High Correlation Between Clearance of Renal Protein‐Bound Uremic Toxins (Indoxyl Sulfate and p‐Cresyl Sulfate) and Renal Water‐Soluble Toxins in Peritoneal Dialysis Patients

Peritoneal dialysis (PD) is characterized by a slow continuous removal of solutes. Traditionally, dialysis adequacy is quantified by referring to the kinetics of urea nitrogen (UN) and creatinine (Cr) clearance. The efficacy of middle molecular substances and protein‐bound solutes as markers for peritoneal dialysis adequacy is not clear. The aim of this cross‐sectional study was to investigate correlations between the clearance of indoxyl sulfate (IS), p‐cresyl sulfate (PCS), UN, and Cr in the peritoneum and kidneys and to compare the overall clearances of IS and PCS between non‐anuric and anuric groups in PD patients. We recruited a total of 175 patients who had been undergoing continuous ambulatory PD (CAPD) or automated PD (APD) for at least 4 months. We measured total IS and PCS concentrations in serum, dialysate, and urine samples. Free IS and PCS concentrations were measured in all serum samples. IS and PCS clearances via both kidney and peritoneum were measured. The mean concentration of IS in the urine samples was 9.2‐fold higher than that in the dialysate samples, and concentration of PCS in the urine samples was 8.5‐fold higher than that in the dialysate samples. Peritoneal UN and Cr clearances were not correlated with peritoneal PCS clearance (P > 0.05) but were mildly correlated with peritoneal IS clearance. The peritoneal IS and PCS clearances in the different peritoneal equilibration test groups were similar. The renal UN and Cr clearances were strongly correlated with renal PCS and IS clearances (P > 0.89, P < 0.001). In addition, non‐anuric patients showed better elimination of total PCS (10.3 mg/day [range, 1.6–19.8] vs. 5.2 mg/day [range, 0–14]; P < 0.001] and IS (37.9 mg/day [range, 25.6–56.7] vs. 24.8 mg/day [range, 17.1–41.6]; P < 0.001) than anuric patients. This cross‐sectional study showed that peritoneal clearance of water‐soluble solutes is not correlated with that of PCS but is mildly correlated with that of IS. However, the renal clearances of IS and PCS show strong positive correlation with the renal clearances of UN and Cr. This study confirms the important role of residual renal function in the removal of protein‐bound uremic toxins.     

Levels of vascular endothelial growth factor and hepatocyte growth factor in sera of patients with rheumatic diseases

Abstract

Angiogenesis plays an important role in the progression of rheumatic disease. We measured the levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in sera from patients with rheumatic diseases and investigated whether these angiogenic factors would be useful in the evaluation of rheumatic diseases. Serum VEGF and HGF levels were determined using ELISA in 128 patients with rheumatic diseases and in 11 healthy controls. Serum VEGF and HGF levels were significantly higher in patients with rheumatic diseases compared to healthy controls [VEGF, 312 ± 20?pg/ml versus 61 ± 8?pg/ml (mean ± SE), P < 0.001; HGF, 935 ± 36?pg/ml versus 413 ± 49?pg/ml, P < 0.01]. Serum VEGF and HGF levels were significantly elevated in patients with adult Still's disease (VEGF, 1021 ± 258?pg/ml; HGF, 1500 ± 295?pg/ml) and were relatively increased in patients with active rheumatoid arthritis (RA) (VEGF, 359 ± 94?pg/ml) and systemic sclerosis (SSc) (VEGF, 356 ± 43?pg/ml; HGF, 1294 ± 224?pg/ml). HGF levels correlated with the clinical course and disease severity in rheumatic disease patients. VEGF levels correlated with the presence of Raynaud's phenomenon (P < 0.05), interstitial lung disease (ILD) (P < 0.05), and serum KL-6 levels (P < 0.01), whereas HGF levels correlated with cryoglobulinemia (P < 0.05), ILD (P < 0.05), serum C-reactive protein (CRP) (P < 0.05), thrombomodulin (P < 0.05), and KL-6 levels (P < 0.05) in rheumatic disease patients. VEGF levels correlated with the skin scores and KL-6 levels in SSc patients and also correlated with the disease activity of RA patients. These data suggest that serum VEGF and HGF levels are related to rheumatic disease activity and the presence of complications. Analysis of VEGF and HGF may be useful in the clinical evaluation of rheumatic disease patients.     

