Optimal paricalcitol starting dose for parathyroid hormone suppression in secondary hyperparathyroidism.
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Comment↗
Biomedical subjects
David A Bushinsky
Publications and source records attributed to David A Bushinsky.
Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics.
Although dietary, genetic, or disease-related excesses in urate production may contribute to hyperuricemia, impaired renal excretion of uric acid is the dominant cause of hyperuricemia in the majority of patients with gout. The aims of this review are to highlight exciting and clinically pertinent advances in our understanding of how uric acid is reabsorbed by the kidney under the regulation of urate transporter (URAT)1 and other recently identified urate transporters; to discuss urate-lowering agents in clinical development; and to summarize the limitations of currently available antihyperuricemic drugs. The use of uricosuric drugs to treat hyperuricemia in patients with gout is limited by prior urolothiasis or renal dysfunction. For this reason, our discussion focuses on the development of the novel xanthine oxidase inhibitor febuxostat and modified recombinant uricase preparations.
Carrier Proteins↗
Isolation and confirmation of a calcium excretion quantitative trait locus on chromosome 1 in genetic hypercalciuric stone-forming congenic rats.
Hypercalciuria is the most common risk factor for kidney stones and has a substantial genetic component. The genetic hypercalciuric stone-forming (GHS) rat model displays complex changes in physiology involving intestine, bone, and kidney and overexpression of the vitamin D receptor, thereby reproducing the human phenotype of idiopathic hypercalciuria. Through quantitative trait locus (QTL) mapping of rats that were bred from GHS female rats and normocalciuric Wistar Kyoto (WKY) male rats, loci that are linked to hypercalciuria and account for a 6 to eight-fold phenotypic difference between the GHS and WKY progenitors were mapped. GHS x WKY rats were backcrossed to breed for congenic rats with the chromosome 1 QTL HC1 on a normocalciuric WKY background. Ten generations of backcrosses produced N10F1 rats, which were intercrossed to produce rats that were homozygous for GHS loci in the HC1 region between markers D1Mit2 and D1Mit32. On a high-calcium diet (1.2% calcium), significantly different levels of calcium excretion were found between male congenic (1.67 +/- 0.71 mg/24 h) and male WKY control rats (0.78 +/- 0.19 mg/24 h) and between female congenic (3.11 +/- 0.90 mg/24 h) and female WKY controls (2.11 +/- 0.50 mg/24 h); the congenics preserve the calcium excretion phenotype of the GHS parent strain. Microarray expression analyses of the congenic rats, compared with WKY rats, showed that of the top 100 most changed genes, twice as many as were statistically expected mapped to chromosome 1. Of these, there is a clear bias in gene expression change for genes in the region of the HC1. Of >1100 gene groups analyzed, one third of the 50 most differentially expressed gene groups have direct or secondary action on calcium metabolism or transport. This is the first QTL for hypercalciuria to be isolated in a congenic animal.
Animals↗
Idiopathic hypercalciuria.
Hypercalcuria is the most common metabolic disorder found in patients with nephrolithiasis. As the prevalence of kidney stones rises in industrialized nations, understanding the pathogenesis and treatment of hypercalciuria becomes increasingly important. Idiopathic hypercalciuria (IH), defined as an excess urine calcium excretion without an apparent underlying etiology, is the most frequent cause of hypercalciuria and will be the focus of this paper. Calcium homeostasis is tightly controlled and slight disturbances in transport at the level of the intestine, bone, and/or kidney can lead to excessive urine calcium excretion and promote stone formation. IH is a systemic disorder with dysregulation of calcium transport at a combination of these calcium regulatory sites. The goal of treatment is to prevent stone formation and relies on a combination of dietary and pharmaceutical interventions. Dietary management includes increasing fluid intake, salt restriction, animal protein restriction, and maintaining a normal calcium intake. Thiazide diuretics have proven effective in preventing calcium stone formation by reducing the urinary excretion of calcium. It is important to note that while decreasing urinary calcium excretion is important the clinician should focus primarily on reducing the supersaturation of calcium oxalate as this determines the true tendency for stone formation.
Animals↗
Genetic hypercalciuric stone-forming rats.
