Heng-Jung Hsu

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.

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.

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.

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.

The association of uremic toxins and inflammation in hemodialysis patients.

Background Cardiovascular disease is the leading cause of mortality in hemodialysis patients and is associated with chronic inflammation. Elevation of uremic toxins, particular protein-bound uremic toxins, is a possible cause of hyper-inflammation in hemodialysis patients. But the association between uremic toxins and inflammatory markers in hemodialysis is still unclear. Methods We conducted a cross-sectional study to evaluate the association of the serum uremic toxins and inflammatory markers in hemodialysis patients. Results The uremic toxins were not associated with inflammatory markers- including high sensitivity C-reactive protein, IL(Interleukin) -1β, IL-6, tumor necrosis factor-α. In multiple linear regression, serum levels of total p-cresol sulfate (PCS) were independently significantly associated with serum total indoxyl sulfate (IS) (standardized coefficient: 0.274, p<0.001), and co-morbidity of diabetes mellitus (DM) (standardized coefficient: 0.342, p<0.001) and coronary artery disease (CAD) (standardized coefficient: 0.128, p = 0.043). The serum total PCS levels in hemodialysis with co-morbidity of DM and CAD were significantly higher than those without co-morbidity of DM and CAD (34.10±23.44 vs. 16.36±13.06 mg/L, p<0.001). Serum levels of total IS was independently significantly associated with serum creatinine (standardized coefficient: 0.285, p<0.001), total PCS (standardized coefficient: 0.239, p = 0.001), and synthetic membrane dialysis (standardized coefficient: 0.139, p = 0.046). Conclusion The study showed that serum levels of total PCS and IS were not associated with pro-inflammatory markers in hemodialysis patients. Besides, serum levels of total PCS were independently positively significantly associated with co-morbidity of CAD and DM.

Association between cold dialysis and cardiovascular survival in hemodialysis patients

BACKGROUND Higher cardiovascular mortality has been noted in patients with chronic kidney disease (CKD). CKD patients are also known to have impaired energy expenditure but the role of energy expenditure in cardiovascular disease is not yet known. Furthermore, the association between cold dialysis (CD) and clinical outcomes in hemodialysis patients is unclear. METHODS This was a single-center retrospective cohort study consisting of two groups: a CD group with dialyzate temperature <35.5 °C and a standard dialysis (SD) group with dialyzate temperature between 35.5 and 37 °C. The end points of the study were overall mortality, cardiac mortality and non-cardiac mortality. The study analyzed the associations between dialyzate temperature and long-term survival in CD and SD groups. Propensity score analysis was used to control for intergroup baseline differences. RESULTS Baseline characteristics of both groups were similar. Kaplan-Meier analysis showed that CD was significantly associated with a lower risk for overall mortality (P = 0.006) and cardiac mortality (P = 0.023) but not for non-cardiac mortality or infectious mortality. After multivariate Cox regression analysis, adjusting for propensity scores and other possible confounding factors, CD remained a significant beneficial factor for overall mortality (P = 0.030) and cardiac mortality (P = 0.034). CONCLUSION Our studies show that CD is significantly and independently associated with a lower risk for overall mortality and cardiac mortality.

Low plasma DHEA-S increases mortality risk among male hemodialysis patients.

OBJECTIVE The incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis. METHOD This was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival. RESULT We found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR)=3.877; P=0.021], non-CVD-related (HR=3.522; P=0.016), and all-cause mortality (HR=3.667; P=0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR=2.933; P=0.033). CONCLUSION The study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.