Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial.

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

HMG-CoA reductase inhibitors (statins) might cause high elevations of creatine phosphokinase (CK) in patients with unnoticed hypothyroidism.

Serious side effects of statins, including severe myopathy and rhabdomyolysis, are rare but important in general practice. Hypothyroidism can cause secondary hypercholesterolemia and myopathy. There have been few reports on the risk of statins in patient with unnoticed hypothyroidism. We analyzed the characteristics of 77 patients with primary hypothyroidism in our hospital. Nine patients (11%) accidentally received statins in the treatment of hypercholesterolemia without diagnosis of hypothyroidism. In such patients, free T4 (FT4) levels were lower, and those of LDH, CK were higher than those in patients not receiving statins. In patients accidentally receiving statins, an inverse correlation between CK and FT4 could not be shown (which was recognized in patients not receiving them). Even after FT4 levels were matched, levels of CK were still higher in the patients accidentally receiving statins. Patients with high CK levels over 1000 U/L were 5 times more frequent (56%) in patients accidentally receiving statins than in those not receiving statins (11%). The present study confirms that statins enhances levels of CK in patients with hypothyroidism. We must not begin and continue to use these drugs without checking the possibility of hypothyroidism.