cholecalciferol and Kidney-Diseases

Treatment using the cell sheet technology has been applied to various organs, including the cornea, heart, esophagus, periodontium, cartilage, middle ear, and lungs. It has been shown that the therapeutic efficacy of cell sheet transplantation involves 2 aspects, supplementation of cells and provision of cytokines to the affected organ. In addition, cell sheet transplantation also promotes repair of damage through the paracrine effects of cytokines derived from the transplanted cells. It is known that in cases of cell transplantation by injection, the transplanted cells are less likely to differentiate into renal tissue to supply cells, but repair is promoted by the actions of the transplanted cell-derived renotropic factors. Renal function requires functional conjugation of various tissues, including blood vessels, glomeruli, renal tubules, and collecting ducts. It is difficult to supply the necessary cells directly to the affected site of the renal tissue composed of complex structures. On the contrary, the 2-dimensional cell sheet can produce proteins such as erythropoietin, and is thus suitable for transplantation into the living body. It would be desirable to develop cell sheet therapy for the suppression of kidney damage in the future, taking advantage of the beneficial characteristics of cell sheets.

Topics: Cell Transplantation; Cells, Cultured; Cholecalciferol; Culture Techniques; Cytokines; Erythropoietin; Humans; Kidney; Kidney Diseases; Regeneration; Renal Insufficiency; Stem Cell Transplantation; Tissue Engineering

Topics: Adult; Algorithms; Calcifediol; Calcitriol; Child; Cholecalciferol; Diabetes Mellitus; Disease Management; Female; Humans; Infant, Newborn; Kidney Diseases; Male; Obesity; Osteoporosis; Pregnancy; Recommended Dietary Allowances; Risk; Vitamin D Deficiency

Reduction in serum 1,25 (OH) (2)D level plays an important role in the pathophysiology of altered bone and mineral metabolism among patients with advanced stages of CKD. The use of vitamin D receptor activators (VDRA) has brought great progress in medical management of CKD-MBD. A number of observational studies have shown that the nonuse of VDRA, and low serum concentrations of 1,25 (OH) (2)D or 25 (OH) D are the predictors of poor clinical outcomes in CKD patients including dialysis patients, raising a possibility that the pleiotropic actions of vitamin D may be systemically involved in the poor survival of patients with CKD-MBD. Randomized controlled trials are needed to clarify whether or not VDRA could be beneficial in the protection of the cardiovascular system and good longevity.

Topics: Bone Diseases, Metabolic; Cardiovascular Diseases; Cholecalciferol; Chronic Disease; Ergocalciferols; Humans; Kidney Diseases; Minerals; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Risk; Vitamin D

The biologically active metabolite of vitamin D, 1,25(OH)(2)D(3), affects mineral homeostasis and has numerous other diverse physiologic functions including effects on growth of cancer cells and protection against certain immune disorders. This article reviews the role of vitamin D hydroxylases in providing a tightly regulated supply of 1,25(OH)(2)D(3). The role of extrarenal 1alpha(OH)ase in placenta and macrophages is also discussed, as well as regulation of vitamin D hydroxylases in aging and chronic kidney disease. Understanding specific factors involved in regulating the hydroxylases may lead to the design of drugs that can selectively modulate the hydroxylases. The ability to alter levels of these enzymes would have therapeutic potential for the treatment of various diseases, including bone loss disorders and certain immune diseases.

Topics: Animals; Cholecalciferol; Cholestanetriol 26-Monooxygenase; Chronic Disease; Cytochrome P450 Family 2; Female; Humans; Kidney; Kidney Diseases; Liver; Macrophages; Mice; Placenta; Pregnancy; Steroid Hydroxylases; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

Serum calcium levels are regulated by the action of parathyroid hormone (PTH). Major drivers of PTH hypersecretion and parathyroid cell proliferation are the hypocalcemia and hyperphosphatemia that develop in chronic kidney disease patients with secondary hyperparathyroidism (SHPT) as a result of low calcitriol levels and decreased kidney function. Increased PTH production in response to systemic hypocalcemia is mediated by the calcium-sensing receptor (CaR). Furthermore, as SHPT progresses, reduced expression of CaRs and vitamin D receptors (VDRs) in hyperplastic parathyroid glands may limit the ability of calcium and calcitriol to regulate PTH secretion. Current treatment for SHPT includes the administration of vitamin D sterols and phosphate binders. Treatment with vitamin D is initially effective, but efficacy often wanes with further disease progression. The actions of vitamin D sterols are undermined by reduced expression of VDRs in the parathyroid gland. Furthermore, the calcemic and phosphatemic actions of vitamin D mean that it has the potential to exacerbate abnormal mineral metabolism, resulting in the formation of vascular calcifications. Effective new treatments for SHPT that have a positive impact on mineral metabolism are clearly needed. Recent research shows that drugs that selectively target the CaR, calcimimetics, have the potential to meet these requirements.

Topics: Calcium; Cholecalciferol; Chronic Disease; Homeostasis; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Receptors, Calcitriol; Receptors, Calcium-Sensing

Hormonal adjuvants, besides being erythropoietic agents, broaden the spectrum of therapeutic options for the treatment of the anaemia of chronic kidney disease (CKD). Lowering elevated parathyroid hormone levels by oral calcium supplementation and phosphate restriction, by varying dialysate calcium concentrations, by administration of vitamin D3 derivatives and, in the near future, by treatment with calcimimetics may prove efficient in some patients to fight extensive requirements of erythropoietic agents. Clinical evidence for a principal role of secondary hyperparathyroidism in resistance to erythropoietin, however, is lacking. Active vitamin D3 derivatives, in addition to their beneficial effects on secondary hyperparathyroidism, appear to exert a direct, stimulatory action on erythroid precursor cells and possibly also an inhibitory action on collagen synthesis by bone marrow stromal cells. Growth hormone (GH) induces insulin-like growth factor (IGF)-1, which in turn counteracts apoptosis similarly to erythropoietin, and fosters proliferation of burst- and colony-forming units-erythroid (BFU-E, CFU-E). If erythropoietic agents improve survival of CKD patients, a similar benefit should apply for strategies that increase synthesis and bioavailabilty of IGF-1. The latter appears to be reduced in CKD patients, and zinc supplementation potentially enhances it via an increase in free IGF-1. Finally, androgens also exert anti-anaemic effects. Nandrolone decanoate constitutes the only androgen currently applicable for selected male dialysis patients over the age of 50 years. It should not be given to women, however, because of serious side effects. Collectively, hormonal interventions offer the potential to reduce requirements of erythropoietic agents, and some may also improve physical performance.

