Biomaterial Database

Possible mechanism of impaired calcium and vitamin D metabolism in nephrotic rats. 1992

M Mizokuchi, and M Kubota, and Y Tomino, and H Koide

Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.

Patients who have nephrotic syndrome and normal renal function are hypocalcemic in spite of the elevated levels of serum parathyroid hormone (PTH) caused by a low serum concentration of 1,25-dihydroxyvitamin D[1,25(OH)2D], presumably because of its loss in urine. However, it has not been established whether the conversion of 25-hydroxyvitamin D[25(OH)D] into 1,25(OH)2D is impaired in the kidney. In this study, we examined the serum levels of vitamin D metabolites, and kinetics of renal 25(OH)D-1-hydroxylase activity in vitro, and nephrogenous cyclic AMP excretion in response to exogenous PTH administration in puromycin aminonucleoside-induced nephrosis in rats. Plasma ionized calcium and the serum levels of vitamin D metabolites were lower, and conversely, the serum PTH level was higher, in nephrotic rats than in controls. Serum 1,25(OH)2D levels were higher in 25(OH)D3-treated nephrotic rats than in untreated nephrotic rats, indicating that the low 1,25(OH)2D level in nephrotic rats is partially due to the low concentration of 25(OH)D. Although PTH levels were higher in nephrotic rats than in control rats, the Vmax of renal 25(OH)D-1-hydroxylase and nephrogenous adenosine 3',5'-monophosphate (cyclic AMP) excretion in response to exogenous PTH were significantly lower in nephrotic animals than in controls. These results suggest that abnormalities in calcium and vitamin D metabolism in nephrotic rats are partially attributable to impaired proximal tubular function.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009404	Nephrotic Syndrome	A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.	Childhood Idiopathic Nephrotic Syndrome,Frequently Relapsing Nephrotic Syndrome,Multi-Drug Resistant Nephrotic Syndrome,Pediatric Idiopathic Nephrotic Syndrome,Steroid-Dependent Nephrotic Syndrome,Steroid-Resistant Nephrotic Syndrome,Steroid-Sensitive Nephrotic Syndrome,Multi Drug Resistant Nephrotic Syndrome,Nephrotic Syndrome, Steroid-Dependent,Nephrotic Syndrome, Steroid-Resistant,Nephrotic Syndrome, Steroid-Sensitive,Nephrotic Syndromes,Steroid Dependent Nephrotic Syndrome,Steroid Resistant Nephrotic Syndrome,Steroid Sensitive Nephrotic Syndrome,Steroid-Dependent Nephrotic Syndromes,Steroid-Resistant Nephrotic Syndromes,Steroid-Sensitive Nephrotic Syndromes,Syndrome, Nephrotic,Syndrome, Steroid-Sensitive Nephrotic
D010281	Parathyroid Hormone	A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.	Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D002112	Calcifediol	The major circulating metabolite of VITAMIN D3. It is produced in the LIVER and is the best indicator of the body's vitamin D stores. It is effective in the treatment of RICKETS and OSTEOMALACIA, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties.	25-Hydroxycholecalciferol,25-Hydroxyvitamin D 3,25-Hydroxycholecalciferol Monohydrate,25-Hydroxyvitamin D3,Calcidiol,Calcifediol Anhydrous,Calcifediol, (3 alpha,5Z,7E)-Isomer,Calcifediol, (3 beta,5E,7E)-Isomer,Calderol,Dedrogyl,Hidroferol,25 Hydroxycholecalciferol,25 Hydroxycholecalciferol Monohydrate,25 Hydroxyvitamin D 3,25 Hydroxyvitamin D3,Anhydrous, Calcifediol,Monohydrate, 25-Hydroxycholecalciferol
D002117	Calcitriol	The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.	1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014807	Vitamin D	A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.
D015090	25-Hydroxyvitamin D3 1-alpha-Hydroxylase	A mitochondrial cytochrome P450 enzyme that catalyzes the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 (also known as 25-hydroxycholecalciferol) in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP27B1 gene, converts 25-hydroxyvitamin D3 to 1-alpha,25-dihydroxyvitamin D3 which is the active form of VITAMIN D in regulating bone growth and calcium metabolism. This enzyme is also active on plant 25-hydroxyvitamin D2 (ergocalciferol).	25-Hydroxycholecalciferol 1-Hydroxylase,CYP27B1,Calcidiol 1-Monooxygenase,Cytochrome P-450 CYP27B1,25-Hydroxycholecalciferol-1-Hydroxylase,25-Hydroxyergocalciferol 1-alpha-Hydroxylase,25-Hydroxyvitamin D 1-alpha-Hydroxylase,25-Hydroxyvitamin D(3) 1 alpha-Hydroxylase,25-Hydroxyvitamin D2 1-hydroxylase,1-alpha-Hydroxylase, 25-Hydroxyergocalciferol,1-alpha-Hydroxylase, 25-Hydroxyvitamin D,1-hydroxylase, 25-Hydroxyvitamin D2,25 Hydroxycholecalciferol 1 Hydroxylase,25 Hydroxyergocalciferol 1 alpha Hydroxylase,25 Hydroxyvitamin D 1 alpha Hydroxylase,25 Hydroxyvitamin D2 1 hydroxylase,25 Hydroxyvitamin D3 1 alpha Hydroxylase,Calcidiol 1 Monooxygenase,Cytochrome P 450 CYP27B1