Explore the vast range of titles available.

Background The majority of incident hemodialysis (HD) patients initiate dialysis via catheters. We sought to identify factors associated with initiating hemodialysis with a functioning arterio-venous (AV) access. Methods We conducted a retrospective chart review of all adult patients, age >18 years seeing a nephrologist with a diagnosis of CKD stage 4 or 5 during the study period between 06/01/2011 and 08/31/2013 to evaluate the placement of an AV access, initiation of dialysis and we conducted a survey of providers about the process. Results The 221 patients (56% female) in the study had median age of 66 years (interquartile range (IQR), 57–75) and were followed for a median of 1.26 years (IQR 0.6–1.68). At study entry, 81%had CKD stage 4 and 19% had CKD stage 5. By the end of study, 48 patients had initiated dialysis. Thirty-four of the patients started dialysis with a catheter (1 failed and 10 maturing AVFs), 9 with an AVF and 5 with an AVG. During the study period, 61 total AV accesses were placed (54 AVF and 7 AVG). A higher urinary protein/ creatinine ratio and a lower eGFR were associated with AV access placement and dialysis initiation. A greater number of nephrology visits were associated with AV access creation but not dialysis initiation. Hospitalizations and hospitalizations with an episode of acute kidney injury (AKI) were strongly associated with dialysis initiation (odds ratio (OR) 13.0 (95% confidence interval (CI) 2.3 to 73.3, p -value = 0.004) and OR 6.6 (95% CI 1.9 to 22.8, p -value = 0.003)). Conclusions More frequent nephrology clinic visits for patients with a recent hospitalization may improve rates of placement of an AV access. A hospitalization with AKI is strongly associated with the need for dialysis initiation. Nephrologists may not be referring the correct patients to get an AV access surgery.

Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran. Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control. This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125mg over 10 minutes, and compared to placebo comprising bacteriostatic saline. A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001. SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.

Background Some nephrologists have advocated an individualized approach to the prescription of bicarbonate hemodialysis. However, the utility of monthly serum bicarbonate levels for guiding and evaluating such treatment decisions has not been evaluated. We sought to define the variability of these measurements and to determine factors that are associated with month-to-month variability in pre-dialysis serum bicarbonate. Methods We examined the monthly variability in serum bicarbonate measurements among 181 hemodialysis patients admitted to a free-standing dialysis unit in the Bronx, NY from 1/1/2008-6/30/2012. All patients were treated with a uniform bicarbonate dialysis prescription (bicarbonate 35 mEq/L, acetate 8 mEq/L). Pre-dialysis serum bicarbonate values were obtained from monthly laboratory reports. Month-to-month variability was defined using a rolling measurement for each time point. Results Only 34 % of high serum bicarbonate values (>26 mEq/L) remained high in the subsequent month, whereas 60 % converted to normal (22–26 mEq/L). Of all low values (<22 mEq/L), 41 % were normal the following month, while 58 % remained low. Using the mean 3-month bicarbonate, only 29 % of high values remained high in the next 3-month period. In multivariable-adjusted longitudinal models, both low and high serum bicarbonate values were associated with greater variability than were normal values (β = 0.12 (95 % CI 0.09–0.15) and 0.24 (0.18 to 0.29) respectively). Variability decreased with time, and was significantly associated with age, phosphate binder use, serum creatinine, potassium, and normalized protein catabolic rate. Conclusions Monthly pre-dialysis serum bicarbonate levels are highly variable. Even if a clinician takes no action, approximately 50 % of bicarbonate values outside a normal range of 22–26 mEq/L will return to normal in the subsequent month. The decision to change the bicarbonate dialysis prescription should not be based on a single bicarbonate value, and even a 3-month mean may be insufficient.

Sodium ferric gluconate complex in hemodialysis patients. II. Adverse reactions in iron dextran-sensitive and dextran-tolerant patients. Iron dextran administration is associated with a high incidence of adverse reactions including anaphylaxis and death. Although dextran, rather than iron, is believed to be the cause of these reactions, it is not known whether iron dextran-sensitive patients can be safely administered another form of parenteral iron, sodium ferric gluconate in sucrose (SFGC). In a 69 center, prospective, double-blind, controlled trial of safety and tolerability of SFGC, the rate of reactions to SFGC and placebo in 144 iron dextran-sensitive patients was compared with 2194 patients who were previously tolerant to iron dextran preparations. Serum tryptase levels, a marker of mast cell degranulation, also were measured. Among 143 iron dextran-sensitive patients exposed to SFGC, three (2.1%) were intolerant. All three had suspected allergic events to SFGC, including one patient with a serious reaction (0.7%). One dextran-sensitive patient (0.7%) had a suspected allergic reaction after placebo. In contrast, among 2194 iron dextran-tolerant patients, reactions to SFGC were significantly less common, with SFGC intolerance seen in seven patients (0.3%; P = 0.020), including five (0.2%) who had suspected allergic events (P = 0.010), but none who had serious events (0.0%; P = 0.061). Two iron dextran-tolerant patients (0.09%) had allergic-like reactions following placebo injections. Two of the three suspected allergic events in the iron dextran-sensitive group were confirmed as mast cell dependent by a 100% increase in serum tryptase, while there were no confirmed allergic events in the iron dextran-tolerant group. Long-term exposure to SFGC in iron dextran-sensitive patients resulted in intolerance in only one additional patient and no serious adverse events. Patients with a history of iron dextran sensitivity had approximately sevenfold higher rates of reaction to both placebo and SFGC compared to iron dextran tolerant patients. However, logistic regression analysis, performed to account for the higher reaction rate to placebo, suggests that this increased reactivity was not drug-specific nor immunologically mediated, but represented host idiosyncrasy. These results support the conclusions that reactions to SFGC can be attributed to pseudoallergy, and that SFGC is not a true allergen.

