Dataset Information

Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

ABSTRACT: Background:The rise in serum ferritin levels among US maintenance hemodialysis patients has been attributed to higher intravenous iron administration and other changes in practice. We examined ferritin trends over time in hemodialysis patients and whether iron utilization patterns and other factors [erythropoietin-stimulating agent (ESA) prescribing patterns, inflammatory markers] were associated with ferritin trajectory. Methods:In a 5-year (January 2007–December 2011) cohort of 81 864 incident US hemodialysis patients, we examined changes in ferritin averaged over 3-month intervals using linear mixed effects models adjusted for intravenous iron dose, malnutrition and inflammatory markers. We then examined ferritin trends across strata of baseline ferritin level, dialysis initiation year, cumulative iron and ESA use in the first dialysis year and baseline hemoglobin level. Results:In models adjusted for iron dose, malnutrition and inflammation, mean ferritin levels increased over time in the overall cohort and across the three lower baseline ferritin strata. Among patients initiating dialysis in 2007, mean ferritin levels increased sharply in the first versus second year of dialysis and again abruptly increased in the fifth year independent of iron dose, malnutrition and inflammatory markers; similar trends were observed among patients who initiated dialysis in 2008 and 2009. In analyses stratified by cumulative iron use, mean ferritin increased among groups receiving iron, but decreased in the no iron group. In analyses stratified by cumulative ESA dose and baseline hemoglobin, mean ferritin increased over time. Conclusions:While ferritin trends correlated with patterns of iron use, increases in ferritin over time persisted independent of intravenous iron and ESA exposure, malnutrition and inflammation.

SUBMITTER: Kim T

PROVIDER: S-EPMC6543884 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

Kim Taehee T Rhee Connie M CM Streja Elani E Obi Yoshitsugu Y Brunelli Steven M SM Kovesdy Csaba P CP Kalantar-Zadeh Kamyar K

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20170201 2

<h4>Background</h4>The rise in serum ferritin levels among US maintenance hemodialysis patients has been attributed to higher intravenous iron administration and other changes in practice. We examined ferritin trends over time in hemodialysis patients and whether iron utilization patterns and other factors [erythropoietin-stimulating agent (ESA) prescribing patterns, inflammatory markers] were associated with ferritin trajectory.<h4>Methods</h4>In a 5-year (January 2007–December 2011) cohort of ...[more]

PMID: 28186572

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Project description:BackgroundOptimal iron levels in patients on hemodialysis are currently unknown, and a higher level than that for the healthy population is usually set for such patients considering the use of erythropoiesis-stimulating agents or the occurrence of chronic inflammation. However, excessive iron causes oxidative stress and impairment of its utilization by cells. Therefore we investigated the relationship between hemoglobin (Hb) level and iron status in hemodialysis patients to identify the optimal iron levels for patients undergoing hemodialysis.MethodsA total of 208 outpatients on maintenance hemodialysis were followed up between July 2006 and June 2007. Men accounted for 64.9% cases [mean age, 59.3 ± 13.1 years and median dialysis history, 7.7 (3.6-13.2) years], and diabetic nephropathy accounted for 25.0% cases. Hemoglobin level was measured twice a month and serum ferritin, serum iron, and total iron-binding capacity were measured once a month. The doses of recombinant human erythropoietin and low-dose iron supplement were adjusted to maintain a hemoglobin level of 10-11 g/dL, according to the guidelines of the Japanese Society for Dialysis Therapy. Hepcidin was measured at baseline. Using the mean values for 1-year period, the relationships among hemoglobin, serum ferritin levels, and transferrin saturation levels were investigated based on a receiver operating characteristic curve and a logistic regression model. In addition, the correlations among serum ferritin, transferrin saturation, and hepcidin levels were analyzed by Pearson product-moment correlation coefficient and linear regression model.ResultsBy receiver operating characteristic curve, the cutoff point of serum ferritin and transferrin saturation levels with a hemoglobin ≥10 g/dL showed <90 ng/mL (sensitivity: 69.1%, specificity: 72.1%, p < 0.001) and ≥20% (sensitivity: 77.6%, specificity: 48.8%, p = 0.302). Upon logistic regression model analysis with a hemoglobin ≥10 g/dL as the endpoint, the analysis of odds ratios relative to a group with serum ferritin ≥90 ng/mL and transferrin saturation <20% revealed that the group with serum ferritin <90 ng/mL and transferrin saturation ≥20% had the highest ratio: 46.75 (95% confidence interval: 10.89-200.70, p < 0.001). In Pearson product-moment correlation coefficient, hepcidin showed a strong positive correlation with serum ferritin [r = 0.78 (95% confidence interval: 0.72-0.83, p < 0.001)] and a weak positive correlation with transferrin saturation [r = 0.18 (95% confidence interval: 0.04-0.31, p = 0.010)]. In the multivariable analyses of the linear regression model, a positive relationship was shown between hepcidin and serum ferritin [β-coefficient of 0.30 (95% confidence interval: 0.27-0.34, p < 0.001)]; however, no relationship was shown with transferrin saturation [β-coefficient of 0.09 (95% confidence interval: -0.31-0.49, p = 0.660)].ConclusionsIn this study, the iron status of serum ferritin <90 ng/mL and transferrin saturation ≥20% was optimal in hemodialysis patients receiving recombinant human erythropoietin for anemia therapy. This result indicates that the threshold values for the optimal iron status may be lower than those currently recommended in iron-level management guideline.

