Chin-Chan Lee

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.

Clinical Value of NGAL, L-FABP and Albuminuria in Predicting GFR Decline in Type 2 Diabetes Mellitus Patients

Objectives Neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid binding protein (L-FABP) are emerging as excellent biomarkers in the urine and plasma for the early prediction of acute and chronic kidney injury. The aims of this prospective study were to determine the role of albuminuria, and that of serum and urine levels of NGAL and L-FABP as predictors of a decline in the glomerular filtration rate (GFR) in patients with type 2 diabetes. Methods A longitudinal cohort study with one hundred forty type 2 diabetic patients was conducted. Serum and urine levels of NGAL and L-FABP, and the urine albumin excretion rate were determined. The correlation between the kidney injury biomarkers and rate of GFR decline was analyzed. Results The eGFR of study subjects decreased significantly as the study progressed (86.4±31.1 vs. 74.4±27.3 ml/min/1.73 m2, P<0.001), and the urine albumin excretion rate increased significantly (264.9±1060.3 vs. 557.7±2092.5 mg/day, P = 0.009). The baseline urine albumin excretion rate and serum L-FABP level were significantly correlated with baseline eGFR (P<0.05). The results of regression analysis for the correlations between the rate of eGFR change and the baseline levels of NGAL and L-FABP, and the urine albumin excretion rate showed that only the urine albumin excretion rate was significantly correlated with the rate of eGFR change (standardized coefficients: −0.378; t: −4.298; P<0.001). Conclusions Tubular markers, such as NGAL and L-FABP, may not be predictive factors associated with GFR decline in type 2 diabetic 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.

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.

Factors associated with chronic musculoskeletal pain in patients with chronic kidney disease

BackgroundChronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited.MethodA cross-sectional study to evaluate the prevalence of chronic MS pain and factors associated with chronic MS pain in patients with early- and late-stage CKD who were not undergoing dialysis, was conducted. In addition, the distribution of pain severity among patients with different stages of CKD was evaluated.ResultsOf the 456 CKD patients studied, 53.3% (n = 243/456) had chronic MS pain. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, as well as with the calcium × phosphate product levels. In CKD patients with hyperuricemia, chronic MS pain showed a negative, independent significant association with diabetes mellitus as a co-morbidity (odds ratio: 0.413, p = 0.020). However, in the CKD patients without hyperuricemia as a co-morbidity, chronic MS pain showed an independent significant association with the calcium × phosphate product levels (odds ratio: 1.093, p = 0.027). Furthermore, stage-5 CKD patients seemed to experience more severe chronic MS pain than patients with other stages of CKD.ConclusionChronic MS pain is common in CKD patients. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, and with the calcium × phosphate product levels in early- and late-stage CKD patients who were not on dialysis.

Association between uremic toxins and depression in patients with chronic kidney disease undergoing maintenance hemodialysis

OBJECTIVE Patients with chronic kidney disease (CKD) who are undergoing maintenance hemodialysis have a higher prevalence of depression than the general population. The underlying cause of this association is unknown, but may be related to accumulation of uremic toxins. Little is known about the association of accumulation of uremic toxins and depression in hemodialysis patients. METHOD We conducted a cross-sectional study of 209 CKD patients from a single institution to evaluate the associations of a soluble small uremic toxin (urea), a soluble large uremic toxin (β2 microglobulin) and two protein-bound uremic toxins [total p-cresol sulfate (PCS) and indoxyl sulfate (IS)] with the presence of depression. RESULTS A total of 47 patients (22.4%) had depression. Depressive patients had lower body mass index, lower serum creatinine, lower serum albumin and lower total IS. Univariate and multivariate logistic regression analyses that adjusted for age, gender and other statistically significant variables indicated that depression was significantly and independently associated with lower serum albumin and lower total IS. The levels of urea, β2 microglobulin and PCS were not significantly associated with depression. CONCLUSION Our results indicate that depression in patients with CKD was significantly and independently associated with lower serum albumin and lower total IS. However, the pathological mechanisms underlying these associations are unknown.