vitamin-d-2 and Chronic-Kidney-Disease-Mineral-and-Bone-Disorder

The prevalence of vitamin D deficiency in hemodialysis patients is high. While most hemodialysis patients are treated with activated vitamin D (1,25[OH]2D) to prevent renal osteodystrophy, clinical practices of the screening and treatment of 25(OH)2D deficiency are highly variable. It is unclear if nutritional vitamin D supplementation with D2 or D3 provides an additional clinical benefit beyond that provided by activated vitamin D treatment in this population.. We will conduct a systematic review of nutritional vitamin D (D2/D3) supplementation and health-related outcomes in hemodialysis patients according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary objective is to assess the impact of nutritional vitamin D supplementation on clinical outcomes relevant in hemodialysis patients, such as mortality, cardiovascular events, infections, and fractures. Secondary outcomes will include anemia, hyperparathyroidism, medication use (erythrocyte-stimulating agents, activated vitamin D), and quality of life. We will search MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov for randomized, controlled trials of nutritional vitamin D supplementation (ergocalciferol/D2 or cholecalciferol/D3) in chronic hemodialysis patients. The Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies. We will perform meta-analyses using standard techniques for the outcomes listed above if pooling is deemed appropriate/sufficient. The results of this systematic review may highlight gaps in our knowledge of the relevance of nutritional vitamin D in end-stage renal disease, allowing for the informed design of clinical trials assessing the impact of nutritional vitamin D therapy in the hemodialysis population in the future.. PROSPERO CRD42014013931.

Topics: Cardiovascular Diseases; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Protocols; Dietary Supplements; Ergocalciferols; Fractures, Bone; Humans; Infections; Renal Dialysis; Renal Insufficiency, Chronic; Research Design; Systematic Reviews as Topic; Vitamin D Deficiency; Vitamins

Calcium mass balance (Ca(MB)) is determined by the difference between Ca absorbed between dialyses (Ca(Abs)) and the Ca removed during dialysis (J(d)Ca(2+)). A mathematical model to quantify (1) Ca(Abs) as a function of Ca intake (Ca(INT)) and the doses of vitamin D analogues, and (2) J(d)Ca(2+) as a function of Ca(2+) dialysance, the mean plasma Ca(2+) ((M)C(pi)Ca(2+)) minus dialysate Ca(2+) (C(di)Ca(2+)), ultrafiltration rate (Q(f)) and treatment time is developed in this paper. The model revealed a basic design flaw in clinical studies of Ca-based as opposed to non-Ca-based binders in that C(di)Ca(2+) must be reduced with the Ca-based binders in order to avoid a positive Ca(MB) relative to the non-Ca-based binders. The model was also used to analyze Ca(MB) in 320 Renal Research Institute hemodialysis patients and showed that all patients irrespective of type of binder were in positive Ca(MB) between dialyses (mean +/- SD 160 +/- 67 mg/day) with current doses of vitamin D analogues prescribed. Calculation of the optimal C(di)Ca(2+) for the 320 Renal Research Institute patients revealed that in virtually all instances, the C(di)Ca(2+) required for neutral Ca(MB), where Ca removal during dialysis was equal to Ca accumulation between dialyses, was less than 2.50 mEq/l and averaged about 2.00 mEq/l. This sharply contradicts the recent KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease - Mineral and Bone Disorder, that suggests a C(di)Ca(2+) of 2.5-3.0 mEq/l. Review of the KDIGO work group discussions shows that this discrepancy stems from the unwarranted work group assumption that intradialytic Ca(MB) is zero. We strongly believe that this guideline for dialysate Ca(2+) is inappropriate and should be modified to more realistically reflect the needs of dialysis patients.

Topics: Acetates; Algorithms; Bone Density Conservation Agents; Calcitriol; Calcium; Calcium Compounds; Calcium Metabolism Disorders; Calcium, Dietary; Chelating Agents; Chronic Kidney Disease-Mineral and Bone Disorder; Dialysis Solutions; Ergocalciferols; Homeostasis; Humans; Intestinal Absorption; Kidney Failure, Chronic; Models, Biological; Phosphorus; Practice Guidelines as Topic; Reference Values; Renal Dialysis; Research Design; Ultrafiltration