Project description:IntroductionThyroid dysfunction is a highly prevalent yet under-recognized complication in hemodialysis patients. In the general population, hypothyroidism has been associated with endothelial dysfunction due to impaired vasodilator synthesis and activity. Little is known about the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with endothelial function in hemodialysis patients.MethodsIn a secondary analysis of 99 patients from the Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) trial, we examined measurements of serum TSH and endothelial function ascertained by fingertip digital thermal monitoring (DTM), a novel method used to measure micro-vascular reactivity, collected within a 90-day period. DTM was used to measure changes in fingertip temperature during and after an ischemic stimulus (blood pressure cuff occlusion) as an indicator of changes in blood flow, and two DTM indices were assessed, namely adjusted (a) Temperature Rebound (TR), defined as the maximum temperature rebound post-cuff deflation, and adjusted (b) Area Under the Temperature Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temperatures. We examined the relationship between serum TSH with impaired TR (separately) and TMP-AUC (both defined as less than the median level of observed values) using multivariable logistic regression.FindingsIn unadjusted and case-mix analyses, higher serum TSH levels (defined as the three highest quartiles) were associated with lower (worse) TR (ref: lowest TSH quartile): ORs (95% CI) 2.64 (1.01-6.88) and 2.85 (1.08-7.57), respectively. In unadjusted and case-mix analyses, higher TSH levels were associated with lower (worse) TMP-AUC: ORs (95% CI) 2.64 (1.01-6.88) and 2.79 (1.06-7.38), respectively.DiscussionIn HD patients, higher serum TSH levels were associated with worse micro-vascular reactivity measured by DTM. Further studies are needed to determine if thyroid hormone supplementation improves endothelial function in hemodialysis patients with lower levels of thyroid function.

Project description:There is accumulating evidence that serum levels of non-high-density lipoprotein cholesterol (non-HDL-C) are a more accurate predictor of cardiovascular outcomes when compared with low-density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non-HDL-C (which includes triglyceride-rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations. We studied the association of baseline and time-dependent serum levels of non-HDL-C with all-cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50 118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time-dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non-HDL-C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (<60 mg/dL) and highest (≥160 mg/dL) categories: 1.88 (1.72-2.06) and 0.73 (0.64-0.83) for all-cause mortality and 2.07 (1.78-2.41) and 0.75 (0.60-0.93) for cardiovascular mortality, respectively (reference, 100-115 mg/dL). In analyses using baseline values, non-HDL-C levels <100 mg/dL were also associated with significantly higher mortality risk across all levels of adjustment. Similar associations were found when evaluating non-HDL/HDL cholesterol ratio and mortality, with the highest all-cause and cardiovascular mortality being observed in patients with decreased non-HDL/HDL-C ratio (<2.5). Contrary to the general population, decrements in non-HDL-C and non-HDL/HDL cholesterol ratio were paradoxically associated with increased all-cause and cardiovascular mortality in patients undergoing incident hemodialysis. The underlying mechanisms responsible for these associations await further investigation.

Dataset Information

Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

Publications

Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

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