Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Ambulatory aortic blood pressure, wave reflections and pulse wave velocity are elevated during the third in comparison to the second interdialytic day of the long interval in chronic haemodialysis patients

Background. Increased arterial stiffness and aortic blood pressure (BP) are independent predictors of cardiovascular outcomes in end-stage renal disease. The 3-day interdialytic interval is associated with elevated risk of cardiovascular morbidity and mortality in haemodialysis. This study investigated differences in ambulatory aortic BP and arterial stiffness between the second and third day of the long interdialytic interval. Methods. Ambulatory BP monitoring with Mobil-O-Graph monitor (IEM, Stolberg, Germany) was performed in 55 haemodialysis patients during a 3-day interval. Mobil-OGraph records oscillometric brachial BP and pulse waves and calculates aortic BP and augmentation index (AIx) as measure of wave reflections, and pulse wave velocity (PWV) as measure of arterial stiffness. Results. Ambulatory aortic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher during the third versus second interdialytic day (123.6 ± 17.0 versus 118.5 ± 17.1 mmHg, P < 0.001; 81.5 ± 11.8 versus 78 ± 11.9 mmHg, P < 0.001, respectively). Similar differences were noted for brachial BP. Ambulatory AIx and PWV were also significantly increased during the third versus second day (30.5 ± 9.9 versus 28.8 ± 9.9%, P < 0.05; 9.6 ± 2.3 versus 9.4 ± 2.3 m/s, P < 0.001, respectively). Differences between Days 2 and 3 remained significant when day-Time and night-Time periods were compared separately. Aortic SBP and DBP, AIx and PWV showed gradual increases from the end of dialysis session onwards. Interdialytic weight gain was a strong determinant of the increase in the above parameters. Conclusions. This study showed significantly higher ambulatory aortic BP, AIx and PWV levels during the third compared with the second interdialytic day. These findings support a novel pathway for increased cardiovascular risk during the third interdialytic day in haemodialysis. © The Author 2015. Published by Oxford University Press

Ambulatory recording of wave reflections and arterial stiffness during intra- and interdialytic periods in patients treated with dialysis

Background and objectives Wave reflections and arterial stiffness are independent cardiovascular risk factors in ESRD. Previous studies in this population included only static recordings before and after dialysis. This study investigated the variation of these indices during intra- and interdialytic intervals and examined demographic, clinical, and hemodynamic variables related to arterial function in patients undergoing hemodialysis. Design, setting, participants, & measurements Between February 2013 and May 2014, a total of 153 patients receiving maintenance hemodialysis in five dialysis centers of northern Greece underwent ambulatory BP monitoringwith the newly introducedMobil-O-Graph device (IEM, Stolberg,Germany) over amidweek dialysis session and the subsequent interdialytic period. Mobil-O-Graph is an oscillometric device that records brachial BP and pulse waves and estimates, via generalized transfer function, aortic BP, augmentation index (AIx) as a measure of wave reflections, and pulse wave velocity (PWV) as an index of arterial stiffness. ResultsAIxwas lower during dialysis than in the interdialytic period of dialysis-on day (Day 1) (mean±6SD, 24.7% 69.7% versus 26.8%69.4%; P<0.001). In contrast, PWV remained unchanged between these intervals (9.31±62.2 versus 9.29±62.3 m/sec; P=0.60). Both AIx and PWV increased during dialysis-off day (Day 2) versus the out-ofdialysis period of Day 1 (28.8%±69.8% versus 26.8%±69.4% [P<0.001] and 9.39±62.3 versus 9.29±62.3 m/sec [P<0.001]). Older age (odds ratio [OR], 1.09; 95%confidence interval [95% CI], 1.02 to 1.15), female sex (OR, 7.56; 95%CI, 1.64 to 34.81), diabetic status (OR, 8.84; 95%CI, 1.76 to 17.48), and higher mean BP (OR, 1.17; 95%CI, 1.09 to 1.27)were associatedwith higher odds of highAIx; higher heart ratewas associatedwith lower odds (OR, 0.71; 95%CI, 0.63 to 0.80) of high AIx. Older age (OR, 2.04; 95%CI, 1.61 to 2.58) and higher mean BP (OR, 1.15; 95%CI, 1.05 to 1.27) were independent correlates of high PWV. Conclusions This study showed a gradual interdialytic increase in AIx, whereas PWV was only slightly elevated during Day 2. Future studies are needed to elucidate the value of these ambulatory measures for cardiovascular risk prediction in ESRD. © 2015 by the American Society of Nephrology

