Nephrolithiasis in Patients with Primary Hyperparathyroidism
Aim 1: To compare the formation product for calcium oxalate and calcium phosphate in urine of stone-forming and non-stone forming patients with primary hyperparathyroidism and healthy controls.
Study design and rationale: The current proposal will compare classic stone risk parameters and assess for crystallization inhibitors in urine of non-stone forming PHPT subjects, stone forming PHPT subjects, and healthy controls.
Experimental protocol: After providing informed consent, subjects from all three groups will be asked to complete a short questionnaire, to collect a 24-hr urine sample and have fasting blood drawn. PHPT subjects will bring the urine to and have blood drawn at the time of their scheduled pre-operative evaluation. PHPT subjects without kidney stones and healthy controls will undergo an evaluation by KUB x-ray to determine the presence of asymptomatic kidney stones. Healthy controls will have these studies at a single 1 hour research visit. Approximately 1 tablespoons of blood will be drawn for this aim.
Aim 2: To compare urinary content of osteopontin and pyrophosphate, two inhibitors of calcium crystal formation and growth, in stone-forming and non-stone forming patients with primary hyperparathyroidism and healthy controls.
Study design and rationale: The study will compare osteopontin and pyrophosphate content in urine of non-stone forming PHPT subjects, stone forming PHPT subjects, and healthy controls.
Experimental protocol: Measurement of urine osteopontin and pyrophosphate will be conducted on the same 24-hr urine specimen collected in Aim 1.
Aim 3: To compare the formation product ratio, urinary osteopontin and urinary pyrophosphate pre- and post-parathyroidectomy in stone-forming and non-stone forming patients with primary hyperparathyroidism.
Study design and rationale: Parathyroidectomy was associated with a significant increase in FPR for calcium oxalate in one published study. Whether similar changes occur in stone-forming vs. non-stone forming PHPT patients has not been studied. Similarly, it is not known what effects parathyroidectomy will have on urine osteopontin and pyrophosphate.
Experimental protocol: Subjects will be asked to collect a second 24-hr urine specimen 2 weeks post-parathyroidectomy, that they will be bring with them at the time of their first post-op visit. Urinary measurements will include pH, magnesium, calcium, oxalate, phosphorus, potassium, sodium, ammonium, chloride, sulfate, uric acid, creatinine and total volume, FPR brushite and CaOx, and osteopontin and pyrophosphate. Blood will be drawn for serum electrolytes and PTH. Approximately 1 tablespoons of blood will be drawn for this aim.
15 stone-forming PHPT patients, 15 non-stone forming PHPT patients and 15 control subjects of any age, gender, or race/ethnicity. Non-stone formers and controls will be matched to the stone-forming PHPT subjects with respect to gender, ethnicity, age (±5 yrs), and BMI (±5 Kg/m2).