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Magnesium and Calcium Metabolism In Humans And Biological Systems

$5,000Z01FY2007CLNIH

Clinical Center

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Abstract

Ten female and 19 male platelet and mononuclear cell donors gave informed consent for two consecutive apheresis procedures using first normal saline (NS) and then CaCl2 as an IV prophylaxis. Blood specimens for determination of total and ionized Ca (tCa, iCa), Pi, intact PTH (iPTH), 1,25-D, and FGF-23, and urine specimens for determination of Ca, Pi, and creatinine (Cre), were collected just prior (Pre) and immediately after (Post) the procedure, and 24 hours (D1), 4 days (D4) and 14 days (D 14) after the procedure. Serum 1,25-D was determined by cartridge extraction radioimmunoassay (RIA) (Mayo Medical Laboratories, Rochester, MN) and serum FGF-23 was determined by an enzyme-linked immunosorbent assay (ELISA) (Immutopics, Inc., San Clemente, CA). Serum iCa was measured on Roche AVL 988-4 (Roswell, GA). The remaining serum and urine analytes were measured on SYNCHRON LX20 analyzer (Beckman Coulter Inc., Brea, CA). The urine excretion of Ca and Pi was estimated using the Ca:Cre and Pi:Cre ratios. The reference range for serum FGF-23 was determined using sera of apparently healthy blood donors (n=111) and was calculated using nonparametric (2.5 97.5) percentile method. Paired t-test was used to compare the results within and between the two groups of apheresis procedures. [unreadable] Except for FGF-23, all of the serum analytes were affected (p<0.05) by apheresis with NS and CaCl2 prophylaxis. In the NS prophylaxis group five donors had abnormally increased FGF-23 (475, 266, 169, 96 and 90, respectively, reference range 0.0 80.4 Relative Units (RU)/mL) that stayed increased throughout the 14 days of monitoring. In addition, FGF-23 remained increased for one donor during the apheresis with CaCl2 prophylaxis. While post-apheresis Pi:Cre was increased for both procedures, this increase was not statistically significant (1.7 vs 1.9, and 1.8 vs 2.0). There was no relationship between the serum concentration of FGF-23 and serum Pi or urine Pi:Cre ratio.[unreadable] In conclusion, routine apheresis procedures has no effect on Pi homeostasis and the production of FGF-23 despite of significant changes that occur in the serum concentrations of Ca, PTH and 1,25-D.[unreadable] [unreadable] Presented at the 2007 AACC Annual Meeting in San Diego,Ca July 22-26. (Cecco SA, Yau Y, Bolan, CD, Leitman SF, Rehak NN. Phosphorus and FGF-23: effect of routine apheresis procedures with and without Ca prophylaxis, Abstract Clin Chem 2007:53:A176.[unreadable] [unreadable] Eight platelet donors (PD) and 21 lymphocyte donors (LD) underwent paired apheresis procedures with and without intravenous calcium chloride (0.6 mg Ca per mL ACD-A) conducted at least 3 weeks apart using a continuous flow device and whole blood to anticoagulant ratio of 8:1 to 11:1. Laboratory evaluations were performed at baseline (pre), immediately after (post), and on day 1, 4, and 14 after apheresis. Compared with PD, LD underwent longer procedures (107 vs 75 min) involving larger volumes processed (7.6 vs 5.0 L) at lower citrate infusion rates (1.3 vs 1.6 mg/kg/min). PD were also younger (48 vs 53 yo), weighed more (92 vs 70 kg), and more likely to be male (81% vs 25%) or African American (43% vs 0%, p<0.05 for all). Baseline laboratories were similar in both groups. In procedures performed without calcium, post-apheresis measurements of serum citrate (1.47 vs 1.11 mmol/L) and intact PTH (91 vs 77 pg/L) were higher (p<0.005), and ionized Ca (0.93 vs 0.97 mmol/L) levels were lower (p<0.01) in PD vs LD; post-apheresis decreases in serum albumin consistent with dilution were similar (12 vs 13%, p>0.4). Urine pH increased significantly post-apheresis in both groups (p<0.0001), while urine pH on day 1 (p<0.01) and serum CO2 levels on day 1 (7%), 4 (6%) and 14 (5%) were significantly increased compared to baseline in LD but not PD. Serum c-telopeptides, a marker of bone breakdown, significantly increased immediately after (+147% and 240%) and on day 1 (+81%) in PD and LD, and at day 4 (+79%) and day 14 (+71%) in LD. Small, statistically significant (p<0.05) changes in serum phosphorus (+8%), albumin (+3%), and total calcium (+2%) were present in both groups up to day 14. Administration of intravenous calcium markedly decreased the immediate post-apheresis changes in intact PTH, ionized calcium and c-telopeptides, but did not markedly impact responses observed at day 4 and 14. In conclusion, citrate-mediated effects are present for up to 2 weeks following apheresis, including changes consistent with acid-base homeostasis, calcium balance, and bone metabolism. The degree of change is further impacted by the length, duration, and intensity of citrate administration and by concomitant intravenous calcium administration. Further studies are underway to determine long term effects on donor bone density and calcium balance.[unreadable] [unreadable] Accepted for Oral Presentation at the AABB 2007 Annual Meeting, October 20 - 23, 2007 in Anaheim, CA. JG Ronquillo, YY Yau, WT Stevens, SA Cecco, F Alvandi, P Byrne, C Matthews, M Collins, RA Wesley, N Rehak, SF Leitman, CD Bolan. Acute and sub-acute citrate mediated effects and responses to intravenous calcium in healthy apheresis donors.

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