Anti-SARS-CoV-2 Spike Antibody Response to the Fourth Dose of BNT162b2 mRNA COVID-19 Vaccine and Associated Factors in Japanese Hemodialysis Patients.

Background: We assessed the anti-SARS-CoV-2 spike antibody response to four doses of BNT162b2 mRNA COVID-19 vaccine in Japanese hemodialysis patients and determined factors associated with the anti-SARS-CoV-2 spike antibody titer after the fourth dose. Methods: Fifty-one patients were enrolled in this single-center, prospective, longitudinal study. Change in anti-SARS-CoV-2 spike antibody titers between after the second and fourth doses were evaluated. Multiple linear regression analysis was used to identify factors associated with the anti-SARS-CoV-2 spike antibody titer after the fourth dose. Results: The anti-SARS-CoV-2 spike antibody titer was higher 4 weeks after the fourth dose compared with 4 weeks after the third dose (30,000 [interquartile range (IQR), 14,000-56,000] vs 18,000 [IQR, 11,000-32,500] AU/mL, p<0.001) and 4 weeks after the second dose (vs 2896 [IQR, 1110-4358] AU/mL, p<0.001). Hypoxia-inducible factor prolyl hydroxylase inhibitor use (standard coefficient [ß]=0.217, p=0.011), and the log-anti-SARS-CoV-2 spike antibody titer 1 week before the fourth dose (ß=0.810, p<0.001) were correlated with the log-anti-SARS-CoV-2 spike antibody titer 4 weeks after the fourth dose, whereas only the log-anti-SARS-CoV-2 spike antibody titer 1 week before the fourth dose (ß=0.677, p<0.001) was correlated with the log-anti-SARS-CoV-2 spike antibody titer 12 weeks after the fourth dose. Conclusion: Hypoxia-inducible factor prolyl hydroxylase inhibitor use and the anti-SARS-CoV-2 spike antibody titer before the fourth dose were associated with the anti-SARS-CoV-2 spike antibody titer after the fourth dose in Japanese hemodialysis patients.

Anti-SARS-CoV-2 spike antibody response to the third dose of BNT162b2 mRNA COVID-19 vaccine and associated factors in Japanese hemodialysis patients.

BACKGROUND: We assessed the anti-SARS-CoV-2 spike antibody response to the third dose of BNT162b2 mRNA COVID-19 vaccine in Japanese hemodialysis patients and determined factors associated with the anti-SARS-CoV-2 spike antibody titer after the third dose of COVID-19 vaccine. METHODS: Overall, 64 patients were enrolled in this single-center, prospective, longitudinal study. Anti-SARS-CoV-2 spike antibody titers were compared between hemodialysis patients and 18 healthcare workers. Multiple linear regression analysis was used to identify factors associated with the anti-SARS-CoV-2 spike antibody titer after the third vaccination. RESULTS: There was no significant difference in anti-SARS-CoV-2 spike antibody titer 4 weeks after the third vaccination between hemodialysis patients and healthcare workers (18,500 [interquartile range, 11,000-34,500] vs. 11,500 [interquartile range, 7,918- 19,500], all values in AU/mL; p = 0.17). Uric acid (standard coefficient [ß] = -0.203, p = 0.02), transferrin saturation (ß = -0.269, p = 0.003), and log-anti-SARS-CoV-2 spike antibody titer 1 week before the third vaccination (ß = 0.440, p < 0.001) correlated with the log-anti-SARS-CoV-2 spike antibody titer 4 weeks after the third vaccination. In contrast, only the log-anti-SARS-CoV-2 spike antibody titer 1 week before the third vaccination (ß = 0.410, p < 0.001) correlated with the log- anti-SARS-CoV-2 spike antibody titer 12 weeks after the third vaccination. CONCLUSION: The anti-SARS-CoV-2 spike antibody titer after the third dose of COVID-19 vaccine was comparable between hemodialysis patients and healthcare workers. Uric acid concentration, transferrin saturation, and anti-SARS-CoV-2 spike antibody titer before the third dose were associated with the anti-SARS-CoV-2 spike antibody titer after the third dose in Japanese hemodialysis patients.

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.

Factors associated with anti-SARS-CoV-2 spike antibody titers after a second BNT162b2 mRNA COVID-19 vaccination in Japanese hemodialysis patients.