Topics: Adjuvants, Pharmaceutic; Androgens; Anemia; Calcitriol; Cholecalciferol; Erythropoiesis; Female; Hormones; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Kidney Diseases; Male; Parathyroid Hormone; Zinc

Topics: Cholecalciferol; Endocrine System Diseases; Humans; Infant, Newborn; Kidney Diseases; Vitamin D; Vitamin D Deficiency

Topics: Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Feedback; Humans; Hypocalcemia; Kidney Diseases; Liver; Osteomalacia; Parathyroid Hormone; Rickets; Seasons; Ultraviolet Rays; Vitamin D

Topics: Amino Acid Sequence; Animals; Calcium; Cholecalciferol; Chronic Disease; Humans; Hydroxycholecalciferols; Hydroxylation; Hyperparathyroidism, Secondary; Kidney Diseases; Metabolic Clearance Rate; Molecular Weight; Parathyroid Hormone; Vitamin D

Topics: Animals; Calcitonin; Calcium; Calcium Metabolism Disorders; Cholecalciferol; Diuretics; Extracellular Space; Glomerular Filtration Rate; Glomerulonephritis; Hypercalcemia; Kidney; Kidney Concentrating Ability; Kidney Diseases; Kidney Failure, Chronic; Metabolic Clearance Rate; Mineralocorticoids; Parathyroid Hormone; Sodium

Topics: Bone Diseases; Calcium; Carcinoma; Cholecalciferol; Chromatin; Dihydroxycholecalciferols; Ergocalciferols; Homeostasis; Humans; Hydroxycholecalciferols; Intestinal Diseases; Intestinal Mucosa; Kidney; Kidney Diseases; Liver; Liver Diseases; Parathyroid Diseases; Receptors, Drug; Skin Diseases; Thyroid Neoplasms; Vitamin D Deficiency

Extensive experimental evidence has established a significant role of calciferol in the maintenance of normal calcium homeostasis. Present knowledge indicates that vitamin D(3) must first be converted to 25-OH-D(3) and then to 1,25(OH)(2)D(3), the most active known form of the steroid. Many of the factors regulating the rate of production of this last steroid from its precurser have been evaluated, and the concept that vitamin D functions as a steroid hormone seems to be well established. Deranged action of calciferol, caused by impaired metabolism of the steroid or through altered sensitivity of target tissues, may be involved in the pathophysiology of several disease states with abnormal calcium metabolism. It is noted that liver disease, osteomalacia due to anticonvulsant therapy, chronic renal failure, hypophosphatemic rickets, hypoparathyroidism, hyperparathyroidism, sarcoidosis and idiopathic hypercalciuria have possible relation to alterations in metabolism or action of vitamin D. The future clinical availability of 1,25(OH)(2)D(3) and other analogs of this steroid may offer potential therapeutic benefit in the treatment of certain of the disease entities discussed.

Topics: Animals; Biological Transport, Active; Bone Resorption; Calcium; Calcium Metabolism Disorders; Cholecalciferol; Collagen; Homeostasis; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Hypoparathyroidism; Hypophosphatemia, Familial; Intestinal Absorption; Kidney; Kidney Diseases; Liver; Liver Diseases; Sarcoidosis; Skin; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency

Topics: Biological Assay; Bone and Bones; Bone Diseases; Chemical Phenomena; Chemistry; Chemistry, Physical; Cholecalciferol; Chronic Disease; Humans; Kidney Diseases; Osteomalacia; Protein Binding; Radioimmunoassay; Research; Rickets; Vitamin D; Vitamin D Deficiency

Topics: Amphibians; Animals; Birds; Calcium; Chemical Phenomena; Chemistry; Chickens; Cholecalciferol; Dactinomycin; Dihydroxycholecalciferols; Fishes; Humans; Hydroxycholecalciferols; Intestinal Mucosa; Kidney; Kidney Diseases; Kinetics; Liver; Mammals; Mixed Function Oxygenases; Reptiles; Skin; Vitamin D

Vascular calcification is an independent risk factor for cardiovascular diseases and all-cause mortality in end stage renal disease, and particularly in hemodialysis patients. Vitamin D deficiency has been shown to be associated with vascular calcification among this category of patients. Cholecalciferol or vitamin D3; the native inactivated 25-hydroxy vitamin D [25(OH)D], has been proposed to have a good impact on vascular calcification and vitamin D deficiency. However, clinical data is still limited.. A prospective, randomized, placebo-controlled study was carried out to evaluate the effect of oral cholecalciferol on vascular calcification and 25(OH)D levels in hemodialysis patients. A total of sixty eligible hemodialysis patients were randomly assigned to either a treatment group (Oral 200.000IU Cholecalciferol per month) or a placebo group, for 3 months. Serum 25-hydroxy vitamin D (25(OH)D), fetuin-A, fibroblast growth factor (FGF-23), osteoprotegerin (OPG), calcium, phosphorus, their product (CaXP) and intact parathyroid hormone (iPTH) levels, were all assessed at baseline and at the end of the study. ClinicalTrials.gov registration number: NCT03602430. Cholecalciferol significantly increased serum levels of 25(OH)D and fetuin-A in the treatment group (p-value < 0.001), while no significant difference was observed in the placebo group. Cholecalciferol administration showed no effect on either FGF-23 or OPG. None of the treatment group patients experienced any adverse effects.. Cholecalciferol was shown to be an effective, tolerable, inexpensive pharmacotherapeutic option to overcome vitamin D deficiency, with a possible modulating effect on fetuin-A, among hemodialysis patients. CLINICALTRIALS.. NCT03602430.

Topics: Adult; alpha-2-HS-Glycoprotein; Biomarkers; Cholecalciferol; Egypt; Female; Fibroblast Growth Factor-23; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Renal Dialysis; Single-Blind Method; Time Factors; Treatment Outcome; Vascular Calcification; Vitamin D; Vitamin D Deficiency; Vitamins

Observational studies suggest that calciferol supplementation may improve laboratory and patient-level outcomes of hemodialysis patients with reduced 25-hydroxyvitamin D [25(OH)D] levels. This randomized controlled trial examined effects of cholecalciferol supplementation in patients on hemodialysis.. Sixty patients with 25(OH)D levels ≤24 ng/ml (≤60 nmol/L) were randomized to receive 50,000 IU oral cholecalciferol or placebo, once weekly for 8 weeks and then monthly for 4 months. At baseline (autumn 2011) and 6 months, testing evaluated muscle strength, functional capacity, laboratory parameters, pulse wave velocity (PWV), and health-related quality of life (HRQOL) using the Kidney Disease Quality of Life-36 survey.. Patients were well matched by treatment allocation. Median age was 62 years (range, 20-86), 52% were women, 55% had a history of diabetes, and mean serum 25(OH)D was 17±5 ng/ml (43±13 nmol/L). Patients were assessed over 6 months by repeated-measures ANOVA. Patients allocated to cholecalciferol had significantly higher values of 25(OH)D (P<0.001), 1,25-dihydroxyvitamin D (P=0.04), and tartrate-resistant acid phosphatase-5b) (P=0.04) and a greater reduction in phosphorus values (P=0.03) than placebo-treated patients Values of serum calcium, intact parathyroid hormone, and episodes of hypercalcemia and hyperphosphatemia did not differ significantly between the groups. No significant differences were detected in muscle strength, functional capacity, PWV, or HRQOL.. In this randomized controlled trial, patients supplemented with cholecalciferol had higher 25(OH)D, 1,25-dihydroxyvitamin D, and tartrate-resistant acid phosphatase-5b levels, without increased calcium or phosphorus values. However, no effects were detected in muscle strength, functional capacity, PWV, or HRQOL.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Biomechanical Phenomena; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Health Status; Humans; Kidney Diseases; Male; Middle Aged; Muscle Strength; New South Wales; Pulse Wave Analysis; Quality of Life; Range of Motion, Articular; Renal Dialysis; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vascular Stiffness; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

To examine the effect of combined calcium and vitamin D3 supplementation on bone mineral density (BMD) inpatients with chronic kidney disease (CKD).. We performed a post-hoc analysis of the DECALYOS II, a 2-year randomized, double-blind, placebo-controlled study of 610 women randomized to: calcium-vitamin D3 fixed combination, calcium plus vitamin D3 separate combination, or placebo. Both active treatment groups received the same daily amount of calcium (1,200 mg) and vitamin D3 (800 IU). BMD of the distal radius was measured by single X-ray absorptiometry at baseline, 12 and 24 months.. At baseline 47.2%, 36.4% and 16.4% of the study population had an eGFR ≥ 60, 45 -59, and < 45 ml/min/1.73 m2, respectively. Both active regimens vs. placebo markedly increased serum 25-hydroxyvitamin D levels from baseline in all eGFR groups (p 0.22 for all time points).. Combined calcium and vitamin D3 supplementation was effective in reducing rate of BMD loss in women with moderate CKD.

