What is the clinical significance of parathyroid hormone‑related peptide (PTH‑rP), and is a low PTH‑rP level clinically relevant in a dialysis patient who has a normal intact PTH?

PTH-rP Clinical Significance in Dialysis Patients

In a dialysis patient with normal serum PTH, a low PTH-rP level has no clinical significance and should not be measured routinely. PTH-rP testing is only clinically useful when evaluating hypercalcemia with suppressed PTH to diagnose humoral hypercalcemia of malignancy—not in the context of normal calcium and normal PTH levels. 1

When PTH-rP Testing Is Appropriate

PTH-rP measurement should only be ordered after confirming hypercalcemia AND documenting a suppressed or inappropriately low PTH level (typically <26 ng/L). 1 The diagnostic algorithm is straightforward:

• First, measure serum calcium and intact PTH simultaneously 2
• If PTH is >26 ng/L, PTH-rP testing predicts a non-elevated result in 95-100% of cases and is uninformative 1
• PTH-rP testing is only useful when PTH is suppressed (<20 pg/mL) in the setting of hypercalcemia 3, 1

Understanding PTH-rP Biology

PTH-rP is not a marker of parathyroid function—it is a tumor-derived peptide that mimics PTH action through the same PTH/PTH-rP receptor. 4, 5 Key biological facts:

• PTH-rP is the major mediator of humoral hypercalcemia of malignancy (HHM), found in up to 100% of HHM patients 5
• Normal plasma PTH-rP is undetectable by current assays—it functions as a local paracrine factor in normal tissues, not a circulating hormone 4, 5
• Elevated PTH-rP occurs with squamous cell carcinomas (lung, head/neck), renal cell carcinoma, breast cancer, and neuroendocrine tumors 3
• Median survival after detecting elevated PTH-rP in malignancy is approximately 1 month 3

Why Low PTH-rP Is Meaningless

A "low" PTH-rP result is clinically irrelevant because PTH-rP is normally undetectable in healthy individuals and dialysis patients without malignancy. 4, 5 The test has:

• Diagnostic sensitivity of only 32% for hypercalcemia of malignancy 1
• Specificity of 95% when PTH is suppressed 1
• No established role in evaluating bone disease, mineral metabolism, or parathyroid function 6

Common Pitfalls in Dialysis Patients

Do not confuse PTH-rP with PTH fragments that accumulate in kidney failure. 6 Critical distinctions:

• "Intact" PTH assays in dialysis patients measure both active PTH(1-84) and inactive C-terminal fragments (7-84), leading to overestimation of true parathyroid activity 6
• PTH biological variation is substantial in hemodialysis patients (~30%), requiring >72% change to be clinically meaningful 6
• PTH levels are not always indicative of bone turnover in dialysis patients—adynamic bone disease can occur despite PTH >400 pg/mL 6
• PTH should be measured in EDTA plasma at 4°C for stability, and biotin supplements can interfere with assays 6, 3

What to Measure Instead

In dialysis patients with normal PTH, focus on established markers of mineral bone disease rather than PTH-rP: 6

• Target intact PTH between 150-300 pg/mL for hemodialysis patients (K/DOQI guidelines) 6
• Maintain serum phosphorus 3.5-5.5 mg/dL and calcium-phosphorus product to prevent vascular calcification 6
• Monitor for adynamic bone disease (low PTH <100 pg/mL) which increases fracture risk 4-fold 6
• Consider bone biopsy if PTH levels don't correlate with clinical picture, as it remains the gold standard for diagnosing bone disease in CKD 6

The bottom line: PTH-rP has zero diagnostic utility in evaluating dialysis patients with normal calcium and normal PTH—it is exclusively a tumor marker for malignancy-associated hypercalcemia with suppressed PTH. 1, 5