BACKGROUND: We investigated factors associated with the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody titer after the second dose of the BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine in Japanese patients undergoing hemodialysis. METHODS: Overall, 75 patients (41 men, 34 women; mean age 71.4 ± 12.2 years) with a hemodialysis duration of 5.7 ± 6.1 [interquartile range, 1.0-8.5] years were enrolled in this single-center, prospective, cross-sectional study. We used multiple linear regression analysis to determine the relationships of the anti-SARS-CoV-2 spike antibody titer with patient demographic and clinical parameters. We also compared the anti-SARS-CoV-2 spike antibody titer between hemodialysis patients and 22 healthcare workers (10 men, 12 women; mean age 48.5 ± 14.4 years). RESULTS: Autoimmune disease presence (standard coefficient [ß] = - 0.290, p = 0.018), lymphocyte counts (ß = 0.261, p = 0.015), hemoglobin levels (ß = 0.290, p = 0.009), and blood urea nitrogen concentrations (ß = 0.254, p = 0.033) were significantly and independently correlated with the log-anti-SARS-CoV-2 spike antibody titer. The anti-SARS-CoV-2 spike antibody titer was significantly lower in hemodialysis patients than in healthcare workers (3589 ± 3921 [813-4468] vs. 12,634 ± 18,804 [3472-10,257] AU/mL; p < 0.002). CONCLUSIONS: Autoimmune disease presence, lymphocyte counts, hemoglobin levels, and blood urea nitrogen concentrations were associated with the anti-SARS-CoV-2 spike antibody titer after the second dose of the BNT162b2 messenger RNA COVID-19 vaccine in Japanese patients undergoing hemodialysis.

Hypertensive patients with carotid artery plaque exhibit increased platelet aggregability.

BACKGROUND: Platelets play an important role in myocardial infarction and ischemic stroke events, but whether platelet aggregability is related to early stage arteriosclerosis remains unclear. METHODS: We used a novel platelet counting system which makes it possible to detect spontaneous platelet aggregation, to evaluate the relationship between platelet aggregability and carotid artery arteriosclerosis in 125 outpatients with primary hypertension (46-73 years old: 65 men, 60 women). All subjects underwent carotid artery ultrasonography to determine whether plaque was present and to estimate intima-media thickness. RESULTS: Patients with carotid artery plaques (Plaque(+), n=63) were older and had higher systolic blood pressures than patients without plaques (Plaque(-), n=62), but no significant differences in sex, body mass index, diastolic blood pressure, plasma concentrations of glucose, total cholesterol, triglyceride, lipoprotein cholesterol, fibrinogen or the platelet count in whole blood were observed between Plaque(+) and Plaque(-) groups. Plaque(+) subjects showed greater spontaneous platelet aggregability and platelet aggregation induced by 2 microM or 0.5 microM of ADP or 0.3 microM of epinephrine than the Plaque(-) group. When age and systolic blood pressure were matched (n=52 in both groups), the Plaque(+) subjects exhibited greater platelet aggregability than the Plaque(-) subjects. Platelet aggregation induced by 2 microM of ADP showed statistical significant positive correlation coefficients with age, HbA1c and diastolic blood pressure. CONCLUSION: Our results indicate that hypertensive patients with carotid artery plaque have increased platelet aggregability. A prospective study is recommended to clarify whether this increase in platelet aggregability promotes the progression of arteriosclerosis.

Cyclooxygenase-2 inhibitors attenuate increased blood pressure in renovascular hypertensive models, but not in deoxycorticosterone-salt hypertension.

COX-2 is an inducible cyclooxygenase (COX) that has been reported to be expressed in the macula densa and surrounding cortical thick ascending limb in normotensive rats. The present study assessed the contribution of COX-2 in three different rat models of hypertension, each characterized by a different activation of the renal renin-angiotensin system. Mean blood pressure (MBP) in the rat 2 kidney-1 clip (2K1C) model was significantly reduced with a COX-2 selective inhibitor, NS-398 (10 mg/kg, p.o., twice a day) (vehicle-administered rats (n = 8): 154 +/- 6 mmHg; NS-398-administered rats (n = 5): 128 +/- 10 mmHg). By contrast, a COX-1 selective inhibitor, mofezolac, did not lower MBP. Increased plasma renin activity (23 +/- 8 ng/kg/h (n = 6) vs. sham operation, 2.4 +/- 0.9 ng/kg/h (n = 4)) was markedly reduced to 6.8 +/- 2.7 ng/ml/h (n = 5) by NS-398, but not by mofezolac. The development of 1 kidney-1 clip (1K1C) hypertension was also inhibited by NS-398 (vehicle (n = 12): 133 +/- 1 mmHg; NS-398 (n = 7): 122 +/- 3 mmHg) accompanied by a reduction in plasma renin activity (3.0 +/- 0.3 ng/ml/h, n = 4) to 1.0 +/- 0.2 ng/ml/h (n = 5). The COX-2 inhibitor increased urinary excretions in the 1K1C model, but not in the 2K1C model. In a deoxycorticosterone acetate (DOCA)-salt model, plasma renin activity was markedly suppressed to less than 0.3 ng/ml/h. The COX-2 inhibitor caused no significant changes in MBP, plasma renin activity, or urinary excretion, suggesting that COX-2 made a lesser contribution in this model. Increased expression of COX-2 mRNA and protein was observed in the kidneys of 1K1C and 2K1C rats, but not in DOCA-salt rats. These results suggest that COX-2 plays a significant role in the development of 2K1C and 1K1C renovascular hypertension, in addition to making a substantial contribution to the diuretic effect in the 1K1C model.