Why check intact Parathyroid Hormone (PTH) in patients with Impaired Renal Function (IRF)?

From the Guidelines

Checking intact parathyroid hormone (iPTH) levels in renal failure is crucial for diagnosing and managing secondary hyperparathyroidism, as it helps guide treatment decisions to prevent complications such as renal osteodystrophy, vascular calcification, and increased cardiovascular morbidity and mortality. In renal failure, the kidneys cannot adequately convert vitamin D to its active form, leading to decreased calcium absorption and increased phosphate retention, which triggers the parathyroid glands to secrete more PTH in an attempt to normalize calcium levels 1. According to the 2017 KDIGO guideline update, in patients with CKD G5D, it is suggested to maintain intact PTH levels in the range of approximately 2 to 9 times the upper normal limit for the assay, and marked changes in PTH levels in either direction within this range should prompt an initiation or change in therapy to avoid progression to levels outside of this range 1.

The target iPTH range varies by CKD stage, but generally aims to prevent both excessive bone turnover from high PTH and adynamic bone disease from overly suppressed PTH. Regular monitoring of iPTH levels is essential, with the frequency of monitoring depending on the disease stage, and more frequent monitoring is recommended in advanced stages. Treatment approaches may include the use of medications like vitamin D analogs, phosphate binders, and calcimimetics, and the choice of treatment should be guided by the patient's iPTH levels and other clinical factors 1.

Some key points to consider when checking iPTH levels in renal failure include:

• The frequency of monitoring iPTH levels, which should be every 3-12 months depending on disease stage
• The target iPTH range, which varies by CKD stage but generally aims to prevent both excessive bone turnover and adynamic bone disease
• The use of medications like vitamin D analogs, phosphate binders, and calcimimetics to manage secondary hyperparathyroidism
• The importance of avoiding overly suppressed PTH levels, which can lead to adynamic bone disease, and excessively high PTH levels, which can lead to renal osteodystrophy and vascular calcification 1.

Overall, checking iPTH levels in renal failure is a critical component of managing secondary hyperparathyroidism and preventing its complications, and should be guided by the most recent and highest quality evidence, such as the 2017 KDIGO guideline update 1.

From the FDA Drug Label

To be administered not more often than every other day Baseline iPTH Level Daily Dose Three Times a Week Dose* Less than or equal to 500 pg/mL 1 mcg 2 mcg More than 500 pg/mL 2 mcg 4 mcg Dose Titration Table 2 Recommended Paricalcitol Capsules Dose Titration Base upon iPTH Level

• To be administered not more often than every other day Dose Adjustment at 2 to 4 Week Intervals iPTH Level Relative to Baseline Paricalcitol Capsule Dose Daily Dosage Three Times a Week Dosage*

Checking intact PTH in renal failure is crucial because it helps to assess and manage secondary hyperparathyroidism, a common complication in patients with chronic kidney disease (CKD).

• Intact PTH levels are used to determine the initial dose and titration of paricalcitol capsules, as well as to monitor the effectiveness of treatment.
• Abnormal PTH levels can lead to hypercalcemia, hyperphosphatemia, and adynamic bone disease, which can be prevented or managed by adjusting the dose of paricalcitol capsules based on iPTH levels 2.
• Monitoring iPTH levels is essential to achieve a stable iPTH level within the target range, which can help to prevent complications associated with secondary hyperparathyroidism in patients with CKD 3.

From the Research

Importance of Checking Intact PTH in Renal Failure

• Intact parathyroid hormone (PTH) levels are crucial in assessing the onset of secondary hyperparathyroidism in patients with renal insufficiency 4.
• Elevated intact PTH levels can occur in patients with mild to moderate renal insufficiency, emphasizing the need for early intervention to prevent secondary hyperparathyroidism 4.
• The determination of plasma intact PTH concentration, especially when combined with plasma ionized calcium value, is a reliable means of studying hyperparathyroidism associated with chronic renal failure 5.

Pathophysiology and Management

• Secondary hyperparathyroidism in chronic kidney disease is caused by a defect in vitamin D activation, leading to hypocalcemia and hyperphosphatemia, which in turn increases parathyroid hormone production 6.
• Understanding the pathophysiology of PTH and using therapeutic agents such as vitamin D analogs, calcium receptor blockers, and parathyroidectomy can reduce the development and associated complications of secondary hyperparathyroidism in patients with chronic kidney disease 6.
• The management of secondary hyperparathyroidism involves correcting and maintaining normal serum calcium and phosphate levels to prevent complications such as hungry bone disease, cardiovascular events, and anemia development 6.

Diagnosis and Treatment

• Secondary hyperparathyroidism is characterized by an increase in parathyroid hormone that is appropriate and in response to a stimulus, most commonly low serum calcium 7.
• Tertiary hyperparathyroidism is characterized by excessive secretion of PTH after longstanding secondary hyperparathyroidism, often resulting in hypercalcemia 7.
• The latest treatment for secondary hyperparathyroidism includes the use of vitamin D receptor activators (VDRAs) and calcimimetics, with a combination of both recognized as the optimal strategy for managing the condition 8.