PURPOSE OF REVIEW: We will describe the pathophysiology of hypercalciuria and the mechanism of the resultant stone formation in a rat model and draw parallels to human hypercalciuria and stone formation. RECENT FINDINGS: Through inbreeding we have established a strain of rats that excrete 8-10 times more urinary calcium than control rats. These genetic hypercalciuric rats absorb more dietary calcium at lower 1,25-dihydroxyvitamin D3 levels. Elevated urinary calcium excretion on a low-calcium diet indicated a defect in renal calcium reabsorption and/or an increase in bone resorption. Bone from hypercalciuric rats released more calcium when exposed to 1,25-dihydroxyvitamin D3. Bisphosphonate significantly reduced urinary calcium excretion in rats fed a low-calcium diet. Clearance studies showed a primary defect in renal calcium reabsorption. The intestine, bone and kidneys of the hypercalciuric rats had increased numbers of vitamin D receptors. When hydroxyproline is added to their diet they form calcium oxalate stones, the most common stone type in humans. Increased numbers of vitamin D receptors may cause hypercalciuria in these rats and humans. SUMMARY: Understanding the mechanism of hypercalciuria and stone formation in this animal model will help clinicians devise effective treatment strategies for preventing recurrent stone formation in humans.
Adsorption↗
RANK ligand and TNF-alpha mediate acid-induced bone calcium efflux in vitro.
Chronic metabolic acidosis stimulates net calcium efflux from bone due to increased osteoclastic bone resorption and decreased osteoblastic collagen synthesis. Previously, we determined that incubation of neonatal mouse calvariae in medium simulating physiological metabolic acidosis leads to a significant, cyclooxygenase-dependent, increase in RNA for bone cell receptor activator of NF-kappaB ligand (RANKL) compared with incubation in neutral pH medium. In this study, we tested the hypothesis that the acid-mediated increase in RANKL expression is a primary mechanism for the stimulated osteoclastic resorption. Acid medium increased the medium concentration of sRANKL without altering the concentration of the decoy receptor osteoprotegerin (OPG). Inhibition of the RANKL pathway with concentrations of OPG up to 25 ng/ml, far greater than physiological, did not significantly decrease the robust acid-induced Ca efflux from bone nor did incubation of the calvariae with a different inhibitor, RANK/Fc (up to 50 ng/ml). Thus acid-induced net Ca efflux appears to involve mechanisms in addition to the RANK/RANKL pathway. Osteoblasts also produce TNF-alpha, another cytokine that stimulates the maturation and activity of osteoclasts. Incubation of calvariae in acid medium caused a significant increase in TNF-alpha levels. Incubation of calvariae with anti-TNF (up to 250 ng/ml) did not significantly decrease acid-induced net Ca efflux. However, the combination of RANK/Fc plus anti-TNF caused a significant but subtotal reduction in acid-induced Ca efflux, whereas the combination of RANK/Fc plus an isotype-matched control for the anti-TNF had no effect on Ca release. Thus simultaneous inhibition of RANKL and TNF-alpha is necessary to reduce acid-induced, cell-mediated net Ca efflux from bone; however, additional osteoblast-produced factors must also be involved in acid-induced, cell-mediated bone resorption.
Animals↗
Regulation of renal calcium receptor gene expression by 1,25-dihydroxyvitamin D3 in genetic hypercalciuric stone-forming rats.
Hypercalciuria in inbred genetic hypercalciuric stone-forming (GHS) rats is due, in part, to a decrease in renal tubule Ca reabsorption. Activation of the renal Ca receptor (CaR) may decrease renal tubule Ca reabsorption and cause hypercalciuria through suppression of Ca-sensitive potassium channel activity. Because the rat renal CaR gene is regulated by extracellular calcium and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and GHS rats have increased renal vitamin D receptor content, the current study was undertaken to determine the level of CaR gene expression in GHS rat kidney and whether CaR gene expression is regulated by 1,25(OH)2D3. Male GHS and normal control (NC) rats were fed a Ca-sufficient diet (0.6% Ca). Western blotting revealed a four-fold increase in CaR protein in GHS rat renal tissue, and 1,25(OH)2D3 administration increased renal CaR in both GHS and NC rats. Northern blot analysis of extracts of renal cortical tissue from GHS and NC rats revealed a major 7-kb transcript of CaR and a more modest 4-kb transcript, both of which were readily detectable. Both Northern blotting and real-time reverse transcription-PCR revealed increased basal CaR mRNA expression levels in GHS rat kidney. 1,25(OH)2D3 administration increased renal CaR mRNA levels 2.0- and 3.3-fold in GHS and NC rats, respectively. Despite the greater incremental increase by 1,25(OH)2D3 in NC rats, CaR mRNA levels remained higher in GHS rat kidney, and the elevation was more sustained. 1,25(OH)2D3 increased CaR mRNA through both elevated CaR gene expression and prolonged tissue half-life. These results demonstrate that GHS rats have high levels of CaR gene expression and CaR protein that may contribute to the hypercalciuria and calcium nephrolithiasis.
