From the Guidelines
Thyroid hormone affects phosphate levels in the kidney by increasing phosphate reabsorption, primarily through the upregulation of sodium-phosphate cotransporters in the proximal tubules. This occurs when thyroid hormone levels are elevated, as in hyperthyroidism, resulting in enhanced phosphate reabsorption from the filtrate back into the bloodstream 1. Conversely, hypothyroidism typically leads to reduced phosphate reabsorption and increased urinary phosphate excretion. The relationship between thyroid function and phosphate handling is part of thyroid hormone's broader role in mineral metabolism, which includes effects on calcium homeostasis as well 1. Key factors to consider in the management of phosphate levels in patients with kidney disease include avoiding high phosphate intake, as it may promote secondary hyperparathyroidism (SHPT), and using calcium-based phosphate binders judiciously to prevent hypercalcemia 1. In patients with chronic kidney disease (CKD), modest increases in parathyroid hormone (PTH) levels may represent an appropriate adaptive response to decreasing kidney function, and treatment should focus on trends in PTH levels rather than a single elevated value 1. Overall, the management of phosphate levels in patients with kidney disease requires a comprehensive approach that takes into account the complex interplay between thyroid hormone, phosphate, calcium, and PTH. Some of the key considerations include:
- Avoiding high phosphate intake to prevent SHPT
- Using calcium-based phosphate binders judiciously to prevent hypercalcemia
- Monitoring trends in PTH levels to guide treatment decisions
- Considering the use of calcitriol and vitamin D analogues in patients with severe and progressive hyperparathyroidism 1. By taking a thoughtful and multifaceted approach to managing phosphate levels, clinicians can help to mitigate the risks associated with kidney disease and improve patient outcomes.
From the Research
Thyroid Hormone and Phosphate Regulation in the Kidney
- The regulation of phosphate in the kidney is a complex process involving several major organs, including the skeleton, intestine, kidney, and parathyroid glands, as well as key regulators such as parathormone, fibroblast growth factor 23, and 1,25-dihydroxyvitamin D 2.
- Thyroid hormones have been shown to play a role in phosphate homeostasis, with studies demonstrating that they can regulate the expression of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene 3.
- The Npt2a gene is implicated in the control of serum phosphate levels, and its expression is up-regulated by the thyroid hormone T3 (3',5-tri-iodothyronine) in rats 3.
- In mice, hypothyroidism has been associated with low levels of serum phosphate and a marked decrease in renal Npt2a protein abundance, while hyperthyroidism has been linked to increased serum phosphate levels 3.
- The transcriptional activity of the Npt2a promoter is dependent on thyroid hormone receptors (TRs) and is specifically increased by T3 in renal cells, suggesting that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner 3.
Mechanisms of Thyroid Hormone Regulation of Phosphate in the Kidney
- The regulation of phosphate in the kidney by thyroid hormones is thought to occur through the transcriptional control of the Npt2a gene, which is mediated by unique thyroid-hormone-responsive elements (TREs) within intron 1 of the Npt2a gene 3.
- The Npt2a gene plays a critical role in controlling phosphate homeostasis, and its regulation by thyroid hormones is essential for maintaining normal serum phosphate levels 3.
- Dysregulation of thyroid hormone levels, such as in hyperthyroidism or hypothyroidism, can lead to abnormalities in phosphate homeostasis, including hyperphosphatemia or hypophosphatemia 4, 5.
- The relationship between thyroid hormone regulation of phosphate in the kidney and kidney function is complex, with high dietary phosphate intake and hyperphosphatemia associated with an increased risk of declining kidney function 6.