THE VITAMIN D CRISIS IN END-STAGE RENAL DISEASE

Patients with End-Stage Renal Disease (ESRD) lose their kidneys ability to produce the active form of Vitamin D; something which inevitably results in serious mineral and hormonal imbalances that lead to the development of bone and heart disease.

Besides the critical role of the kidneys in filtering toxic waste and maintaining fluid balance, they are also fundamental in the activation of vitamin D. Whenever you get Vitamin D through sunshine or by eating certain foods, you obtain an inactive form (Cholecalciferol) that must then be converted by the liver and kidneys into its active form known as calcitriol (figure 1). When the kidneys fail, such as in ESRD patients, the body is then unable to produce calcitriol and as a result, calcium will be poorly absorbed from the intestine.

From here you may think that it would be obvious for calcium blood levels to drop dramatically due to poor absorption of this mineral, right? Well, this does not happen as it is absolutely crucial to keep blood calcium levels within a normal range to support life. However, in order to compensate for the decline in calcium absorption, the body up-regulates the synthesis of parathyroid hormone (PTH) which stimulates osteoclasts to cause bone breakdown (resorption) and lead to the release of calcium into the blood. Consequently, the skeleton takes a very hefty toll as bones are drained of their vital calcium in order to sustain adequate levels of this mineral in circulation.

Not only is calcitriol important in ensuring that the intestine effectively absorbs calcium; but this vitamin down-regulates the actions of PTH. As ESRD patients cannot produce calcitriol, the parathyroid gland excessively secretes PTH as there is no red light signal telling it when to stop: a condition called secondary hyperthyroidism. Unfortunately, this causes excessive bone resorption and weakening of the skeleton; ultimately leading to the development of conditions such as osteoporosis and osteomalacia in these patients (figure 2). While symptoms of bone disease may take years to appear, alterations to the structure of the skeleton occur early on and consequently, doctors refer to this as the “silent crippler” of kidney disease.

Moreover, the inability to produce calcitriol may explain why cardiovascular disease is so common in End-Stage Renal patients. Studies have shown that Vitamin D could be implicated in the regulation of the renin-angiotensin system by decreasing the formation of a hormone called angiotensin II. To put it simply, calcitriol could lower blood pressure and help preserve the elasticity of blood vessels, helping to reduce the risk of cardiovascular disease. Additionally, this vitamin is known to down-regulate inflammatory molecules and to improve oxidative mechanisms against free radicals; consequently decreasing the risk of developing atherosclerosis.

Lastly, the over-production of PTH may cause great rises in blood calcium levels that are very dangerous. This is because the excess calcium will deposit in the blood vessels and soft tissues, causing them to harden and induce their lose of function. For example, when arteries harden they lose elasticity and their capacity to transport blood across the body is impaired. For all the mentioned reasons (figure 3), it is unsurprising that patients whose kidneys fail to activate Vitamin D are at a much greater risk of having heart attacks, strokes and arrhythmias.

The crucial role of the kidneys in calcitriol synthesis means that ESRD patients should regularly monitor their calcium and PTH levels, but more importantly their bone and cardiovascular health. Lastly, it is worth pointing out that taking large doses of vitamin D supplements is of little help as the kidneys are unable to activate this compound into calcitriol. Therefore, it is essential for these patients to be given the active form of Vitamin D directly into them as early as possible as to reduce the risk of bone and heart disease. Nevertheless, this kind of therapy can be dangerous and must be given under strict medical supervision.