Topics: Absorptiometry, Photon; Age Factors; Analysis of Variance; Biomarkers; Bone Density; Calcium; Chi-Square Distribution; Cholecalciferol; Chronic Disease; Dietary Supplements; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Institutionalization; Kidney Diseases; Placebos; Radius; Time Factors; Treatment Outcome; Vitamin D

The optimal treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) is unknown.. We conducted a randomized, blinded, 3-month trial in vitamin D-deficient CKD stage 3 and 4 patients with parathyroid hormone (PTH) values above the Kidney Disease Outcomes Quality Initiative target, comparing cholecalciferol (4000 IU/d x 1 month, then 2000 IU/d; n = 22) to doxercalciferol (1 microg/d; n = 25).. There was no difference in baseline demographics or lab tests, except a slightly higher estimated GFR (eGFR) in the doxercalciferol group. There was a significant increase in vitamin D level in the cholecalciferol group (14 +/- 6 to 37 +/- 10 ng/ml; P < 0.001) but no change in the doxercalciferol group. The PTH decreased by 27% +/- 34% in the doxercalciferol group (P = 0.002) and decreased by 10% +/- 31% in the cholecalciferol group (P = 0.16), but the difference between treatments was NS (P = 0.11). Similar results were found when absolute PTH change from baseline to end point was analyzed in a repeated-measures ANOVA model. The serum calcium and urine calcium excretions were not different. Additional non-mineral-related end points, albuminuria, and BP were evaluated, and although trends were present, this did not reach significance.. This prospective, randomized trial demonstrated a within-group reduction in PTH in the doxercalciferol-treated patients but no significant difference between the doxercalciferol and cholecalciferol patients. Larger, long-term studies are needed to demonstrate efficacy of mineral-related and non-mineral-related end points and safety.

Topics: Aged; Biomarkers; Calcium; Cholecalciferol; Chronic Disease; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Single-Blind Method; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

Studies addressing the effects of vitamin D(3) supplementation on secondary hyperparathyroidism in patients with moderate chronic kidney disease are scarce.. Post hoc analysis of the randomized clinical trial Vitamin D, Calcium, Lyon Study II (DECALYOS II) to assess effects according to baseline estimated glomerular filtration rate (eGFR).. Multicenter, randomized, double-blinded, placebo-controlled study of 639 elderly women randomly assigned to calcium-vitamin D(3) fixed combination; calcium plus vitamin D(3) separate combination, or placebo.. Placebo or calcium (1,200 mg) and vitamin D(3) (800 IU) in fixed or separate combination.. Proportion of participants with a mean decrease in intact parathyroid hormone (iPTH) level of 30% or greater. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and categorized as 60 or greater, 45 to 59, and less than 45 mL/min/1.73 m(2).. 610 participants had an eGFR at baseline: 288 (47.2%), 222 (36.4%), and 100 (16.4%) were in each decreasing eGFR category. Across decreasing eGFR groups, 88%, 86%, and 89% had 25-hydroxyvitamin D (25[OH]D) levels less than 15 ng/mL at baseline. On treatment, similar improvements in the proportion of participants achieving 25(OH)D levels greater than 30 ng/mL at 6 months were seen in all kidney function groups (43%, 49%, and 41%, respectively). Active regimens versus placebo increased mean 25(OH)D levels from baseline in all eGFR groups at all times (P < 0.001 for all). The proportion with a 30% or greater decrease in iPTH level at 6 months was 50% in all eGFR groups on treatment versus 6% to 9% for placebo (P < 0.001 for all). The effects of the intervention on iPTH levels did not differ according to baseline eGFR (interaction P > 0.1 for all times).. This study included only elderly white women.. Vitamin D(3) was effective in increasing 25(OH)D and decreasing iPTH levels in patients with moderate chronic kidney disease.

Topics: Aged, 80 and over; Calcium, Dietary; Cholecalciferol; Chronic Disease; Dietary Supplements; Double-Blind Method; Female; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Parathyroid Hormone; Severity of Illness Index; Vitamins

Data on the efficacy and safety of long-term vitamin D supplementation in chronic kidney disease (CKD) are scarce. We assessed the effects of the 12-month vitamin D(3) treatment on mineral metabolism and calciotropic hormones in patients with CKD stages 2-4.. Eighty-seven patients (mean age 66 years, men/women 33/54) were randomized to cholecalciferol treatment with either 5,000 or 20,000 IU/week. Serum calcium, phosphate, 25(OH)D(3), 1,25(OH)(2)D(3), PTH and urinary mineral concentrations were obtained at baseline and after 4, 8 and 12 months.. The median serum mineral concentrations were normal and not changed throughout the study. The number of hypercalciuric patients slightly increased with higher dose, but no sustained rise in calciuria was present. Vitamin D insufficiency/deficiency was revealed in 72 (83%) patients at baseline and 37 (43%) at month 12. The 25(OH)D(3) levels increased more with higher dose; a rise in 1,25(OH)(2)D(3) was less impressive. The parathyroid hormone (PTH) concentrations were reduced, but the number of subjects with PTH below the lower limit for CKD stage 3 increased equally with both doses.. Vitamin D insufficiency/deficiency in CKD significantly improved after the 12-month cholecalciferol treatment, with higher dose being more effective and equally safe. Further studies of vitamin D(3) effects on bone metabolism are warranted.

Topics: Aged; Cholecalciferol; Chronic Disease; Dietary Supplements; Female; Hormones; Humans; Kidney Diseases; Male; Minerals; Vitamin D Deficiency

In a double-blind controlled study, 15 patients received 1,25-dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease.

Topics: Adult; Alkaline Phosphatase; Bone and Bones; Calcium; Cholecalciferol; Clinical Trials as Topic; Dihydroxycholecalciferols; Double-Blind Method; Female; Humans; Hydroxycholecalciferols; Kidney Diseases; Male; Middle Aged; Parathyroid Hormone; Phosphates; Renal Dialysis; Skin

Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects.. Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration.. Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001).. Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown.. NCT01835639. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Child; Cholecalciferol; Dietary Supplements; Humans; Kidney Diseases; Proteinuria; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

The pathogenesis of kidney damage involves complicated interactions between vascular endothelial and tubular cell destruction. Evidence has shown that vitamin D may have anti-inflammatory effects in several models of kidney damage. In this study, we evaluated the effects of synthetic vitamin D on levofloxacin-induced renal injury in rats. Forty-two white Albino rats were divided into six groups, with each group comprising seven rats. Group I served as the control (negative control) and received intraperitoneal injections of normal saline (0.5 ml) once daily for twenty-one days. Group II and Group III were treated with a single intraperitoneal dose of Levofloxacin (50 mg/kg/day) and (100 mg/kg/day), respectively, for 14 days (positive control groups). Group IV served as an additional negative control and received oral administration of vitamin D3 (500 IU/rat/day) for twenty-one days. In Group V, rats were orally administered vitamin D3 (500 IU/rat/day) for twenty-one days, and intraperitoneal injections of Levofloxacin (50 mg/kg/day) were administered on day 8 for 14 days. Group VI received oral vitamin D3 supplementation (500 IU/rat/day) for twenty-one days, followed by intraperitoneal injections of Levofloxacin (100 mg/kg/day) on day 8 for fourteen days. Blood samples were collected to measure creatinine, urea, malondialdehyde, glutathione reductase, and superoxide dismutase levels. Compared to the positive control group, vitamin D supplementation lowered creatinine, urea, and malondialdehyde levels, while increasing glutathione reductase and superoxide dismutase levels. Urea, creatinine, and malondialdehyde levels were significantly (p<0.05) higher in rats administered LFX 50mg and 100mg compared to rats given (LFX + vitamin D). The main findings of this study show that vitamin D reduces renal dysfunction, suggesting that vitamin D has antioxidant properties and may be used to prevent renal injury.

