Metabolic and calcium kinetic studies in idiopathic hypercalciuria

Liberman, Uri; Sperling, Oded; Atsmon, A; Frank, Margaret; Modan, Michaela; Vries, A. De

doi:10.1172/jci105940

Cited by 81 publications

(36 citation statements)

References 30 publications

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“…Studies using radio-labeled calcium that have compared intestinal calcium absorption in patients with IH to that in normal subjects find consistently increased calcium uptake in IH ( Figure 1, panel a) [9;10]. Although not measured in these studies, other work has shown that gut calcium secretion is not altered in subjects with IH, meaning that net absorption is also increased [11]. Absorption is higher in IH at all levels of calcium intake [12], and reflects an increase in active calcium transport by the intestine.…”

mentioning

confidence: 76%

“…Overall, it appears that renal mineral conservation must be abnormal in IH, and bone mineral loss somehow facilitated so that despite the absence of diet calcium to balance renal losses, serum calcium can remain normal and serum PTH suppressed. This is further suggested by studies of calcium kinetics using 47 Ca which demonstrate a larger exchangeable calcium pool and higher calcium turnover, together with increased rates of both bone formation and resorption, in 9 subjects with IH compared to 3 normal subjects [11].A possible mechanism that could explain bone mineral lability and abnormal renal tubule conservation of calcium, as well as increased gut absorption of calcium, would be altered tissue …”

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confidence: 94%

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New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Worcester

Coe

2008

Seminars in Nephrology

145

125

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Idiopathic hypercalciuria (IH) is the commonest metabolic abnormality in patients with calcium kidney stones. It is characterized by normocalcemia, absence of diseases that cause increased urine calcium, and calcium excretion that is above 250 mg/day in women and 300 mg/day in men. Subjects with IH have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, negative calcium balance is commonly seen in balance studies, especially on a low calcium diet. The mediator of decreased renal calcium reabsorption is not clear; it is not associated with either an increase in filtered load of calcium or altered PTH levels. There is an increased incidence of hypercalciuria in first-degree relatives of those with IH, but IH appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion. Increased tissue vitamin D response may be responsible for the manifestations of IH in at least some patients. Definition of HypercalciuriaCalcium, the most abundant cation in human beings, is an important participant in many physiologic processes, including hormonal secretion, cardiac contraction, blood clotting, and neurotransmission. In addition, growth and repair of our skeleton demands an adequate supply of calcium, and careful maintenance of extracellular calcium concentrations. For this reason, prevailing levels of intracellular and extracellular calcium are tightly regulated, by a complex system of control mechanisms. These mechanisms control calcium absorption by gut and renal tubular epithelia, as well as fluxes of calcium on and off bone, during varying dietary calcium intakes. In healthy, non-pregnant adults, whose skeleton is no longer growing, net intestinal calcium absorption is matched by renal excretion, and provides sufficient calcium for skeletal maintenance; however, under pathologic conditions, some urine calcium may derive from bone loss.Abnormalities of calcium homeostasis could result in a number of undesired consequences, including abnormally high or low serum calcium levels, or inadequate maintenance of bone mineral. Hypercalciuria might be defined as any level of urine calcium that exceeds net intestinal absorption, leading to net loss of calcium. However, in practice net intestinal absorption is seldom measured, and under the assumption that urine calcium is primarily derived from intestinal absorption, the working definition of hypercalciuria is urine calcium excretion that exceeds that found in the majority of healthy adults eating their usual diets. In practice, this is usually defined as a daily calcium excretion over 250 mg/day in women or 300Mailing address: Elaine Worcester, M.D., Nephrology Section, Suite 511 / MC 5100, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, Phone: 773-702-7459, Fax: 773-702-5818. Publisher's Disclaimer: This is a PDF file ...

