Seroresponse to Inactivated and Recombinant Influenza Vaccines Among Maintenance Hemodialysis Patients.

RATIONALE & OBJECTIVE: High-dose influenza vaccine provides better protection against influenza infection in older adults than standard-dose vaccine. We compared vaccine seroresponse among hemodialysis patients over a period of 4 months after administration of high-dose trivalent inactivated (HD-IIV3), standard-dose quadrivalent inactivated (SD-IIV4), or quadrivalent recombinant quadrivalent (RIV4) influenza vaccine. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: Patients at 4 hemodialysis clinics who received influenza vaccine. EXPOSURE: Type of influenza vaccine. OUTCOME: Hemagglutination inhibition (HI) titers were measured at baseline and at 1, 2, 3, and 4 months after vaccination. The primary outcome was seroprotection rates at HI titers of at least 1:40 and at least 1:160 (antibody levels providing protection from infection in approximately 50% and 95% of immunocompetent individuals, respectively) at 1, 2, 3, and 4 months after vaccination. ANALYTICAL APPROACH: We calculated geometric mean titer as well as seroprotection and seroconversion rates. Adjusted generalized linear models with additional trend analyses were performed to evaluate the association between vaccine type and outcomes. RESULTS: 254 hemodialysis patients were vaccinated against influenza with HD-IIV3 (n = 141), SD-IIV4 (n = 36), or RIV4 (n = 77). A robust initial seroresponse to influenza A strains was observed after all 3 vaccines. Geometric mean titer and seroprotection (HI titer ≥1:160) rates against influenza A strains were higher and more sustained with HD-IIV3 than SD-IIV4 or RIV4. More than 80% of patients vaccinated with HD-IIV3 were seroprotected (HI titer ≥1:160) at month 4 (P < 0.001), whereas, among patients vaccinated with SD-IIV4 or RIV4, seroprotection rates were similar to those at baseline. Seroprotection rates were lower against B strains for all vaccines. LIMITATIONS: Because of the use of observational data, bias from unmeasured confounders may exist. Some age subgroups were small in number. Clinical outcome data were not available. CONCLUSIONS: Hemodialysis patients exhibited high seroprotection rates after all 3 influenza vaccines. The seroresponse waned more slowly with HD-IIV3 compared with SD-IIV4 and RIV4 vaccines.

Modeled Daily Ingested, Absorbed and Bound Phosphorus: New Measures of Mineral Balance in Hemodialysis Patients.

BACKGROUND: Control of predialysis serum phosphorus in hemodialysis patients is challenging. We explored the utility of a novel kinetic phosphorus modeling program. METHODS: As part of a quality assurance program, urea kinetic modeling results were combined with those from phosphorus kinetic modeling to compute modeled daily ingested phosphorus (DIP) and components making up this metric, including absorbed, bound, and nonabsorbed, nonbound phosphorus. RESULTS: In 182 hemodialysis patients, DIP averaged 1,089 ± 348 mg/day in men and 934 ± 292 in women (p < 0.002) and correlated substantially with body weight. DIP/kg bodyweight (12.8 ± 3.40 mg/kg) was not significantly different between the sexes. Prescribed equivalent binder dose (EBD) was 4.98 ± 3.61 and 4.53 ± 3.02 g/day in men and women, respectively (p NS). Protein catabolic rate (PCR) was significantly higher in men (64.4 ± 18) g/day vs. women (48.2 ± 15.6, p < 0.001), and the DIP/PCR ratio was 17.4 ± 4.81 in men vs. 20.1 ± 5.76 in women (p < 0.001). Presence of residual kidney function was associated with a lower prescribed EBD dose (4.08 ± 2.62 vs. 5.38 ± 3.81 g/day, p < 0.01). Self-reported poor binder compliance was associated with higher DIP or DIP/kg as well as higher prescribed EBD. In anuric patients, DIP/kg was increased in patients consuming diets with high phosphate additive content and those reporting poor compliance with the prescribed dose of phosphate binders. CONCLUSIONS: The combination of urea kinetic and phosphorus modeling can be used to estimate measures related to phosphorus intake. High DIP/PCR or DIP/kg body weight values in anuric patients suggest consumption of a diet high in phosphorus additives or noncompliance with the prescribed amount of phosphorus binders.

Going Upstream: Coordination to Improve CKD Care.