Topics: Animals; Antioxidants; Cholecalciferol; Creatinine; Glutathione; Glutathione Reductase; Kidney; Kidney Diseases; Levofloxacin; Malondialdehyde; Oxidative Stress; Rats; Superoxide Dismutase; Urea; Vitamin D

Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial-mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.

Topics: Actins; Animals; Antigens, CD; Cadherins; Calcitriol; Cell Line; Cholecalciferol; Epithelial-Mesenchymal Transition; Female; Fibrosis; Humans; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Male; Mice; Mice, Inbred ICR; Organ Size; Transforming Growth Factor beta; Vimentin; Vitamin D; Vitamin D Deficiency

Lead (Pb) is a toxic heavy metal and nephropathy is common with chronic exposure. Although vitamin D (VD) and calcium (Ca) showed promising protections, their co-administration was not previously investigated in Pb nephrotoxicity. This study measured the potential interactions and remedial effects of VD and/or Ca on established Pb nephropathy.. Fifty adult male mice were equally distributed into: negative controls (NC), positive controls (PC), Ca, VD and VDC groups. The study duration was seven weeks and all groups, except the NC, received Pb acetate in drinking water (500 mg/L) throughout the study. The Ca, VD and VDC groups also received oral Ca (50 mg/kg; five times/week) and/or intramuscular VD (1000 IU/kg; three times/week) from week four till the end of the study.. The PC group showed substantial reduction in serum VD, hypocalcaemia, hypercalciuria and proteinuria alongside marked tissue inflammation, oxidative stress and apoptosis/necrosis. Pathological alterations were also detected in the mRNAs and proteins of the VD-metabolising enzymes, receptor and binding protein alongside several Ca-membrane channels, membrane transporters, intracellular binding proteins and mediators. While both monotherapies equally demonstrated moderate improvements, the VDC showed the utmost corrective actions on serum and tissue Pb concentrations, the inflammatory and antioxidative markers, the expressions of renal VD/Ca-molecules and tissue integrity. Moreover, the results were comparable between the VDC and NC groups.. This report is the first to reveal potential enhanced remedial outcomes for combining VD and Ca against pre-existing Pb nephrotoxicity and the enhancements could be dependent on Ca-regulatory pathways.

Topics: Animals; Apoptosis; Biomarkers; Calcium; Calcium Channels; Calcium Signaling; Caspases; Cholecalciferol; Cytokines; Dietary Supplements; Homeostasis; Intracellular Space; Kidney; Kidney Diseases; Lead; Male; Mice, Inbred BALB C; Oxidative Stress; RNA, Messenger

Malakoplakia is a rare disease characterized by the presence of nongranulomatous macrophage infiltration. In most cases, it affects the urinary tract. Malakoplakia can cause acute kidney injury when it is localized in the kidneys.. Here, we report the case of a 65-year-old female patient with renal malakoplakia responsible for hypercalcemia. During her initial assessment, she was also diagnosed 25-OH vitamin D insufficiency, for which she was prescribed oral cholecalciferol. Three months later, she developed severe hypercalcemia with normal 25-OH vitamin D and parathyroid hormone levels and high 1,25-dihydroxyvitamin D levels.. After a superimposed granulomatous disease was excluded, malakoplakia cells were suspected to be responsible for the abnormal 25-hydroxyvitamin D3 1-alpha-hydroxylase activity, which was confirmed by immunohistochemistry.. Cholecalciferol was stopped, the patient was rehydrated with intravenous physiological saline, and prednisone was initiated to decrease the enzyme activity.. Six months later, she displayed normal serum calcium, 25-OH vitamin D and 1,25-dihydroxyvitamin D levels.. This case illustrates that malakoplakia may exhibit ectopic 25-hydroxyvitamin D3 1-alpha-hydroxylase activity and cause severe hypercalcemia upon vitamin D supplementation. Therefore, such supplementation should not be given in malakoplakia patients without an actual deficiency and requires careful monitoring of serum calcium.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Aged; Calcium; Cholecalciferol; Dietary Supplements; Ectopic Gene Expression; Female; Humans; Hypercalcemia; Kidney Diseases; Malacoplakia; Parathyroid Hormone; Vitamin D Deficiency; Vitamins

Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1α-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin-D3-1α-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.

Topics: Albuminuria; Animals; Cholecalciferol; Kidney Diseases; Kidney Glomerulus; Mice, Inbred C57BL; Mice, Knockout; Parathyroid Hormone; Podocytes; Proteinuria; Rats; Rats, Wistar

Topics: Cholecalciferol; Dietary Supplements; Female; Health Status; Humans; Kidney Diseases; Male; Quality of Life; Renal Dialysis; Vascular Stiffness; Vitamin D Deficiency; Vitamins

Vascular calcification is prevalent in patients with chronic kidney disease and leads to increased cardiovascular morbidity and mortality. Although several reports have implicated mitochondrial dysfunction in cardiovascular disease and chronic kidney disease, little is known about the potential role of mitochondrial dysfunction in the process of vascular calcification. This study investigated the effect of α-lipoic acid (ALA), a naturally occurring antioxidant that improves mitochondrial function, on vascular calcification in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial membrane potential and ATP production, the disruption of mitochondrial structural integrity and concurrently increased production of reactive oxygen species. These Pi-induced functional and structural mitochondrial defects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol, subsequent activation of caspase-9 and -3, and chromosomal DNA fragmentation. Intriguingly, ALA blocked the Pi-induced VSMC apoptosis and calcification by recovery of mitochondrial function and intracellular redox status. Moreover, ALA inhibited Pi-induced down-regulation of cell survival signals through the binding of growth arrest-specific gene 6 (Gas6) to its cognate receptor Axl and subsequent Akt activation, resulting in increased survival and decreased apoptosis. Finally, ALA significantly ameliorated vitamin D(3) -induced aortic calcification and mitochondrial damage in mice. Collectively, the findings suggest ALA attenuates vascular calcification by inhibiting VSMC apoptosis through two distinct mechanisms; preservation of mitochondrial function via its antioxidant potential and restoration of the Gas6/Axl/Akt survival pathway.