Animals↗
Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats.
Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation.
Animals↗
First- and second-generation immunometric PTH assays during treatment of hyperparathyroidism with cinacalcet HCl.
BACKGROUND: First-generation immunometric assays for "intact" parathyroid hormone (iPTH) also measure large N-terminally truncated PTH fragments, whereas second-generation assays, such as the "bio-intact" PTH (biPTH) assay, measure only full-length biologically active PTH(1-84). This study compared iPTH and biPTH assays during cinacalcet treatment in subjects with secondary HPT receiving dialysis. METHODS: Four hundred and ten subjects were enrolled in a 26-week randomized, double-blind, placebo-controlled trial of oral cinacalcet (or placebo), 30 to 180 mg once daily, and efficacy was assessed using biPTH and iPTH assays. RESULTS: Compared with control treatment, cinacalcet improved the management of secondary HPT. Both biPTH and iPTH decreased by 38%+/- 3% during weeks 13 to 26 in the cinacalcet group; biPTH increased by 23%+/- 4% and iPTH increased by 9.5%+/- 3% in the control group (P < 0.001). Fifty-six percent of cinacalcet subjects and 10% of control subjects had a > or = 30% reduction in biPTH, and 61% and 11%, respectively, had a > or = 30% reduction in iPTH. Significant correlations between biPTH and iPTH levels were observed throughout the study. Both assays correlated similarly with bone-specific alkaline phosphatase levels. The ratio of biPTH to iPTH was maintained at 56% +/- 1% after treatment in both treatment groups. Increasing serum calcium levels were associated with a decreasing ratio of biPTH to (iPTH-biPTH). CONCLUSION: These data show that PTH can be monitored with either iPTH or biPTH assays during therapy with cinacalcet, and that cinacalcet therapy does not exert a major influence on the ratio between PTH(1-84) and large, N-terminally truncated PTH fragments.
Adult↗
Mechanism and function of high vitamin D receptor levels in genetic hypercalciuric stone-forming rats.
UNLABELLED: The functional status and mechanism of increased VDR in GHS rats were investigated. Basal VDR and calbindins were increased in GHS rats. 1,25(OH)(2)D(3) increased VDR and calbindins in controls but not GHS rats. VDR half-life was prolonged in GHS rats. This study supports the mechanism and functional status of elevated VDR in GHS rats. INTRODUCTION: Genetic hypercalciuric stone-forming (GHS) rats form calcium kidney stones from hypercalciuria arising from increased intestinal calcium absorption and bone resorption and decreased renal calcium reabsorption. Normal serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels and increased vitamin D receptor (VDR) protein suggest that high rates of expression of vitamin D-responsive genes may mediate the hypercalciuria. The mechanism of elevated VDR and state of receptor function are not known. MATERIALS AND METHODS: GHS and non-stone-forming control (NC) male rats (mean, 249 g), fed a normal calcium diet, were injected intraperitoneally with 1,25(OH)2D3 (30 ng/100 g BW) or vehicle 24 h before cycloheximide (6 mg/100 g, IP) and were killed 0-8 h afterward. Duodenal VDR was measured by ELISA and Western blot, and duodenal and kidney calbindins (9 and 28 kDa) were measured by Western blots. RESULTS AND CONCLUSIONS: Duodenal VDR protein by Western blot was increased 2-fold in GHS versus NC rats (633 +/- 62 versus 388 +/- 48 fmol/mg protein, n = 4, p < 0.02), and 1,25(OH)2D3 increased VDR and calbindins (9 and 28 kDa) further in NC but not GHS rats. Duodenal VDR half-life was prolonged in GHS rats (2.59 +/- 0.2 versus 1.81 +/- 0.2 h, p < 0.001). 1,25(OH)2D3 prolonged duodenal VDR half-life in NC rats to that of untreated GHS rats (2.59 +/- 0.2 versus 2.83 +/- 0.3 h, not significant). This study supports the hypothesis that prolongation of VDR half-life increases VDR tissue levels and mediates increased VDR-regulated genes that result in hypercalciuria through actions on vitamin D-regulated calcium transport in intestine, bone, and kidney.
Animals↗
Mechanism of acid-induced bone resorption.
