The pathogenesis of idiopathic hypercalciuria: evidence for parathyroid hyperfunction.

Area of Science:

• Nephrology
• Endocrinology
• Metabolic Disorders

Background:

• Renal calculi (kidney stones) are a significant health concern.
• Hypercalciuria, characterized by elevated urinary calcium, is a major risk factor for kidney stone formation.
• The precise causes of idiopathic hypercalciuria remain incompletely understood.

Purpose of the Study:

• To investigate the underlying causes of idiopathic hypercalciuria.
• To compare calcium metabolism and parathyroid hormone (PTH) levels in patients with renal calculi and healthy controls.
• To explore the relationship between plasma calcium, urinary calcium, and nephrogenous cyclic adenosine monophosphate (cAMP) in different patient groups.

Main Methods:

• Studied 17 healthy subjects and 76 patients with renal calculi, including those with primary hyperparathyroidism, idiopathic hypercalciuria, and normocalciuric stone formers.
• Measured fasting plasma calcium (corrected for albumin), plasma parathyroid hormone, and nephrogenous cAMP levels.
• Assessed urinary calcium excretion during a free diet and after an oral calcium load.
• Evaluated responses to thiazide medication.

Main Results:

• Fasting plasma calcium was significantly higher in patients with idiopathic hypercalciuria (2.40 +/- 0.10 mmol/l) compared to controls (2.28 +/- 0.05 mmol/l).
• Patients with primary hyperparathyroidism showed the highest plasma calcium (2.62 +/- 0.07 mmol/l) and PTH levels.
• Fasting urinary calcium and post-load increase were greatest in idiopathic hypercalciuria and primary hyperparathyroidism groups.
• Nephrogenous cAMP correlated positively with plasma calcium in primary hyperparathyroidism and negatively in controls, with no correlation in idiopathic hypercalciuria.

Conclusions:

• Increased parathyroid gland activity is the most likely cause of idiopathic hypercalciuria.
• The metabolic patterns observed did not align with previously described absorptive or renal hypercalciuria.
• Findings suggest a potential role for parathyroid hormone in the pathogenesis of kidney stones in idiopathic hypercalciuria patients.