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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. One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients. Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis (PD) patients already receiving standard phosphorus-lowering therapies.Methods An 8 week, randomized, double blind, placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients. Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were randomized to niacinamide or placebo and prescribed 250 mg twice daily, with titration to 750 mg twice daily, as long as safety parameters were not violated. Phosphate binders, active vitamin D, and cinacalcet were kept constant during the study. The primary end point was change in plasma phosphorus. Secondary end points included changes in lipid parameters.Results 15 patients started on the study drug (8 niacinamide, 7 placebo) and 7 in each arm had at least one on-study phosphorus measurement. The niacinamide treatment group experienced an average 0.7 ± 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 ± 0.8 mg/dL increase. The treatment effect difference (1.1 mg/dL) was significant (p= 0.037). No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated. Two of the 8 patients randomized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects. Adverse effects may limit the use of niacinamide in PD patients.Conclusion Niacinamide, when added to standard phosphorus-lowering therapies, resulted in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks. [ClinicalTrials.gov number NCT00508885 (ClinicalTrials.gov)]

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. Methods:The HEMO Study was a randomized multicenter study evaluating the effects of high-dose versus standard-dose and high-flux versus low-flux hemodialysis. There were 1,846 patients enrolled, with a mean follow-up of 2.84 years. Results:Factors associated with the baseline presence of CBVD included age (P< 0.0001), presence of any cardiac disease (P< 0.0001), and diabetes mellitus (P< 0.0001). There were 65 deaths caused by CBVD (event rate, 1.2/100 patient-years). Multivariate Cox regression using a backward-variables selection procedure showed that diabetes, lower albumin level, greater hematocrit, and lower body mass index at baseline were associated significantly with subsequent CBVD death. There was no effect of flux or dose on overall rate of CBVD deaths. However, an interaction was found between baseline CBVD status and flux intervention on CBVD death (P= 0.016). In the subgroup of patients without the baseline presence of CBVD, high-flux dialysis was associated with a lower risk for death caused by CBVD (P= 0.016). A borderline interaction between years of dialysis therapy and flux on subsequent CBVD death was detected (P= 0.05). The beneficial effect of high flux was evident in those on hemodialysis therapy for longer than 3.7 years (P= 0.012). Conclusion:High flux was associated with decreased CBVD mortality in those without known CBVD at baseline and those on hemodialysis therapy for longer than 3.7 years. This secondary analysis strengthens, but does not prove, the hypothesis that high-flux treatment may attenuate the death rate from vascular disease.

Insulin-like growth factor 1 (IGF1) has been shown to improve renal function in healthy subjects, as well as those with chronic renal failure. To our knowledge, IGF1 has not been shown to be efficacious in patients who were already undergoing dialysis. We present the case of a 70-year-old woman with end-stage renal disease (ESRD) and overt uremic symptoms treated with IGF1 after peritoneal dialysis was discontinued because of complications. There was a significant improvement in her inulin clearance during the course of treatment. The patient remained well and did not require dialytic support for 19 weeks. Although further data are necessary, we believe this case shows that IGF1 may be a short-term alternative to dialysis in patients with ESRD.

There is extensive literature supporting an important role for acidosis in inducing net protein breakdown, both in experimental animals and humans. However, the clinical importance of the moderate intermittent metabolic acidosis frequently observed in hemodialysis patients has not been determined. We performed a cross-sectional analysis of the baseline laboratory data in the first 1,000 patients recruited to the Hemodialysis Study, looking for correlations between predialysis serum total carbon dioxide levels and parameters related to dietary intake and nutritional status. We found the mean predialysis serum total carbon dioxide level was moderately low (21.6 ± 3.4 mmol/L; mean ± SD) despite the use of bicarbonate dialysate and an average single-pool Kt/V of 1.54. Predialysis serum total carbon dioxide level correlated negatively with normalized protein catabolic rate (P< 0.001), suggesting patients with lower serum total carbon dioxide levels have a greater protein intake. The degree of acidosis observed in our patients does not seem to have a deleterious effect on the nutritional status of these patients because correlation of serum total carbon dioxide level with nutritional parameters, such as serum creatinine and serum albumin levels, was either negative or not statistically significant. Further investigation of the effect of modifying serum bicarbonate concentration on nutritional markers is needed to test these hypotheses.

Twenty-two chronic hemodialysis patients with hypertension were treated with prazosin. Eight patients had volume-responsive hypertension, 11 volume-independent, and 3 high-renin hypertension. Blood pressure fell in all volume-responsive patients from a predialysis level of 175 ± 5/100 ± 3 to 148 ± 4/75 ± 3 mm Hg (p< 0.001) after 3 months of therapy. Prazosin alone was effective in volume-responsive patients at a dose of 5 ± 1.0 mg daily. The blood pressure fell in volume-independent patients from 192 ± 7/105 ± 2 mm Hg predialysis to 155 ± 6/80 ± 3 after 3 months (p< 0.001). Two were controlled on prazosin alone at a dose of 12 ± 2 mg daily. Nine required 27 ± 5 mg of prazosin daily as well as additional antihypertensive treatment. The blood pressure fell from 183 ± 3/109 ± 6 mm Hg predialysis to 173 ± 17/85 ± 3 mm Hg in high-renin patients after 3 months. One patient was controlled on 40 mg of prazosin daily. Two required 40 mg of prazosin daily as well as additional antihypertensive medication. Eleven patients described transient dizziness within the first month of therapy. One patient had recurrent syncope necessitating prazosin withdrawal. Prazosin is an effective antihypertensive agent which can be used in all types of hypertensive dialysis patients either alone or in combination with minimal side effects.

Twenty-two chronic hemodialysis patients with hypertension were treated with prazosin. Eight patients had volume-responsive hypertension, 11 volume-independent, and 3 high-renin hypertension. Blood pressure fell in all volume-responsive patients from a predialysis level of 175 ± 5/100 ± 3 to 148 ± 4/75 ± 3 mm Hg (p< 0.001) after 3 months of therapy. Prazosin alone was effective in volume-responsive patients at a dose of 5 ± 1.0 mg daily. The blood pressure fell in volume-independent patients from 192 ± 7/105 ± 2 mm Hg predialysis to 155 ± 6/80 ± 3 after 3 months (p< 0.001). Two were controlled on prazosin alone at a dose of 12 ± 2 mg daily. Nine required 27 ± 5 mg of prazosin daily as well as additional antihypertensive treatment. The blood pressure fell from 183 ± 3/109 ± 6 mm Hg predialysis to 173 ± 17/85 ± 3 mm Hg in high-renin patients after 3 months. One patient was controlled on 40 mg of prazosin daily. Two required 40 mg of prazosin daily as well as additional antihypertensive medication. Eleven patients described transient dizziness within the first month of therapy. One patient had recurrent syncope necessitating prazosin withdrawal. Prazosin is an effective antihypertensive agent which can be used in all types of hypertensive dialysis patients either alone or in combination with minimal side effects.

Substantial evidence exists that peritoneal dialysis, as currently practiced, cannot alone remove adequate amounts of phosphorus in well-nourished patients. Current efforts should address the possibility of developing improved nontoxic oral phosphorus binders and/or different compositions of dialysate fluid.