Minor Elevation in C-Reactive Protein Levels Predicts Incidence of Erythropoiesis-Stimulating Agent Hyporesponsiveness among Hemodialysis Patients

Kimachi, Miho; Fukuma, Shingo; Yamazaki, Shin; Yamamoto, Yosuke; Akizawa, Tadao; Akiba, Takashi; Saitō, Akira; Fukuhara, Shunichi

doi:10.1159/000438870

Cited by 26 publications

(27 citation statements)

References 29 publications

(65 reference statements)

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“…A disturbance in the crosstalk between inflammation, iron metabolism and erythropoiesis may, therefore, favor ESA hyporesponsiveness. The best predictors for ESA response appear to be IL-6 and CRP [88,89]. Studies conducted by our group showed that HD patients with poorer response to ESA present higher levels of pro-inflammatory cytokines [90,91]; moreover, in studies using a rat model of chronic renal failure, we found that the severity of the inflammatory state was related to the reduction in the rHuEPO response [92].…”

Section: Hypoxia and Human Diseasesmentioning

confidence: 66%

The HIF System Response to ESA Therapy in CKD‐Anemia

Ribeiro¹,

Belo²,

Reis³

et al. 2017

Hypoxia and Human Diseases

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Anemia is a common complication of chronic kidney disease (CKD) associated with disease progression and increased mortality. This anemia is mainly due to inadequate production of erythropoietin (EPO) by the failing kidneys, resulting from the reduction in renal EPO-producing cells (REPC) or from dysregulation of the hypoxia-inducible factor (HIF) system that regulates several genes related to hypoxia, angiogenesis, fibrosis and glucose metabolism, among others. In this chapter, we present a review on the HIF system in CKD-anemia, the HIF response to erythropoiesis-stimulating agents (ESA) therapy and its potential involvement in the development of ESA resistance by enhancing kidney fibrosis and inflammation. Due to concerns related to ESA use, new drugs to correct anemia are under study, being the prolyl hydroxylase inhibitors the most promising candidates.

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Section: Hypoxia and Human Diseasesmentioning

confidence: 66%

The HIF System Response to ESA Therapy in CKD‐Anemia

Ribeiro¹,

Belo²,

Reis³

et al. 2017

Hypoxia and Human Diseases

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“…Chronic inflammation produces cytokines, thus inhibiting erythropoiesis and shortening the lifespan of red blood cells [19, 20]. In patients with secondary hyperparathyroidism, parathyroid hormone can reduce the synthesis of endogenous EPO, inhibit the maturation of erythrocyte precursors, and shorten the erythrocyte lifespan by increasing the osmotic fragility of erythrocytes [21, 22].…”

Section: Discussionmentioning

confidence: 99%

Association between Serum Magnesium and Erythropoietin Responsiveness in Hemodialysis Patients: A Cross-Sectional Study

Song

et al. 2019

Kidney Blood Press Res

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Background/Aims: As shown in the China Health and Nutrition Survey, serum magnesium is associated with anemia. However, the roles of magnesium in anemia and erythropoietin (EPO) responsiveness remain unclear in maintenance hemodialysis (MHD) patients. This study aims to investigate the level of serum magnesium and its relationship with EPO responsiveness in MHD patients. Methods: A total of 307 MHD patients were recruited for this survey. Laboratory data and anthropometrics were collected. EPO responsiveness was evaluated by the erythropoietin resistance index (ERI). The subjects were divided into 3 groups according to serum magnesium concentrations (group A, the lowest tertile; group B, the middle tertiles; and group C, the highest tertile). Multivariate logistic regressions were conducted to evaluate the factors that may be associated with EPO responsiveness. Results: The mean serum magnesium level was significantly higher than normal levels in MHD patients, while no hypomagnesemia was observed. A multivariate logistic regression model revealed that high-sensitivity C-reactive protein, intact parathyroid hormone, serum albumin, and magnesium levels were correlated with a high ERI. The OR of a high ERI was found to be 2.57 (95% CI 1.330–4.975, p = 0.005) for group A and 1.66 (95% CI 0.878––3.140, p > 0.05) for group B compared with the OR for group C. Conclusion: Serum magnesium levels were higher than normal levels in MHD patients. A high serum magnesium level was correlated with good EPO responsiveness and was therefore suggested to be a protective factor for EPO hyporesponsiveness.

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“…While BMI is indeed an imperfect measure of adiposity compared with other metrics of obesity [36-38], this index remains the most easily applicable measure of body build in routine assessments in daily clinical practice and provides valuable information on the global nutritional status, including both muscle and fat mass [39]. Second, our study included only Japanese HD patients who tend to be older and have longer dialysis vintage than those in other countries [40, 41]; as such, the results may not be generalizable to patients from other geographical areas. However, given the aging of the worldwide HD population and consequent improvements in the outcomes in HD patients, we feel it reasonable to expect decent external validity of our findings, at least in other countries or regions where the clinical outcomes of HD patients are better or comparable to those in Japan.…”

Section: Discussionmentioning

confidence: 99%

Body Mass Index Change and Hospitalization Risk in Elderly Hemodialysis Patients: Results from Japanese Dialysis Outcomes and Practice Patterns Study

et al. 2018

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Background: Short-term weight gains and losses are associated with a lower and higher mortality risk, respectively, in patients undergoing hemodialysis (HD). However, little is known about their association with the risk of subsequent hospitalization. Methods: In a prospective cohort of 1,804 HD patients aged ≥65 years enrolled in the Japanese Dialysis Outcomes and Practice Patterns Study phases 3 (2005–2008) and 4 (2009–2011), we examined the associations between changes in body mass index (BMI) over a 4-month baseline period (<–3%, –3 to <–1%, –1 to <1% [reference], 1 to <3%, and ≥3%) and subsequent risk of all-cause, cardiovascular, and noncardiovascular hospitalization using Cox models with adjustment for potential confounders. Results: During a median follow-up of 1.2 years, we noted 1,028 incident hospitalizations for any cause, including 275 and 753 hospitalizations for cardiovascular and noncardiovascular causes, respectively. An L-shaped association was observed between BMI change and all-cause hospitalization. The multivariable-adjusted hazard ratios (HRs; 95% CI) of all-cause hospitalization associated with BMI changes of <–3%, –3 to <–1%, 1 to <3%, and ≥3% (vs. –1 to <1%) were 1.29 (1.01–1.65), 1.22 (0.98–1.51), 1.04 (0.83–1.29), and 1.10 (0.83–1.45), respectively. Qualitatively similar associations were present for cardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.58 [1.06–2.37], 1.09 [0.75–1.58], 0.99 [0.72–1.36], and 0.91 [0.51–1.64], respectively) but not for noncardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.19 [0.90–1.57], 1.26 [0.99–1.59], 1.06 [0.84–1.35], and 1.18 [0.86–1.63], respectively). Conclusions: Decreases in BMI over a relatively short-term period were independently associated with higher risk of subsequent hospitalization, particularly cardiovascular-related hospitalization, among elderly HD patients.

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Minor Elevation in C-Reactive Protein Levels Predicts Incidence of Erythropoiesis-Stimulating Agent Hyporesponsiveness among Hemodialysis Patients

Cited by 26 publications

References 29 publications

The HIF System Response to ESA Therapy in CKD‐Anemia

The HIF System Response to ESA Therapy in CKD‐Anemia

Association between Serum Magnesium and Erythropoietin Responsiveness in Hemodialysis Patients: A Cross-Sectional Study

Body Mass Index Change and Hospitalization Risk in Elderly Hemodialysis Patients: Results from Japanese Dialysis Outcomes and Practice Patterns Study

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