Mechanism of Kidney Stone Formation in Hyperparathyroidism
Hyperparathyroidism causes kidney stones primarily through hypercalciuria, which leads to calcium salt supersaturation in urine, promoting stone formation and nephrocalcinosis. 1, 2
Pathophysiological Mechanisms
Primary Pathway: Calcium Dysregulation
- Elevated PTH levels cause increased bone resorption, releasing calcium into the bloodstream 1
- Hypercalcemia results from excessive calcium mobilization from bones 3
- Hypercalciuria occurs as the kidneys filter excess serum calcium 4, 2
- Calcium salt supersaturation in urine promotes crystal formation and aggregation 4
Secondary Contributing Factors
- Altered vitamin D metabolism in hyperparathyroidism affects calcium absorption 1
- Phosphate imbalance contributes to calcium-phosphate product formation 1
- Urinary pH changes affect the solubility of calcium salts 2
Types of Hyperparathyroidism and Stone Risk
Primary Hyperparathyroidism
- Characterized by hypercalcemia with inappropriately elevated PTH 5
- 10-22% of patients develop hypercalcemia, a major risk factor for stones 1
- Kidney stones are reported in patients with primary hyperparathyroidism, though not universally 4
- Calcium oxalate and calcium phosphate supersaturation significantly increases 4
Secondary Hyperparathyroidism
- Develops in response to chronic hypocalcemia, often in chronic kidney disease 6
- PTH increases in response to hyperphosphatemia, hypocalcemia, and decreased vitamin D 1
- Calcium-phosphorus product can exceed critical thresholds, leading to calcifications 1
Tertiary Hyperparathyroidism
- Occurs after longstanding secondary hyperparathyroidism 7
- Autonomous PTH secretion continues despite normal or elevated calcium levels 7
- Particularly common after renal transplantation 6
Clinical Implications
Stone Risk Assessment
- No significant differences in preoperative 24-hour urine metabolic profiles between hyperparathyroid patients with and without stones 4
- Routine 24-hour urine evaluation cannot predict which patients will develop stones 4
- Other factors beyond hypercalciuria must contribute to stone formation in some patients 4
Treatment Effects on Stone Risk
- Successful parathyroidectomy significantly decreases:
- Serum calcium (10.8 to 9.3 mg/dl)
- Urinary calcium (319 to 156 mg per day)
- Calcium oxalate supersaturation (8.6 to 5.7)
- Calcium phosphate supersaturation (1.6 to 0.9) 4
Management Considerations
Monitoring
- Regular assessment of calcium, phosphorus, and PTH levels based on disease severity 5
- Kidney function monitoring is essential as hyperparathyroidism can impair renal function 2
Treatment
- Parathyroidectomy is indicated for symptomatic patients, including those with kidney stones 1, 5
- Medical management includes:
- Optimizing vitamin D levels (target >30 ng/mL)
- Ensuring adequate dietary calcium intake
- Using calcimimetics for severe hyperparathyroidism 5
Clinical Pitfalls and Caveats
- Not all patients with hyperparathyroidism and hypercalciuria develop stones, suggesting additional factors are involved 4
- Residual risk of nephrocalcinosis may persist even after successful parathyroidectomy 2
- Declining renal function in hyperparathyroidism may warrant surgical intervention (eGFR <60 ml/min/1.73m²) 2
- PTH assay variations can affect diagnosis and management decisions 1
Understanding this pathophysiology helps clinicians anticipate, monitor for, and manage the renal complications of hyperparathyroidism, particularly kidney stone formation.