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Association between serum ferritin and mortality: findings from the USA, Japan and European Dialysis Outcomes and Practice Patterns Study.

ABSTRACT: Background:The Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin-mortality association and relative influence of IV iron and inflammation in the USA, where ferritin levels have recently increased dramatically, and in Europe and Japan, where ferritin levels are lower and anemia management practices differ. Methods:Data from 18 261 patients in Phases 4 and 5 (2009-15) of the international Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, were analyzed. Using Cox regression, we modeled the association between baseline ferritin and 1-year mortality with restricted cubic splines and assessed the impact of potential confounders. Results:Median ferritin levels were 718 ng/mL in the USA, 405 in Europe and 83 in Japan. High ferritin levels were associated with elevated mortality (relative to region-specific medians) in all three regions. The strength of this association was attenuated more by adjustment for malnutrition and inflammation than by IV iron and erythropoiesis-stimulating agent dose in each region. Conclusion:The utility of high ferritin as a biomarker for clinical risk due to excess iron stores may be limited, although caution regarding IV iron dosing to higher upper ferritin targets remains warranted. Research to resolve biomarker criteria for iron dosing, and whether optimal anemia management strategies differ internationally, is still needed.

SUBMITTER: Karaboyas A

PROVIDER: S-EPMC6275147 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Association between serum ferritin and mortality: findings from the USA, Japan and European Dialysis Outcomes and Practice Patterns Study.

Karaboyas Angelo A Morgenstern Hal H Pisoni Ronald L RL Zee Jarcy J Vanholder Raymond R Jacobson Stefan H SH Inaba Masaaki M Loram Lisa C LC Port Friedrich K FK Robinson Bruce M BM

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20181201 12

<h4>Background</h4>The Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin-mortality association and relative influence of IV iron and inflammation in the US ...[more]

PMID: 30010940

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Project description:BackgroundHemodialysis (HD) patients are commonly prescribed phosphate binders (PBs) to manage serum phosphorus levels, as hyperphosphatemia is strongly associated with poorer survival. Nonadherence with the PB prescription is associated with elevated serum phosphorus levels. We studied associations between patient satisfaction with their PB and serum phosphorus levels and mortality rates.MethodsAdult HD patients in Germany, Italy, Spain and the UK in the Dialysis Outcomes and Practice Patterns Study were administered a survey instrument in late 2017. Patients were asked about their satisfaction with their PBs, as measured through three questions (difficulty, inconvenience and dissatisfaction) on a 5-point Likert scale, with each dichotomized into average worst versus good responses. These were used as predictors in linear regression models of continuous serum phosphorus levels and in Cox proportional hazards models of mortality, with adjustments for demographics, comorbidities and laboratory values.ResultsPatients having greater difficulty, inconvenience and dissatisfaction with their PB had higher serum phosphorus levels in adjusted models {+0.21 mg/dL [95% confidence interval (CI) ±0.23], +0.30 (±0.21) and 0.36 (±0.22), respectively}, and higher odds of having serum phosphorus levels ≥6.0 mg/dL. Measures of dissatisfaction were also associated with an elevated risk of mortality, with adjusted hazard ratios of 2.2 (95% CI 1.3-3.6), 1.6 (1.0-2.6) and 1.7 (1.1-2.7), respectively; this association was not strongly affected by adjustment for baseline serum phosphorous level.ConclusionsSelf-reported difficulty, inconvenience and dissatisfaction in taking one's prescribed PBs were associated with elevated serum phosphorus levels and serum phosphorus levels above clinically meaningful thresholds. While the mechanism for the association with mortality is unclear, patient-reported satisfaction should be considered when attempting to manage patient serum phosphorus levels.

Project description:ObjectivesPatients with end-stage renal disease (ESRD) treated with hemodialysis suffer a high burden of poor functional status. Poor functional status is known as a strong, consistent predictor of mortality. However, little is known about the trajectory of functional status and its association with clinical outcomes in the ESRD population. We examined the association between a change in the functional status over time and all-cause mortality among patients on hemodialysis.Design and methodsThis was a prospective cohort study of 817 patients with ESRD on hemodialysis with repeat measures of functional status, who enrolled in the Japan Dialysis Outcomes and Practice Patterns Study phase V. The functional status was assessed based on the Katz Index and Lawton-Brody instrumental activities of daily living scale, and the assessments were conducted twice over a median of 361 (range: 339-378) days between 2012 and 2013. We classified patients into 2 groups based on having or not having at least a 1-point decline in the functional status score. To evaluate the association between the decline in the functional status and all-cause mortality with adjustment for potential confounders, a Cox regression analysis was conducted.ResultsOver the study period, 19.9% of the patients showed a decline in the functional status score. During the follow-up period, 44 (5.4%) patients died. Using the Cox regression analysis and adjusting for potential confounders, it was determined that the decline in functional status score was significantly associated with higher mortality (incidence rate: 2.2 vs. 7.0 per 100 person-years; adjusted hazard ratio: 2.68; 95% confidence interval: 1.31-5.50).ConclusionsThe present study provides evidence that ESRD patients on hemodialysis demonstrating a decline in the functional status are at elevated risk of mortality. Our findings strengthen the evidence underpinning the importance of interventions to maintain the functional status in this vulnerable population.