Levels of vascular endothelial growth factor and hepatocyte growth factor in sera of patients with rheumatic diseases

 Angiogenesis plays an important role in the progression of rheumatic disease. We measured the levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in sera from patients with rheumatic diseases and investigated whether these angiogenic factors would be useful in the evaluation of rheumatic diseases. Serum VEGF and HGF levels were determined using ELISA in 128 patients with rheumatic diseases and in 11 healthy controls. Serum VEGF and HGF levels were significantly higher in patients with rheumatic diseases compared to healthy controls [VEGF, 312 ± 20 pg/ml versus 61 ± 8 pg/ml (mean ± SE), P < 0.001; HGF, 935 ± 36 pg/ml versus 413 ± 49 pg/ml, P < 0.01]. Serum VEGF and HGF levels were significantly elevated in patients with adult Still's disease (VEGF, 1021 ± 258 pg/ml; HGF, 1500 ± 295 pg/ml) and were relatively increased in patients with active rheumatoid arthritis (RA) (VEGF, 359 ± 94 pg/ml) and systemic sclerosis (SSc) (VEGF, 356 ± 43 pg/ml; HGF, 1294 ± 224 pg/ml). HGF levels correlated with the clinical course and disease severity in rheumatic disease patients. VEGF levels correlated with the presence of Raynaud's phenomenon (P < 0.05), interstitial lung disease (ILD) (P < 0.05), and serum KL-6 levels (P < 0.01), whereas HGF levels correlated with cryoglobulinemia (P < 0.05), ILD (P < 0.05), serum C-reactive protein (CRP) (P < 0.05), thrombomodulin (P < 0.05), and KL-6 levels (P < 0.05) in rheumatic disease patients. VEGF levels correlated with the skin scores and KL-6 levels in SSc patients and also correlated with the disease activity of RA patients. These data suggest that serum VEGF and HGF levels are related to rheumatic disease activity and the presence of complications. Analysis of VEGF and HGF may be useful in the clinical evaluation of rheumatic disease patients. Received: February 19, 2002 / Accepted: August 13, 2002 Acknowledgment We are grateful to Ms. Aki Nomura for assistance with the ELISA of VEGF and HGF.     

Early mortality in multiple myeloma: Experiences from a single institution

Objective: Multiple myeloma (MM) is a hematological malignancy that presents with infection, anemia, bone lesions, renal function impairment, and hypercalcemia. The survival of MM patients has improved in recent decades; however, early mortality remains a critical problem. The aim of this study was to identify the etiologies and clinical variables associated with early mortality in MM. In addition, the effects of bortezomib on reducing early mortality incidence were investigated.

Method and materials: Medical records from 122 MM patients diagnosed between November 2007 and December 2013 were retrospectively reviewed. Early mortality was defined as death by any cause within the first 180 days after pathological diagnosis.

Results: In newly diagnosed MM patients, early mortality occurred in 22.95% of patients. Infection accounted for 67.86% of early deaths. Multivariate analyses by Cox proportional-hazards regression showed that higher β2-microglobulin (P?<?0.001) and serum lactate dehydrogenase (P?<?0.001) levels, and lower serum albumin levels (P?<?0.001) were associated with early mortality. Both first-line and greater than or equal to second-line bortezomib treatments were not associated with superior 180-day overall survival (P?=?0.546 for first-line bortezomib treatment; P?=?0.066 for greater than or equal to second-line bortezomib treatment).

Conclusion: Our results suggest that infection is the leading cause of early death in MM. High β2-microglobulin, high serum lactate dehydrogenase, and low serum albumin levels are poor prognostic factors for early mortality. Bortezomib therapy does not appear to reduce the incidence of early mortality in MM patients.     