Topics: Animals; Apoptosis; Axl Receptor Tyrosine Kinase; Calcium; Caspase 3; Caspase 9; Cells, Cultured; Cholecalciferol; Cytochromes c; DNA Fragmentation; Humans; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mitochondria; Muscle, Smooth, Vascular; Phosphates; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Receptor Protein-Tyrosine Kinases; Thioctic Acid; Vascular Calcification; Vascular Diseases

Vitamin D deficiency is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effects of oral cholecalciferol supplementation on mineral metabolism, inflammation, and cardiac dimension parameters in long-term hemodialysis (HD) patients.. This 1-year prospective study included 158 HD patients. Serum levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone, and plasma brain natriuretic peptide as well as circulating bone metabolism and inflammation parameters were measured before and after supplementation. Baseline 25(OH)D and 1,25(OH)(2)D levels were measured twice (end of winter and of summer, respectively). Therapy with paricalcitol, sevelamer, and darbepoietin was evaluated.. There was an increase in serum 25(OH)D and 1,25(OH)(2)D levels after supplementation. Conversely, serum calcium, phosphorus, and intact parathyroid hormone were decreased. There was a reduction in the dosage and in the number of patients who were treated with paricalcitol and sevelamer. Darbepoietin use was also reduced, with no modification of hemoglobin values. Serum albumin increased and C-reactive protein decreased during the study. Brain natriuretic peptide levels and left ventricular mass index were significantly reduced at the end of the supplementation.. Oral cholecalciferol supplementation in HD patients seems to be an easy and cost-effective therapeutic measure. It allows reduction of vitamin D deficiency, better control of mineral metabolism with less use of active vitamin D, attenuation of inflammation, reduced dosing of erythropoiesis-stimulating agents, and possibly improvement of cardiac dysfunction.

Topics: Administration, Oral; Aged; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; C-Reactive Protein; Calcitriol; Calcium; Chelating Agents; Cholecalciferol; Chronic Disease; Darbepoetin alfa; Dietary Supplements; Ergocalciferols; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Inflammation Mediators; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Parathyroid Hormone; Phosphorus; Polyamines; Prospective Studies; Renal Dialysis; Serum Albumin; Sevelamer; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: Accidental Falls; Aged; Bone Density Conservation Agents; Calcitriol; Cholecalciferol; Female; Fractures, Bone; Humans; Kidney Diseases; Vitamin D Deficiency

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2-4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2--5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2-4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.

Topics: Adolescent; Biomarkers; Calcifediol; Child; Child, Preschool; Cholecalciferol; Chronic Disease; Female; Humans; Hyperparathyroidism, Secondary; India; Kidney Diseases; Male; Parathyroid Hormone; Prevalence; Prospective Studies; Time Factors; Treatment Outcome; Vitamin D Deficiency; Vitamins

Various complications consequent on disordered calcium and phosphate homeostasis occur frequently in chronic kidney disease (CKD) patients. Particularly, vascular calcification has high morbidity and mortality rates. There is a clear need for a better CKD model to examine various aspects of this disordered homeostasis.. Oral dosing with adenine induced CKD in rats in only 10 days. Serum calcium, phosphate and parathyroid hormone were measured and calcification in aorta was assessed histologically. The effects of varying phosphorus content of diet or treatment with phosphate binders or active vitamin D(3) on these parameters were examined.. After adenine dosing, significant hyperphosphatemia, hypocalcemia and secondary hyperparathyroidism (2HPT) were observed during the experimental period of 15 weeks. Aortic calcification was detected in only some of the animals even at 15 weeks (approximately 40%). Treatment with vitamin D(3) for 18 days, even at a low dose (100 ng x kg(-1), 3-4 times week(-1), p.o), caused aortic calcification in all animals and increases in serum calcium levels up to the normal range. The vitamin D(3)-induced calcification was significantly inhibited by phosphate binders which lowered serum phosphate levels and the calcium x phosphate product, although serum calcium levels were elevated.. These data suggest that rats dosed orally with adenine provide a more useful model for analysing calcium/phosphate homeostasis in severe CKD. Controlling serum calcium/phosphate levels with phosphate binders may be better than vitamin D(3) treatment in hyperphosphatemia and 2HPT, to avoid vascular calcification.

Topics: Adenine; Animals; Aortic Diseases; Biomarkers; Blood Urea Nitrogen; Calcinosis; Calcium; Calcium Carbonate; Chelating Agents; Cholecalciferol; Chronic Disease; Creatinine; Disease Models, Animal; Disease Progression; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hypocalcemia; Kidney Diseases; Male; Parathyroid Hormone; Phosphates; Polyamines; Rats; Rats, Wistar; Sevelamer; Severity of Illness Index; Time Factors

Chronic renal failure has been referred to as a state of cellular calcium toxicity. The aim of this study was to investigate the status of free cytosolic calcium ([Ca(2+)](i)), intracellular calcium reserves and the capacitative calcium entry in peripheral blood mononuclear cells (PBMCs) of early-stage chronic kidney disease (CKD) patients, and to determine the effect of vitamin D(3) supplementation on these parameters.. The study involved 44 patients with CKD stages 2-3; 27 of them were treated with cholecalciferol (5000 IU/week) for 12 months. [Ca(2+)](i) was measured using Fluo-3 AM fluorimetry. Intracellular calcium reserves were emptied by the application of thapsigargin (Tg), a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase. 2-Aminoethyl-diphenyl borate (2APB) was used to examine the capacitative calcium entry.. [Ca(2+)](i) of CKD patients was substantially higher in comparison with healthy subjects: 123 (115-127) versus 102 (98-103) nmol/l, P < 0.001. The calcium concentration of Tg-sensitive stores and the capacitative calcium entry were also significantly increased in CKD patients. After the 12-month vitamin D(3) supplementation, there was a marked decrease in [Ca(2+)](i) [105 (103-112) nmol/l, P < 0.001 versus baseline], independently of the increase in 25(OH)D(3) or the decrease in PTH levels. No significant changes in intracellular calcium reserves and the capacitative calcium entry were found.. Our results demonstrate that (1) [Ca(2+)](i), intracellular calcium stores and the capacitative calcium entry were significantly increased already in early stages of CKD; (2) long-term vitamin D(3) supplementation normalized [Ca(2+)](i) without any effect on intracellular calcium reserves or the capacitative calcium entry.

Topics: Adult; Aged; Calcium; Cholecalciferol; Chronic Disease; Dietary Supplements; Homeostasis; Humans; Kidney Diseases; Middle Aged; Receptors, Purinergic P2; Receptors, Purinergic P2X7

Previous work in our laboratory has shown that long-term treatment with Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula used for the promotion of overall wellness in Chinese medicine, can enhance the mitochondrial functional ability and antioxidant capacity in various tissues of both male and female rats. To investigate whether the VI-28 treatment regimen could afford tissue protection against oxidative injury, the effects of long-term VI-28 treatment (80 or 240 mg/kg/d x 30) on oxidative stress-induced tissue damage in various organs (brain, heart, liver, and kidney) were examined in female rats. The results indicated that long-term VI-28 treatment invariably protected against oxidative tissue damage in the rat models of cerebral/myocardial ischemia-reperfusion injury, CCl4 hepatotoxicity, and gentamicin nephrotoxicity. The tissue protection was associated with increases in the levels and activities of mitochondrial antioxidant components as well as with the preservation of mitochondrial structural integrity. This was evidenced by decreases in the sensitivity of mitochondria to Ca2+-induced permeability transition, and in the levels of mitochondrial malondialdehyde production, Ca2+ loading, and cytochrome c release in the tissues examined. Interestingly, the VI-28 treatment increased red cell CuZn-superoxide dismutase (CuZn-SOD) levels, and these levels correlated positively with the degree of tissue protection afforded by long-term VI-28 treatment in rats. The generalized tissue protection afforded by long-term VI-28 treatment may have clinical implications in the prevention of age-related diseases, and VI-28 treatment may possibly delay the aging process.

