I-Wen Wu

p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease

Background. Indoxyl sulphate (IS) and p-cresyl sulphate (PCS) are uraemic toxins that have similar protein binding, dialytic clearance and proinflammatory features. However, only a few prospective studies have evaluated possible associations between these two retained solutes and renal disease progression in chronic kidney disease (CKD) patients. Methods. This prospective observational study evaluated independent associations between serum total IS and PCS with renal progression in a selected cohort of patients having different stages of CKD. Baseline PCS and IS were correlated with renal progression [defined as decrements in estimated glomerular filtration rate (eGFR) > 50% from baseline or progression to end-stage renal disease (ESRD)] and death during a follow-up period of 24 months. Results. Of 268 patients, 35 (13.1%) had renal progression and 14 (5.2%) died after a mean follow-up of 21 ± 3 months. Univariate Cox regression analysis followed by multivariate analysis showed that high-serum PCS levels were associated with renal progression and all-cause mortality independent of age, gender, diabetes status, albumin levels, serum IS, serum creatinine, Ca × P product, intact parathyroid hormone, haemoglobin or high-sensitivity C-reactive protein level. Serum IS was only associated with renal progression; however, the predictive power of serum IS was weakened when serum PCS was also present in the analytical model. Conclusions. In addition to traditional and uraemia-related risk factors such as renal function, serum IS and PCS levels may help in predicting the risk of renal progression in patients having different stages of CKD.

Multidisciplinary predialysis education decreases the incidence of dialysis and reduces mortality—a controlled cohort study based on the NKF/DOQI guidelines

BACKGROUND Observational studies have demonstrated that multidisciplinary predialysis education (MPE) improves the post-dialysis outcomes of chronic kidney disease (CKD) patients. However, the beneficial effect of MPE remains unclear in prospective controlled studies. METHODS All CKD patients who visited the outpatient nephrology clinics at two centres of the Chang Gung Memorial Hospital in 2006-07 were enrolled. The incidence of dialysis and mortality were compared between MPE recipients and non-recipients. The content of the MPE was standardized in accordance with the NKF/DOQI guidelines. Prognostic factors for progression to end-stage renal disease (ESRD) and all-cause mortality were analysed by using the Cox proportional hazards model. RESULTS Of 573 patients, 287 received MPE. Dialysis was initiated in 13.9% and 43% of the patients in the MPE and non-MPE groups, respectively (P < 0.001). The mean follow-up period was 11.7 +/- 0.9 months. The overall mortality was 1.7% and 10.1% in the MPE and non-MPE groups, respectively (P < 0.001). Cox regression analysis revealed that diabetes, estimated glomerular filtration rate (eGFR), high-sensitive C-reactive protein (hs-CRP) and MPE assignment were significant independent predictors for progression to ESRD. Independent prognostic factors for mortality included age, diabetes, eGFR, hs-CRP and MPE assignment. CONCLUSIONS MPE based on the NKF/DOQI guidelines may decrease the incidence of dialysis and reduce mortality in late-stage CKD patients.

Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients—a prospective cohort study

BACKGROUND The mortality rate of elderly hemodialysis (HD) patients is high. Serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) are associated with cardiovascular (CV) disease and mortality in renal patients. The association between such biomarkers and mortality in elderly HD patients has a high clinical value but remains unclear. METHODS This prospective cohort study investigated the association of serum IS and PCS with all-cause and CV mortality in elderly HD patients. Multivariate Cox regression analysis was used to estimate the risk of all-cause and CV mortality in this prospective cohort. RESULTS Of 112 patients, 45 deaths (18 CV deaths) were identified after a mean follow-up of 33.2 months. The cumulative and CV survival of patients with lower free PCS was significantly better than high free PCS patients. In multivariate Cox regression analysis, serum free PCS was associated with all-cause and CV mortality after various adjustments, including age, gender and diabetes status (Model 1), albumin (Model 2), Ca × P product and intact parathyroid hormone (Model 3), hemoglobin and high-sensitivity C-reactive protein (Model 4) and hierarchically selected covariates (age, diabetes status and albumin, Model 5). CONCLUSION Serum free PCS levels may help in predicting risk of all-cause and CV mortality in elderly HD patients beyond traditional and uremia related risk factors.

Depression and suicide risk in hemodialysis patients with chronic renal failure.

