenomas (APAs) from idiopathic hyperaldosteronism (IHA). CONCLUSIONS The postlosartan ARR and PAC were shown to have better accuracy for the diagnosis of PA than the captopril test. With a postlosartan ARR >60, APAs can be adequately differentiated from IHA.

Prevalence and clinical correlates of somatic mutation in aldosterone producing adenoma-Taiwanese population

Primary aldosteronism (PA) is a common form of secondary hypertension and has significant cardiovascular consequences. Mutated channelopathy due to the activation of calcium channels has been recently described in aldosterone-producing adenoma (APA). The study involved 148 consecutive PA patients, (66 males; aged 56.3 ± 12.3years) who received adrenalectomy, and were collected from the Taiwan PA investigator (TAIPAI) group. A high rate of somatic mutation in APA was found (n = 91, 61.5%); including mutations in KCNJ5 (n = 88, 59.5%), ATP1A1 (n = 2, 1.4%), and ATP2B3 (n = 1, 0.7%); however, no mutations in CACNA1D were identified. Mutation-carriers were younger (<0.001), had lower Cyst C (p = 0.042), pulse wave velocity (p = 0.027), C-reactive protein (p = 0.042) and a lower rate of proteinuria (p = 0.031) than non-carriers. After multivariate adjustment, mutation carriers had lower serum CRP levels than non-carriers (p = 0.031. Patients with mutation also had a greater chance of recovery from hypertension after operation (p = 0.005). A high incidence of somatic mutations in APA was identified in the Taiwanese population. Mutation-carriers had lower CRP levels and a higher rate of cure of hypertension after adrenalectomy. This raises the possibility of using mutation screening as a tool in predicting long-term outcome after adrenalectomy.

N-Acetylcysteine for the Management of Anemia and Oxidative Stress in Hemodialysis Patients

Background/Aims: To explore the efficacy of oral N-acetylcysteine (NAC) supplementation for anemia and oxidative stress in hemodialysis (HD) patients. Methods: Of the eligible patients (n = 325) in an outpatient HD unit, 49 received NAC 200 mg orally thrice a day during the first 3 months, while the other 276 patients not receiving NAC were observed. Results: During the 4-month study, 11 patients receiving NAC withdrew but had no severe adverse effects, while 49 patients not receiving NAC had negative confounding events. Thus only the data of the remaining patients, 38 taking NAC and 227 not taking NAC, were analyzed for efficacy. The demographic and laboratory data of both groups were similar at baseline. When the erythropoietin dosage was stable throughout, only the NAC group had a significant increase in hematocrit, accompanied with a decrease in plasma levels of 8-isoprostane and oxidized low-density lipoprotein. Analyzed as a nested case-control study, NAC supplementation was also found to be a significant predictor of positive outcomes in uremic anemia. Conclusions: Oral NAC supplementation may be a promising therapy for uremic anemia and oxidative stress in HD patients.

Rosiglitazone in diabetes control in hemodialysis patients with and without viral hepatitis infection: effectiveness and side effects.

OBJECTIVE— Thiazolidinedione (TZD) may provide an additional benefit of cardiovascular protection in diabetic patients through targeting of insulin resistance. However, use of a TZD is hampered by possible effects of fluid retention and hepatotoxicity. In this study we aimed to determine whether the risk of TZD-induced fluid retention or hepatic injury is higher in hemodialysis patients with persistent viral hepatitis infection. RESEARCH DESIGN AND METHODS—This was a prospective, cohort study on hemodialysis patients. Type 2 diabetic patients with A1C levels of >8% were followed for at least 12 months. Rosiglitazone was initiated at 2–4 mg/day. The primary outcome was the target A1C (<7%) achieved and dosages of rosiglitazone. Secondary outcomes included changes in lipid profile and inflammatory biomarkers. Safety evaluations were number of hypoglycemic episodes, changes in liver transaminase levels, cardiothoracic ratio (CTR), fluid status control during dialysis, and events of symptomatic heart failure. RESULTS—A total of 78 patients, including 15.4% (n = 12) hepatitis B surface antigen–positive and 16.7% (n = 13) anti–hepatis C virus (HCV)-positive patients, were enrolled. The mean follow-up period was 15.4 ± 3.8 months. The diabetic response rate (A1C <7%) to rosiglitazone was 86.1%. The serum triglyceride level was reduced (194 ± 112.5 to 168 ± 88 mg/dl, P = 0.037) more significantly than the total cholesterol level (178 ± 42.1 to 174 ± 46.5 mg/dl, P = 0.13). High-dose rosiglitazone (8 mg/day) reduced the serum level of C-reactive protein and increased the serum adiponectin level significantly. After rosiglitazone, interdialysis weight gain (2.07 ± 1.6 to 3.2 ± 1.2 kg, P < 0.01) and mean CTR (48.2 ± 5.6 to 50.4 ± 6.2%, P = 0.0213) of individuals increased significantly. Nevertheless, liver aminotransferase (aspartate aminotransferase and alanine aminotransferase) levels did not show a tendency to increase in patients (n = 25) with viral hepatitis B or C infections. CONCLUSIONS—Among regular hemodialysis patients with chronic viral hepatitis infections, rosiglitazone may be safely used for diabetes control. However, one must be aware that a possible effect of its use is a deterioration in cardiovascular reserve.

