Frequency of renal phosphate leak among patients with calcium nephrolithiasis

Prié, Dominique; Ravery, Vincent; Boccon-Gibod, L; Friedlander, Gérard

doi:10.1046/j.1523-1755.2001.00796.x

Cited by 91 publications

(64 citation statements)

References 18 publications

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“…The rationale for the latter study was based on the well-known finding that high-P i diets elicit a decrease in the renal production and serum concentration of 1,25(OH) 2 D (17). Moreover, we demonstrated that P i supplementation of Npt2 Ϫ/Ϫ mice over a 4-day period corrects renal 1␣OHase activity and the serum concentration of 1,25(OH) 2 D, as well as the associated hypercalciuria (22), which is a known risk factor for renal calcification (18,19). In the present study, we report that both 1␣OHase gene ablation and P i supplementation lead to a significant reduction in urinary Ca excretion and a dramatic decrease in renal calcification in Npt2 Ϫ/Ϫ mice.…”

Section: In Npt2supporting

confidence: 66%

“…Our data support the hypothesis that the adaptive increase in serum 1,25(OH) 2 D, in response to hypophosphatemia, serves as a trigger for the cascade of events leading to the development of renal mineral deposits in Npt2 Ϫ/Ϫ mice. Moreover, our data are relevant to the finding that a significant proportion of stone-forming patients with hypercalciuria exhibit hypophosphatemia, secondary to a decrease in renal tubular P i reabsorption (18).…”

Section: Discussionmentioning

confidence: 78%

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1α-Hydroxylase gene ablation and P_isupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene

Tenenhouse¹,

Gauthier²,

Chau³

et al. 2004

American Journal of Physiology-Renal Physiology

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-Arnaud. 1␣-Hydroxylase gene ablation and P i supplementation inhibit renal calcification in mice homozygous for the disrupted Na-P i cotransporter gene Npt2a. Am J Physiol Renal Physiol 286: F675-F681, 2004. First published December 2, 2003 10.1152/ ajprenal.00362.2003.-Disruption of the major renal Na-phosphate (P i) cotransporter gene Npt2a in mice leads to a substantial decrease in renal brush-border membrane Na-P i cotransport, hypophosphatemia, and appropriate adaptive increases in renal 25-hydroxyvitamin D 3-1␣-hydroxylase (1␣OHase) activity and the serum concentration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D]. The latter is associated with increased intestinal Ca absorption, hypercalcemia, hypercalciuria, and renal calcification in Npt2 Ϫ/Ϫ mice. To determine the contribution of elevated serum 1,25(OH) 2D levels to the development of hypercalciuria and nephrocalcinosis in Npt2 Ϫ/Ϫ mice, we examined the effects of 1␣OHase gene ablation and long-term Pi supplementation on urinary Ca excretion and renal calcification by microcomputed tomography. We show that the urinary Ca/creatinine ratio is significantly decreased in Npt2 Ϫ/Ϫ /1␣OHase Ϫ/Ϫ mice compared with Npt2 Ϫ/Ϫ mice. In addition, renal calcification, determined by estimating the calcified volume to total renal volume (CV/TV), is reduced by ϳ80% in Npt2 Ϫ/Ϫ /1␣OHase Ϫ/Ϫ mice compared with that in Npt2 Ϫ/Ϫ mice. In Npt2 Ϫ/Ϫ mice derived from dams fed a 1% Pi diet and maintained on the same diet, we observed a significant decrease in urinary Ca/creatinine that was also associated with ϳ80% reduction in CV/TV when compared with counterparts fed a 0.6% diet. Taken together, the present data demonstrate that both 1␣OHase gene ablation and P i supplementation inhibit renal calcification in Npt2 Ϫ/Ϫ mice and that 1,25(OH)2D is essential for the development of hypercalciuria and nephrocalcinosis in the mutant strain. phosphate wasting; hypophosphatemia; hypercalciuria; nephrocalcinosis; 1,25-dihydroxyvitamin D THE TYPE IIA Na-phosphate (P i ) cotransporter Npt2a is the most abundant Na-P i cotransporter in mouse kidney (23) and is expressed in the brush-border membrane (BBM) of proximal tubular cells (6) where the bulk of filtered P i is reabsorbed. Studies in our laboratory demonstrated that mice homozygous for the disrupted Npt2a gene (Npt2) exhibit an increase in urinary P i excretion, an ϳ80% loss in BBM Na-P i cotransport, and significant hypophosphatemia (2). In addition, Npt2 Ϫ/Ϫ mice fail to respond to P i deprivation with an adaptive increase in BBM Na-P i cotransport (11) and to parathyroid hormone (PTH) with a decrease in transport (27). These findings underscore the significant role of Npt2a in renal P i reabsorption and its regulation by dietary P i and PTH.Hypophosphatemia, induced by feeding a low-P i diet, is an important stimulus for increased renal synthesis of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D] by the cytochrome P-450 25-hydroxyvitamin D 3 -1␣-hydroxylase (CYP27B1, hereafter referred to as 1␣OHase) (9). We showed that hypophosphatemi...

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Section: In Npt2supporting

confidence: 66%

Section: Discussionmentioning

confidence: 78%

1α-Hydroxylase gene ablation and P_isupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene

Tenenhouse¹,

Gauthier²,

Chau³

et al. 2004

American Journal of Physiology-Renal Physiology

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“…This disease is often referred to as IH because of increased intestinal absorption of calcium, and it can be associated with a mild renal phosphate leak, despite the lack of parathyroid hyperactivity. 38 Association of increased 1,25(OH) 2 D levels with renal calcifications was observed in mouse models that lack Fgf23 39 or Klotho 40 or individuals with CYP24A1 mutations, 35 even in the setting of low or normal urinary phosphate excretion. Finally, excessive phosphaturia, even with normal or low urinary calcium, can cause nephrocalcinosis in humans as is seen in XLH 41 or in phosphate enema-induced nephrocalcinosis.…”

Section: Serum 125(oh) 2 D Phosphate and Trp May Be Predictors Of mentioning

confidence: 99%

Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis

Dasgupta

Wee

Reyes

et al. 2014

Journal of the American Society of Nephrology

130

110

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Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na + )-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH) 2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P,0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH) 2 vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.

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“…To pursue this question, Prie et.al. [31] studied 207 calcium stone formers with normal PTH levels and compared them to 105 normal subjects of similar age (although there was a higher percentage of females among the normals, 53% vs. 31% of the stone formers). The stone formers of both sexes had a significantly decreased renal phosphate threshold (TmPi) compared to normal subjects; values were normally distributed, but shifted to lower values among the stone formers.…”

Section: Renal Mineral Handling In Ihmentioning

confidence: 99%

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Worcester

Coe

2008

Seminars in Nephrology

146

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 ...

show abstract

Frequency of renal phosphate leak among patients with calcium nephrolithiasis

Cited by 91 publications

References 18 publications

1α-Hydroxylase gene ablation and P_isupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene

1α-Hydroxylase gene ablation and P_isupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene

Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

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Frequency of renal phosphate leak among patients with calcium nephrolithiasis

Cited by 91 publications

References 18 publications

1α-Hydroxylase gene ablation and Pisupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene

1α-Hydroxylase gene ablation and Pisupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene

Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Contact Info

Product

Resources

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1α-Hydroxylase gene ablation and P_isupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene

1α-Hydroxylase gene ablation and P_isupplementation inhibit renal calcification in mice homozygous for the disruptedNpt2agene