Care coordination for patients with chronic kidney disease has been shown to be effective in improving outcomes and reducing costs. However, few patients with CKD benefit from this systematic management of their kidney disease and other medical conditions. As a result, outcomes for patients with kidney disease are not optimal, and their cost of care is increased. For those patients who transition to kidney failure treatment in the United States, the transition does not go as well as it could. The effectiveness of treatments to delay progression of kidney disease in contemporary clinical practice does not match the efficacy of these treatments in clinical trials. Conservative care for kidney disease, which should be an option for patients who are very old and very sick, is not considered often enough or seriously enough. Opportunities for early and even pre-emptive transplantation are missed, as are opportunities for home dialysis. The process of dialysis access creation is rarely optimal. The consequence is care which is not as good as it could be, and much more expensive than it should be. We describe our initial efforts to implement care coordination for chronic kidney disease in routine clinical care and attempt to project some of the benefits to patients and the cost savings.

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.

Nutrition, vitamin D, and health outcomes in hemodialysis: time for a feeding frenzy?

PURPOSE OF REVIEW: The role of nutrition and nutritional supplementation in dialysis recently has been reinvigorated, with small clinical trials exploring surrogate outcomes and larger epidemiologic studies generating treatment hypotheses requiring further study. The present review focuses on major aspects of nutrition and outcomes in hemodialysis patients: protein and calorie intake and nutritional vitamin D supplementation. RECENT FINDINGS: Building on data from small studies, two large, quasi-experimental cohort studies showed significant mortality benefits associated with oral nutritional supplements provided during dialysis, suggesting potential options for ameliorating the protein-energy wasting that is common in dialysis patients and associated with poor outcomes. Multiple cohort studies suggest, both in the general population and in dialysis, that higher 25(OH) vitamin D levels are associated with improved outcomes; however, no major mortality trials exist in dialysis, and the smaller, surrogate studies conducted to date have been disappointing, showing no consistent benefits in surrogate outcomes including inflammation and anemia, despite appropriate responses of vitamin D levels to repletion. SUMMARY: Nutritional interventions are attractive options for improving outcomes in dialysis patients. Nutritional protein supplements have considerable promise, but require further study, preferably in a large, generalizable pragmatic trial. Small nutritional vitamin D supplementation trials in dialysis have had disappointing results. In the absence of new data, there appears to be no role for routine assessment or repletion of 25(OH) vitamin D deficiency or insufficiency in dialysis.

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.

Infection prevention and the medical director: uncharted territory.

Infections continue to be a major cause of disease and contributor to death in patients on dialysis. Despite our knowledge and acceptance that hemodialysis catheters should be avoided and eliminated, most patients who begin dialysis initiate treatment through a central vein hemodialysis catheter. Dialysis Medical Directors must be the instrument through which our industry changes. We must lead the charge to educate our dialysis staff and our dialysis patients. We must also educate ourselves so that we not only know that our facility policies are consistent with the best evidence available, but we must also know where local and federal regulations differ. When these differences impact on patient care, we must speak out and have these regulations changed. But it is not enough to know the rules and write them. We must lead by example and show our patients, our nephrology colleagues and our dialysis staff that we always follow these same policies. We need to practice what we preach and be willing and available to redirect those individuals who have difficulty following the rules. In order to effectively change process meaningful data must be collected, analyzed and acted upon. Dialysis Medical Directors must direct and lead the quality improvement process. We hope this review provides Dialysis Medical Directors with the necessary tools to effectively drive this process and improve care.

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.

Iron indices and intravenous ferumoxytol: time to steady-state.

BACKGROUND: The ongoing nature of iron loss in patients receiving hemodialysis makes it difficult to maintain adequate iron stores without supplementation. The effects of ferumoxytol on iron indices have been measured 35 days after baseline, but no study has assessed indices at earlier points in time. OBJECTIVE: To evaluate the time to transferrin saturation (TSAT) and ferritin stabilization, the point at which TSAT and serum ferritin levels can be accurately measured during a 13-treatment period following a loading dose of ferumoxytol. METHODS: Ferumoxytol was administered according to the package insert to 15 adults undergoing hemodialysis. Vital signs were recorded before treatment, 30 and 60 minutes after receiving ferumoxytol, and at the end of treatment to monitor for adverse reactions and hemodynamic instability. Monitoring continued for a 13-treatment period (30 days) after drug administration. Blood was collected throughout the study to measure TSAT, ferritin, hemoglobin (Hb), and C-reactive protein (CRP). RESULTS: TSAT values at 14, 21, and 28 days after drug administration were not significantly different from those at 7 days, signifying that TSAT values stabilized by day 7. Serum ferritin values at day 14 were significantly lower than those 7 days after drug administration (p = 0.028). Although serum ferritin values at days 21 and 28 tended to decrease relative to values at day 14, the differences were not statistically significant. Therefore, it appears that serum ferritin stabilized by day 14 after drug administration. Mean (SD) Hb values at screening and at end of the study were 11.7 (1.0) g/dL and 12.0 (0.9) g/dL, respectively (p = NS). CRP also did not change significantly throughout the study period. CONCLUSIONS: Dialysis patients achieve stable iron indices quickly. TSAT stabilized by day 7 and ferritin stabilized 14 days after a loading dose of ferumoxytol 1 g. Adverse effects were minimal and did not necessitate discontinuation of ferumoxytol.

