The association between chronic musculoskeletal pain and clinical outcome in chronic kidney disease patients: a prospective cohort study.

BACKGROUND AND OBJECTIVES: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. METHOD: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. RESULT: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004-8.444; p = .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p = .535). CONCLUSION: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.

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) -1ß, 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.

Chronic kidney disease stage is a modulator on the association between high-sensitivity C-reactive protein and coronary vasospastic angina.

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1-3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.

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.

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

BACKGROUND: Chronic 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. METHOD: A 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. RESULTS: Of 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. CONCLUSION: Chronic 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 (ß2 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, ß2 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.

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.

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.

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.

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.

Ureteral endometriosis with obstructive uropathy.

Endometriosis is a common disease, but ureteral involvement is rare. The symptoms and signs of ureteral endometriosis mimic those of ureteral malignancy. This case report describes a woman who presented with chronic back pain for 5 years. Imaging studies showed a right small contracted kidney with hydronephrosis and a bladder tumor. Endometriosis of the right lower ureter was ultimately diagnosed. The patient was healthy without recurrence during follow-up. It is difficult to differentiate between ureteral endometriosis and malignancy; in fact, renal loss may occur before diagnosis. Ureteral endometriosis should be considered for women with ureteral obstruction manifesting as chronic backache.

Factors associated with mortality from non-occlusive mesenteric ischemia in dialysis patients.

BACKGROUND: Among dialysis patients, acute mesenteric ischemia is mostly caused by non-occlusive mesenteric ischemia (NOMI). There is a very high mortality rate associated with this complication, but prognostic factors associated with NOMI are not well-known. METHOD: In this study, we retrospectively reviewed the records of dialysis patients to identify prognostic factors associated with mortality from NOMI. Overall, there were 541 patients on hemodialysis (HD) and 158 patients on peritoneal dialysis (PD) in our hospital from January 2007 to December 2008. Among these 699 patients, we diagnosed NOMI by surgical and/or radiological criteria. A total of 12 dialysis patients (9 on HD and 3 on PD) developed NOMI during the study period. RESULT: The incidence of NOMI was 1.04% per patient-year for all dialysis patients (0.95% for HD and 1.35% for PD patients). Most of the 12 patients had chronic hypotension (83.3%, 10/12). Four patients expired following development of NOMI. Our results showed that mortality was significantly higher in patients who were administered a cyclooxygenase (COX) inhibitor prior to ischemia. Hypobicarbonemia during NOMI, which might indicate the severity of hypoperfusion, is also associated with higher mortality. CONCLUSION: NOMI is rare in dialysis patients. COX inhibitor administration should be given with caution in long-term hypotensive dialysis patients.

Lack of association between plasma dehydroepiandrosterone sulfate (DHEA-S) levels and depression in hemodialysis patients: a cross-sectional study.

OBJECTIVE: Depression is common in hemodialysis patients. Reduced DHEA-S levels have been shown to be associated with depression in general population. Abnormalities in hormone production and metabolism are found in hemodialysis patients. However, the association between DHEA-S levels and depression in hemodialysis patients has not been established. METHOD: We conducted a cross-sectional study, in which 80 patients under regular hemodialysis were studied, and their serum DHEA-S levels were analyzed. RESULTS: The prevalence of depression in our studied hemodialysis population is 37.5% (30/80). The DHEA-S level was 1138.1+/-1216.9 ng/mL in male patients and 502.1+/-389.4 ng/mL in female patients. The levels were not significantly different between patients with or without depression (910.8+/-1127.1 ng/mL vs. 769.3+/-848.3 ng/mL, P=0.533). As compared to the non-depressed patients, the depressed patients were more likely to be male, with lower body mass index, consuming more alcohol, and with more co-morbidity. The prevalence of depression was not associated with age, educational background, smoking, duration of dialysis, hemoglobin, albumin, CRP, ferritin, and urea clearance (Kt/V and URR). The serum DHEA-S levels exhibited significant and independent associations with age, gender, diabetes mellitus, and the levels of serum albumin. CONCLUSION: The study suggested a lack of association between plasma DHEA-S levels and depression in hemodialysis patients.

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.

Increased expression of hypoxia-inducible factor 1alpha in the nasal polyps.

PURPOSE: The etiology and mechanism of nasal polyps are still not well known. A newly discovered transcriptional factor, hypoxia-inducible factor (HIF), is a DNA-binding protein. Hypoxia-inducible factor is demonstrated to associate with various neoplasms. We investigate the expression of HIF-1alpha protein in nasal polyps compared with inferior turbinate mucosa, further examining the correlation to the computed tomography (CT) scoring and duration of symptoms with HIF-1alpha expression. MATERIALS AND METHODS: Surgical specimens of polyps from 38 patients undergoing endoscopic sinus surgery had immunohistochemical staining for HIF-1alpha and vascular endothelial growth factor. Thirty-six patients who had undergone septomeatoplasty were collected as a control group. The severity of the disease was judged by the Lund-Mackay scoring system by CT scanning. RESULT: The expression of HIF-1alpha and vascular endothelial growth factor were significantly increased in nasal polyps than in the control group. No correlation was found between the severity of CT scan and duration of symptoms to the HIF-1alpha expression. CONCLUSION: We suggest that HIF-1alpha may play a role in the pathogenesis of nasal polyps.

An outbreak of methicillin-resistant Staphylococcus aureus infections related to central venous catheters for hemodialysis.

OBJECTIVES: To determine risk factors for hemodialysis catheter-related bloodstream infections (HCRBSIs) and investigate whether use of maximal sterile barrier precautions would prevent HCRBSIs. SETTING: Tertiary-care medical center hemodialysis unit. DESIGN: Open trial with historical comparison and case-control study of risk factors for HCRBSIs. METHODS: Prospective surveillance was used to compare HCRBSI rates for 1 year before and after implementation of maximal sterile barrier precautions. A case-control study compared 50 case-patients with HCRBSI with 51 randomly selected control-patients. RESULTS: The HCRBSI rate was 1.6% per 100 dialysis runs (CI95, 1.1%-2.3%) in the first year and 0.77% (CI95, 0.5%-1.1%) in the second year (P = .0106). The most frequent cause of HCRBSI was MRSA in the first year (15 of 32) and MSSA in the second year (13 of 18). Ten MRSA blood isolates in the first year were identical by PFGE. Diabetes mellitus was a risk factor for HCRBSI. Age, gender, site of hemodialysis central venous catheter (CVC), other underlying diseases, coma score, APACHE II score, serum albumin level, and cholesterol level were not associated with HCRBSI and did not change between the 2 years. Hospital stay was prolonged for case-patients (32.78 +/- 20.96 days) versus control-patients (22.75 +/- 17.33 days), but mortality did not differ. CONCLUSIONS: Use of maximal sterile barrier precautions during the insertion of CVCs reduced HCRBSIs in dialysis patients and seemed cost-effective. Diabetes mellitus was associated with HCRBSI. An outbreak of MRSA in the first year was likely caused by cross-infection via medical personnel.