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

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.