Does the Parathyroid Hormone (PTH) cutoff change in Chronic Kidney Disease (CKD)?

From the Guidelines

The PTH cutoff values do change in Chronic Kidney Disease (CKD), with a recommended target range of approximately 2 to 9 times the upper normal limit for the assay in patients with CKD G5D. For patients with normal kidney function, the target PTH range is typically 10-65 pg/mL, but this range increases as kidney function declines. In early CKD (stages 1-3), PTH targets remain close to normal, but in advanced CKD (stages 4-5) and especially in dialysis patients, higher PTH levels are considered acceptable. This adjustment is necessary because as kidney function declines, phosphate retention occurs, vitamin D activation decreases, and calcium absorption is impaired, all leading to secondary hyperparathyroidism, as suggested by the 2017 KDIGO guideline update 1.

Key Considerations

• The kidneys become resistant to PTH action, requiring higher levels to maintain calcium-phosphate homeostasis.
• Clinicians use these adjusted PTH targets when making treatment decisions about medications like vitamin D analogs, calcimimetics, and phosphate binders in CKD patients to prevent both excessive bone turnover from high PTH and adynamic bone disease from overly suppressed PTH.
• Marked changes in PTH levels in either direction within the recommended range should prompt an initiation or change in therapy to avoid progression to levels outside of this range, as recommended by the KDIGO guideline update 1.

Clinical Implications

• The recommended target range of 2-9 times the upper limit of normal is roughly equivalent to 130-600 pg/mL, depending on the assay used.
• Regular monitoring of PTH levels is crucial in CKD patients to ensure that levels remain within the target range and to adjust treatment accordingly.
• Treatment decisions should be individualized based on the patient's specific needs and clinical status, taking into account the potential risks and benefits of different therapies.

From the FDA Drug Label

The mean age of the patients was 13. 6 years, 69% were male, 86% were Caucasian, and 8% were Asian. The initial dose of paricalcitol capsules was 1 mcg three times a week. Serum iPTH, calcium, and phosphorus levels were monitored every 2 to 4 weeks with a goal to maintain levels within target ranges: iPTH 35 to 70 pg/mL for CKD stage 3, iPTH 70 to 100 pg/mL for CKD stage 4, calcium < 10.2 mg/dL, phosphorous < 5. 8 mg/dL.

The Parathyroid Hormone (PTH) cutoff does change in Chronic Kidney Disease (CKD), with different target ranges for CKD stage 3 (iPTH 35 to 70 pg/mL) and CKD stage 4 (iPTH 70 to 100 pg/mL) 2.

From the Research

Parathyroid Hormone (PTH) Cutoff in Chronic Kidney Disease (CKD)

• The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend maintaining serum PTH concentration within target ranges defined according to the stage of CKD 3.
• For patients with CKD stage 5, the target PTH range is 150-300 pg/ml 3.
• Secondary hyperparathyroidism develops early in patients with CKD, and controlling PTH, calcium, and phosphorus levels is crucial to reduce poor outcomes 4.
• The PTH cutoff may vary depending on the stage of CKD and the presence of secondary hyperparathyroidism.

Factors Influencing PTH Cutoff

• The quality of the PTH assay is crucial in determining the therapeutic decision 3.
• Vitamin D insufficiency is linked to secondary hyperparathyroidism in non-dialysis CKD, and correction of low 25(OH)D levels is a recognized management approach 5.
• The level of 25(OH)D above which suppression of PTH progressively diminishes may be higher than that recommended for the general population 5.

Management of Secondary Hyperparathyroidism

• Therapies for managing rising PTH include vitamin D analogues, calcimimetics, and management of serum mineral concentrations with diet, binders, and dialysis 6.
• Novel approaches, such as the development of calcifediol in an extended-release formulation, have shown promise in lowering PTH in CKD stage G3-G4 without clinically meaningful increases in serum calcium and phosphate levels 5.
• Parathyroidectomy has become a primary treatment option for severe hyperparathyroidism in patients who are medically fit for operative intervention 6.