Sevelamer carbonate.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, safety data, and place in therapy of sevelamer carbonate for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD). DATA SOURCES: A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1966-August 2009) was conducted using the key words chronic kidney disease, hyperphosphatemia, and sevelamer carbonate. All published articles regarding sevelamer carbonate were included. References of selected articles, data from multiple presentations, and abstract publications were reviewed. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, presentations, and clinical trials of sevelamer carbonate in humans were reviewed; relevant clinical data were selected and included. DATA SYNTHESIS: Sevelamer carbonate is approved to control serum phosphorus levels and treat hyperphosphatemia in patients with CKD who are on dialysis. In clinical trials, sevelamer carbonate has been shown to lower serum phosphorus levels and calcium-phosphorus product to a similar extent as sevelamer hydrochloride. Significantly fewer patients receiving treatment with sevelamer carbonate were likely to report any gastrointestinal adverse event compared with those on sevelamer hydrochloride treatment. Further, sevelamer carbonate is associated with significant effects on decreasing low-density lipoprotein cholesterol levels and may cause less metabolic acidosis than sevelamer hydrochloride. Additionally, sevelamer hydrochloride was removed from the market in October 2009; sevelamer carbonate is now the only available formulation. CONCLUSIONS: Sevelamer carbonate is a treatment option for hyperphosphatemia in patients with CKD who are on dialysis. Clinical data indicate that sevelamer carbonate effectively lowers serum phosphorus levels while having minimal effect on serum calcium or serum chloride levels. The role of sevelamer carbonate in the treatment of hyperphosphatemia relative to other phosphate-binding drugs, including calcium salts and lanthanum, has not yet been established.

Volatility of elevated serum ferritin in anemic hemodialysis patients.

BACKGROUND: Value of serum ferritin (SF) as an iron store index in hemodialysis (HD) patients has been questioned, especially at ranges >or=200. The objective of this study was to determine the variability of SF in patients with high SF (500-1,200.) and low TSAT (or=18 years, HD >or=90 days, SF 500-1,200., TSAT or=22,500 IU/week or >or=225 IU/kg/week and or=100., >or=200. and >or=300. were 61.0%, 29.3% and 12.2%, respectively, and 27% exhibited positive changes in SF. CONCLUSIONS: SF is a volatile and imprecise indicator of tissue iron stores in anemic HD patients with high SF and low TSAT. This volatility limits clinical utility of SF in this population.

Challenge of effectively using erythropoiesis-stimulating agents and intravenous iron.

Clinicians who manage anemia in patients with chronic kidney disease, both on and off dialysis therapy, face several challenges: maintain stable hemoglobin (Hb) levels in their patients, avoid overshooting Hb targets, balance intravenous (IV) iron and erythropoiesis-stimulating agents (ESAs), and improve ESA response to use the lowest effective ESA dose. Special attention to ESA hyporesponsiveness, as well as the role of insufficient iron, is required. The efficacy of IV iron in managing these challenges, particularly in hemodialysis patients who have anemia despite adequate ESA doses, was shown in the randomized controlled Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) clinical trial and its 6-week follow-up extension study, DRIVE-II. These studies provide suggestive evidence of the ability of IV iron to reduce ESA requirements and maintain improved Hb levels in anemic hemodialysis patients with serum ferritin levels of 500 to 1,200 ng/mL and transferrin saturations of 25% or less.

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.

Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study.

Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation (TSAT). The Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) trial was designed to evaluate the efficacy of intravenous ferric gluconate in such patients. Inclusion criteria were hemoglobin or=225 IU/kg per wk or >or=22,500 IU/wk. Patients with known infections or recent significant blood loss were excluded. Participants (n=134) were randomly assigned to no iron (control) or to ferric gluconate 125 mg intravenously with eight consecutive hemodialysis sessions (intravenous iron). At randomization, epoetin was increased 25% in both groups; further dosage changes were prohibited. At 6 wk, hemoglobin increased significantly more (P=0.028) in the intravenous iron group (1.6 +/- 1.3 g/dl) than in the control group (1.1 +/- 1.4 g/dl). Hemoglobin response occurred faster (P=0.035) and more patients responded after intravenous iron than in the control group (P=0.041). Ferritin 800 ng/ml had no relationship to the magnitude or likelihood of responsiveness to intravenous iron relative to the control group. Similarly, the superiority of intravenous iron compared with no iron was similar whether baseline TSAT was above or below the study median of 19%. Ferritin decreased in control subjects (-174 +/- 225 ng/ml) and increased after intravenous iron (173 +/- 272 ng/ml; P<0.001). Intravenous iron resulted in a greater increase in TSAT than in control subjects (7.5 +/- 7.4 versus 1.8 +/- 5.2%; P<0.001). Reticulocyte hemoglobin content fell only in control subjects, suggesting worsening iron deficiency. Administration of ferric gluconate (125 mg for eight treatments) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT

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 nephrologist as a primary care provider for the hemodialysis patient.

