Between- and Within-Patient Associations of Nutritional and Inflammatory Status with Erythropoiesis-Stimulating Agent Responsiveness in Maintenance Hemodialysis: A 36-Month Longitudinal Study

Abstract Background The contributions of between-patient differences and within-patient changes in nutritional and inflammatory status to erythropoiesis-stimulating agent (ESA) responsiveness remain unclear. We examined longitudinal associations of the geriatric nutritional risk index (GNRI) and C-reactive protein (CRP) with ESA resistance in maintenance hemodialysis. Methods This retrospective 36-month study included 69 hemodialysis patients. Monthly GNRI and log-transformed CRP were decomposed into between-patient and within-patient components. Random-intercept mixed-effects models assessed associations with log-transformed ESA resistance index (ERI). Sensitivity analyses used weekly ESA dose as an alternative outcome, adjusting for hemoglobin and dry weight. Generalized estimating equations assessed next-month ERI after adjustment for current ERI. Results Among 2,048 observations, between-patient (β = −0.0273, P = 0.0014) and within-patient (β = −0.0159, P < 0.001) GNRI were inversely associated with concurrent ERI. Between-patient CRP showed a borderline association (β = 0.4361, P = 0.051), whereas within-patient CRP was not associated with ERI. Neither GNRI component was significantly associated with weekly ESA dose. Among 1,921 consecutive-month pairs, between-patient GNRI (β = −0.00240, P = 0.003) and CRP (β = 0.05085, P = 0.013) were associated with next-month ERI, whereas within-patient components were not. Conclusions GNRI was associated with concurrent ERI, but not with ESA dose in the alternative-outcome analysis. Between-patient nutritional and inflammatory differences, rather than short-term within-patient changes, were associated with subsequent ERI. Shared mathematical components of GNRI and ERI warrant consideration.