Background Depression and suicide are well established as prevalent mental health problems for patients on hemodialysis. Objective The authors examined the demographic and psychological factors associated with depression among hemodialysis patients and elucidated the relationships between depression, anxiety, fatigue, poor health-related quality of life, and increased suicide risk. Method This cross-sectional study enrolled 200 end-stage renal disease patients age ≥18 years on hemodialysis. Psychological characteristics were assessed with the Mini-International Neuropsychiatric Interview, the Hospital Anxiety and Depression Scale, the short-form Health-Related Quality of Life Scale, and Chalder Fatigue Scale, and structural equation modeling was used to analyze the models and the strength of relationships between variables and suicidal ideation. Results Of the 200 patients, 70 (35.0%) had depression symptoms, and 43 (21.5%) had had suicidal ideation in the previous month. Depression was significantly correlated with a low body mass index (BMI) and the number of comorbid physical illnesses. Depressed patients had greater levels of fatigue and anxiety, more common suicidal ideation, and poorer quality of life than nondepressed patients. Results revealed a significant direct effect for depression and anxiety on suicidal ideation. Conclusion Among hemodialysis patients, depression was associated with a low BMI and an increased number of comorbid physical illnesses. Depression and anxiety were robust indicators of suicidal ideation. A prospective study would prove helpful in determining whether early detection and early intervention of comorbid depression and anxiety among hemodialysis patients would reduce suicide risk.

The impact of self-management support on the progression of chronic kidney disease—a prospective randomized controlled trial

BACKGROUND Chronic kidney disease (CKD) is a public health problem worldwide. Multidisciplinary intervention helps improve outcomes for CKD patients. We conducted an open-label, randomized controlled trial to examine the impact of self-management support (SMS) in the outcome of late-stage CKD patients. METHODS Incidental CKD (Stages III-V) patients were randomized into self-management support (SMS) and non-SMS groups and followed up for 12 months. SMS comprised health information, patient education, telephone-based support and the aid of a support group. The primary end points were absolute estimated glomerular filtration rate (eGFR) alteration and number of hospitalization events. The secondary end points were an eGFR decrease of up to 50%, end-stage renal disease (ESRD) demanding renal replacement therapy (RRT), all-cause mortality or a composite secondary end point. RESULTS The study included 54 patients; 27 patients were randomized into an SMS group and the same number into a non-SMS group. The absolute eGFR at the end of the study was significantly higher in SMS patients than in the non-SMS group (29.11 ± 20.61 versus 15.72 ± 10.67 mL/min; P < 0.05). There were fewer hospitalization events for SMS patients than for non-SMS patients [5 (18.50%) versus 12 (44.47%); P < 0.05]. One patient (3.7%) in the SMS group and nine (33.3%) in the non-SMS group had an eGFR reduction of >50% (P < 0.05). However, survival analysis of the composite secondary end points of ESRD that required RRT and all-cause mortality revealed no differences between the two groups. CONCLUSIONS Our randomized study suggests that a standardized SMS program may play a significant role in reducing CKD progression and morbidity of late-stage CKD patients.

Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: a randomized crossover study

BACKGROUND Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients. METHODS Fifty-one Stage 5 predialysis CKD patients with hemoglobin <10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator (CERA, A) and CERA alone (B), with a 4-week washout period in between. Mean changes of serum creatinine, estimated glomerular filtration rate (eGFR) and hemoglobin levels from the baseline were compared between two treatments. RESULTS The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A, and 5.14 mg/dL and 5.61 g/dL in the Treatment B group, respectively (treatment effect P = 0.025, period effect P = 0.467, carryover effect P = 0.384). The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A, and 9.63 g/dL and 9.54 g/dL in the Treatment B group, respectively (treatment effect P = 0.039, period effect P = 0.001, carryover effect P = 0.060). Use of AST-120 significantly reduced IS and p-cresyl sulfate (PCS) levels. Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels (B = 0.049, P = 0.005). CONCLUSIONS Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients. The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels. The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients.

Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury—beyond the direct renin inhibition

Chronic renal ischemia leads to renal fibrosis and atrophy. Activation of the renin-angiotensin–aldosterone system is one of the main mechanisms driving chronic renal ischemic injury. The aim of the present study was to define the effect of aliskiren in chronic ischemia of the kidney. Two-kidney, one-clip mice were used to study chronic renal ischemia. Aliskiren significantly lowered the blood pressure in mice with renal artery constriction (92.1±1.1 vs. 81.0±1.8 mm Hg, P<0.05). Renin expression was significantly increased in ischemic kidneys when treated with aliskiren. In addition, (Pro)renin receptor expression was decreased by aliskiren in ischemic kidneys. Aliskiren treatment significantly increased klotho expression and reduced the expression of fibrogenic cystokines, caspase-3 and Bax in ischemic kidneys. Histological examination revealed that aliskiren significantly reduced the nephrosclerosis score (4.5±1.9 vs. 7.3±0.4, P<0.05). Immunofluorescence staining also showed that aliskiren decreased the deposition of interstitial collagen I in ischemic kidneys. In conclusion, direct renin inhibition significantly reduced renal fibrosis and apoptosis following chronic renal ischemia.

The relationship between psychological factors, inflammation, and nutrition in patients with chronic renal failure undergoing hemodialysis.

Objective: Hemodialysis has an adverse impact on the immunological, nutritional, and emotional status of patients. The biochemical markers of inflammation and nutrition were studied as well as the relationship of these factors to emotional symptoms. Method: One hundred and ninety-five patients undergoing hemodialysis were enrolled. The mean age was 58.5 years. Emotional symptoms were assessed using the Mini International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale, Chalder Fatigue Scale, and Short-form Health-related Quality of Life. Venus blood was collected for laboratory assessment of serum hemoglobin, albumin, ferritin, C-reactive protein, interleukin (IL) 1β), IL-6, and tumor necrosis factor a. Results: Among the 195 subjects (92 men and 103 women), 47 (24.1%) fulfilled the criteria for a major depressive disorder (MDD). The IL-6 level in patients with a MDD was significantly higher than in the patients without a MDD. Significant correlation was observed among the following factors: IL-6, fatigue, and quality of life for both physical and mental components. The albumin levels showed a significant correlation with the IL-6 and depression scores. Conclusions: These results show that the serum levels of albumin and IL-6 might be laboratory markers associated with the expression of emotional symptoms in patients undergoing hemodialysis. Prospective studies are needed to determine the causal relationships among these variables.

Survival Analysis of Taiwan Renal Registry Data System (TWRDS) 2000-2009

The increasing dialysis population is a global phenomenon. Taiwan still sat on the top of list regarding to dialysis prevalence, although incidence rate continuously fell in 2009 analysis. It is very interesting to ask the reason of dissociation between prevalence and incidence, and the survival trends of modern era. The purpose of this short review is to present trends of prevalence and survival after nationwide implementation of continuous quality improvement measurements since 2005. The 2009 data from TWRDS suggested 2 interesting finding and 1 prediction. First, the patient survival was reduced in the modern cohort in comparison to 1990-2001 cohorts. Second, the demographic characteristics of patients entering dialysis are changing. There are more diabetic and elderly patients in 2000- 2009 cohorts than older cohort. This ultimate phenomenon may contribute in part to the decrease survival of modern cohort. The current nationwide epidemiological data analysis suggested tentative prediction of future dialysis trend. Approximately 100 patients per million population increase in ESRD prevalence would be expected if the practice pattern and patient demography kept the same pace. Further effort should be given to slow down the increase of ESRD prevalence.

Metabolic syndrome loses its predictive power in late-stage chronic kidney disease progression - A paradoxical phenomenon

BACKGROUND Metabolic syndrome (MS) is a significant determinant of CKD. The aim of this study was to determine the possible impact of MS on CKD progression. METHODS 746 CKD subjects were included. The presence of MS was determined according to the modified criteria proposed by the Adult Treatment Panel (ATP) III. The study endpoints were stage-to-stage CKD progression or starting renal replacement therapy during the study period. CKD Stages 1, 2 and 3 were defined as early-stage CKD, while CKD Stages 4 and 5 were defined as late-stage CKD. RESULTS Early-stage CKD patients with MS had a higher risk of CKD progression than those without MS. Cox regression analysis showed that MS was a significant determinant of CKD progression in early-stage (HR: 1.60, p=0.041) but not late-stage CKD patients (HR: 1.00, p=0.975). The results of subgroup analysis in non-diabetic subjects also showed that only early-stage CKD subjects with MS had significant risks of CKD progression (HR: 2.21, p=0.010). In diabetic patients, the association between MS and CKD progression was not significant in both early- and late-stage CKD. CONCLUSIONS Our findings suggested that the impact of MS on CKD progression might be prominent in non-diabetic early-stage CKD subjects, and became non-significant in diabetic late-stage CKD and diabetic CKD patients.