Why Dialysis Patients Have High PTH and Low Calcium and Iron
Dialysis patients develop elevated PTH primarily due to impaired phosphate excretion and reduced active vitamin D production by failing kidneys, which together stimulate parathyroid hormone secretion; calcium levels are typically low due to decreased intestinal calcium absorption from vitamin D deficiency and phosphate retention; iron deficiency results from chronic blood loss through dialysis procedures, reduced dietary intake, and impaired iron absorption in uremia.
Elevated Parathyroid Hormone (PTH)
Primary Mechanisms
Phosphate retention is the fundamental driver of secondary hyperparathyroidism in dialysis patients, as hyperphosphatemia increases bone resistance to PTH and directly stimulates PTH secretion 1.
Vitamin D deficiency develops early in CKD and worsens as kidney function declines, since failing kidneys cannot adequately convert 25-(OH)D to active 1,25-dihydroxyvitamin D (calcitriol), removing a key suppressor of PTH secretion 1, 2.
Hypocalcemia directly stimulates PTH release through calcium-sensing receptors on parathyroid cells, creating a compensatory response to maintain serum calcium 1.
The fraction of intestinal calcium absorption decreases early in Stage 3 CKD and progressively worsens, with initiation of dialysis failing to improve absorption 1.
Clinical Context
In large dialysis populations, 25.4% of patients demonstrate frank hyperparathyroidism (iPTH >400 pg/mL), though paradoxically 43% have oversuppressed PTH (<100 pg/mL) from aggressive treatment 3.
The relationship between PTH and calcium shows moderate inverse correlation, but specific PTH levels cannot reliably predict calcium values due to individual variability in skeletal PTH responsiveness 1.
Important caveat: High PTH does not exclude adynamic bone disease, as some patients demonstrate low bone turnover despite PTH values exceeding 400 pg/mL, likely due to accumulation of inhibitory PTH fragments 1.
Low Calcium Levels
Pathophysiologic Mechanisms
Reduced intestinal absorption occurs from vitamin D deficiency, with net intestinal calcium balance becoming negative when dietary intake falls below 20 mg/kg/day 1.
Inadequate dietary intake is common, with dialysis patients averaging only 549 mg/day calcium intake, representing 80% of recommended daily allowance 1.
Phosphate binding reduces available calcium, as elevated phosphate levels complex with calcium in the circulation 1.
Hypocalcemia was associated with increased mortality (p=0.006) in a prospective cohort of 433 dialysis patients, with particular association to cardiac ischemic disease and congestive heart failure 1.
Dialysis-Related Factors
Standard dialysate calcium concentration of 2.5 mEq/L represents a balance between preventing hypocalcemia and avoiding excessive calcium loading that contributes to vascular calcification 1.
Lower dialysate calcium (1.5-2.0 mEq/L) may be used to stimulate PTH in adynamic bone disease, but increases cardiac arrhythmia risk through QT interval prolongation 1.
Low Iron Levels
While the provided evidence does not directly address iron deficiency in dialysis patients, this is a well-established clinical phenomenon resulting from:
- Chronic blood loss through dialysis circuit retention, frequent laboratory testing, and occult gastrointestinal bleeding from uremic platelet dysfunction
- Reduced dietary intake from protein restriction and uremic anorexia
- Impaired iron absorption from uremic inflammation and hepcidin elevation
- Increased iron utilization when erythropoiesis-stimulating agents are administered
Clinical Implications
The interplay between calcium, phosphate, and PTH creates a "basic conflict" where adequate PTH suppression risks excessive calcium loading and tissue injury, while inadequate control worsens bone disease 1.
Both extremes of PTH are problematic: very low PTH (<100 pg/mL) associates with adynamic bone disease and fracture risk, while very high PTH (>800 pg/mL) correlates with 243% higher risk of hyperphosphatemia and 376% higher risk of elevated alkaline phosphatase 1, 4.
Management requires monitoring PTH trends rather than single values, as marked changes in either direction should prompt therapeutic adjustment even within the suggested range of 2-9 times upper normal limit 1, 5.
Hypocalcemia below 7.5 mg/dL or symptomatic hypocalcemia requires withholding calcimimetics and increasing calcium-containing phosphate binders or vitamin D until calcium reaches 8 mg/dL 6.