Toros Kapoian

Ferric Gluconate Reduces Epoetin Requirements in Hemodialysis Patients with Elevated Ferritin

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

Effects of erythropoietin, angiotensin II, and angiotensin-converting enzyme inhibitor on erythroid precursors in patients with posttransplantation erythrocytosis.

BACKGROUND Angiotensin-converting enzyme inhibitors (ACEI) have become the treatment of choice for posttransplantation erythrocytosis (PTE). Yet the pathogenesis of PTE and the mechanisms of action of ACEI remain unclear. Therefore, we studied the dose response to erythropoietin (Ep), angiotensin II (AII), and the ACEI enalaprilat on the in vitro proliferation of erythroid progenitors in patients with PTE and in controls. We also evaluated ACE polymorphism in the two groups. METHODS Twelve patients with PTE and 12 renal transplant patients without PTE were studied. Erythroid burst-forming units (BFU-E) were isolated from peripheral blood using standard methods. Ep sensitivity was determined for four patients with PTE and three control patients, using 0-3 U/ml Ep. AII dose response was studied in four patients with PTE and five control patients, using AII concentrations of 0-1000 nM. The effect of enalaprilat was studied in eight patients with PTE and eight control patients, using drug concentrations of 0-10 ng/ml. ACE gene insertion/deletion polymorphism was determined by polymerase chain reaction. RESULTS PTE patients showed a significant shift of the Ep response curve to the left compared with controls, with 50% maximal growth occurring at a lower Ep concentration (0.3 U/ml vs. 0.95 U/ml, P<0.025.) However, there was no difference in the number of BFU-E colonies between PTE patients and controls. AII added to the growth medium produced only minor stimulation in both groups. PTE patients showed significant inhibition of BFU-E growth with 10 ng/ml enalaprilat, but controls showed no inhibition of BFU-E growth with ACEI. There was no difference in ACE polymorphism between PTE and controls. CONCLUSIONS Our data suggest that PTE is associated with increased erythroid progenitor sensitivity to Ep. The effect of ACEI to decrease hematocrit in patients with PTE may be due to inhibition of red cell precursor growth.

Recirculation, urea disequilibrium, and dialysis efficiency: Peripheral arteriovenous versus central venovenous vascular access

When accurate, non-urea-based methods of measuring recirculation are used, recirculation is usually absent in arteriovenous (AV) accesses. When urea-based methods are used to measure recirculation in AV accesses, falsely elevated recirculation rates are common. These errors are due to AV and venovenous disequilibrium (peripheral vein method), delayed systemic sampling (two-needle methods), and errors in urea measurement (all methods). The literature suggests that recirculation in central venovenous (CV) catheters is approximately 5%. The methods used for these determinations have all been urea based. However, there are few theoretical problems in using urea-based measurements for measuring recirculation in this setting, making it more likely that these values are accurate. When hemodialysis via CV and AV accesses are compared, equilibrated Kt/V values differ significantly for the same single-pool Kt/V when 15-second postdialysis blood urea nitrogen values are used for modeling, but differ minimally when 2-minute postdialysis samples are used. The impact of transient retrograde blood flow in the superior vena cava on recirculation and whether dialysis efficiency is influenced by the exact site of CV catheter placement (superior vena cava v right atrium) is uncertain.

Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial

Locally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D <30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean±SD serum 25(OH)D increased from 16.0±5.9 ng/ml at baseline to 39.2±14.9 ng/ml in the ergocalciferol arm and did not change (16.9±6.4 ng/ml and 17.5±7.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms (P=0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes.

A dearth of data: the problem of phosphorus in prescription medications

A high dietary intake of phosphorus is considered by most to be a significant health threat for dialysis patients. Efforts to include the phosphorus content of foods on the nutrition label in the US have, to date, been fruitless. Another source of phosphorus, largely unrecognized, is prescription medications. These may contain phosphorus as indicated on their package label; the amount is not quantified. We examined the labels of the branded forms of 200 of the most widely prescribed medications in Dialysis Clinic centers in the United States and found that 23 (11.5%) contained phosphorus. A sampling of different doses and manufacturers (generic and branded) of these drugs was analyzed for phosphorus content and found levels as high as 111.5 mg/dose (40 mg paroxetine). Notable were the phosphorus content of a generic 10 mg lisinopril (32.6 mg) and a generic 10 mg amlodipine (40.1 mg). The significant potential for iatrogenic injury accruing from the use of these drugs warrants efforts at remediation. Specific information on the phosphorus content of medications used by dialysis population needs to be made available to the dialysis community.