Low-Density Lipoprotein Cholesterol: Association with Mortality and Hospitalization in Hemodialysis Patients

Background/Aims: Hypocholesterolemia is a common finding in hospitalized elderly people, critically ill surgical patients, septic patients and end-stage renal disease patients. The different effect of lipid subfractions on patients with end-stage renal disease has never been demonstrated. We aim to study the effect of lipid subfractions on hospitalization and mortality in maintenance hemodialysis (MHD) patients. Methods: Lipid subfractions, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured in 210 patients with MHD in a single dialysis center. Patients were stratified into three groups based on the tertiles of lipid levels, and differences in patient characteristics and survival were evaluated. Results: Of a total of 22 deceased patients in our MHD cohort, infection-related mortality (50%) was higher than cardiovascular-related mortality (18.2%). Significant differences (p < 0.05) in the duration and frequency of hospitalization and in mortality events were observed when patients were divided into different subgroups according to the tertiles of baseline TC and LDL-C levels. Patients with lower LDL had significantly lower levels of albumin, TC and TG. The LDL-C tertiles were similar in terms of age, hypertension, diabetes, biochemical results, hematocrit, adequacy of hemodialysis and normalized protein catabolism rate. Both TC and LDL-C predicted survival (p < 0.001), but not TG and HDL-C in the Kaplan-Meier model. The Cox proportional hazard model demonstrated that baseline serum LDL-C was the best lipid subfraction in predicting all-cause death with an adjusted hazard ratio (95% confidence interval) for each 10 mg/dl of 0.752 (0.631–0.898; p = 0.002). Conclusions: We firstly demonstrated that lipid subfractions, including TC and LDL-C, predict poor outcomes in a MHD cohort with high infection-related mortality.

Uremic Pruritus, Dialysis Adequacy, and Metabolic Profiles in Hemodialysis Patients: A Prospective 5-Year Cohort Study

Background Uremic pruritus is a common and intractable symptom in patients on chronic hemodialysis, but factors associated with the severity of pruritus remain unclear. This study aimed to explore the associations of metabolic factors and dialysis adequacy with the aggravation of pruritus. Methods We conducted a 5-year prospective cohort study on patients with maintenance hemodialysis. A visual analogue scale (VAS) was used to assess the intensity of pruritus. Patient demographic and clinical characteristics, laboratory parameters, dialysis adequacy (assessed by Kt/V), and pruritus intensity were recorded at baseline and follow-up. Change score analysis of the difference score of VAS between baseline and follow-up was performed using multiple linear regression models. The optimal threshold of Kt/V, which is associated with the aggravation of uremic pruritus, was determined by generalized additive models and receiver operating characteristic analysis. Results A total of 111 patients completed the study. Linear regression analysis showed that lower Kt/V and use of low-flux dialyzer were significantly associated with the aggravation of pruritus after adjusting for the baseline pruritus intensity and a variety of confounding factors. The optimal threshold value of Kt/V for pruritus was 1.5 suggested by both generalized additive models and receiver operating characteristic analysis. Conclusions Hemodialysis with the target of Kt/V ≥1.5 and use of high-flux dialyzer may reduce the intensity of pruritus in patients on chronic hemodialysis. Further clinical trials are required to determine the optimal dialysis dose and regimen for uremic pruritus.

Atorvastatin Increases Erythropoietin-Stimulating Agent Hyporesponsiveness in Maintenance Hemodialysis Patients: Role of Anti-Inflammation Effects

Erythropoietin-stimulating agent (ESA) hyporesponsiveness is aggravated by chronic inflammation in maintenance hemodialysis (MHD) patients. Dyslipidemia is prevalent in MHD patients. Statin therapy has been demonstrated to not only be effective in lowering lipid levels, but also numerous pleiotropic effects including anti-inflammatory, anti-fibrotic and endothelial function improvement. Recently, a retrospective study has shown that statin therapy decreases ESA requirements in MHD patients. We conducted a prospective study to analyze the effect of statin therapy on ESA hyporesponsiveness, and especially emphasized its anti-inflammatory benefits in MHD patients. This prospective study enrolled 30 patients with baseline cholesterol >220 mg/dl. Low-dose atorvastatin (10 mg/day) was prescribed for 12 weeks. We prospectively recorded patients’ biochemistry and hematological profiles, ESA prescription and some inflammatory markers at baseline, 4 weeks and 12 weeks. Statistically significant changes were noted after 4 and 12 weeks of statin therapy for cholesterol (272.5 ± 41.1 to 184.4 ± 37.6 and 196.4 ± 40.2 mg/dl, p < 0.05) and ESA hyporesponsiveness, which demonstrated as erythropoietin to hematocrit ratio (EHR) (129.3 ± 58.2 to 122.3 ± 53.5 and 121.0 ± 53.3 EPO U/Hct/week, p < 0.05). Mean values for proinflammatory cytokines included interleukin-6 and tumor necrotic factor-α levels decreased by 30.8 and 10.6%, respectively. Thus, these data suggest that statin therapy may improve ESA hyporesponsiveness in dialysis patients. This improvement in ESA hyporesponsiveness is associated with the effects of statins on inflammation.

Metabolic syndrome predicts hospitalization in hemodialysis patients: a prospective Asian cohort study.

Background/Aims: Metabolic syndrome (MS) increases morbidity and mortality in the general population. The effects of individual components of MS differ in hemodialysis (HD) patients, but the composite effects of MS in this population are unknown. Methods: We performed a prospective, cohort study including 235 HD patients who were followed up for 3 years. We used modified Asian criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) to define the presence of MS, and compared the hospitalizations and deaths in patients with and without MS. Results: Patients with MS had a lower hospitalization-free ratio, greater annual hospitalization days and frequency than those without MS. The relative risk of the presence of MS was 1.669 in predicting first hospitalization for all causes. Conclusion: The modified Asian criteria for MS successfully predicted the risk of hospitalization as compared with NCEP ATP III criteria in HD patients.