Topics: Animals; Carbon Tetrachloride; Carnosine; Chemical and Drug Induced Liver Injury; Cholecalciferol; Cytoprotection; DNA Damage; Drugs, Chinese Herbal; Female; Gentamicins; Hypoxia-Ischemia, Brain; Kidney Diseases; Liver Diseases; Male; Myocardial Reperfusion Injury; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase; Time Factors; Yang Deficiency

To determine the effect of various doses of vitamin D(2) and D(3), as well as ambulatory status (a surrogate for sun exposure), on 25-OH-D levels.. Cross-sectional study with multiple regression analysis.. A state veterans home for veterans and their spouses.. Three hundred two of 609 eligible residents.. Serum 25-OH-D and parathyroid hormone (PTH) level, supplemental dose of vitamins D(2) and D(3) per kilogram of body weight, and 3 levels of ambulatory status.. The mean 25-OH-D level was 28.6 + 9.2 ng/mL; 6.6% of subjects had values of 16 ng/mL or below. Thirty-two percent of participants had 25-OH-D levels below 30 ng/mL and PTH elevation based on stage of kidney disease, evidence that the suboptimal 25-OH-D level had physiologic consequences. Residents unable to transfer independently had 25-OH-D levels 1.6 ng/mL lower than those able to transfer independently. A regression analysis performed in residents unable to transfer independently (less likely to be exposed to the sun) demonstrated that the average increase in 25-OH-D level per 100 IU of D(3) in a 70-kg resident was 2.1 ng/mL versus 1.8 ng/mL for vitamin D(2).. Nursing home residents should receive at least 800-1000 IU of D(3) per day in an effort to maintain optimal vitamin D levels.

Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Calcifediol; Cholecalciferol; Cross-Sectional Studies; Drug Monitoring; Ergocalciferols; Female; Geriatric Assessment; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Mobility Limitation; Nursing Homes; Parathyroid Hormone; Regression Analysis; Severity of Illness Index; Sunlight; Treatment Outcome; Veterans; Vitamin D Deficiency; Wisconsin

Abnormalities of bone mineral metabolism in patients with stage-5 chronic kidney disease may contribute to the high incidence of cardiovascular disease. Noninvasive imaging methods may help predict the simultaneous presence of vasculopathy and bone disease. Accordingly, we measured pulse wave velocity and bone mineral density (BMD), and T-scores (number of SDs below the BMD of a younger reference group) of the spine by both dual energy x-ray absorptiometry and quantitative computed tomography (QCT) in 110 maintenance hemodialysis patients. Older age, white race, diabetes mellitus, lower diastolic blood pressure, and lower albumin levels were associated with lower QCT-assessed T-scores (each P<0.05). After age and multivariable adjustment, pulse wave velocity (PWV) increased as QCT BMD decreased (the prevalence of PWV >or=9 m/s was 32.4%, 61.8%, and 76.5% for participants in the highest to the lowest tertile of QCT-assessed BMD; P<0.001). In contrast, there was no relationship between spine dual energy x-ray absorptiometry-BMD and PWV. In unadjusted models, thoracic spine QCT-assessed T-scores correlated significantly, albeit weakly, with aorta calcification (r=0.22; P=0.01) but not with coronary calcification. The odds ratio of PWV >or=9 m/s for patients taking vitamin D(3) or its analogs was 0.51 (95% CI: 0.19 to 1.39). In conclusion, low spine BMD is associated with increased PWV in stage-5 chronic kidney disease, supporting the notion of a close interaction of vascular and bone disease in this patient group. QCT and not dual energy x-ray absorptiometry should be used to assess spine BMD in dialysis patients.

Topics: Absorptiometry, Photon; Adult; Aged; Blood Pressure; Bone Density; Calcinosis; Cholecalciferol; Female; Humans; Kidney Diseases; Lumbar Vertebrae; Male; Middle Aged; Pulsatile Flow; Regional Blood Flow; Renal Dialysis; Tomography, X-Ray Computed; Vascular Diseases

1. In humans, two of the principal characteristics of vascular ageing are arterial wall calcification and decreased arterial distensibility, which induce organ damage. To amplify arterial calcium accumulation in laboratory animals, it is necessary to use an overdose of vitamin D(3). 2. The aim of the present study was to assess the impact of arterial calcium overload on renal function. 3. Adult male Wistar rats were randomly divided into two groups: control and treated rats. Treated rats were injected 10 days before the experiment with a single dose of vitamin D(3) (300 000 IU/kg, i.m.). 4. Treated rats showed a decrease in renal blood flow and glomerular filtration rate. Tubular parameters were not modified under basal conditions. In contrast, a statistically significant increase in the fractional excretion of Na, K, Ca and H(2)O were observed in treated rats after the acute increment of sodium distal delivery, suggesting that the reabsorptive capacity of the thick ascending limb may be altered in treated rats. 5. Thus, Na(+)/K(+)-ATPase activity was evaluated in homogenates from renal cortex and medulla. Rats with arterial calcinosis presented a diminished activity of Na(+)/K(+)-ATPase in medulla homogenates. 6. An increment in the abundance of the Na-K-2Cl cotransporter (NKCC2) was observed in renal medulla homogenates from treated rats. It is suggested that this may compensate for the inefficiency of Na(+)/K(+)-ATPase under basal conditions but, in the presence of acute distal sodium overload, the increment in NKCC2 abundance may not be sufficient to compensate for the decrease in Na(+)/K(+)-ATPase activity. 7. In summary, in our experimental model of arterial calcinosis, renal function is impaired, presenting a vascular compromise and altered function of the medullar thick ascending limb that becomes evident in the presence of acute high distal sodium delivery.

Topics: Animals; Aorta, Abdominal; Calcinosis; Cholecalciferol; Kidney Diseases; Kidney Tubules, Distal; Male; Rats; Rats, Wistar; Renal Artery

In vascular smooth muscle, calcium overload is a highly pathogenic event, which increases with advancing age. An increase in the calcium content of arterial wall may be produced in rats by treatment with vitamin D3. The aim of this study was to evaluate the renal clearance of sulfanilamide (a model organic anion, preferentially eliminated by the kidneys) and other parameters of global renal function in rats with arterial calcinosis. Arterial calcinosis was produced in adult rats by means of a single dose of vitamin D3 (300,000 UI/kg bw, i.m.) 5 days before the experiment. Treated rats showed a large increase in calcium content of aortic tissue and an increase in systolic arterial pressure. No modifications were observed in plasma calcium levels and in plasma lipid profiles. Statistically significant decrements were observed in renal clearance of sulfanilamide, in renal blood flow, in fractional excretion of sodium and potassium. A slight decrease, not statistically different, was observed in the glomerular filtration rate. Rats with arterial calcinosis also showed an increment of total calcium levels in renal tissue, in fractional excretion of calcium and in the expression of organic anion transporter 1 (OAT1). Histological studies revealed tubular alterations. In summary, modifications in hemodynamics and tubular parameters are early manifestations of nephropathy in rats with arterial calcinosis, some of which may account for the changes observed in organic anions renal depuration. It is important to mention that the decrease in clearance of organic anions were seen in spite of the increase in expression of OAT1.

