Elucidation of the Role of Calcium Sensor in Absorptive Hypercalciuria
Study ID: STU 012014-024
aim 1: Subjects will participate in 3 phases of study: Baseline, acute phase, and chronic phase. Phase 2 will commence immediately after the completion of the Phase 1. Phase 3 will commence immediately after the completion of Phase 2. aim 1a: Subjects will follow an instructed diet at home for days 1 and 2. Subjects will be studied in outpatient research laboratory on Day 3. aim 2: Subjects will participate in 3 phases of study including: aaaxsupplemented diet 3, mixture of aa-supplemented diet 3, and placebo-supplemented phase. The order of the phases will be random. each phase will last 5 days, and a 14-day washout will commence immediately after the completion of the phase 1, followed by phase 2. Phase 3 will commence immediately after the completion of the phase 2 washout. aim 1: During Baseline, patients will follow an instructed diet at home for days 1 and 2. on days 3-4, they will be kept on a constant metabolic diet and 3 liters total fluids. on the evening of day 2 (4pm), subjects will be admitted to the CRu for metabolic study. They will have a metabolic dinner at 5pm and will fast except for distilled water load after the evening meal. They will have 300cc distilled water at 8pm and again at 11pm. at 6am on day 3, they will empty their bladder and discard the urine. They will then be given 600cc of distilled water to start a fasting 2hr urine collection until 8am for total volume, pH, calcium, phosphorus and creatinine. at 8am a baseline fasting blood will be collected. after the blood draw, fractional intestinal calcium absorption will be measured by dual isotope technique. The oral isotope will be given with 100 mg of calcium in 90cc of ensure containing 100mg elemental calcium, followed by 50cc of distilled water to rinse. The patient will be nPo for 4 hours following the dual isotope procedure. Following the stable isotope administration, a 24-hr urine will be collected. urine samples will be measured for stable isotope by mass spectroscopy. on day 4, urine will be collected in a 24-hr pool. Fasting venous blood sample will be obtained at 8am. Subjects will be discharged on the morning of day 5. acute Drug Phase Same as baseline phase, with single dose of Sensipar 60mg with oral isotope on day 17. Chronic Drug Phase Subjects will take Sensipar 30mg BiD for a total of 15 days. on the 31st day, they will undergo the same study procedures as Baseline phase. aim 1a: Subjects will follow an instructed diet at home for days 1 and 2. on day 3, after 12 hours of overnight fast subjects will empty their bladder at 6am and discard the urine. They will then drink 300cc of distilled water to start a fasting 2hr urine collection at home from 6am until 8am. Subjects will arrive at the outpatient research lab at 7:45am to complete the 2hr urine collection at 8am. Fasting blood will be collected at 8am and subjects will receive a single oral dose of Sensipar 30-60 mg. Post load: Subjects will drink 250cc of distilled water at 8:00am and collect 2hr urine between 8am and 10am followed by full serum at 10am. aim 2: each subject will be studied during three 5-day phases separated by 14-day washout. The 3 experimental diets will be provided in random order. The normal-protein diet will consist of 800 mg calcium, 800 mg phosphorus, 100 mmol sodium and 2.5 liters of total fluid daily. on days 1 - 4, the supplemental amino acids will be divided among the 3 meals in amounts proportional to the protein content of each meal, with the amount of aaa and mixed aa added to the low-protein diet adjusted to increase protein intake from normal to high. on days 4 and 5, subjects will be admitted to the inpatient CRu to collect 24-hr urine and fasting blood at 8 aM. Serum concentration of aaa will be measured in a fasting state and post-prandially. Subjects will be discharged the morning of day 6.
Aim 1: Recruited for the study will be three hypercalciuric patients with kidney stones and three normal participants without stones between 21-70 years of age, of either gender and any ethnicity. Kidney stone forming subjects will be designated as severely hypercalciuric with urinary calcium >= 300mg/day. Aim 2: Recruited for the study will be three hypercalciuric patients with kidney stones and three normal participants without stones between 21-70 years of age, of either gender and any ethnicity. Kidney stone forming subjects will be designated as severely hypercalciuric with urinary calcium >= 300mg/day.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- KHASHAYAR SAKHAEE
CHARLES Y. C. PAK AND VARIOUS
aim 1: explore whether calcimimetic agents (increase CaSR activation) enhance intestinal calcium absorption and urinary calcium excretion in hypercalciuric kidney stone formers and normal controls. aim 1 a: This aim proposes to explore the effect calcium sensitizer on renal tubular calcium handling, calciotropic hormones, DGF x 23 and Klotho. aim 2: assess whether ingestion of aromatic amino acids (aaa, known activators of the CaSR) enhances urine calcium excretion.