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Patients with chronic kidney disease (CKD) have high blood eosinophil count but its clinical implication is uncertain. Since eosinophils may induce tubulointerstitial injury and arteriosclerosis, eosinophilia might be related to poor clinical outcomes. This retrospective cohort study included 2,877 patients whose estimated glomerular filtration rate (eGFR) was 10–60 mL/min/1.73 m2. The exposure was time-updated blood eosinophil counts. The outcomes were 1) initiation of renal replacement therapy (RRT) and 2) cardiovascular events and mortality. We analyzed the associations between eosinophil counts and outcomes using marginal structural models (MSM). Over a median follow-up of 6.5 years, eosinophil counts were measured a median of 22 times per patient (4 times a year per patient). There was a negative correlation between eosinophil count and eGFR. In total, 433 patients initiated RRT, 275 developed cardiovascular events, and 165 died. In MSM, higher eosinophil counts (≥ 289/µL) showed a 1.83-fold (95% confidence interval:1.33–2.51) higher rate of RRT initiation than lower eosinophil counts after adjustment for time-dependent confounders. Higher eosinophil counts were also associated with a higher rate of cardiovascular events and mortality in MSM (hazard ratio, 1.71 [95% confidence interval:1.30–2.25]). In conclusion, patients with CKD who had higher eosinophil counts showed worse kidney outcome.

In the Japan Dialysis Active Vitamin D (J-DAVID) trial, oral alfacalcidol numerically, but not significantly, increased the risk of cardiovascular events among patients undergoing hemodialysis. Because the cardiovascular effect of alfacalcidol could be modulated by bone turnover status, this post-hoc analysis of the J-DAVID examined how alkaline phosphatase (ALP), a more precise marker of bone turnover than parathyroid hormone (PTH), modifies the impact of alfacalcidol. The J-DAVID was a 48-month, open-label, randomized controlled trial comparing oral alfacalcidol with no vitamin D receptor activators (VDRAs) use in terms of cardiovascular events among 976 hemodialysis patients without secondary hyperparathyroidism. This post-hoc analysis included 959 patients with available data on baseline ALP. The median [25–75th percentile] baseline ALP level was 234 [183–296] U/L. In a Cox proportional hazards model, ALP did not significantly modify the effect of alfacalcidol on the rate of cardiovascular events or all-cause death (P for effect modification=0.54 and 0.74, respectively). The effect of alfacalcidol on time-series changes in calcium, phosphate, and intact PTH were similar across ALP subgroups. In conclusion, oral alfacalcidol did not significantly affect cardiovascular outcomes irrespective of bone turnover status.