Impact of Renal Survival on the Course and Outcome of Systemic Lupus Erythematosus Patients Treated With Chronic Peritoneal Dialysis

This longitudinal study investigated whether renal survival can affect the course and outcome of systemic lupus erythematosus (SLE) patients treated with chronic peritoneal dialysis (PD). Thirty-five SLE patients, out of 1115 end-stage renal disease (ESRD) patients treated with chronic PD, were seen between 1990 and 2007 at the Chang Gung Memorial Hospital. Patients were followed up for a mean of 38.8 ± 22.9 months. There were no significant differences between patients with short renal survival (<3 years) and long renal survival (>3 years) for the various demographic variables such as age, sex, PD duration, immunosuppressive drug administration, or exchange system (P > 0.05). Interestingly, before PD, patients with short renal survival had lower serum complement levels than patients with long renal survival (C3, 40.2 ± 14.4 vs 76.3 ± 18.5 mg/dL, P < 0.001; and C4, 14.8 ± 4.7 vs 22.4 ± 8.1 mg/dL, P < 0.05). However, the differences in complement levels between the groups disappeared after PD (C3, 76.5 ± 27.3 vs 84.2 ± 27.8 mg/dL; and C4, 26.7 ± 11.3 vs 22.6 ± 10.8 mg/dL, both P > 0.05). Patients with short renal survival were more likely to have a high peritoneal solute transporter rate (PSTR) than their long renal survival counterparts (χ²-test, P = 0.02, and AUROC = 0.744 and P = 0.040); however, there were no significant differences for other variables such as cardiothoracic ratio (CTR), Kt/V, residual renal function, exit site infection, and peritonitis (P > 0.05). Finally, Kaplan–Meier analysis revealed that the two groups did not differ in patient and technical survival (P > 0.05). Therefore it was concluded that renal survival might be associated with PSTR, but not with patient and technical survival in SLE patients treated with PD.     

The relationship between oxidized serum albumin and blood pressure in hypoalbuminemic peritoneal dialysis patients

Background: Oxidative stress produces molecular modifications of serum albumin that disturb its biological functions and interfere with its detection by the bromocresol green assay (BCG). Oxidative stress, inflammation, and hypoalbuminemia are common peritoneal dialysis (PD). This study aimed to evaluate the relationship between serum albumin, oxidized serum albumin (OSA), oncotic pressure, and blood pressure in hypoalbuminemic PD patients. Methods: Twenty-four PD patients with serum albumin levels <3.5 g/dl enrolled in the study. Data were compared between participants with the mean arterial pressure (MAP) <105 mmHg (n = 12) and MAP ≥ 105 mmHg (n = 12). Results: Serum albumin levels were ≤3.0 g/dl and similar in both groups (p = 0.298). The calculated OSA and oncotic pressure were significantly higher in patients with MAP ≥ 105 mmHg than in those with MAP < 105 mmHg. MAP was positively and marginally correlated with serum albumin levels (measured by BCG) (r = 0.34, p = 0.05), and positively and significantly correlated with the calculated OSA and oncotic pressure (r = 0.44, p = 0.015, r = 0.58, p = 0.002; respectively). The oncotic pressure was positively correlated with the calculated OSA (r = 0.47, p = 0.011). Conclusion: OSA, undetectable by the commonly used BCG, may contribute to higher blood pressure in hypoalbuminemic PD patients.     

Effects of Lowering Dialysate Calcium Concentration on Bone Metabolic Markers in Hemodialysis Patients With Suppressed Serum Parathyroid Hormone: A Preliminary Study

Although the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend a dialysate calcium concentration between 2.5 and 3.0 mEq/L, its optimal concentration remains unclear. A total of 53 hemodialysis patients with intact parathyroid hormone (PTH) levels <150 pg/mL were enrolled in this prospective observational study. A dialysate calcium concentration was converted from 3.0 to 2.75 mEq/L and bone metabolic markers including bone alkaline phosphatase (BAP) and tartrate‐resistant acid phosphatase‐5b (TRACP‐5b) were examined. After 3 months, serum corrected calcium levels decreased (P < 0.001), while serum intact PTH, BAP and TRACP‐5b levels increased (P < 0.05, P < 0.05 and P < 0.001, respectively). Multiple regression analyses showed that the amount of change in BAP was significantly associated with dialysis vintage (P < 0.01). In conclusion, the lowering of dialysate calcium concentration stimulated parathyroid gland and bone remodeling in hemodialysis patients with suppressed PTH, particularly with longer dialysis vintage.     

