Nephrocalcinosis and its relationship to treatment of hereditary rickets

Goodyer, Paul; Kronick, Jonathan B.; Jequier, Sigrid; Reade, T; Scriver, Charles R.

doi:10.1016/s0022-3476(87)80245-7

Cited by 79 publications

(36 citation statements)

References 8 publications

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“…In both cases, these patients would be treated not only with phosphate supplementation, but with unnecessary and potentially harmful high dosage of active vitamin D metab olites as well [13].…”

Section: Introductionmentioning

confidence: 99%

A New Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria: Implications for Correct Diagnosis and Treatment

Tieder¹,

Arie²,

Bab³

et al. 1992

Nephron

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Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature. We describe here a new kindred of Jewish Yemenite origin (unrelated to other Israeli families) with typical HHRH. Two additional members of this family suffer from a milder asymptomatic form of the disease, which presents as absorptive hypercalciuria without signs or symptoms of bone disease. It seems to us that HHRH is underdiagnosed, due to its similarity to other hypophosphatemic syndromes in clinical, radiological and most biochemical parameters. Therefore, it is recommended that urinary calcium excretion and serum 1,25-di-hydroxyvitamin D concentrations be measured in every patient with hypophosphatemic rickets/and or osteomalacia before the initiation of any therapy. The correct diagnosis of HHRN is of immense therapeutic implications. Phosphate therapy alone could cause a complete remission in HHRH, while the addition of active vitamin D metabolites, as is recommended in hypophosphatemic vitamin D resistant rickets, could cause deterioration in the patient’s condition.

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Section: Introductionmentioning

confidence: 99%

A New Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria: Implications for Correct Diagnosis and Treatment

Tieder¹,

Arie²,

Bab³

et al. 1992

Nephron

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“…The vitamin D deficiency is caused by decreased 25(OH)-vitamin D-1␣-hydroxylase activity (7)(8)(9)(10). Conventional therapy consists of oral administration of pharmacologic doses of vitamin D and phosphate, though hypercalciuria and nephrocalcinosis are frequent complications of such therapy (11)(12)(13)(14)(15). Nephrocalcinosis can lead to renal insufficiency and renal tubular acidosis (15).…”

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confidence: 99%

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

Baum

Loleh

Saini

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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X-linked hypophosphatemia is the most prevalent inherited form of rickets. In this disorder, rickets results from hyperphosphaturia and inappropriately normal levels of 1,25(OH) 2-vitamin D. Current therapy with oral phosphate and vitamin D improves the rickets, but has significant morbidity and does not significantly affect the short stature and hypophosphatemia. In the present study, we demonstrate that Hyp mice, which have a mutation homologous to that in patients with X-linked hypophosphatemia, have a 2-fold greater urinary prostaglandin E 2 (PGE2) excretion than C57͞B6 mice. To determine whether PGs were involved in the pathogenesis of this disorder, Hyp and C57͞B6 mice received i.p. injections with vehicle or indomethacin (1 mg͞kg of body weight twice daily for 4 days) and were studied Ϸ12 h after the last dose of indomethacin. In the Hyp mice, indomethacin treatment decreased the fractional excretion of phosphate from 13.0 ؎ 3.2% to 2.2 ؎ 1.1% (P < 0.05), and increased serum phosphate from 2.9 ؎ 0.2 mg͞dl to 4.1 ؎ 0.2 mg͞dl (P < 0.05). There was no effect of indomethacin in C57͞B6 mice. Indomethacin did not affect serum creatinine or inulin clearance, demonstrating that the normalization of urinary phosphate excretion was not caused by changes in glomerular filtration rate. Indomethacin treatment increased renal brush border membrane vesicle NaPi-2 protein abundance in Hyp mice to levels comparable to that of C57͞B6 mice, but had no effect in C57͞B6 mice. In vitro isolated perfused proximal tubule studies demonstrate directly that 10 ؊6 M bath indomethacin normalized the phosphate transport defect in Hyp mice but had no effect on C57͞B6 mice. In conclusion, there is dysregulation of renal PG metabolism in Hyp mice, and indomethacin treatment normalizes the urinary excretion of phosphate by a direct tubular effect.X-linked hypophosphatemia ͉ rickets ͉ sodium͞phosphate cotransporter NaPi-2

