Beckie Michael

Time-Dependent Associations between Iron and Mortality in Hemodialysis Patients

The independent association between the indices of iron stores or administered intravenous iron, both of which vary over time, and survival in patients who are on maintenance hemodialysis (MHD) is not clear. It was hypothesized that the observed associations between moderately high levels of three iron markers (serum ferritin, iron, and iron saturation ratio) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome (MICS). Time-dependent Cox regression models were examined using prospectively collected data of the 2-yr (July 2001 to June 2003) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States. After time-dependent and multivariate adjustment for case mix, administered intravenous iron and erythropoietin doses, and available surrogates of MICS, serum ferritin levels between 200 and 1200 ng/ml (reference 100 to 199 ng/ml), serum iron levels between 60 and 120 microg/ml (reference 50 to 59 microg/ml), and iron saturation ratio between 30 and 50% (reference 45 to 50%) were associated with the lowest all-cause and cardiovascular death risks. Compared with those who did not receive intravenous iron, administered intravenous iron up to 400 mg/mo was associated with improved survival, whereas doses >400 mg/mo tended to be associated with higher death rates. The association between serum ferritin levels >800 ng/ml and mortality in MHD patients seems to be due mostly to the confounding effects of MICS. For ascertaining whether the observed associations between moderate doses of administered intravenous iron and improved survival are causal or due to selection bias by indication, clinical trials are warranted.

Development of an HCV infection risk stratification algorithm for patients on chronic hemodialysis

OBJECTIVE:The prevalence of hepatitis C virus (HCV) in patients on chronic hemodialysis (HD) is near 9%. Transaminases, which are lower in HD patients, are not effective in screening for HCV. Our aim was to design an HCV risk stratification strategy incorporating lowered aminotransferase levels and other clinical parameters.METHODS:Patient serum from 168 consecutive HD patients was analyzed for AST, ALT, ferritin, and hepatitis C antibody. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for lower transaminase values. Multivariate classification and regression tree analysis was used to determine the best combination of variables to predict risk for HCV infection.RESULTS:Median AST and ALT levels were higher in anti-HCV Ab(+) patients (p < 0.05). Applying a lower cutoff value for ALT of 16 IU/L resulted in a sensitivity of 61.1%, a specificity of 66.7%, a positive predictive value of 33.9%, and a negative predictive value of 86.0% for detection of HCV infection. Multivariate classification and regression tree analysis derived an algorithm using patient age, months on HD, and AST, resulting in a 97.2% sensitivity and a 51.9% specificity for the detection of HCV(+) HD patients.CONCLUSIONS:A lower normal cutoff value of 18 IU/L for AST and 16 IU/L for ALT increased sensitivity and specificity for the detection of HCV infection in HD patients. An algorithm combining lower transaminases with clinical parameters improved both sensitivity and specificity in HCV detection. Prospective confirmation of this algorithm would allow more selective HCV enzyme immunoassay and polymerase chain reaction testing in dialysis units.

Drug insight: Safety of intravenous iron supplementation with sodium ferric gluconate complex.

Intravenous iron is necessary for optimal management of anemia in patients receiving hemodialysis and is utilized in the majority of these patients in the US. The availability of nondextran formulations of intravenous iron has significantly improved the safety of its use. The nondextran iron formulation sodium ferric gluconate complex (SFGC) has been extensively studied in the hemodialysis population, with two large phase IV trials documenting its safety. SFGC is efficacious and, at recommended doses, is associated with a low incidence of adverse events. There have been few comparative studies of the nondextran intravenous iron preparations; however, they are known to have different pharmacokinetic characteristics. There is also evidence to indicate that these compounds differ in terms of their cytotoxic and proinflammatory properties, and their propensity to induce oxidative stress. This paper reviews the current literature on the safety of SFGC and examines the emerging safety issues surrounding the use of intravenous iron.

Postprocedural Aspiration Test to Predict Adequacy of Dialysis Following Tunneled Catheter Placement

The objective of the study was to determine if a timed aspiration technique with a 20-ml syringe can be used to predict adequacy of blood flow in tunneled dialysis catheters. Sixteen patients referred for de novo placement or manipulation of failing tunneled hemodialysis catheters had the time it takes to fill a 20-ml syringe with the plunger fully withdrawn measured to the nearest tenth of a second. These measurements were correlated with flow rates recorded in dialysis just prior to (if failed catheter) and in the following dialysis session with adequacy determined as at least 300 ml/min. Syringe-filling time (22 catheters in 16 patients) was plotted against adequacy of dialysis. The mean time to fill a 20-ml syringe was 2.2 sec, with a range of 1.0–4.7 sec. The mean time to fill syringes for catheters with adequate dialysis was 1.7 ± 0.5 sec, and for inadequate catheters, it was 2.8 ± 0.8 sec. These differences are statistically significant (p < 0.001). Using a filling time of greater than or equal to 2 sec as a threshold gives the highest sensitivity (100%) for predicting inadequate dialysis while maintaining high specificity (75%). To achieve a specificity of 100%, a 3-sec cutoff would be necessary, but would lead to a sensitivity of only 20%. A simple and objective aspiration technique can be performed at the time of tunneled dialysis catheter placement/manipulation to reasonably predict adequacy of subsequent dialysis.