Associations of Peritoneal Glucose Load With Male Sexual Dysfunction and Depression in Peritoneal Dialysis Patients

This cross‐sectional study examined possible associations of peritoneal glucose load with male sexual dysfunction and depression in peritoneal dialysis patients. Compared to patients with peritoneal glucose load ≤3 g/kg per day, those with load >3 g/kg per day had higher Beck Depression Inventory scores, (18.9 ± 5.4 vs. 11.4 ± 5.8, P = 0.002) and lower International Index of Erectile Function scores, serum total testosterone and DHEA [(15.4 ± 6.4 vs. 45.1 ± 20.7, P < 0.001), (8.5 ± 3.0 vs. 13.9 ± 3.2, P < 0.001), (113.9 ± 58.8 vs. 280.2 ± 128.3, P < 0.001); respectively)]. Of participants with peritoneal glucose load >3 g/kg per day, 84.6% had mild to moderate erectile dysfunction and 92.3% had abnormal Beck Depression Inventory scores. Peritoneal glucose load inversely correlated with International Index of Erectile Function scores (P < 0.001), total serum testosterone (P = 0.002) and serum DHEA (P = 0.001); and directly with Beck Depression Inventory scores (P < 0.001) and serum estradiol (P < 0.001). This study demonstrated higher prevalence of sexual dysfunction, depression and sex hormone disturbances in male peritoneal dialysis patients receiving higher peritoneal glucose load.     

Risk Factors for Encapsulating Peritoneal Sclerosis in Long‐Term Peritoneal Dialysis: A Retrospective Observational Study

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long‐term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long‐term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non‐EPS. To evaluate the impact of PD‐associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non‐EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non‐EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long‐term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD‐associated peritonitis could be critical in preventing EPS.     

Peritoneal Protein Losses Depend on More Than Just Peritoneal Dialysis Modality and Peritoneal Membrane Transporter Status

Peritoneal protein clearance (PPCl) depends upon vascular supply and size selective permeability. Some previous reports suggested PPCl can distinguish fast peritoneal membrane transport due to local or systemic inflammation. However, as studies have been discordant, we wished to determine factors associated with an increased PPCl. Consecutive patients starting peritoneal dialysis (PD) who were peritonitis-free were studied. Data included a baseline peritoneal equilibration test (PET), measurement of dialysis adequacy, 24-h dialysate PPCl and body composition measured by multifrequency bioimpedance. 411 patients, mean age 57.2 ± 16.6 years, 60.8% male, 39.4% diabetic, 20.2% treated by continuous ambulatory peritoneal dialysis (CAPD) were studied. Mean PET 4-h Dialysate/Serum creatinine was 0.73 ± 0.13, with daily peritoneal protein loss 4.6 (3.3–6.4) g, and median PPCl 69.6 (49.1–99.6) mL/day. On multivariate analysis, PPCl was most strongly associated with CAPD (β 0.25, P < 0.001), extracellular water (ECW)/total body water (TBW) ratio (β 0.21, P < 0.001), skeletal muscle mass index (β 0.21, P < 0.001), log N-terminal brain natriuretic peptide (NT-proBNP) (β 0.17, P = 0.001), faster PET transport (β 0.15, P = 0.005), and normalized nitrogen appearance rate (β 0.13, P = 0.008). In addition to the longer dwell times of CAPD, greater peritoneal creatinine clearance and faster PET transporter status, we observed an association between increased PPCl and ECW expansion, increased NT-proBNP, estimated dietary protein intake and muscle mass, suggesting a link to sodium intake and sodium balance, increasing both ECW and conduit artery hydrostatic pressure resulting in greater vascular protein permeability. This latter association may explain reports linking PPCl to patient mortality.     

Pigment Epithelium‐Derived Factor as a New Predictor of Mortality Among Chronic Kidney Disease Patients Treated With Hemodialysis

Pigment epithelium‐derived factor (PEDF) plays a protective role against atherosclerosis. Although serum PEDF level is increased in patients undergoing regular hemodialysis (HD), the pathophysiological role of PEDF in HD patients is unknown. We measured serum PEDF levels in 74 HD patients, and the association between serum PEDF and adverse events such as all‐cause death and cardiovascular accident was evaluated prospectively. During the follow up of 45.4 ± 25.1 months, 24 patients (32.4%) experienced cardiovascular accident and 18 (24.3%) died. Significantly higher incidences of all‐cause mortality and cardiovascular accident were observed in the lower PEDF group than in the higher PEDF group. After adjusting for propensity score calculated from multiple confounding factors (age, gender, systolic blood pressure, history of previous cardiovascular disease, level of carbonyl content, albumin, hemoglobin, total cholesterol, creatinine, C‐reactive protein, dialysis vintage, Kt/V‐urea and history of diabetes), lower predialytic PEDF was a significant risk factor for all‐cause mortality (relative hazard = 6.060, standard error = 0.68467, P = 0.0085). Lower levels of predialytic PEDF was associated with an increased risk of mortality.     

