Assessment of Calcium Metabolism, Parathyroid Function and Vitamin D Status in Disorders of Mineral Metabolism
The patients will be placed on a constant metabolic diet for 3 days. Venous blood will be obtained before breakfast on all 3 days. Urine will be collected on all 3 days of the diet in 24-hour pools. Bone mineral density will be measured. Selected x-rays may be done to confirm or support diagnosis. Additional tests may be included depending on the nature of the specific objective.
Alternatively on day 4, three 8-hour urine collections will be obtained following the start of an infusion of magnesium sulfate solution over four hours. Checks for blood pressure, pulse and reflexes will be done each hour during the infusion. A blood sample will be collected before and at the end of the infusion. On Day 5, an ammonium chloride load may be given followed by hourly urine samples and arterialized venous blood samples. A bone biopsy may be done to assess the quality of the bone.
The basic protocol described above may be modified in multiple ways including: urine may be analyzed for crystallization studies; in selected patients, the classic ammonium chloride load test may be done to exclude renal tubular acidosis, the [Double Quote]state of the bone[Double Quote] may be determined directly by a bone biopsy and magnesium deficiency, a potential cause for calcium and parathyroid dysfunction, may be determined by the magnesium infusion. Additionally, in selected patients the classic urine to blood PCO2 ratio will be calculated following an oral bicarbonate load.
A sub-study for 30 subjects per year will include: the classic ammonium chloride load test on day 1, and on day 2 the classic urine to blood PCO2 ratio will be calculated following an oral bicarbonate load. All subjects will undergo an evaluation by KUB to determine the presence of asymptomatic kidney stones. The subjects to be studied include a personal history of kidney stones, a family history of kidney stones, or abnormalities on biochemical studies that promote kidney stone development. An abdominal/pelvic CT will be obtained in these subjects in the following situations: a) Patients in whom a stone is suspected based on clinical history suggestive of stones, but was not seen on KUB b) Patients in whom the KUB suggests a possible stone but is questionable due to bowel artifacts c) Patients in whom a KUB was inadequate because of poor visibility due to stool or other artifacts such as foreign bodies which obscure the renal parenchyma.Intestinal calcium absorption (IA) will be determined will be determined by dual-tracer stable isotope technique in which 46Ca will be given orally and 42Ca will be administered intravenously.
For a select group of subjects (up to 10 subjects per year), we will perform a four day inpatient evaluation as described above, prescribe a standard of care treatment for their disorder and ask them to repeat the 4 day evaluation after 24 days.
Screening will include blood samples and a 24-hour urine collection. Other optional tests may be performed.
Inpatient/outpatient subjects for evaluation:
Individuals enrolled in this study may be from any segment of the community. These individuals may suffer from unusual disorders of mineral metabolism previously mentioned, or they may present with hyper- or hypocalcemia or calciuria of unknown etiology or be normal controls. They may be either sex, any ethnicity, and ages 12-90.
Subject Selection Criteria for the KUB/CT Sub-study:
1) Family history of kidney stones
2) Personal history of symptoms suggestive of kidney stones without a confirmed diagnosis
3) Biochemical findings that place a subject at risk for kidney stones include:
a. A non-ionic gap metabolic acidosis (CO2 < 22)
b. Low serum potassium (< 3.5mEq/l) suggestive of a distal renal tubular scidosis
c. Hypocitraturia (urinary citrate < 450mg/day)
d. Alkaline urine (pH > 6.5)
e. Abnormal findings on the ammonium chloride challenge including failure to achieve a urine pH < 5.5 following 50mEq of ammonium chloride
f. Abnormal findings on the bicarbonate load including a urinary – blood pCO2 < 25 mmHg
Subjects may be either sex, any ethnicity and race, and ages 4-90.