Pharmacokinetics of Intraperitoneal Fluconazole during Continuous Cycling Peritoneal Dialysis

OBJECTIVE: To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD). DESIGN: Prospective, nonrandomized, single-dose, open-label study. PARTICIPANTS: Five noninfected volunteer CCPD patients. INTERVENTIONS: Patients received a single dose of intraperitoneal fluconazole 200 mg during their long daytime dwell. Blood samples were collected before and 1, 3, 6, 12 (end of first dwell), 24 (after overnight cycling), 48, 72, 96, and 120 hours after dosing. Used dialysate was collected throughout the study. Unless the patient was anuric, urine was collected for the first 48 hours. MAIN OUTCOME MEASURE: Fluconazole concentrations were assayed by gas–liquid chromatography. Pharmacokinetic parameters were calculated using standard noncompartmental techniques. RESULTS: The bioavailability of intraperitoneal fluconazole was 96% ± 2% over a 12-hour dwell, absorption half-life was 2.5 ± 1.2 hours, serum elimination half-life was 71.65 ± 12.76 hours, and volume of distribution was 0.66 ± 0.13 L/kg. Peritoneal clearance was 5.96 ± 0.93 mL/min and proportional to total dialysate volume. Renal clearance was proportional to renal creatinine clearance. CONCLUSIONS: Current treatment guidelines for fungal peritonitis suggest fluconazole 200 mg intraperitoneally every 24 hours. Our data suggest that this dose, administered every 48 hours, is more than sufficient to maintain serum and peritoneal concentrations above the minimum inhibitory concentration for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.

Efficacy of Tissue Plasminogen Activator for Thrombolysis in Central Venous Dialysis Catheters

Background:  Low blood flow is a frequent complication of central‐vein (CV) dialysis catheters. Since thrombotic occlusion accounts for many cases of reduced blood flow, it is common practice to administer empiric thrombolytic therapy in an attempt to restore catheter patency and improve function.

Intradialytic Hypotension Strikes Again

Intradialytic hypotension (IDH) has plagued hemodialysis (HD) patients and their caregivers since the early days of renal replacement therapy. Its persistence in the current era is evident from the results of the 1426-patient Hemodialysis (HEMO) study in this issue of JASN in which a median of 12.5

Efficacy and Safety Results with the LifeSite Hemodialysis Access System versus the Tesio-Cath Hemodialysis Catheter at 12 Months

PURPOSE To compare the performance and safety of a fully subcutaneous vascular access device, the LifeSite hemodialysis access system, versus a tunneled hemodialysis catheter, the Tesio-Cath, at 1 year after implantation. MATERIALS AND METHODS Sixty-eight patients who required hemodialysis received implantation of the LifeSite device or a Tesio-Cath device as a part of this multicenter study. Thirty-four patients were treated in each group. The endpoints observed included blood flow rates and associated venous pressures, overall and device-related adverse events, the need for thrombolytic infusions, device-related infections (DRIs) and associated hospitalizations, and technical device survival. RESULTS During the 12-month observation period, significantly higher venous pressures were required in patients with the Tesio-Cath to achieve blood flow rates comparable with those achieved with the LifeSite device. Patients in the LifeSite group experienced a significantly lower rate of non-device-related adverse events (P < .001), device-related adverse events (P < .016), need for thrombolytic infusions (P < .002), and DRIs (P < .013) compared with patients in the Tesio-Cath group. There was a trend toward a lower number of hospital days per month for DRIs in the LifeSite group, with the rate for the Tesio-Cath group being twice that in the LifeSite group. The use of the LifeSite device was also associated with a significantly higher probability of device survival for 12 months after censoring for planned removals (P < .031). CONCLUSIONS The results of the present study demonstrate superior device performance and technical device survival, reduced complications, and the need for fewer interventions with the LifeSite hemodialysis access system compared with a standard hemodialysis catheter during a 1-year time period after implantation.

The Phosphate Content of Prescription Medication A New Consideration

Background: Phosphate restriction is needed in most dialysis patients. The package inserts from some medications indicate that phosphate may be part of the excipient fraction of drugs. It is unclear whether its amount may be clinically significant since the phosphate content is unquantified. Methods: We reviewed the package inserts for the branded formulations of the most widely used drugs at a dialysis chain. We measured the phosphate levels in a sample of the branded form of these drugs and some of their generic formulations. We also reviewed the available package inserts of 16 selected generic drug manufacturers for the presence of phosphate in drugs that were phosphate free in their branded formulation. Results: We identified 12 prescription products that contained phosphate, 9 of which contained clinically significant quantities (>10 mg per daily dose) notably in both branded and generic forms of amlodipine, lisinopril, paroxetine and bisoprolol. Phosphate was rarely present in a generic drug when its corresponding branded formulation was phosphate free. Conclusion: Commonly prescribed drugs may contain clinically important levels of phosphate.