Vitamin D Overdose and Urinary Calcium Excretion
Yes, calcium will show up in the urine (hypercalciuria) with vitamin D overdose in adults without known renal disease. Hypercalciuria is a well-established manifestation of vitamin D toxicity and occurs through increased intestinal calcium absorption driven by elevated vitamin D metabolites 1, 2.
Mechanism and Clinical Evidence
Vitamin D toxicity causes hypercalciuria through enhanced intestinal calcium absorption, which directly increases urinary calcium excretion. The active metabolite calcitriol increases digestive calcium absorption, and since urinary calcium excretion correlates directly with digestive calcium absorption, vitamin D metabolites increase calciuria 3. This relationship has been demonstrated across multiple studies showing that vitamin D supplementation increases urinary calcium excretion 2.
Key Laboratory Findings in Vitamin D Overdose
The typical biochemical profile includes:
- Hypercalciuria (elevated urinary calcium) - consistently present and often the earliest laboratory abnormality 2, 4
- Hypercalcemia (elevated serum calcium) - develops as toxicity progresses 1, 2
- Suppressed parathyroid hormone (PTH) - due to hypercalcemia feedback 1
- Elevated 25(OH)D levels - typically >150 ng/mL, with acute toxicity at >200 ng/mL 1
Dose-Response Relationship
Long-term vitamin D supplementation increases the risk of both hypercalcemia (RR: 1.54; 95% CI: 1.09-2.18) and hypercalciuria (RR: 1.64; 95% CI: 1.06-2.53) 2. Importantly, hypercalciuria can occur even before serum calcium becomes elevated, making urinary calcium measurement a sensitive early marker of vitamin D excess 4.
Clinical Implications and Monitoring
The urine calcium/creatinine ratio in a random spot urine should be obtained when vitamin D toxicity is suspected, along with serum calcium, 25(OH)D, and intact PTH levels 5. Hypercalciuria may persist even after serum calcium normalizes, and can lead to nephrocalcinosis and kidney stone formation 4, 3.
Risk Factors for Hypercalciuria
Certain patients are predisposed to developing hypercalciuria with vitamin D supplementation:
- Patients with absorptive hypercalciuria - have enhanced intestinal calcium absorption that is exacerbated by vitamin D 4
- Patients with elevated baseline 1,25-dihydroxyvitamin D - more prone to hypercalciuria and hyperoxaluria 6
- Immobilized patients - require dose reduction of active vitamin D to prevent hypercalciuria and hypercalcemia 5
Important Caveat
While vitamin D supplementation increases hypercalciuria risk, meta-analysis of long-term studies showed a tendency toward fewer kidney stones in the vitamin D group (RR: 0.66; 95% CI: 0.41-1.09), though this was not statistically significant 2. However, combined vitamin D and calcium supplementation does increase kidney stone incidence, with one additional stone per 273 women supplemented over 7 years 1.
Management Approach
When vitamin D overdose is confirmed:
- Immediately discontinue all vitamin D supplementation 7
- Measure urinary calcium excretion via spot urine calcium/creatinine ratio 5
- Institute a low-calcium diet temporarily and increase fluid intake 1
- Monitor for nephrocalcinosis via renal ultrasonography if hypercalciuria is present 5
- Treat hypercalcemia aggressively if calcium exceeds 14 mg/dL with IV hydration, loop diuretics, glucocorticoids, calcitonin, and bisphosphonates 1
The hypercalciuria may persist for weeks to months after discontinuation of vitamin D due to the long half-life of 25(OH)D stores 4.