Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid, and aorta of uremic rats.

Klotho plays an important role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Klotho is highly expressed in the kidney and parathyroid glands, but its presence in the vasculature is debated. Renal Klotho is decreased in CKD, but the effect of uremia on Klotho in other tissues is not defined.

Cardiac and renal effects of atrasentan in combination with enalapril and paricalcitol in uremic rats.

Background/aims: The search for new therapies providing cardiorenal protection in chronic kidney disease (CKD) has led to treatments that combine conventional renin-angiotensin-aldosterone-system inhibitors with other drugs that exhibit potential in disease management.

Methods: In rats made uremic by renal ablation, we examined the effects of addition of the endothelin-A receptor antagonist atrasentan to a previously examined combination of enalapril (angiotensin converting enzyme inhibitor) and paricalcitol (vitamin D receptor activator) on cardiac and renal parameters. The effects of the individual and combined drugs were examined after a 3-month treatment.

Use of aspirin associates with longer primary patency of hemodialysis grafts.

Extended-release dipyridamole plus low-dose aspirin (ERDP/ASA) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts, but the individual contributions of each component are unknown. Here, we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a randomized trial that compared ERDP/ASA and placebo in newly created grafts. We used Cox proportional hazards regression, adjusting for prespecified baseline comorbidities and covariates.

Effects of sodium thiosulfate on vascular calcification in end-stage renal disease: a pilot study of feasibility, safety and efficacy.

Background And Objectives: Vascular calcification is a major contributor to morbidity and mortality in hemodialysis. The objective of this pilot study was to determine the feasibility, safety and efficacy of sodium thiosulfate (STS) in the progression of vascular calcification in hemodialysis patients.

Methods: Chronic hemodialysis patients underwent a battery of cardiovascular tests.

A randomized, parallel, open-label study to compare once-daily sevelamer carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing in CKD patients on hemodialysis.

Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing.

Study Design: Randomized parallel open-label study.

Setting & Participants: Hemodialysis patients.

The effect of oral niacinamide on plasma phosphorus levels in peritoneal dialysis patients.

Background: Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality. Current treatment options include dietary restriction, dialysis, and phosphate binders. Treatment using the latter is frequently limited by cost, tolerability, and calcium loading.

Effect of dipyridamole plus aspirin on hemodialysis graft patency.

Background: Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity.

Relation of serum fetuin-A levels to coronary artery calcium in African-American patients on chronic hemodialysis.

Vascular calcium deposition in end-stage renal disease occurs commonly, but its relation to cardiovascular risk factors and fetuin-A levels in African Americans is not known. Compliant African American patients who were undergoing hemodialysis (HD; n = 17) agreed to undergo 64-slice multidetector computed tomography for the assessment of coronary artery calcium score (CACS). The relation between traditional cardiovascular risk factors (i.

Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial.

Context: The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters. Early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis. Small, inconclusive trials have suggested that antiplatelet agents may reduce thrombosis of new fistulas.

A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients.

Background And Objectives: Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies. A prospective, randomized, double-blind, placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide.

Design, Setting, Participants, & Measurements: Hemodialysis patients with phosphorus levels > or =5.

Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients.

Background And Objectives: Secondary analysis of the Hemodialysis Study showed that serum beta(2)-microglobulin levels predicted all-cause mortality and that high-flux dialysis was associated with decreased cardiac deaths in hemodialysis patients. This study examined the association of serum beta(2)-microglobulin levels and dialyzer beta(2)-microglobulin kinetics with the two most common causes of deaths: Cardiac and infectious diseases. Cox regression analyses were performed to relate cardiac or infectious deaths to cumulative mean follow-up predialysis serum beta(2)-microglobulin levels while controlling for baseline demographics, comorbidity, residual kidney function, and dialysis-related variables.

Cerebrovascular disease in maintenance hemodialysis patients: results of the HEMO Study.

Background: Cerebrovascular disease (CBVD) in hemodialysis patients is associated with significant morbidity and mortality. A secondary analysis of CBVD in the Hemodialysis (HEMO) Study was performed. Specific objectives were to: (1) determine risk factors for the presence of CBVD at baseline, (2) assess risk factors for the subsequent occurrence of cerebrovascular deaths, and (3) analyze the effects of dose and flux on cerebrovascular mortality.

Association of achieved dialysis dose with mortality in the hemodialysis study: an example of "dose-targeting bias".

In the intention-to-treat analysis of the Hemodialysis Study, all-cause mortality did not differ significantly between the high versus standard hemodialysis dose groups. The association of mortality with delivered dose within each of the two randomized treatment groups was examined, and implications for observational studies were considered. Time-dependent Cox regression was used to relate the relative risk (RR) for mortality to the running mean of the achieved equilibrated Kt/V (eKt/V) over the preceding 4 mo.

Dialysis dose and the effect of gender and body size on outcome in the HEMO Study.

Background: Gender and body size have been associated with survival in hemodialysis populations. In recent observational studies, overall mortality was similar in men and women and higher in small patients. The effect of dialysis dose in each of these subgroups has not been tested in a clinical trial.

Effect of dialysis dose and membrane flux in maintenance hemodialysis.

Background: The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain.

Methods: We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer.

Results: In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.

Relationship between volume status and blood pressure during chronic hemodialysis.

Background: The relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial.

Methods: We determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross-sectional analysis of a subset of patients (N=468) from the Hemodialysis (HEMO) Study.