HCV-RNA qualitative assay based on transcription mediated amplification improves the detection of hepatitis C virus infection in patients on hemodialysis: Results from five hemodialysis units in central Greece

Background: End-stage renal disease patients (ESRD) on maintenance hemodialysis (HD) are at increased risk of acquiring hepatitis C virus (HCV) infection. An early and accurate diagnosis of HCV infection is important for the prevention of viral transmission and the management of ESRD patients on HD but conventional ELISA and PCR have often failed to reveal active HCV infection. Objectives: This study evaluated the prevalence of HCV infection in ESRD patients from all HD units in central Greece using a sensitive HCV-RNA transcription mediated amplification (TMA) assay and compared its sensitivity with that of anti-HCV ELISA. Stud); design: Anti-HCV antibody (third generation ELISA), HCV-RNA (TMA) and HCV genotypes (HCV TMA-LiPA) were determined in 366 ESRD Greek patients. Results: In total, 132 (36%) ESRD patients were HCV positive by ELISA or TMA; 44 by TMA alone, 16 by ELISA alone and 72 positive by both assays. More than half of the viraemic patients had genotype 3a. Conclusions: HCV-RNA (TMA) assay appears to increase the accuracy in the diagnosis of HCV infection in HD patients compared to the anti-HCV ELISA and could serve as an additional screening tool in these patients. (c) 2005 Elsevier B.V. All rights reserved

Hepatitis E virus antibodies in hemodialysis patients: An epidemiological survey in central Greece

Hepatitis E virus (HEV) is the causative agent for enteric non-A, non-B hepatitis. Transmission is mainly via the fecal-oral route but the possibility of an additional parenteric transmission has been raised. Patients undergoing chronic hemodialysis (HD) have an increased risk of exposure to blood transmitted agents. Previous studies concerning prevalence of antibodies to HEV (anti-HEV) among HD patients gave conflicting results. The aim of the study presented here was to determine the prevalence of anti-HEV among HD patients of a well-defined semi-rural region in central Greece (Thessalia region). All patients (n=351, 234 males, mean age 60 +/- 14 years) who were being treated in the HD units of central Greece (n=5) during 2001 were tested for anti-HEV antibody. Two commercially available specific solid-phase enzyme-linked immunoassays were applied for anti-HEV detection. Hepatitis B virus markers, antibodies to HCV, HIV and HTLV were also screened in all patients by commercially available assays. Serum aminotransferase (AST, ALT) levels were measured by spectrophotometry. 17 anti-HEV-positive patients were found and prevalence was 4.8%, varying from 1.8 - 9.8% in the various HD units. Prevalence of HBsAg and anti-HCV was 5.7% (2.9 - 15%) and 23.6% (11.5 - 36.2%) respectively. The anti-HEV prevalence was increased compared to healthy blood donors in Greece (0.26%, p < 0.01). The highest prevalence of anti-HEV was seen at the HD unit of the General Hospital of Karditsa (9.8%). Risk factors for anti-HEV antibody were not identified: no association was found between anti-HEV positivity and age or sex, duration of HD, hepatitis B or C virus infection markers, previously elevated aminotransferase levels or history of transfusion. Our investigation of HEV infection in the cohort of HD patients in central Greece showed that the prevalence of anti-HEV was greater than in healthy blood donors. There was no association to blood borne infections (HBV, HCV). The high prevalence of anti-HEV we found in one HD unit was probably related to a local infection in the past. However, long-term prospective studies are needed in an attempt to identify whether intra-unit factors are also responsible for the increased prevalence of serologic markers of HEV infection among HD patients

Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial

Aims: To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis- dependent chronic kidney disease (NDCKD). Materials and methods: FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis- stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein &gt; 20 mg/L were excluded. In this post-hoc analysis, response was defined as 65 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). Results: 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on 651 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Conclusion: Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders, &lt; 30% responded at any subsequent time point. Earlier consideration of alternative therapy could improve anemia management in this population