Is there a correlation between Chronic Kidney Disease (CKD) and parathyroid disorder?

From the Guidelines

There is a strong correlation between chronic kidney disease (CKD) and parathyroid disorders, with secondary hyperparathyroidism being a common complication of CKD. As kidney function declines in CKD, the kidneys become less efficient at converting vitamin D to its active form and at excreting phosphate, leading to decreased calcium absorption and elevated phosphate levels in the blood 1. These imbalances trigger the parathyroid glands to secrete excess parathyroid hormone (PTH), a condition known as secondary hyperparathyroidism. This compensatory mechanism attempts to normalize calcium levels but can lead to bone disease, vascular calcification, and other complications. In advanced CKD, particularly in patients on dialysis, this disorder can progress to tertiary hyperparathyroidism, where the parathyroid glands become autonomously overactive.

Management of CKD-related parathyroid disorders typically includes:

• Dietary phosphate restriction
• Phosphate binders (such as calcium acetate, sevelamer, or lanthanum)
• Vitamin D analogs (calcitriol, paricalcitol)
• Calcimimetics like cinacalcet In severe cases unresponsive to medical therapy, parathyroidectomy may be necessary, with total parathyroidectomy with autotransplantation (TPTX + AT) being a commonly used surgical approach 1. However, recent studies suggest that total parathyroidectomy (TPTX) may have advantages over TPTX + AT in reducing the relapse of secondary hyperparathyroidism 1. Regular monitoring of calcium, phosphate, and PTH levels is essential for patients with CKD to detect and manage these parathyroid abnormalities early, as highlighted in the Kidney Disease: Improving Global Outcomes 2017 clinical practice guideline update 1.

Key considerations in the management of CKD-related parathyroid disorders include:

• The importance of preventing and treating secondary hyperparathyroidism to reduce the risk of morbidity and mortality in patients with CKD
• The need for individualized treatment approaches, taking into account the patient's kidney function, phosphate levels, and PTH levels
• The potential benefits and risks of different treatment options, including medical therapy and surgical intervention.

From the FDA Drug Label

Three 6-month, multicenter, randomized, double-blind, placebo-controlled clinical studies of similar design were conducted in patients with CKD on dialysis. A total of 665 patients were randomized to cinacalcet and 471 patients to placebo The average baseline iPTH level by the Nichols IRMA was 712 pg/mL, with 26% of the patients having a baseline iPTH level > 800 pg/mL. In the primary efficacy analysis, 40% of the patients on cinacalcet and 5% of placebo-treated patients achieved an iPTH ≤ 250 pg/mL (p < 0. 001)

There is a correlation between CKD and parathyroid disorder, as evidenced by the high baseline iPTH levels in patients with CKD on dialysis, indicating secondary hyperparathyroidism. The use of cinacalcet, a treatment for secondary hyperparathyroidism, resulted in a significant reduction in iPTH levels, suggesting a link between CKD and parathyroid disorder 2.

• Key findings:
  • High baseline iPTH levels in patients with CKD on dialysis
  • Significant reduction in iPTH levels with cinacalcet treatment
  • Correlation between CKD and secondary hyperparathyroidism

From the Research

Correlation between CKD and Parathyroid Disorder

• Chronic Kidney Disease (CKD) is associated with an increased risk of developing secondary hyperparathyroidism (SHPT) due to defects in vitamin D activation, leading to hypocalcemia and hyperphosphatemia 3.
• The relationship between vitamin D deficiency and SHPT in CKD patients is well-established, with vitamin D therapy being a crucial aspect of managing SHPT 4.
• SHPT is a common complication of CKD, characterized by an adaptive increase in parathyroid hormone levels, which can become maladaptive over time and lead to increased morbidity and mortality 5.
• The pathophysiology of SHPT involves the retention of phosphorus, reductions in calcium and vitamin D levels, and the proliferation of parathyroid cells, making it a complex pathology to manage 6.
• Treatment strategies for SHPT in CKD patients include phosphate binders, vitamin D receptor activators, calcimimetics, and invasive options like parathyroidectomy (PTX) and thermal ablation, with PTX being an effective option for reducing symptoms and improving radiological outcomes 7.

Key Factors Contributing to the Correlation

• Hypocalcemia and hyperphosphatemia due to impaired renal function 3
• Vitamin D deficiency and impaired activation of vitamin D in the kidneys 4
• Parathyroid gland hyperplasia and increased parathyroid hormone production 5
• Retention of phosphorus and reductions in calcium and vitamin D levels 6

Clinical Implications

• Early detection and management of SHPT are crucial to prevent complications such as bone deformities, vascular calcification, cardiovascular events, and mortality 7.
• Treatment strategies should aim to maintain acceptable levels of mineral metabolism parameters to slow down or prevent the development of SHPT 6.
• Further research is needed to explore the molecular mechanisms of parathyroid gland hyperplasia and evaluate the impacts of various treatments on CKD patients 7.