PURPOSE OF REVIEW: This review presents our current understanding of the way metabolic acidosis induces calcium efflux from bone, and in the process, buffers additional systemic hydrogen ions associated with acidosis. RECENT FINDINGS: Acid-induced changes in bone mineral are consistent with a role for bone as a proton buffer. In response to metabolic acidosis in an in-vitro bone organ culture system, we observed a fall in mineral sodium, potassium, carbonate and phosphate, which each buffer protons and in vivo should increase systemic pH towards the physiologic normal. Initially, metabolic acidosis stimulates physicochemical mineral dissolution and subsequently cell-mediated bone resorption. Acidosis suppresses the activity of bone-resorbing cells, osteoblasts, decreasing gene expression of specific matrix proteins and alkaline phosphatase activity. There is concomitant acid stimulation of prostaglandin production by osteoblasts, which acting in a paracrine manner increases synthesis of the osteoblastic receptor activator of nuclear factor kappa B ligand (RANKL). The acid induction of RANKL then stimulates osteoclastic activity and recruitment of new osteoclasts to promote bone resorption and buffering of the proton load. Both the regulation of RANKL and acid-induced calcium efflux from bone are mediated by prostaglandins. SUMMARY: Metabolic acidosis, which occurs during renal failure, renal insufficiency or renal tubular acidosis, results in decreased systemic pH and is associated with an increase in urine calcium excretion. The apparent protective function of bone to help maintain systemic pH, which has a clear survival advantage for mammals, will come partly at the expense of its mineral stores.
Acidosis↗
Calcium oxalate crystal localization and osteopontin immunostaining in genetic hypercalciuric stone-forming rats.
BACKGROUND: The inbred genetic hypercalciuric stone-forming (GHS) rats develop calcium phosphate (apatite) stones when fed a normal 1.2% calcium diet. The addition of 1% hydroxyproline to this diet does not alter the type of stone formed, while rats fed this diet with 3% hydroxyproline form mixed apatite and calcium oxalate stones and those with 5% hydroxyproline added form only calcium oxalate stones. The present study was designed to determine the localization of stone formation and if this solid phase resulted in pathologic changes to the kidneys. METHODS: GHS rats were fed 15 g of the standard diet or the diet supplemented with 1%, 3%, or 5% hydroxyproline for 18 weeks. A separate group of Sprague-Dawley rats (the parental strain of the GHS rats), fed the standard diet for a similar duration, served as an additional control. At 18 weeks, all kidneys were perfusion-fixed for structural analysis, detection of crystal deposits using the Yasue silver substitution method, and osteopontin immunostaining. RESULTS: There were no crystal deposits found in the kidneys of Sprague-Dawley rats. Crystal deposits were found in the kidneys of all GHS rats and this Yasue-stained material was detected only in the urinary space. No crystal deposits were noted within the cortical or medullary segments of the nephron and there was no evidence for tubular damage in any group. The only pathologic changes occurred in 3% and 5% hydroxyproline groups with the 5% group showing the most severe changes. In these rats, which form only calcium oxalate stones, focal sites along the urothelial lining of the papilla and fornix of the urinary space demonstrated a proliferative response characterized by increased density of urothelial cells that surrounded the crystal deposits. At the fornix, some crystals were lodged within the interstitium, deep to the proliferative urothelium. There was increased osteopontin immunostaining in the proliferating urothelium. CONCLUSION: Thus in the GHS rat, the initial stone formation occurred solely in the urinary space. Tubular damage was not observed with either apatite or calcium oxalate stones. The apatite stones do not appear to cause any pathological change while those rats forming calcium oxalate stones have a proliferative response of the urothelium, with increased osteopontin immunostaining, around the crystal deposits in the fornix.
Animal Feed↗
Chronic acidosis-induced alteration in bone bicarbonate and phosphate.