Hypoglycemia in Diabetic Patients Undergoing Chronic Hemodialysis

The aim of our study was to determine if different hypoglycemic therapies are associated with more frequent episodes of hypoglycemia in diabetes patients undergoing long-term hemodialysis. We conducted a prospective cohort study that included 102 diabetes patients who were undergoing long-term hemodialysis. The frequency of symptomatic hypoglycemic episodes, intradialytic hypotension, antihypertension medication, hypoglycemic therapy regimens, dialysate contents, and laboratory data were reviewed. The duration of follow-up was three months. Fifty-four (52.9%) patients were categorized as hypoglycemic and 48 (47.1%) patients as non-hypoglycemic. The serum albumin levels of the hypoglycemic and non-hypoglycemic patients were 3.18 ± 0.34 g/dL and 3.44 ± 0.33 g/dL respectively (P < 0.001). The prevalence of intradialytic hypotension is significantly higher in the hypoglycemic patients (44.4%) than in the non-hypoglycemic patients (20.8%) (P = 0.012). The risk of hypoglycemia differed significantly between the patients taking oral hypoglycemic agents (OHAs) and those receiving purely insulin therapy (P = 0.035). Multivariate analysis revealed that the serum albumin (odds ratio [OR] 0.093, 95% confidence interval [CI] 0.021–0.409), intradialytic hypotension (OR 2.755, 95% CI 1.048–7.228), and OHA therapy (OR 0.337, 95% CI 0.128–0.888) were independent factors of hypoglycemia. The patients treated only with meglitinides as hypoglycemic therapy had a significantly lower risk of hypoglycemia than those receiving mixed insulin therapy (P = 0.016). Frequent episodes of intradialytic hypotension and hypoalbuminemia are powerful clinical predictors of hypoglycemia in diabetes patients undergoing hemodialysis. It was also found that OHAs do not pose a higher risk of hypoglycemia than insulin in diabetic patients undergoing hemodialysis.     

Does Whey Protein Supplementation Improve the Nutritional Status in Hypoalbuminemic Peritoneal Dialysis Patients?

Limited data are available regarding the effects of whey protein on the nutritional status of the peritoneal dialysis population. This study evaluated the effects of whey protein supplementation for 12 weeks on the nutritional status in hypoalbuminemic peritoneal dialysis patients. Thirty‐six stable adult patients on maintenance peritoneal dialysis with serum albumin levels <3.5 g/dL were enrolled in the study and were divided into two groups similar in their serum albumin and normalized protein equivalent of total nitrogen appearance (nPNA). Nineteen patients were instructed to receive 1.2 g/kg per day of protein diet and additional whey protein supplement at a dose of 25% of the instructed daily protein diet (whey protein group), and 17 patients were instructed to receive 1.2 g/kg per day protein diet without additional whey protein supplementation (control group). Nutritional status was assessed using two measures: nPNA and lean tissue mass index (LTI) obtained by whole‐body bioimpedance spectroscopy technique. In the whey protein group serum albumin and nPNA significantly increased from baseline to week 6 (P < 0.001, P = 0.034; respectively) and from week 6 to week 12 (P < 0.001, P = 0.001; respectively); LTI significantly increased from week 6 to week 12 (P = 0.022). Compared to the control group at week 12, serum albumin, nPNA and LTI values were significantly higher in the whey protein group (P < 0.001, P = 0.002, P = 0.001; respectively). This study demonstrated for the first time that oral supplementation with whey protein improves nutritional status and is well tolerated in hypoalbuminemic PD patients.     

Variation in initial kidney replacement therapy for end-stage renal disease due to lupus nephritis in the United States

Objective

Little is known about the patterns of use of initial kidney replacement therapies among patients with lupus nephritis (LN) end‐stage renal disease (ESRD). We aimed to identify sociodemographic and clinical factors associated with variation in initial kidney replacement therapies among LN ESRD patients.

