Serum phosphate as an independent factor associated with cholesterol metabolism in patients undergoing hemodialysis: a cross-sectional analysis of the DREAM cohort.

BACKGROUND: Hyperphosphatemia is a risk factor for cardiovascular outcomes in patients with chronic kidney disease. In an experimental model, hyperphosphatemia promoted atherosclerosis by activating sterol regulatory element-binding protein 2, which controls cholesterol homeostasis. In the present study, we hypothesized that serum phosphate level is associated with cholesterol metabolism in patients with kidney failure. METHODS: We conducted a single-center cross-sectional study including 492 patients undergoing hemodialysis and 100 healthy controls not on statin or ezetimibe treatment. Serum lathosterol and campesterol levels were measured as a marker of cholesterol synthesis and absorption, respectively. As compared with the control group, the hemodialysis patients had higher median phosphate {5.8 mg/dL [interquartile range (IQR 5.0-6.6) versus 3.3 (3.0-3.6); P < .001], lower lathosterol [1.2 µg/mL (IQR 0.8-1.7) versus 2.6 (1.9-3.4); P < .001] and higher campesterol levels [4.5 µg/mL (IQR 3.6-6.0) versus 4.1 (3.2-5.4); P = .02]. Serum phosphate correlated positively to campesterol in the control group (Spearman's r = 0.21, P = .03) and in hemodialysis patients (Spearman's r = 0.19, P < .001). The positive association between phosphate and campesterol levels in the hemodialysis group remained significant in multivariable-adjusted linear regression analysis. There was no significant association between phosphate and lathosterol in either group. CONCLUSIONS: An independent association was found between phosphate and campesterol levels in patients with kidney failure. This study suggests a novel relationship between phosphate and cholesterol metabolism, both of which could affect cardiovascular outcomes in this population.

Oxidative Stress and Inflammation as Predictors of Mortality and Cardiovascular Events in Hemodialysis Patients: The DREAM Cohort.

AIM: Both oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease (CVD). The serum level of derivatives of reactive oxygen metabolites (d-ROMs) is a measure of the total amount of hydroperoxides serving as a marker of oxidative stress. We investigated whether d-ROMs could predict the clinical outcomes in hemodialysis patients and whether the associations of d-ROMs with the outcomes are independent of a marker of inflammation, C-reactive protein (CRP). METHODS: This was a prospective cohort study in hemodialysis patients. The key exposures were the serum levels of d-ROMs and CRP. The outcome measures were all-cause mortality and new CVD events. RESULTS: A total of 517 patients were analyzed. d-ROMs correlated positively with CRP. During follow-up for 5 years, 107 patients died, and 190 patients experienced new CVD events. In the Kaplan-Meier analyses, both higher d-ROMs and higher CRP levels predicted higher risks for mortality and CVD events. By Cox proportional-hazard regression analysis adjusted for potential confounders excluding CRP, d-ROMs exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for CRP. Using the same model, CRP exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for d-ROMs. When we analyzed new CVD events as the outcome, CRP was a significant predictor, whereas the level of d-ROMs was not. CONCLUSIONS: Although d-ROMs predicted mortality and CVD events in unadjusted models, the associations of d-ROMs with these outcomes were not independent of CRP. Oxidative stress and inflammation appear to share common causal pathways.

Decreased serum adrenal androgen dehydroepiandrosterone sulfate and mortality in hemodialysis patients.

BACKGROUND: Endocrine and metabolic abnormalities may affect the survival of hemodialysis patients. Serum dehydroepiandrosterone sulfate (DHEA-S), an adrenal androgen with anabolic properties, is known to be lowered in ill patients and predicts poor outcome in the general population and in those with cardiac disease. The aims of this study were to examine a possible change in the DHEA-S level in dialysis patients and its association with survival in this population. METHODS: This was an observational cohort study in 494 prevalent hemodialysis patients (313 men and 181 women) in urban area of Osaka, Japan. The main exposure was the baseline DHEA-S level in December 2004 and the key outcome was all-cause mortality during the subsequent 5 years. Also, DHEA-S levels were compared between the hemodialysis patients and 122 matched healthy controls. RESULTS: The median (inter-quartile range) DHEA-S levels were 771 (447-1351) and 414 (280-659) ng/mL for male and female dialysis patients, respectively, and these values were significantly lower by 40-53% than the healthy control levels. Among the hemodialysis patients, DHEA-S was lower in women, those with older age, pre-existing cardiovascular disease, lower serum albumin and higher C-reactive protein. During the follow-up, we recorded 101 deaths. A low DHEA-S level was a significant predictor of all-cause mortality independent of potential confounders in male, but not in female, hemodialysis patients. CONCLUSIONS: The serum DHEA-S level is decreased in hemodialysis patients and associated with mortality in men. These results support the growing observational evidence that uremia-induced endocrine alterations including decreased sex hormones may be linked to adverse clinical outcomes.

Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate.

BACKGROUND: Chronic kidney disease (CKD) is a newly recognized high-risk condition for cardiovascular disease (CVD), and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR). METHODS: The subjects were 182 participants of a health check-up program including those with normal (>or= 90 mL/min/1.73 m2, N = 79) and mildly reduced eGFR (60-89 mL/min/1.73 m2, N = 103) which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR < 60 mL/min/1.73 m2. No one had proteinuria. We measured serum levels of C-reactive protein (CRP) and thioredoxin (TRX) as the markers of inflammation and oxidative stress, respectively. RESULTS: As compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C) and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance. CONCLUSIONS: We showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.

Adult Henoch-Schönlein purpura with severe abdominal pain treated with dapsone and factor XIII concentrate.

We describe an adult patient with Henoch-Schönlein purpura who had arthralgia, severe abdominal pain, and low plasma factor XIII activity. Corticosteroids were not used because of his history of multidrug-resistant pulmonary tuberculosis. Dapsone had no immediate effect on his abdominal pain, but appeared to have some effect on the purpura and arthralgia. Marked improvement of the abdominal pain was observed immediately after the administration of factor XIII concentrate. Factor XIII concentrate may be useful for alleviating abdominal pain in Henoch-Schönlein purpura patients when corticosteroids are contraindicated