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Background <p>Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are promising therapeutic alternatives for renal anemia because their hematopoietic effects are less influenced by inflammation. However, HIF-PHIs did not improve anemia in some cases, even at increasing doses. Since non-hemodialysis patients and various HIF-PHIs have not yet been examined, this study aimed to explore the factors associated with HIF-PHI resistance index (HRI) in all patients with chronic kidney disease (CKD) who received HIF-PHIs.</p> Methods <p>This single-center, retrospective observational study included patients with dialysis-dependent or non-dialysis-dependent CKD who received HIF-PHIs. Spearman’s rank correlation coefficients were calculated between the HRI and each factor. Factors associated with a high HRI were evaluated using univariate logistic regression analysis, followed by multivariate logistic regression analysis using statistically significant factors as covariates.</p> Results <p>The controlling nutritional status (CONUT) score was strongly correlated with HRI (score ≥ 5 [moderate to severe malnutrition] was associated with a high HRI). Further analysis of daprodustat (<i>n</i> = 38) showed that this association remained significant after adjusting for potential confounders (OR = 2.2; 95% CI, 1.09–4.44; <i>p</i> = 0.028).</p> Conclusion <p>Malnutrition, which is closely associated with anemia, may contribute to the reduced responsiveness to HIF-PHIs. A high HRI may be undesirable for any patient because of safety concerns and economic burden.</p>

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Association of nutritional indices with hyporesponsiveness to hypoxia-inducible factor-prolyl hydroxylase inhibitors in patients with chronic kidney disease: a single-center retrospective observational study

  • 期刊论文

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  • 发表日期：

    2026年6月16日

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  • Takuya Minamishima,
  • Hiroyuki Mizoguchi,
  • Nobuhiro Nishibori,
  • Hiroaki Ikesue

摘要

Background

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are promising therapeutic alternatives for renal anemia because their hematopoietic effects are less influenced by inflammation. However, HIF-PHIs did not improve anemia in some cases, even at increasing doses. Since non-hemodialysis patients and various HIF-PHIs have not yet been examined, this study aimed to explore the factors associated with HIF-PHI resistance index (HRI) in all patients with chronic kidney disease (CKD) who received HIF-PHIs.

Methods

This single-center, retrospective observational study included patients with dialysis-dependent or non-dialysis-dependent CKD who received HIF-PHIs. Spearman’s rank correlation coefficients were calculated between the HRI and each factor. Factors associated with a high HRI were evaluated using univariate logistic regression analysis, followed by multivariate logistic regression analysis using statistically significant factors as covariates.

Results

The controlling nutritional status (CONUT) score was strongly correlated with HRI (score ≥ 5 [moderate to severe malnutrition] was associated with a high HRI). Further analysis of daprodustat (n = 38) showed that this association remained significant after adjusting for potential confounders (OR = 2.2; 95% CI, 1.09–4.44; p = 0.028).

Conclusion

Malnutrition, which is closely associated with anemia, may contribute to the reduced responsiveness to HIF-PHIs. A high HRI may be undesirable for any patient because of safety concerns and economic burden.