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confidence: 76%

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confidence: 94%

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Worcester

Coe

2008

Seminars in Nephrology

145

125

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“…Since a is high in absorptive hypercalciuria, one would expect EFC or net secreted Ca to be lower than in the control group. In the study of Liberman et al (27). EFC varied from 31 mg to 178 mg/day with a mean value of 99 mg/day among patients with idiopathic hypercalciuria.…”

Section: Discussionmentioning

confidence: 98%

“…Although the value of CaA -Cauv of + 49±27 SD mg/day was less than in the control group, it may have still reflected the net secreted calcium. The endogenous fecal calcium (EFC) has been shown to be inversely related to the fractional Ca absorption (26,27), and directly related to calcium intake (26). Since a is high in absorptive hypercalciuria, one would expect EFC or net secreted Ca to be lower than in the control group.…”

Section: Discussionmentioning

confidence: 99%

The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA

Pak¹,

Oata²,

Lawrence³

et al. 1974

J. Clin. Invest.

496

137

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A B S T R A C T The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58+3.63 SD gmol/g creatinine; normal, 4.02±0.70 umol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (CaA), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by 'I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their CaA exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion.of Ca and a suppression of cAMP excretion. The urinary Ca of 453±+154 SD mg/day was significantly higher than the control group's 211+42 mg/ day. The urinary cAMP of 2.26±0.56 umol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hvpercalciuria was kc'ceiz(l for plblicatifn 9 July 1073 and in rezxsed form 11 September 1973. corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since CaA was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their CaA exceeded urinal Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.

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“…Conversely, both defects might contribute to explain bone mass in HSFs (7,19). These characteristics of strontium handling suggest that HSFs could represent a specific group of hypercalciuric patients having a disorder of cellular calcium transport predisposing to hypercalciuria, stone production, and low bone mass.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones

Vezzoli

Macrina

Rubinacci

et al. 2016

CJASN

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Background and objectives Idiopathic hypercalciuria is a frequent defect in calcium kidney stone formers that is associated with high intestinal calcium absorption and osteopenia. Characteristics distinguishing hypercalciuric stone formers from hypercalciuric patients without kidney stone history (HNSFs) are unknown and were explored in our study.Design, setting, participants, & measurements We compared 172 hypercalciuric stone formers with 36 HNSFs retrospectively selected from patients referred to outpatient clinics of the San Raffaele Hospital in Milan from 1998 to 2003. Calcium metabolism and lumbar bone mineral density were analyzed in these patients. A strontium oral load test was performed: strontium was measured in 240-minute urine and serum 30, 60, and 240 minutes after strontium ingestion; serum strontium concentration-time curve and renal strontium clearance were evaluated to estimate absorption and excretion of divalent cations.Results Serum strontium concentration-time curve (P,0.001) and strontium clearance (4.961.3 versus 3.562.7 ml/min; P,0.001) were higher in hypercalciuric stone formers than HNSFs, respectively. The serum strontiumtime curve was also higher in hypercalciuric stone formers with low bone mineral density (n=42) than in hypercalciuric stone formers with normal bone mineral density (n=130; P=0.03) and HNSFs with low (n=22; P=0.01) or normal bone mineral density (n=14; P=0.02). Strontium clearance was greater in hypercalciuric stone formers with normal bone mineral density (5.363.4 ml/min) than in hypercalciuric stone formers and HNSFs with low bone mineral density (3.662.5 and 3.162.5 ml/min, respectively; P=0.03). Multivariate regression analyses displayed that strontium absorption at 30 minutes was positively associated calcium excretion (P=0.03) and negatively associated with lumbar bone mineral density z score (P=0.001) in hypercalciuric stone formers; furthermore, hypercalciuric patients in the highest quartile of strontium absorption had increased stone production risk (odds ratio, 5.06; 95% confidence interval, 1.2 to 20.9; P=0.03).Conclusions High calcium absorption in duodenum and jejunum may expose hypercalciuric patients to the risk of stones because of increased postprandial calcium concentrations in urine and tubular fluid. High calcium absorption may identify patients at risk of bone loss among stone formers.

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Metabolic and calcium kinetic studies in idiopathic hypercalciuria

Cited by 81 publications

References 30 publications

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones

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