Topics: Animals; Aorta, Abdominal; Aortic Diseases; Blood Pressure; Calcinosis; Calcium; Cholecalciferol; Disease Models, Animal; Glomerular Filtration Rate; Kidney Diseases; Kidney Function Tests; Male; Organic Anion Transport Protein 1; Randomized Controlled Trials as Topic; Rats; Rats, Wistar; Renal Circulation; Sulfanilamide; Sulfanilamides; Systole; Time Factors

1Alpha,25-dihydroxyvitamin D3 (active form of vitamin D3; vitamin D3) has been reported to induce the upregulation of thrombomodulin and downregulation of tissue factor (TF) on monocytes. The possibility exists that vitamin D3 prevents the development of disseminated intravascular coagulation (DIC). In particular, monocyte TF production plays an important role in the pathophysiology of DIC in septic patients. We have attempted to determine whether vitamin D3 is effective against DIC in a rat model induced by lipopolysaccharides (LPS) (30 mg/kg, 4 h) or TF (3.75 U/kg, 4 h) using selective hemostatic parameters, markers of organ dysfunction and pathological findings (assessment of glomelular fibrin deposition). Vitamin D3 was administered orally each day at a dose of 2.0 mg/kg/day for 3 days, or low molecular weight heparin (LMWH 200 u/kg; i.v.) was given 10 min before the injection of TF or LPS in each treatment group. Vitamin D3 was effective against DIC in the rat model induced by LPS only, whereas LMWH was effective against DIC in both rat models induced by either TF or LPS. The anti-DIC effect of vitamin D3 was equal to (or more potent than) that of LMWH. The results suggested that vitamin D3 was useful for the treatment of LPS-induced DIC, and that the assessment of a drug's efficacy should be done carefully given the markedly different results obtained according to the agents used to induce DIC.

Topics: Administration, Oral; Animals; Anticoagulants; Cholecalciferol; Coagulants; Disease Models, Animal; Disseminated Intravascular Coagulation; Fibrin; Heparin; Kidney Diseases; Kidney Glomerulus; Lipopolysaccharides; Male; Rats; Rats, Wistar; Sepsis; Thromboplastin; Thrombosis

Topics: Cholecalciferol; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Uremia

Serum osteocalcin has been found to correlate with bone formation. However, present literature gives only limited data on osteocalcin and bone histomorphometry in patients undergoing peritoneal dialysis. This study assessed serum osteocalcin, dialysate osteocalcin, peritoneal clearance of osteocalcin (Clp-osteocalcin) and mass transfer of osteocalcin (MTp-osteocalcin), and evaluated relationships between these values and bone histomorphometry. Eighteen patients were treated by continuous ambulatory peritoneal dialysis (CAPD). Bone biopsies, serum and dialysate osteocalcin, serum levels of parathyroid hormone, alkaline phosphatase, aluminum, phosphate, Ca2+ and vitamin D3 metabolites were measured at the start and in 10 of the patients a year later. Serum osteocalcin was found to be elevated. Osteocalcin was detected in the dialysate resulting in significant values of Clp-osteocalcin and MTp-osteocalcin. Serum and dialysate levels of osteocalcin correlated significantly (r = 0.66, P < 0.001) and like MTp-osteocalcin with serum levels of alkaline phosphatase and PTH. Histomorphometry showed that osteitis fibrosa was the predominant bone disease detected. Serum concentration of osteocalcin correlated with osteoid thickness, eroded and osteoclast surfaces, aluminum staining, and some of the bone dynamic parameters. Dialysate osteocalcin, MTp-osteocalcin, PTH and alkaline phosphatase correlated with practically the same histomorphometric parameters as serum osteocalcin. No correlations were seen between Clp-osteocalcin and any histomorphometric parameters. Serum osteocalcin was elevated above the normal range, and significant positive correlations between serum osteocalcin and bone formation parameters were found. Serum osteocalcin correlated with almost the same histomorphometric parameters as PTH. Thus, serum levels of PTH and osteocalcin gave additional information to one another as non-invasive parameters in this group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biopsy; Bone Density; Bone Diseases, Metabolic; Cholecalciferol; Dialysis Solutions; Female; Humans; Kidney Diseases; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Peritoneal Dialysis, Continuous Ambulatory

Topics: Cholecalciferol; Ergocalciferols; Female; Humans; Hypercalcemia; Kidney; Kidney Diseases; Middle Aged; Parathyroid Hormone

By use of a single-cartridge system, 1,25-dihydroxyvitamin D [1,25(OH)2D] is extracted and purified from a plasma or serum sample. Proteins are removed and 1,25(OH)2D is liberated from the sample with acetonitrile. The acetonitrile extract is applied to the nonpolar octadecylsilanol silica cartridge, in which 1,25(OH)2D is retained while polar compounds are eluted. Then by "phase-switching" on the same cartridge, 1,25(OH)2D is sufficiently resolved from other vitamin D metabolites and extraneous lipophilic compounds to allow its quantification by radioreceptor assay according to an established procedure. Mean (and SD) values for 1,25(OH)2D in serum of 29 normal, 27 chronic renal failure, and nine pregnant subjects were 28.2 (11.3), 10.9 (5.2), and 47.3 (12.9) ng/L, respectively. Results compared well with those of an established radioreceptor procedure. This procedure offers the advantage of a single rapid purification step not involving "high-performance" liquid chromatography or evaporation, under nitrogen, of polar solvents such as acetonitrile or methanol.

Topics: 24,25-Dihydroxyvitamin D 3; Calcitriol; Cholecalciferol; Dihydroxycholecalciferols; Female; Humans; Kidney Diseases; Labor, Obstetric; Pregnancy; Radioligand Assay; Specimen Handling

Topics: Animals; Bird Diseases; Calcinosis; Calcium; Cardiovascular Diseases; Cholecalciferol; Coturnix; Diet; Female; Kidney Diseases; Microscopy, Electron; Plants; Proteoglycans; Quail

Vitamin D3 metabolites and iPTH were measured in 26 patients at various times after renal transplantation. Hypercalcaemia (serum Ca greater than 2.62 mmol/L, 14 patients) was associated with hyperparathyroidism (p less than 0.02) and raised 1,25(OH)2D3 (p less than 0.05) but raised 1,25(OH)2D3 was also found in most patients in the normocalcaemic group. Lower 25(OH)D3 concentrations were found in the group with normal 1,25(OH)2D3 compared to the group with elevated 1,25(OH)2D3 (p less than 0.05). Low values of 24,25(OH)2D3 were found in both the normocalcaemic and hypercalcaemic patients (p less than 0.002). Impaired creatinine clearance (less than or equal to 55 ml/min, mean: 38 ml/min) was not associated with reduced 1,25(OH)2D3. No difference in D3 metabolites was found between hypophosphataemic and normophosphataemic patients.

