Vitamin D & the Kidney

Dr. Usama A. Azim
Sharaf El Din, M.D
Prof. of Internal Medicine and
Nephrology Cairo University,
Head of the Egyptian Vascular
Calcification Group

Introduction
Vitamin D is a member of fat-soluble vitamins that
include, in addition, vitamin A,
vitamin E and vitamin K. Vitamin D
is synthesized within the skin when
exposed to ultraviolet (UV) rays. The
cutaneous precursor of vitamin D
is 7-dehydrocholesterol (7-DHC).
Melanin in the skin blocks UV from
reaching 7-DHC, thus limiting vitamin
D production, as do clothing and
sunscreen. In addition, the intensity of
UV rays from sunlight varies according
to season and latitude, so the longer
the distance from the equator, the less
time of the year we can rely on solar
exposure to produce Vitamin D [1].
The Vitamin D of animal source is called
cholecalciferol or vitamin D3. Animal
foodstuffs (e.g., fsh, meat, offal or
organ meat, egg, and dairy products)
are the main sources for naturally
occurring vitamin D3. The plant source
of vitamin D includes mushroom,
almond, soy beans, soy and almond
milk. Plant source vitamin D is called
ergocalciferol (derived from the plant sterol, ergosterol) or vitamin D2.
However, the vast majority of animal
and plant foods, with the exception
of the fatty fsh, don›t have enough
concentration of vitamin D to supply
the human daily requirement of 600 or
800 IU.
Vitamin D is metabolized by a set of
cytochrome P450 enzymes, namely,
25-hydroxylase, 1-hydroxylase, and
24-hydroxylase. CYP2R1 is the most
important
25-hydroxylase that metabolizes
vitamin D to 25 hydroxyvitamin
D(25OHD). CYP27B1 is the key
1α-hydroxylase that metabolizes
25OHD to the hormonal form
1,25-dihydroxyvitamin D (1,25(OH)2
D). Both 25OHD and 1,25(OH)2 D
are catabolized by 24-hydroxylase
known as CYP24A1 into the inactive
24,25(OH)2D and 1,24,25(OH)3 D [2].
Vitamin D2 is different from vitamin D3
with less afnity to vitamin D binding
protein (DBP), thus its elimination and
catabolism is much faster than vitamin
D3. Therefore, unless given daily,
Vitamin D2 supplementation does not
result in as adequate blood level of
25OHD compared to vitamin D3 [3].
1,25(OH)2 D is the ligand for the
vitamin D receptor (VDR). VDR is
found in nearly every tissue and
thousands of VDR binding sites are
detected throughout the genome
controlling hundreds of genes. It is
worth mentioning that 1,25(OH)2D2
and 1,25(OH)2D3 have comparable
afnities for the VDR Role of the kidney in
vitamin D metabolism
Thekidney is the major (if not the only)
source of circulating 1,25(OH)2D . All
skeletal and extra-skeletal actions
of vitamin D are mediated through
binding of 1,25(OH)2D to VDR in
different tissues.
The molecular weight of DBP is 52
kDa [5]. Because of their comparable
MW to albumin, vitamin D bound
to DBP is fltered at glomeruli like
albumin. Reabsorption of vitamin DVDBG complex at proximal tubular
cells is mediated by megalin present
at the brush border [6]. In chronic
kidney disease (CKD) patients,
increased urine albumin excretion
(UAE) is associated with increased
fltration of vitamin D- VDBG
complex. In addition, CKD patients
may have down regulation of
megalin [6]. In nephrotic syndrome
patients, more signifcant loss of
vitamin D with DBP occurs in the
urine