No abstract

This study was undertaken to evaluate the effects of dietary K intake, independent of whether the accompanying anion is Cl- or HCO3-, on urinary Ca excretion in healthy adults. The effects of KCl, KHCO3, NaCl and NaHCO3 supplements, 90 mmol/day for four days, were compared in ten subjects fed normal constant diets. Using synthetic diets, the effects of dietary KCl-deprivation for five days followed by recovery were assessed in four subjects and of KHCO3-deprivation for five days followed by recovery were assessed in four subjects. On the fourth day of salt administration, daily urinary Ca excretion and fasting UCa V/GFR were lower during the administration of KCl than during NaCl supplements (delta = -1.11 +/- 0.28 SEM mmol/day; P less than 0.005 and -0.0077 +/- 0.0022 mmol/liter GFR; P less than 0.01), and lower during KHCO3 than during control (-1.26 +/- 0.29 mmol/day; P less than 0.005 and -0.0069 +/- 0.0019 mmol/liter GFR; P = 0.005). Both dietary KCl and KHCO3 deprivation (mean reduction in dietary K intake -67 +/- 8 mmol/day) were accompanied by an increase in daily urinary Ca excretion and fasting UCaV/GFR that averaged on the fifth day +1.31 +/- 0.25 mmol/day (P less than 0.005) and +0.0069 +/- 0.0012 mmol/liter GFR (P less than 0.005) above control. Both daily urinary Ca excretion and fasting UCaV/GFR returned toward or to control at the end of recovery. These observations indicate that: 1) KHCO3 decreases fasting and 24-hour urinary Ca excretion; 2) KCl nor NaHCO3, unlike NaCl, do not increase fasting or 24-hour Ca excretion and 3) K deprivation increases both fasting and 24-hour urinary Ca excretion whether the accompanying anion is Cl- or HCO3-. The mechanisms for this effect of K may be mediated by: 1) alterations in ECF volume, since transient increases in urinary Na and Cl excretion and weight loss accompanied KCl or KHCO3 administration, while persistent reductions in urinary Na and Cl excretion and a trend for weight gain accompanied K deprivation; 2) K mediated alterations in renal tubular phosphate transport and renal synthesis of 1.25-(OH)2-vitamin D, since KCl or KHCO3 administration tended to be accompanied by a rise in fasting serum PO4 and TmPO4 and a fall in fasting UPO4 V/GFR, a fall in serum 1,25-(OH)2-D and a decrease in fasting UCa V/GFR, while dietary KCl or KHCO3 deprivation were accompanied by a reverse sequence.

A metabolite of vitamin D believed to be the metabolically active form in the intestine has recently been isolated in pure form from intestine and unequivocally identified in this laboratory as 1,25-dihydroxycholecalciferol (1,25-(OH)2D3)(1, 2). Simultaneously, Lawson et al. provided evidence for this structure with a partially purified material from kidney homogenates (3). This metabolite acts more rapidly than 25-(OH)D3 to initiate intestinal calcium transport (4-6). The kidney is the site of synthesis of 1,25-(OH)2D3 from 25-(OH)D3 (7); this observation was confirmed by Gray et al. (8). Other experiments have provided strong evidence that 1,25-(0H2)D3 is the metabolically active form of vitamin D in the intestine (9-11). It, therefore, seemed possible that the concentration of 1,25-(OH)2D3 in the serum and intestinal mucosa plays an important role in the adaptation of calcium absorption to the concentration of calcium in the diet (12).This report demonstrates that dietary calcium concentration has a profound effect on the in vivo production of 1,25-(OH)2D3 and 21,25-(OH)2D3. Furthermore, these alterations in metabolite balance correlate with changes in serum calcium, but not serum phosphate concentration. An independent study has also shown that dietary strontium has an equally marked effect on the production of 1, 325 pmoles of tritiated 25-(OH)D3 was administered intrajugularly in 0.05 ml of 95% ethanol with mild ether anethesia. The rats were fasted at this time, but water continued to be available ad libitum. 12 hr later the rats were killed by decapitation and blood serum was collected. The upper 50 cm of small intestine was quickly removed, flushed with ice-cold saline, slit open, and the mucosa was scraped off with a glass slide. The kidneys and livers were removed. The fore-and hind-limbs were stripped of muscle, the long bones were split, and the marrow was discarded. All tissues were stored at -16'C until they were extracted with chloroform and methanol (14). In early experiments, the tissue from 3 to 4 animals fed the same diet was combined before extraction, while in later experiments the serum calcium concentrations of the rats were analyzed for similarity before pooling of tissues. In other cases, the tissues from each animal were analyzed individually.Radioactive metabolites were separated on a 2 X 15 cm column containing 10 g of Sephadex LH-20 equilibrated with 35% Skellysolve B (petroleum ether, b.p. 67-680C) in 65% chloroform (15). The tissue extracts were applied to the column in 1 ml of the same solvent mixture and eluted with a further 190 ml. Recovery of radioactivity from the columns varied from 90 to 105%.The elution position of 1,25-(OH)2D3 on this column has been established (2, 8). The less-polar metabolite was identified as 21,25-(OH)2D3 by cochromatography. A sample of the 2131

Previous studies demonstrated that the administration of NaHCO3 or sodium citrate had either only a small effect to reduce urinary Ca excretion or no effect, but that potassium citrate significantly reduced urinary Ca excretion. In order to further evaluate and compare the effects of NaHCO3 and of KHCO3, we performed ten metabolic balances in healthy men during 18 control days, 12 days of NaHCO3, 60 mmol/day and 12 days of KHCO3, 60 mmol/day. Six subjects were fed a low Ca diet (5.2 +/- 0.7 SD mmol/day) and three of these were also given calcitriol (0.5 microgram 6-hourly). Four subjects ate a normal Ca diet (19.5 +/- 1.3 mmol/day). For all 10 subjects, KHCO3 administration reduced urinary Ca excretion from control by -0.9 +/- 0.7 mmol/day, P less than 0.001. Net intestinal Ca absorption did not change detectably so that Ca balances became less negative by a +0.9 +/- 0.9 mmol/day; P = 0.01. KHCO3 administration was also accompanied by more positive PO4 and Mg balances. NaHCO3 administration had no significant effect on urinary Ca excretion or Ca balance. NaHCO3 and KHCO3 administration were accompanied by equivalently more positive Na or K balances, respectively and equivalently more negative acid balances (HCO3 retention). Neither NaHCO3 or KHCO3 altered fasting serum HCO3 concentrations, blood pH, serum 1,25-(OH)2-D or PTH concentrations. We conclude that KHCO3 promotes more positive Ca balances by either enhancing renal Ca retention or skeletal Ca retention or both.