Can a patient with end‑stage renal disease on hemodialysis and documented calciphylaxis have a low intact parathyroid hormone (iPTH) level?

Can Calciphylaxis Occur with Low iPTH in Hemodialysis Patients?

Yes, calciphylaxis can absolutely occur in hemodialysis patients with low intact parathyroid hormone (iPTH) levels, and this presentation has become increasingly recognized as distinct from the historical association with severe hyperparathyroidism.

Evolution of Calciphylaxis Phenotypes

The clinical profile of calciphylaxis has shifted dramatically over time:

• Historical presentation: Early descriptions linked calciphylaxis to severe hyperparathyroidism, and parathyroidectomy was often curative 1
• Contemporary presentation: More recent cases demonstrate calciphylaxis occurring in patients with low PTH levels and, when assessed by bone biopsy, evidence of adynamic bone disease 1
• This shift reflects a fundamental change in the pathophysiology—from high-turnover bone disease to low-turnover states 1

Mechanism: Adynamic Bone Disease as the Culprit

The connection between low iPTH and calciphylaxis centers on adynamic bone disease:

• Impaired calcium buffering: Adynamic bone cannot appropriately take up or release calcium, losing its normal regulatory function for calcium-phosphate homeostasis 1
• Minimal calcium loading causes hypercalcemia: Without functional bone turnover, even small calcium loads (from binders, dialysate, or vitamin D) lead to marked hypercalcemia 1
• Metastatic calcification risk: When bone fails to accrue calcium, other tissues become vulnerable to pathologic calcium deposition, with calciphylaxis representing the most severe manifestation 1
• PTH suppression below 150 pg/mL in dialysis patients directly causes adynamic bone disease, increasing fracture risk and eliminating the bone's capacity to buffer calcium-phosphate loads 2

Clinical Evidence Supporting Low-PTH Calciphylaxis

Direct case reports confirm this phenomenon:

• A pediatric ESRD patient developed severe calciphylaxis with low serum PTH and a normal calcium-phosphorus product, ultimately dying despite aggressive treatment 3
• This case demonstrates that calciphylaxis can occur even when traditional risk factors (elevated PTH, high Ca×P product) are absent 3

Critical Pitfall: Over-Suppression of PTH

The most dangerous error in dialysis patients is targeting normal-range PTH:

• Target PTH for Stage 5 CKD/dialysis is 150-300 pg/mL—not the normal range 1, 2
• Suppressing PTH below 65 pg/mL causes adynamic bone disease with increased fracture risk and impaired calcium-phosphate buffering 4, 2
• This creates a paradoxical situation where aggressive PTH suppression (often with excessive vitamin D or calcimimetics) increases rather than decreases the risk of soft tissue calcification 1

Management Implications for Low-PTH Calciphylaxis

When calciphylaxis occurs with low iPTH, the treatment strategy differs fundamentally:

• Stop all vitamin D therapy immediately to allow PTH to rise 1
• Reduce or eliminate calcium-based phosphate binders 1
• Lower dialysate calcium to 1.0-2.0 mEq/L (rather than the standard 2.5 mEq/L) to stimulate endogenous PTH release and increase bone turnover 1, 4
• The goal is to increase bone turnover by allowing PTH to rise back into the target range of 150-300 pg/mL 1, 2

Distinguishing Features from High-PTH Calciphylaxis

The clinical context matters:

• High-PTH calciphylaxis (historical): Associated with severe hyperparathyroidism (PTH >800 pg/mL), high calcium-phosphorus product, and high-turnover bone disease 5, 6
• Low-PTH calciphylaxis (contemporary): Associated with over-treatment of secondary hyperparathyroidism, adynamic bone, and impaired calcium buffering capacity 1, 3
• Both phenotypes can coexist in the same dialysis population, requiring individualized assessment of PTH levels and treatment history 1

Common Clinical Scenario

A typical presentation involves a hemodialysis patient who:

1. Previously had elevated PTH and received aggressive vitamin D therapy
2. Developed "well-controlled" PTH levels (often <150 pg/mL)
3. Subsequently develops painful skin lesions consistent with calciphylaxis
4. Has normal or only mildly elevated calcium-phosphorus product 3

This scenario reflects iatrogenic adynamic bone disease from PTH over-suppression 1, 2.