Topics: Adult; Cholecalciferol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Hypercalcemia; Kidney Diseases; Kidney Transplantation; Parathyroid Hormone

Plasma concentrations of vitamin D3, 25-OH-D3, 24, 25(OH)2D3 and 1, 25(OH)2D3 were measured in patients with various diseases using the multiple assay system previously reported. In patients with hyperparathyroidism, the plasma levels of 1, 25(OH)2D3 tended to increase, while the levels of 24, 25(OH)2D3 tended to decrease in many cases. On the other hand, plasma 1, 25(OH)2D3 levels were low, while 24, 25(OH)2D3 levels were high in patients with hypoparathyroidism. No significant differences in the levels of plasma D3 derivatives among idiopathic-, postoperative- and pseudo- hypoparathyroidism were observed. In a majority of hemodialyzed patients with advanced renal failure who showed no overt bone changes on X-ray films, both the plasma 1, 25(OH)2D3 and 24, 25(OPH)2D3 levels were distributed from normal to very low. In a majority of patients with osteoporosis and hypoparathyroidism, plasma 1, 25(OH)2D3 levels rose quickly after the administration of 1 alpha-OH-D3. In hypophosphatemic vitamin D resistant rickets, however, the response to the relatively large amounts of 1 alpha-OH-D2 was poor, although the concentrations of plasma 24, 25(OH)2D3 were elevated by the 1 alpha-OH-D3 administration in most of these cases. The plasma 1, 25(OH)2D3 and 24, 25(OH)2D3 concentrations in patients with senile osteoporosis were distributed from lower to higher range than those of normal adults. There was a relatively good correlation between plasma levels of 25-OH-D3 and D3 only in cases with plasma D3 levels higher than 5 ng/ml. In addition, a hyperbolic regression curve was obtained between the plasma D3 and 25-OH-D3 ratio. These results may indicate that a possible negative feedback homeostatic mechanism exists between plasma levels of D3 and 25-OH-D3, but only with low plasma levels of D3.

Topics: Calcitriol; Cholecalciferol; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Hypoparathyroidism; Kidney Diseases; Parathyroid Diseases; Pseudohypoparathyroidism

It is evident that there has been enormous progress within the last decade in our understanding of vitamin D metabolism and its interaction with calcium, phosphate, parathyroid hormone, and a number of other factors. As a result largely of therapeutic trials with various metabolites of vitamin D, we now know something of their probable involvement in the development of rickets and osteomalacia. We do not yet have a clear comprehension of exactly how these metabolites influence bone mineralization other than through their indirect effect on serum calcium and phosphate. Nonetheless it seems likely that at least one, and perhaps more, of the metabolites do exert a more direct effect. One must conclude that a deficiency of the 1alpha-hydroxylase is probably not the only defect in renal insufficiency, although it currently that there must well known. It is premature to go so far as to suggest that there must be another metabolite not being synthesized in the diseased or absent kidney.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Bone and Bones; Calcification, Physiologic; Calcium; Cholecalciferol; Humans; Hydroxylation; Hypophosphatemia, Familial; Kidney Diseases; Minerals; Osteomalacia; Phosphates; Vitamin D

Topics: Child; Cholecalciferol; Humans; Hypercalcemia; Hypertension; Infant; Kidney Diseases; Rickets

In 36 patients with incipient and advanced renal failure (CCr 80--30 ml/min X 1.73 m2), serum chemistry including ionized Ca, serum PTH and fractional intestinal absorption of Ca (whole body counter; two-dose-technique; 47Ca p.o. and i.v. to correct for urinary and endogenous fecal loss were measured. Quantitative bone histology after in vivo tetracycline double labeling was evaluated from undecalcified sections before and 18 months after therapy with vitamin D3 or 5,6-trans-25-OH-CC in a dose sufficient to raise intestinal absorption and/or urinary excretion of Ca. Intestinal absorption of Ca was impaired in some patients at a GFR of 60 ml/min/1.73 m2. After up to 10000 U/d 5,6-trans-25-OH-CC and 8000 IU/d vitamin D3, respectively, fractional intestinal absorption of Ca rose and was normalized in all patients. There was a concomitant rise in urinary Ca. Serum PTH fell, but did not always return into the normal range. Ionized Ca rose in all patients. Bone histology was evaluated in 17 of these 36 patients after informed consent was obtained. The mass of mineralized bone (Vv) rose in 7/17 patients, pointing to a positive calcium balance. Volumetric density of osteoid (Vvos) and surface density of osteoid (Svos) fell in 10/17 patients concomitant with an increase in the fraction of mineralizing seams and a decrease in the number of lamellae in osteoid seams. Osteoclastic resorption (OCl) fell as did the fraction of woven osteoid seams. However, woven osteoid failed to disappear completely and osteoclastic resorption stayed elevated in some patients. 5,6-trans-25-OH-CC and vitamin D3, in doses that normalized intestinal absorption of Ca, failed to restore completely bone histology to normal although mineralization and collagen texture of osteoid were consistently improved. The dose response characteristics to vitamin D of different abnormalities of Ca metabolism appear to be non-uniform.

Topics: Adolescent; Adult; Bone and Bones; Calcium; Cholecalciferol; Female; Humans; Intestinal Absorption; Kidney Diseases; Male; Middle Aged

The relative toxicity and metabolic effectiveness of cholecalciferol (CC) and 25-hydroxycholecalciferol (25-HCC) in chicks were evaluated by feeding six graded levels of each and observing gross and microscopic pathology as well as several metabolic parameters of calcium metabolism. Renal tubular calcification was observed when CC was fed at the rate of 10.0 mg/kg of diet and when 25-HCC was fed at the rate of 0.1 mg/kg diet. Thus, 100-fold increase in toxicity results when the hydroxylated form of CC is fed. Both microscopic renal lesions and increased renal calcium and inorganic phosphate concentrations occurred in chicks with normal serum calcium concentrations.

Topics: Alkaline Phosphatase; Animals; Body Weight; Calcinosis; Calcium; Chickens; Cholecalciferol; Dose-Response Relationship, Drug; Hydroxycholecalciferols; Kidney; Kidney Diseases; Kidney Tubules; Phosphorus

Topics: Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hydroxycholecalciferols; Kidney; Kidney Diseases; Phosphates; Vitamin D

Topics: Benzothiadiazines; Calcium; Cholecalciferol; Cyclic AMP; Diuretics; Humans; Kidney Diseases; Kidney Tubules; Malabsorption Syndromes; Parathyroid Hormone; Phosphates; Sodium Chloride Symporter Inhibitors

The examples of tubular proteinuria, postobstructive diuresis, tubular function in terminal renal failure and the hereditary defects of tubular transport mechanisms are used to demonstrate the difficulty in elucidating defects of renal membrane transports in man. She is caused by the impossibility of applying the appropriate techniques to evaluate membrane functions in man and by the complexity of human disease. The rapidly growing knowledge of physiologic membrane functions in the kidney should however enable some progress in the field of human pathophysiology in a not too remote future.

Topics: Cell Membrane Permeability; Cholecalciferol; Creatinine; Diuresis; Humans; Kidney Diseases; Kidney Tubules; Sodium

Topics: Adenosine Triphosphatases; Amino Acids; Child, Preschool; Cholecalciferol; Fanconi Syndrome; Humans; Hypophosphatemia, Familial; Infant; Kidney Diseases; Kidney Tubules; Magnesium; Magnesium Deficiency; Male; Phosphorus; Potassium

Topics: Adolescent; Adult; Aged; Cholecalciferol; Female; Humans; Intestinal Absorption; Kidney Diseases; Liver Diseases; Malabsorption Syndromes; Male; Middle Aged; Osteomalacia; Tritium

Topics: Alloxan; Calcinosis; Cholecalciferol; Dihydrotachysterol; Ergocalciferols; Islands; Islets of Langerhans; Kidney Diseases; Kidney Tubules; Nephrocalcinosis; Pancreas; Pathology; Rats; Research