Role Of Phosphorus And FGF 23 In Patients With Dent Disease

Study Overview
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Brief Summary
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Patients with Dent disease have suppressed levels of FGF 23 which contributes to hypercalciuria, kidney stones, nephrocalcinosis and renal failure. Supplementation with phosphorus may reduce hypercalciuria.

Official Title
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Role Of Phosphorus And FGF 23 In Patients With Dent Disease

Conditions
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Dent Disease

Intervention / Treatment
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* Drug: Phosphorus Supplement
* Other: Observation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be recruited from those in the RKSC Dent Registry Diagnostic criteria for Dent disease Observational arm include: <18 years old LMWP (at least 5 times above the upper limit of normal) and at least 1 of the following criteria: 1. Hypercalciuria, 2. Kidney stones, 3. Nephrocalcinosis, 4. Hypophosphatemia, 5. Renal phosphate leak, 6. Aminoaciduria, 7. Glucosuria without diabetes mellitus, 8. Hematuria, 9. Renal insufficiency, 10. Family history with x-linked inheritance or 1 of the above criteria (1-9) and confirmed genetic mutation of CLCN5 or OCRL1. Diagnostic criteria for Dent disease Intervention arm include: >18 years old LMWP (at least 5 times above the upper limit of normal) and at least 1 of the following criteria: 1. Hypercalciuria, 2. Kidney stones, 3. Nephrocalcinosis, 4. Hypophosphatemia, 5. Renal phosphate leak, 6. Aminoaciduria, 7. Glucosuria without diabetes mellitus, 8. Hematuria, 9. Renal insufficiency, 10. Family history with x-linked inheritance or 1 of the above criteria (1-9) and confirmed genetic mutation of CLCN5 or OCRL1. Idiopathic calcium nephrolithiasis with renal phosphate leak Male patients > 18 years old History of symptomatic calcium oxalate or calcium phosphate stone, hypercalciuria (>250 mg/24 hrs), renal phosphate leak (TMP/GFR <2.07 mg/dl) Idiopathic calcium nephrolithiasis without renal phosphate leak Male patients > 18 years old History of symptomatic calcium oxalate or calcium phosphate stone, hypercalciuria (>250 mg/24 hrs), renal phosphate leak (TMP/GFR <2.07 mg/dl) Exclusion Criteria: Exclusion for Dent disease include: primary or secondary hyperparathyroidism, hyperthyroidism, chronic diarrhea states; intake of thiazide diuretics, glucocorticoids, or estrogens within one month of the study. Exclusion criteria for calcium stone formers include: primary or secondary hyperparathyroidism, hyperthyroidism, estimated GFR <40 ml/mn/1.73m2, chronic diarrhea states; intake of thiazide diuretics, glucocorticoids, or estrogens within one month of the study. Exclusion criteria include history of symptomatic or asymptomatic kidney stone disease; primary or secondary hyperparathyroidism; estimated GFR <40 ml/min/1.73m2, chronic diarrhea states; intake of thiazide diuretics, glucocorticoids, or estrogens within one month of the study.
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dent Disease Intervention<br>Dent Disease subjects will receive 2 week supplementation with phosphorus | Drug: Phosphorus Supplement<br>* 250 mg po qid<br>* Other names: K-phos neutral;|
| Experimental: Kidney Stone subjects<br>Kidney stone with or without phosphate leak subjects will receive 2 week supplementation with phosphorus | Drug: Phosphorus Supplement<br>* 250 mg po qid<br>* Other names: K-phos neutral;|
| Placebo Comparator: Dent Disease Observation<br>Dent disease subjects will not get phosphorus | Other: Observation<br>* Baseline blood and urine measurements only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urine Total Protein | Urine protein tests detect and/or measure protein being released into the urine. Normal urine protein elimination is less than 150 mg/day | baseline, day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dent, Dents, Dent Disease, Phosphorus Supplements, FGF 23