Methods

Patients with incident LN ESRD (1995–2006) were identified in the US Renal Data System. Age, sex, race, ethnicity, medical insurance, employment status, residential region, clinical factors, and comorbidities were considered as potential predictors of ESRD treatment choice, i.e., peritoneal dialysis (PD), hemodialysis (HD), or preemptive kidney transplantation in age‐adjusted and multivariable‐adjusted logistic regression analyses.

Results

Of the 11,317 individuals with incident LN ESRD, 82.0% initiated HD, 12.2% initiated PD, and 2.8% underwent preemptive kidney transplantation. Receiving initial PD was significantly associated with earlier calendar year, female sex, higher albumin and hemoglobin levels, and lower serum creatinine levels. African Americans (versus whites), Medicaid beneficiaries and those with no health insurance (versus private insurance), and those unemployed (versus employed) had significantly reduced PD initiation. Comorbidities including congestive heart failure, peripheral vascular disease, and the inability to ambulate were also associated with decreased PD. Many sociodemographic and clinical factors favoring PD were associated with preemptive kidney transplant (versus dialysis) as well.

Conclusion

Few patients with LN ESRD receive initial PD or preemptive kidney transplantation. Race, ethnicity, employment, and medical insurance type are strongly associated with initial kidney replacement therapy choice. Future studies need to investigate the appropriateness of sociodemographic and clinical variation and the comparative effectiveness of kidney replacement therapies for LN ESRD.     

Influence of Residual Renal Function in Carotid Modeling as a Marker of Early Atherosclerosis in Dialysis Patients

Atherosclerosis is frequently present in patients with chronic kidney disease (CKD) treated with dialysis. We evaluated the association between residual renal function (RRF), phosphate level, inflammation and other risk factors in carotid modeling as a marker of early atherosclerosis in peritoneal dialysis (PD) compared with hemodialysis (HD) patients. We studied 39 stable PD and 53 HD patients on renal replacement therapy (RRT) for 3 to 36 months duration. B‐mode ultrasonography was used to determine carotid artery intima media thickness (CIMT). We classified patients with atherosclerosis if they have CIMT >10 mm and or presence of plaque. Out of our total dialysis population studied of 92 patients, 16.3% were diabetics and 57.6% were on hemodialysis. Expectedly, PD patients had a higher RRF (P < 0.001), 24 h urine volume (P < 0.001); C‐reactive protein (P = 0.047), and a lower serum phosphate (P = 0.01), PTH (P < 0.05), alkaline phosphatase (P < 0.05), and albumin levels (P < 0.001) compared to hemodialysis patients. Atherosclerosis was found in 66.3% of patients and in 100% of a diabetic population. There was no significant difference in the presence of atherosclerosis between PD and HD patients [56.4 vs 73.6% HD, respectively]. Multiple regression analysis showed age, diabetes, HD modality, RRF, phosphate, PTH and pulse pressure as independent parameters associated with atherosclerosis. Apart from the traditional risk factors like age and diabetes, our study showed a link of atherosclerosis with metabolic abnormalities secondary to renal failure. We demonstrated a novel, independent association between RRF and atherosclerosis, underlining the importance of preservation of the RRF in dialysis patients.     

Serum myeloperoxidase level predicts reperfusion in patients with myocardial infarction receiving thrombolytic therapy

