Is there a correlation between Parathyroid Hormone (PTH) and Chronic Kidney Disease (CKD)?

From the Guidelines

Yes, there is a strong correlation between parathyroid hormone (PTH) and chronic kidney disease (CKD), with increased PTH and incident secondary hyperparathyroidism being independently associated with CKD progression and cardiovascular events, mortality, and fractures. As kidney function declines in CKD, phosphate retention occurs, leading to decreased vitamin D activation and calcium absorption, which triggers increased PTH secretion [ 1 ]. This condition, known as secondary hyperparathyroidism, is a common complication of CKD. PTH levels typically rise when estimated glomerular filtration rate (eGFR) falls below 60 ml/min/1.73m², and continue to increase as CKD progresses.

Key Points to Consider

• The optimal PTH level in patients with CKD not on dialysis remains undefined, but observational data suggest that high and progressively increasing PTH levels warrant investigation [ 1 ].
• Management includes monitoring serum calcium, phosphate, and PTH levels regularly, with treatment focusing on controlling phosphate through dietary restriction and phosphate binders like calcium acetate, sevelamer, or lanthanum.
• Vitamin D supplementation (calcitriol or vitamin D analogs) helps suppress PTH production, while calcimimetics like cinacalcet may be needed in advanced cases [ 1 ].
• The relationship between PTH and CKD is important because uncontrolled secondary hyperparathyroidism can lead to bone disease, vascular calcification, and increased cardiovascular risk in CKD patients.

Treatment Approach

• Low-dose active vitamin D could be a helpful supplement to nutritional vitamin D and dietary phosphate restriction for controlling PTH [ 1 ].
• Extended-release calcifediol can increase 25-(OH)D to unusually high levels (>125 nmol/l) and further suppress PTH, but clinically relevant outcome data are needed before considering availability and costs [ 1 ].
• Novel calcimimetics (etelcalcetide, evocalcet, and upacicalcet) have a similar or superior efficacy to cinacalcet for PTH reduction in CKD G5D [ 1 ].

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. Reduction in iPTH levels correlated with the plasma cinacalcet concentrations in patients with CKD.

Correlation between PTH and CKD: There is a correlation between PTH and CKD, as evidenced by the reduction in iPTH levels in patients with CKD treated with cinacalcet, a calcimimetic agent that directly lowers PTH levels by increasing the sensitivity of the calcium-sensing receptor to activation by extracellular calcium 2, 2.

• Key points:
  • Reduction in iPTH levels correlated with plasma cinacalcet concentrations in patients with CKD.
  • Cinacalcet decreases iPTH and Ca x P levels regardless of disease severity, duration of dialysis, and whether or not vitamin D sterols were administered.

From the Research

Correlation between PTH and CKD

• The relationship between parathyroid hormone (PTH) and chronic kidney disease (CKD) is complex, with PTH playing a crucial role in mineral metabolism 3.
• Increases in serum phosphate and PTH aggravate vascular calcification (VC) and bone loss in CKD 4.
• High PTH levels are associated with hyperphosphatemia, hypocalcemia, and hypermagnesemia in end-stage renal disease (ESRD) patients 3.
• There is a statistically significant positive correlation between PTH and phosphorus, and a significant negative correlation between PTH and calcium 3.
• PTH contributes to the development of hyperparathyroidism in CKD, which is presumed due to reduced calcium efflux from bone 5.

Mechanisms underlying the correlation

• PTH regulates bone loss and vascular calcification in CKD through various mechanisms, including osteogenic differentiation and Wnt inhibitor Sclerostin 4.
• Hyperphosphatemia, decreased serum calcitriol, and downregulation of the PTH1 receptor contribute to the decreased calcemic response to PTH in CKD 5.
• PTH1 receptor signaling plays a crucial role in the regulation of calcium deposition in vascular smooth muscle cells (VSMCs) 4.

Clinical implications

• Frequent assessment of PTH levels is necessary to prevent mineral decompensation and complications like bone disease and extra skeletal calcification in ESRD patients 3.
• Management of CKD-mineral bone disease (CKD-MBD) requires consideration of phosphate control, as well as calcium and PTH levels 6, 7.