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“…(29,30,42,43) Although nephrocalcinosis is a major concern in XLH management, its association with impaired renal function in XLH appears less pronounced (40,42,(44)(45)(46) than in hypoparathyroidism.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

“…Vitamin D dose (40,41) and hypercalciuria (42) appear as major factors for nephrocalcinosis in some studies, whereas other studies have found that the phosphate dose is a stronger predictor of nephrocalcinosis. (29,30,42,43) Although nephrocalcinosis is a major concern in XLH management, its association with impaired renal function in XLH appears less pronounced (40,42,(44)(45)(46) than in hypoparathyroidism. (47) Therefore, revisiting this issue in the modern era, as proposed by Liu and colleagues, (19) is important.…”

mentioning

confidence: 96%

1,25-Dihydroxyvitamin D as Monotherapy for XLH: Back to the Future?

Ovejero

Gafni

Collins

2016

Journal of Bone and Mineral Research

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T he identification in the year 2000 of mutations in fibroblast growth factor 23 (FGF23) as the genetic cause of autosomal dominant hypophosphatemic rickets (ADHR) was a seminal discovery in the field of bone and mineral homeostasis.(1)Alterations in FGF23 levels were subsequently identified as the common abnormality in a number of phosphate homeostasis disorders, including X-linked hypophosphatemic rickets (XLH), (2) tumor-induced osteomalacia (TIO), (3) fibrous dysplasia of bone, (4) autosomal recessive hypophosphatemic rickets (ARHR), (5) cutaneous skeletal hypophosphatemia syndrome (CSHS), (6) familial tumoral calcinosis, (7) and others. The primary actions of FGF23 are to regulate blood phosphate and 1,25-dihydroxyvitamin D 3 (1,25-D) levels by its actions on renal sodium/phosphate cotransporters and 25-hydroxyvitamin D hydroxylation. (8) The fact that PTH, like FGF23, is also important in regulating phosphate and vitamin D homeostasis invokes the existence of an FGF23-Vitamin D-PTH axis that is key to many important aspects of bone and mineral biology. It is a complicated axis that involves the interaction of multiple receptors, a coreceptor, Klotho, (9) and multiple disparate but interacting signaling and enzymatic pathways. (10,11) Unraveling, in a hierarchical fashion, the roles of these complicated, intersecting, and overlapping pathways is important for both understanding mineral homeostasis physiology, and for the treatment of phosphate disorders. This has proved a significant challenge. Although a large number of very informative mouse models have been developed to understand and query this axis, at times the complexity of these models introduces potential confounders that are difficult to control for, and yield results inconsistent with observed human physiology. Thus, it is often difficult to understand and contextualize the findings and apply them to human mineral physiology and pathophysiology. The number of clinical studies conducted in this area is limited, and often focused on renal failure cohorts, the physiology of which differs significantly from those with normal renal function.Although a complete understanding of the FGF23-Vitamin D-PTH axis is lacking, there are a number of findings that are generally accepted to be true. These include: (1) FGF23 directly inhibits phosphate reabsorption and the generation of active vitamin D, 1,25-dihydroxyvitamin D 3 (1,25-D) at the level of the proximal renal tubule leading to a lowering of blood phosphate and 1,25-D levels (8) ; (2) in a classical feedback fashion, increases in blood phosphate and 1,25-D increase FGF23 levels (12,13) ; and (3) frank or relative FGF23-mediated reductions in serum 1,25-D lead to a compensatory increase in PTH, especially evident in the more severe forms of FGF23 excess such as TIO and renal failure. (14,15) The phosphaturic effects of increased PTH exacerbate the phosphate-lowering effects of FGF23 in patients with intact renal function such as TIO and XLH (reviewed in Blau and Collins (11) ). As for the hierarchic...

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Nephrocalcinosis and its relationship to treatment of hereditary rickets

Cited by 79 publications

References 8 publications

A New Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria: Implications for Correct Diagnosis and Treatment

A New Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria: Implications for Correct Diagnosis and Treatment

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

1,25-Dihydroxyvitamin D as Monotherapy for XLH: Back to the Future?

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