The role of nephrologists as de facto primary care providers (PCP) for dialysis patients is of increasing interest. We sought to determine the proportion of patients who rely on nephrologists for primary care and to identify demographic variables associated with this primary care responsibility. We reviewed the charts of 158 patients receiving hemodialysis at a suburban, freestanding, teaching hospital affiliated outpatient unit from December 1999 through January 2001. In addition, each patient was interviewed and completed a survey. Non-nephrologists were considered to be a patient's PCP if there was chart, survey or interview evidence of such a relationship. Of the 158 patients, only 56 patients had a PCP. The nephrologist thus was the de facto PCP in 65% of hemodialysis patients, a responsibility that was 3.3-fold more likely for patients not enrolled in a health maintenance organization (HMO) or managed care organization (MCO). In the non-HMO/MCO group, patients with a PCP had been on dialysis for less time than those without a PCP [2.7 vs. 4.6 years (P=0.0006)]. Only 32% of patients on dialysis <1 year had nephrologists as de facto PCP vs. 71% of those on dialysis more than 1 year (P=0.0002). This association between time on dialysis and de facto use of nephrologists as PCP was not accounted for by the shorter time on dialysis of HMO/MCO enrollees. The extent to which the nephrologist fulfills the often unsought role as PCP needs further investigation.

Mesangial cell apoptosis induced by stimulation of the adenosine A3 receptor: signaling and apoptotic events.

Mesangial cell apoptosis has been proposed as a means of resolution of glomerular hypercellularity in proliferative forms of glomerular disease. We previously demonstrated that adenosine causes mesangial cell apoptosis by stimulating the A3-type adenosine receptor. This is a G protein-coupled receptor shown to activate kinases involved in apoptotic signaling. In this work, we assessed changes in phosphorylation of the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK)1/2 and in levels of specific pro- and antiapoptotic proteins following exposure of mesangial cells to the A3 adenosine receptor agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA). Cultured mesangial cells were incubated with IB-MECA for 30 minutes and 6, 24, and 48 hours. IB-MECA was used at a concentration (30 microM) that induces a reproducible degree of mesangial cell apoptosis. Changes in ERK1/2 phosphorylation and in protein levels of Bcl-2, Bax, and caspase 3 were assessed by Western blot analysis. IB-MECA markedly increased phosphorylation of ERK1/2. This effect peaked at 5 minutes, dissipated by 20 minutes, and was abolished by the inhibitor of ERK phosphorylation, compound U0126, in a dose-dependent manner. This inhibitor had no effect on the extent of IB-MECA-induced apoptosis. Bcl-2 levels progressively declined, whereas those of Bax and activated caspase 3 increased. These observations indicate that stimulation of the A3-type adenosine receptor causes mesangial cell apoptosis via mechanisms independent of ERK activation. The observations also point to an imbalance in the expression of antiapoptotic (Bcl-2) and proapoptotic (Bax, caspase 3) proteins as a potential mechanism underlying adenosine-induced mesangial cell apoptosis.

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. METHODS: We prepared tissue plasminogen activator (tPA) from 50 mg lyophilized powder, which was diluted (1 mg/mL) in sterile water for injection. A volume of 1 mL was frozen in 3 cc polystyrene syringes at -20 degrees C and thawed at room temperature when needed. tPA was then administered into the arterial and venous ports of the central venous catheter in a volume equal to the manufacturer's stated luminal volume and was allowed to dwell for 30 minutes. RESULTS: tPA was administered 62 times in 25 patients with 30 catheters (11 Tesio, 17 PermCath, 2 Shiley) for treatment of low blood flow (pump speed < 250 mL/min). Complete restoration of patency was achieved in 23 episodes (mean blood flow pre-tPA 130 mL/min; post-tPA 320 mL/min); partial restoration of patency was achieved in 20 episodes (mean blood flow pre-tPA 69 mL/min; post-tPA 233 mL/min). tPA was just as likely to be effective in patients with complete catheter occlusion (i.e., no blood flow) as it was when some initial blood flow was present. Nineteen episodes failed to respond to tPA. These episodes occurred in 13 catheters, 12 of which ultimately underwent radiologic evaluation; an extraluminal cause for low blood flow was found in all 12 catheters (6 malpositioned, 6 fibrin sheaths). CONCLUSIONS: tPA at a dose of 1 mg/mL is effective for restoring patency in CV dialysis catheters. Failure to respond to tPA strongly suggests an extraluminal cause of catheter malfunction.