What is the connection between Parathyroid Hormone (PTH) and Chronic Kidney Disease (CKD)?

From the Guidelines

The connection between parathyroid hormone (PTH) and chronic kidney disease (CKD) is a critical aspect of managing mineral and bone disorder in patients with CKD, with elevated PTH levels associated with increased morbidity and mortality 1.

Pathophysiology of PTH and CKD

In CKD, as kidney function declines, the kidneys become less efficient at converting vitamin D to its active form and at excreting phosphate, leading to decreased calcium levels and increased phosphate levels in the blood. These imbalances stimulate the parathyroid glands to secrete more PTH, resulting in secondary hyperparathyroidism. This elevated PTH works to normalize calcium levels by increasing bone resorption, enhancing calcium reabsorption in the kidneys, and promoting vitamin D activation. However, this compensatory mechanism becomes problematic over time, contributing to renal osteodystrophy, vascular calcification, and increased cardiovascular risk.

Management of PTH and CKD

Management typically involves:

• Dietary phosphate restriction
• Phosphate binders (such as calcium acetate, sevelamer, or lanthanum)
• Vitamin D supplements or analogs (calcitriol, paricalcitol)
• Calcimimetics like cinacalcet that directly reduce PTH secretion Regular monitoring of calcium, phosphate, PTH, and vitamin D levels is essential for effective treatment. The use of calcitriol and vitamin D analogues should not be routinely used in adult patients with CKD G3a to G5 not on dialysis, but may be considered in patients with CKD G4 to G5 with severe and progressive hyperparathyroidism 1.

Recent Evidence

Recent RCTs, such as the PRIMO and OPERA studies, have shown that paricalcitol does not reduce left ventricular mass index (LVMI) and does not modify diastolic function, but may increase the risk of hypercalcemia 1. These findings support the cautious use of vitamin D analogs in patients with CKD.

Key Considerations

• Elevated PTH levels are associated with increased morbidity and mortality in patients with CKD
• Management of PTH and CKD requires a comprehensive approach, including dietary restriction, phosphate binders, and careful use of vitamin D analogs and calcimimetics
• Regular monitoring of calcium, phosphate, PTH, and vitamin D levels is essential for effective treatment.

From the FDA Drug Label

The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of PTH synthesis and secretion. Cinacalcet, the active ingredient in cinacalcet tablets, is a calcimimetic agent that directly lowers PTH levels by increasing the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. Reductions in iPTH and Ca x P were maintained for up to 12 months of treatment. Cinacalcet decreased iPTH and Ca x P levels regardless of disease severity (i. e., baseline iPTH value), duration of dialysis, and whether or not vitamin D sterols were administered.

Connection between PTH and CKD: There is a direct relationship between PTH and CKD, as CKD can lead to secondary hyperparathyroidism due to disturbances in calcium and phosphate homeostasis.

• PTH levels: In patients with CKD, PTH levels are often elevated, which can lead to bone disease and other complications.
• Cinacalcet treatment: Cinacalcet has been shown to reduce PTH levels in patients with CKD on dialysis, which can help to mitigate the effects of secondary hyperparathyroidism.
• CKD severity: The relationship between PTH and CKD severity is complex, and cinacalcet treatment has been shown to be effective in reducing PTH levels regardless of disease severity 2, 2, 2.

From the Research

Connection between PTH and CKD

• The relationship between parathyroid hormone (PTH) and chronic kidney disease (CKD) is complex, with PTH playing a crucial role in the development of secondary hyperparathyroidism (SHP) in CKD patients 3, 4, 5, 6, 7.
• Defects in vitamin D activation in the kidneys due to CKD lead to hypocalcemia and hyperphosphatemia, resulting in a compensatory increase in PTH production and causing SHP 3.
• Elevated PTH levels are associated with increased risks of bone deformities, vascular calcification, cardiovascular events, and mortality in CKD patients 4, 5, 6, 7.
• Current therapeutic strategies for SHP in CKD patients include phosphate binders, vitamin D receptor activators, calcimimetics, and parathyroidectomy, with ongoing research focused on developing new drugs to overcome the limitations of current treatments 6, 7.

Pathophysiology of PTH in CKD

• The pathophysiology of PTH in CKD involves alterations in calcium, phosphorus, and vitamin D metabolism, leading to increased PTH synthesis and secretion 3, 5.
• The activation of vitamin D in the kidneys is impaired in CKD, leading to a decrease in active vitamin D levels and an increase in PTH production 3, 4.
• The consequences of uncontrolled SHP in CKD patients include soft-tissue and vascular calcification, cardiovascular disease, and calcific uremic arteriolopathy (CUA) 5.

Treatment Options for SHP in CKD

• Treatment options for SHP in CKD patients include medical interventions such as vitamin D analogs, calcium receptor blockers, and parathyroidectomy 3, 6.
• Phosphate binders, vitamin D receptor activators, and calcimimetics are also used as first-line treatments for SHP in CKD patients 6.
• Invasive options like parathyroidectomy (PTX) and thermal ablation are considered when medical treatments fail, with PTX effectively reducing symptoms and improving radiological outcomes 6.