Project description:BackgroundSudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L.Study designProspective cohort study.Setting & participants55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015).PredictorDialysate potassium concentration at study entry.OutcomesCox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders.ResultsDuring a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 [95% CI, 0.91-1.01] for mortality and 0.98 [95% CI, 0.88-1.08] for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 [95% CI, 0.05-0.14] mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration).LimitationsData were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding.ConclusionsIn combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.

Project description:BackgroundHemodialysis patients are exposed to disease- and treatment-related stresses, and use various coping strategies to deal with these stresses. Although some studies have reported the association of coping strategies with mortality or health-related quality of life (QOL) in some populations, the effect of coping strategies on clinical outcomes in hemodialysis patients remains unclear. We investigated the association in a longitudinal design among Japanese hemodialysis patients.MethodsWe examined Japanese hemodialysis patients who participated in the Dialysis Outcomes and Practice Patterns Study (DOPPS) IV, which was conducted between 2009 and 2012. The exposure variable was stress coping strategy, as assessed using subscales in Coping Strategies Inventory Short Form: problem-focused engagement, problem-focused disengagement, emotion-focused engagement, and emotion-focused disengagement. Hazard ratios were estimated using Cox proportional hazard model for all-cause mortality and mean differences for change in health-related QOL in 1 year were estimated using a regression model.ResultsAmong 1,354 patients, only problem-focused engagement was significantly associated with longer survival; other subscales were not associated with all-cause mortality after adjustment for potential confounding factors. In terms of health-related QOL, the subscale of problem-focused engagement was also associated with improvement in physical functioning and mental health among 1,045 patients. Emotion-focused disengagement was associated with deterioration in mental health, but not with change in physical functioning. The other subscales were not associated with change in physical functioning or mental health.ConclusionsAmong hemodialysis patients, "problem-focused engagement" coping strategies were associated with longer survival and also with improvement in physical functioning and mental health. To achieve greater longevity and improve QOL in hemodialysis patients under ongoing stresses, problem-focused engagement should be encouraged.

Project description:Patients receiving long-term dialysis have among the highest mortality and hospitalization rates. In the nonrenal literature, functional dependence is recognized as a contributor to subsequent disability, recurrent hospitalization, and increased mortality. A higher burden of functional dependence with progressive worsening of kidney function has been observed in several studies, suggesting that functional dependence may contribute to both morbidity and mortality in dialysis patients.Prospective cohort study.7,226 hemodialysis patients from 12 countries in the DOPPS (Dialysis Outcomes and Practice Patterns Study) phase 4 (2009-2011) with self-reported data for functional status.Patients' ability to perform 13 basic and instrumental activities of daily living was summarized to create an overall functional status score (range, 1.25 [most dependent] to 13 [functionally independent]).Cox regression was used to estimate the association between functional status and all-cause mortality, adjusting for several demographic and clinical risk factors for mortality. Median follow-up was 17.2 months.The proportion of patients who could perform each activity of daily living task without assistance ranged from 97% (eating) to 47% (doing housework). 36% of patients could perform all 13 tasks without assistance (functional status = 13), and 14% of patients had high functional dependence (functional status < 8). Functionally independent patients were younger and had many indicators of better health status, including higher quality of life. Compared with functionally independent patients, the adjusted HR for mortality was 2.37 (95% CI, 1.92-2.94) for patients with functional status < 8.Possible nonresponse bias and residual confounding.We found a high burden of functional dependence across all age groups and across all DOPPS countries. When adjusting for several known mortality risk factors, including age, access type, cachexia, and multimorbidity, functional dependence was a strong consistent predictor of mortality.

Dataset Information

Association between serum ferritin and mortality: findings from the USA, Japan and European Dialysis Outcomes and Practice Patterns Study.

Publications

Association between serum ferritin and mortality: findings from the USA, Japan and European Dialysis Outcomes and Practice Patterns Study.

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