Identical National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) hematologic and iron targets apply to chronic kidney disease (CKD), peritoneal dialysis (PD), and hemodialysis (HD) patients, yet intravenous (i.v.) nondextran iron therapy is FDA approved only in HD patients. This is because oral iron has been considered adequate in CKD and PD patients, and delivering a parenteral therapy on a frequent basis to an outpatient population with notoriously poor vascular access presents logistical complexities. However, recognition of the need for more aggressive treatment of anemia in the CKD and PD population is growing. This awareness, along with the improved safety profiles of the new, nondextran irons, is tipping the risk-benefit ratio toward more widespread use of i.v. iron in these patients. This article provides a summary of the literature and of our own experience using i.v. iron therapy in CKD and PD patients. Our protocol relies on early monitoring and intervention with i.v. ferric gluconate before severe iron deficiency develops. The proactive approach allows for relatively infrequent treatments at only moderately \"high\" doses (250 mg) of ferric gluconate. The convergence of convenience and safety may expedite more energetic anemia prevention and treatment in PD and CKD patients.

The effectiveness of anemia management in patients with end stage renal disease (ESRD) has increased over the past 4 years. However, approximately 26% of treated patients still do not meet the minimum hemoglobin (Hgb) value of 11 g/dl that is recommended by the K/DOQI Clinical Practice Guidelines (National Kidney Foundation [NKF], 2001). One of the main obstacles to good patient outcome may be iron deficiency, which is common in both the predialysis and dialysis period. Since iron is needed for Hgb synthesis, iron depletion exacerbated anemia and reduces the response to recombinant erythropoietin (rEPO) therapy. Health care providers can significantly improve patient outcome by addressing iron deficiency more rigorously. A good starting point is the establishment of an iron deficiency management protocol that includes early evaluation of iron status and aggressive iron therapy. Iron therapy, in turn, can be optimized by administering safe and effective iron supplements and by implementing maintenance iron regimens to prevent the recurrence of iron deficiency. By making these simple improvements to their treatment approach, clinicians can enhance the effectiveness of anemia management in patients with ESRD.

The proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), act in concert to balance thrombus formation and degradation, thereby modulating the development of arterial thrombosis and excessive bleeding. PAI-1 is upregulated by the renin-angiotensin system (RAS), specifically by angiotensin II, the product of angiotensin converting enzyme (ACE) cleavage of angiotensin I, which is produced by the cleavage of angiotensinogen (AGT) by renin (REN). ACE indirectly stimulates the release of t-PA which, in turn, activates the corresponding fibrinolytic system. Single polymorphisms in these pathways have been shown to significantly impact plasma levels of t-PA and PAI-1 differently in Ghanaian males and females. Here we explore the involvement of epistatic interactions between the same polymorphisms in central genes of the RAS and fibrinolytic systems on plasma t-PA and PAI-1 levels within the same population (n = 992). Statistical modeling of pairwise interactions was done using two-way ANOVA between polymorphisms in the ETNK2, RENIN, ACE, PAI-1, t-PA, and AGT genes. The most significant interactions that associated with t-PA levels were between the ETNK2 A6135G and the REN T9435C polymorphisms in females (p = 0.006) and the REN T9435C and the TPA I/D polymorphisms (p = 0.005) in males. The most significant interactions for PAI-1 levels were with REN T9435C and the TPA I/D polymorphisms (p = 0.001) in females, and the association of REN G6567T with the TPA I/D polymorphisms (p = 0.032) in males. Our results provide evidence for multiple genetic effects that may not be detected using single SNP analysis. Because t-PA and PAI-1 have been implicated in cardiovascular disease these results support the idea that the genetic architecture of cardiovascular disease is complex. Therefore, it is necessary to consider the relationship between interacting polymorphisms of pathway specific genes that predict t-PA and PAI-1 levels.