Chronic metabolic acidosis increases urinary calcium excretion without altering intestinal calcium absorption, suggesting that bone mineral is the source of the additional urinary calcium. In vivo and in vitro studies have shown that metabolic acidosis causes a loss of mineral calcium while buffering the additional hydrogen ions. Previously, we studied changes in femoral, midcortical ion concentrations after 7 days of in vivo metabolic acidosis induced by oral ammonium chloride. We found that, compared with mice drinking only distilled water, ammonium chloride induced a loss of bone sodium and potassium and a depletion of mineral HCO3(-) and phosphate. There is more phosphate than carbonate in neonatal mouse bone. In the present in vitro study, we utilized a high-resolution scanning ion microprobe with secondary ion mass spectroscopy to test the hypothesis that chronic acidosis would decrease bulk (cross-sectional) bone phosphate to a greater extent than HCO3(-) by localizing and comparing changes in bone HCO3(-) and phosphate after chronic incubation of neonatal mouse calvariae in acidic medium. Calvariae were cultured for a total of 51 h in medium acidified by a reduction in HCO3(-) concentration ([HCO(-)]; pH approximately 7.14, [HCO3(-)] approximately 13) or in control medium (pH approximately 7.45, HCO3(-) approximately 26). Compared with incubation in control medium, incubation in acidic medium caused no change in surface total phosphate but a significant fall in cross-sectional phosphate, with respect to the carbon-carbon bond (C2) and the carbon-nitrogen bond (CN). Compared with incubation in control medium, incubation in acidic medium caused no change in surface HCO3(-) but a significant fall in cross-sectional HCO3(-) with respect to C2 and CN. The fall in cross-sectional phosphate was significantly greater than the fall in cross-sectional HCO3(-). The fall in phosphate indicates release of mineral phosphates, and the fall in HCO3(-) indicates release of mineral HCO3(-), both of which would be expected to buffer the additional protons and help restore the pH toward normal. Thus a model of chronic acidosis depletes bulk bone proton buffers, with phosphate depletion exceeding that of HCO3(-).
Acidosis↗
The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease.
Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH < or = 250 pg/ml compared with placebo patients (20%; P = 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH > or =30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism.
Adult↗
Molecular mechanisms of primary hypercalciuria.
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Bone Resorption↗
Quantitative trait loci for hypercalciuria in a rat model of kidney stone disease.
Hypercalciuria is the most common risk factor for kidney stones and has a recognized familial component. The genetic hypercalciuric stone-forming (GHS) rat is an animal model that closely resembles human idiopathic hypercalciuria, with excessive intestinal calcium absorption, increased bone resorption, and impaired renal calcium reabsorption; overexpression of the vitamin D receptor (VDR) in target tissues; and calcium nephrolithiasis. For identifying genetic loci that contribute to hypercalciuria in the GHS rat, an F2 generation of 156 rats bred from GHS female rats and normocalciuric WKY male rats was studied. The calcium excretion was six- to eightfold higher in the GHS female than in the WKY male progenitors. Selective genotyping of those F2 rats with the highest 30% and lowest 30% rates of calcium excretion was performed, scoring 98 markers with a mean interval of 23 cM across all 20 autosomes and the X chromosome. With the use of strict criteria for significance, significant linkage was found between hypercalciuria and a region of chromosome 1 at D1Rat169 (LOD, 2.91). Suggestive linkage to regions of chromosomes 4, 7, 10, and 14 was found. The proportion of phenotypic variance contributed by the region on chromosome 1, with appropriate adjustments, was estimated to be 7%. Candidate genes encoding the VDR and the calcium-sensing receptor were localized to regions on rat chromosomes 7 and 11, respectively, but the suggestive quantitative trait locus on chromosome 7 was not in the region of the VDR gene locus. Identification of genes that contribute to hypercalciuria in this animal model should prove valuable in understanding idiopathic hypercalciuria and kidney stone disease in humans.
Animals↗
Bone buffering of acid and base in humans.
The sources and rates of metabolic acid production in relation to renal net acid excretion and thus acid balance in humans have remained controversial. The techniques and possible errors in these measurements are reviewed, as is the relationship of charge balance to acid balance. The results demonstrate that when acid production is experimentally increased among healthy subjects, renal net acid excretion does not increase as much as acid production so that acid balances become positive. These positive imbalances are accompanied by equivalently negative charge balances that are the result of bone buffering of retained H+ and loss of bone Ca2+ into the urine. The data also demonstrate that when acid production is experimentally reduced during the administration of KHCO3, renal net acid excretion does not decrease as much as the decrease in acid production so that acid balances become negative, or, in opposite terms, there are equivalently positive HCO3- balances. Equivalently positive K+ and Ca2+ balances, and thus positive charge balances, accompany these negative acid imbalances. Similarly, positive Na+ balances, and thus positive charge balances, accompany these negative acid balances during the administration of NaHCO3. These charge balances are likely the result of the adsorption of HCO3- onto the crystal surfaces of bone mineral. There do not appear to be significant errors in the measurements.
Acid-Base Equilibrium↗
Nephrolithiasis: site of the initial solid phase.
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Animals↗