Polymorphonuclear leukocytes play a central role in all stages of the atherothrombotic inflammatory process. The atherothrombotic activity of polymorphonuclear leukocytes is exerted by mediators such as myeloperoxidase (MPO). Although the role of MPO has been studied with respect to the development of adverse cardiac events in acute coronary syndromes (ACS), the association of this molecule with effectiveness of reperfusion in patients receiving thrombolysis is not yet known. The study population consisted of a total of 158 patients with acute coronary syndromes. Final diagnosis was ST-segment elevation myocardial infarction in 86 patients, 80 of whom received thrombolysis. Blood samples were drawn at presentation of the patients and serum myeloperoxidase levels were measured. Reperfusion was defined in terms of electrocardiographic ST-segment resolution. The serum levels of MPO were found to be correlated with rates of in-hospital adverse events including death (P < 0.001), reinfarction (P < 0.001), recurrent ischemia (P < 0.001), arrhythmias (P < 0.001), clinical heart failure (P < 0.001), and cardiogenic shock (P < 0.001). There was a significant difference in serum MPO levels between subjects with three-vessel disease and two- or one-vessel disease (P < 0.001). Pre-lytic serum high-sensitivity C-reactive protein levels in patients with successful reperfusion were lower than in patients with failed reperfusion (P < 0.001). Analysis of patients with ST segment elevation myocardial infarction receiving thrombolytic therapy revealed that pre-lytic serum MPO levels in patients with successful reperfusion were significantly lower than those of patients with failed reperfusion (P < 0.001). In the present study, serum MPO levels were found to be a strong predictor of response to thrombolytic treatment in patients with ST-segment elevation myocardial infarction. Therefore the level of inflammatory activity in acute coronary syndromes seems to influence the effectiveness of fibrinolysis.     

Preoperative level of serum amyloid A is superior to C‐reactive protein in the prognosis of esophageal squamous cell carcinoma

Preoperative elevations in the levels of serum amyloid A (SAA) or C‐reactive protein (CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252 patients with ESCC who had undergone surgery with curative‐intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1‐, 3‐, and 5‐year overall survival (OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant (r² = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis.     

Adherence to Phosphate Binder Therapy Is the Primary Determinant of Hyperphosphatemia Incidence in Patients Receiving Peritoneal Dialysis

We investigated the major determinant of hyperphosphatemia incidence among patients receiving peritoneal dialysis. Seventy‐six patients aged 25–55 years who had received peritoneal dialysis for more than 3 months were recruited. The patients were divided into three groups according to their serum phosphorus levels (Group 1, ≥6 mg/dL; Group 2, 5.9–4.8 mg/dL; and Group 3, <4.8 mg/dL). Renal dietitians interviewed the patients to determine their phosphate intake and adherence to phosphate binder therapy. No statistical differences in demographics or phosphate intake were identified among the groups. However, adherence to phosphate binders was greater in Group 3 than in Groups 1 and 2 (96.3% vs. 21.4% and 52.4%, respectively; P < 0.001). Multivariate analysis showed that adherence to phosphate binder therapy was the only significant contributor to serum phosphorus levels (P= 0.0001). Adherence to diet was better than adherence to phosphate binder therapy among patients receiving peritoneal dialysis, and the latter determined the incidence of hyperphosphatemia.     

Expression of breast cancer anti‐estrogen resistance 1 in relation to vascular endothelial growth factor,p53, and prognosis in esophageal squamous cell cancer

The purpose of this study was to clarify the role of breast cancer anti‐estrogen resistance 1 (BCAR1) expression in relation to vascular endothelial growth factor (VEGF), p53, and proliferation in esophageal squamous cell cancer (ESCC). Expression of BCAR1, VEGF, p53, and the ki‐67 proliferative index were examined by tissue microarray and immunohistochemistry in 106 specimens with ESCC and matched adjacent normal tissues. Among them, 40 cases were simultaneously examined by Western blot. Both Western blot and immunohistochemistry showed that BCAR1 expression was substantially higher in ESCC than in adjacent normal tissues (P < 0.001). BCAR1 expression was significantly connected with degree of tumor differentiation, with poorly differentiated tumors showing higher BCAR1 expression (P < 0.001). BCAR1 expression was significantly and positively correlated with VEGF and p53 expression levels (r= 0.541, P < 0.001; r= 0.374; P < 0.001) but not proliferative index (r= 0.44; P= 0.066). Additionally, a significant relationship was also observed between VEGF and p53 (r= 0.321; P= 0.001). Kaplan–Meier survival analysis revealed that patients with high BCAR1 expression had significantly shorter survival times than those with low BCAR1 expression levels (median survival 40 months vs. 27 months, P= 0.09). Multivariate analysis also revealed that levels of BCAR1 expression (hazard ratio 2.250, P= 0.015) was a significant and independent prognostic indicator. High expression of BCAR1 is associated with elevated VEGF and p53 expression levels, as well as poor prognosis in ESCC. Therefore, BCAR1 may be a potential candidate for predicting prognosis and a new therapy target for ESCC.