X linked hypophosphataemia: treatment, height gain, and nephrocalcinosis.

Reusz, György; Hoyer, Peter F.; Lucas, M; Krohn, H. P.; Ehrich, J H; Brodehl, J.

doi:10.1136/adc.65.10.1125

Cited by 48 publications

(29 citation statements)

References 21 publications

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“…However, the amount of la-(OH)D, administered to our XLH patients can be considered as elevated. Indeed, it has been shown that among children with XLH, hypercalcemic and hypercalciuric episodes are significantly more frequent with doses of l,25-(OH)2D3 higher than 40 or 20 ng/kg/day, respectively, than with doses lower than 40 or 20 ng/kg/day [9], In adult patients, treatment with doses of 1-2 pg/day have been recommended recently [1], These considerations bring to mind the well-known experiences of vitamin D overtreatment as cause of nephrocalcinosis in vitamin-Dresistant rickets [7], Two recent studies [23,24] found no correlation between nephrocalcinosis and the doses of vita- 530 Tieder/Blonder/Strauss/Shaked/M aor/ G abizon/ Manor/Sela…”

Section: Discussionmentioning

confidence: 99%

Hyperoxaluria Is Not a Cause of Nephrocalcinosis in Phosphate-Treated Patients with Hereditary Hypophosphatemic Rickets

Tieder

Blonder²,

Strauß³

et al. 1993

Nephron

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The treatment of X-linked hypophosphatemia (XLH) consists of phosphate and vitamin D₃ derivatives. Transient hypercalciuria and hypercalcemia are well-known signs of vitamin D intoxication. Despite urinary calcium excretion control, the danger of nephrocalcinosis in treated patients has been emphasized. It has recently been suggested that hyperoxaluria might be a causative factor of nephrocalcinosis other than calcium in phosphate-treated XLH patients. We measured urinary oxalate and phosphate excretion in 12 patients with the syndrome of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) receiving only oral phosphates and in 5 XLH patients receiving both oral phosphates and vitamin D. No correlation was found between the dosage of phosphate supplements or urinary phosphate excretion and urinary oxalate excretion, in either group of patients. Nephrocalcinosis, presenting as hyperechogenicity of the medullary pyramids, was found in 2 of the 5 XLH patients and only in 2 HHRH patients who had been treated with excessive doses of vitamin D₂ and calcium, prior to the true diagnosis being established. We conclude: (1) hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets; (2) prolonged phosphate treatment alone does not induce nephrocalcinosis in HHRH patients, and (3) we believe that in XLH patients, nephrocalcinosis is essentially due to vitamin D overdosage at some stage, or noncompliance in phosphate intake, leading to repeated undetected hypercalciuric periods.

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Section: Discussionmentioning

confidence: 99%

Hyperoxaluria Is Not a Cause of Nephrocalcinosis in Phosphate-Treated Patients with Hereditary Hypophosphatemic Rickets

Tieder

Blonder²,

Strauß³

et al. 1993

Nephron

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“…There are some reports indicating a strong association between high oral phosphorus intake and nephrocalcinosis in children (Reusz et al, 1990), and in rats (Matsuzaki et al, 1996;Zalups et al, 1983). High phosphorus supplementation causes a depression of kidney function.…”

Section: Kidney Functionmentioning

confidence: 99%

High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women

et al. 2001

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Objective: Assessment of the physiological effects of a diet rich in phosphorus in young women. Design: Control period I Ð commercial basic diet containing 1700 mg P and 1500 mg Caaday for 4 weeks. Supplementation period Ð a 6 week high-phosphorus period of 3008 mg P and 1995 mg Caaday. Control period II Ð 4 weeks washout with basic diet as in period I. Setting: Institute of Nutritional Science, Friedrich Schiller University, Jena. Subjects: Ten healthy women, aged 20 ± 30 y. Interventions: Orange juice and tablets, containing supplements of Ca 5 (PO 4 ) 3 OH and NaH 2 PO 4 , totalling 1436 mg elemental phosphorus per day. Results: There was an increase of 10.7 AE 13.7 pgaml in serum PTH, a decrease of 0.6AE 0.6 ngaml in serum osteocalcin, an increase of 73.6 AE 136.6 nmolammol creatinine in urinary pyridinoline and of 19.3 AE 36.0 nmola mmol creatinine in urinary deoxypyridinoline, and a decrease of 2.6 AE 9.3 mgal in urinary microalbumin. All changes were insigni®cant. There were no changes in serum levels of Ca, PO 4 or Zn, in serum concentration of 1,25-(OH) 2 D 3 , and in urinary b-2-microglobulin excretion. Phosphorus supplementation caused intestinal distress, soft stools or mild diarrhoea. Conclusions: In spite of a high phosphorus supplementation no signi®cant changes in bone-related hormones, pyridinium crosslinks as markers of bone resorption and parameters of renal function in young women were found.

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“…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: 92%

“…(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%

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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X linked hypophosphataemia: treatment, height gain, and nephrocalcinosis.

Cited by 48 publications

References 21 publications

Hyperoxaluria Is Not a Cause of Nephrocalcinosis in Phosphate-Treated Patients with Hereditary Hypophosphatemic Rickets

Hyperoxaluria Is Not a Cause of Nephrocalcinosis in Phosphate-Treated Patients with Hereditary Hypophosphatemic Rickets

High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women

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

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