People with type 2 diabetes and early kidney disease consistently show low vitamin D levels in their blood, and the worse their kidney function, the lower their vitamin D levels tend to be.
Mechanism
Synthesis from 1 study
When the kidneys start to fail, the liver makes too much of a protein that grabs onto vitamin D and locks it away. This stops vitamin D from doing its job, so levels keep dropping the worse the kidneys get.
Most probable mechanism
As kidney function declines, the liver produces more vitamin D-binding protein, which traps most of the vitamin D in the blood so it cannot reach the kidneys or other tissues. This prevents the body from using vitamin D properly, causing levels to drop further as kidney damage worsens.
Chronic kidney dysfunction triggers increased hepatic synthesis of vitamin D-binding protein in response to hypocalcemia and vitamin D deficiency.
Elevated vitamin D-binding protein binds over 85% of circulating vitamin D and its active metabolite 1,25(OH)2D, reducing the concentration of free, biologically active vitamin D.
Reduced free vitamin D limits delivery to renal tubules, impairing local conversion to the active form 1,25(OH)2D and diminishing calcium absorption in the intestine.
Diminished active vitamin D action reduces renal calcium reabsorption and fails to suppress parathyroid hormone, perpetuating mineral imbalance and further suppressing vitamin D activation.
The sequestration of vitamin D by excess binding protein results in progressively lower serum 25(OH)D levels as kidney function declines, with the lowest levels observed in the most advanced stages of impairment.
Evidence from Studies
Supporting (1)
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