Recent evidence suggests that the traditional syndromes known as renal osteodystrophy, secondary hyperparathyroidism, and vitamin D deficiency are related to mortality in persons with moderate to advanced chronic kidney disease (CKD). The so-called 'kidney bone disease', also known as 'mineral and bone disorders', is defined to include bone disorders, mineral disarrays, and vascular calcification. We have identified 14 common and clinically relevant conditions of contemporary nature that are related to the kidney bone disease, including calcitriol (active vitamin D) deficiency, 25(OH)-vitamin D deficiency, biochemical hyperparathyroidism, relatively low parathyroid hormone (PTH) level, increased serum alkaline phosphatase (hyperphosphatasemia), elevated fibroblast growth factor (FGF)-23, high turnover bone disease, adynamic bone disease, uremic osteoporosis, vascular calcification, hyper- and hypophosphatemia, and hyper- and hypocalcemia. We present a critical review of these 14 conditions with emphasis on patient survival and other pertinent clinical outcomes. We also review unresolved controversies surrounding the management of these conditions by administration of nutritional vitamin D (ergocalciferol and cholecalciferol), vitamin D receptor activators (calcitriol, alphacalcidiol, doxercalciferol), D-mimetics (paricalcitol, maxacalcitol), calcimimetics (cinacalcet), recombinant PTH (teriparatide), and receptor activator of nuclear factor-kappaB ligand modulators (denosumab); compare mortality predictability of PTH and alkaline phosphatase; and examine potential risks of bone disorders and mineral disarrays in CKD patients.

Topics: Alkaline Phosphatase; Calcinosis; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hypocalcemia; Hypophosphatemia; Kidney Failure, Chronic; Minerals; Osteoporosis; Parathyroid Hormone; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Despite the enormous cardiovascular disease epidemic and poor survival among individuals with chronic kidney disease (CKD), traditional risk factors such as hypercholesterolemia, hypertension, and obesity appear not as relevant as was previously thought, nor would their management improve survival in patients with CKD who are undergoing dialysis. On the contrary, kidney disease wasting (KDW) (also known as the malnutrition-inflammation complex), renal anemia, and kidney bone disease (KBD) appear to be the 3 most important nontraditional risk factors associated with cardiovascular disease in CKD. KBD-associated hyperparathyroidism may contribute to worsening refractory anemia and KDW/inflammation. The main cause of secondary hyperparathyroidism is active vitamin D deficiency. Hence, treatment of patients with KBD with vitamin D analogs, especially those with lesser effects on calcium and phosphorus such as paricalcitol, may be the most promising option for improving CKD outcomes. By conducting survival analyses in a 2-year (7/2001 to 6/2003) cohort of 58,058 patients on hemodialysis, we recently found that associations between high serum parathyroid hormone and increased death risk were masked by the demographic and clinical characteristics of patients, and that alkaline phosphatase had an incremental association with mortality. Administration of paricalcitol was associated with improved survival in time-varying models. We now present additional subgroup analyses that show that administration of any dose of paricalcitol, when compared with no paricalcitol, is associated with better likelihood of survival in virtually all subgroups of patients on hemodialysis. Because these associations may be secondary to bias by indication, randomized clinical trials are necessary to verify the findings of this and similar observational studies.

Topics: Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Renal Dialysis; Risk Factors; Survival Analysis; Vitamin D

There has been an emphasis over the last several years to identify and treat chronic kidney disease (CKD) and its complications as they evolve rather than waiting until the patient reaches end-stage renal disease (ESRD), also known as CKD stage 5. The number of patients who will be identified and prescribed therapies for complications such as secondary hyperparathyroidism (SHPT) is greater than initially proposed.. To review the pathways, complications, management, and estimated treatment costs of CKD-related SHPT.. An electronic literature search of MEDLINE (January 1980 through January 2007) was conducted for English-language publications using the base search term secondary hyperparathyroidism. To refine subsequent searches, the authors added Boolean operators to the following secondary and tertiary search terms: parathyroid hormone, chronic kidney disease, renal osteodystrophy, adynamic bone disease, vascular calcification, cardiovascular disease, vitamin D, vitamin D analogs, hypercalcemia, hyperphosphatemia, calcimimetics, costs, prevalence, and economics.. The initial MEDLINE search produced 278 relevant articles. After refining the search terms, the authors triaged the results for English-language publications relevant to the discussion of SHPT and its complications in CKD, eliminating 149 publications. The remaining 129 publications were accepted for review. These articles represent a growing body of primarily observational evidence that demonstrates that elevated intact parathyroid hormone (PTH) levels cause deleterious physiological results across a variety of organ systems, including the cardiovascular and skeletal systems. Specific complications associated with SHPT are left ventricular hypertrophy (LVH), renal osteodystrophy (ROD), and extraskeletal calcification. Medical management of the PTH/vitamin D/calcium and phosphorus imbalances in SHPT focus on regulating PTH levels via vitamin D therapy. The class of calcimimetics is a newer treatment modality that has favorable effects on biochemical laboratory values, such as serum calcium and phosphorus levels, but current data do not show differences on hard endpoint patient-oriented outcomes compared with standard generic agents. The direct drug costs in April 2007 U.S. dollars of treating CKD-associated elevations in PTH in predialysis patients range from $8.40 per patient per week ($437 per year) for oral generic calcitriol to $88.90 per patient per week ($4,623 per year) for oral paricalcitol (expressed as 85% of average wholesale price [AWP] for brand drugs or 70% of AWP for generic drugs). The direct drug costs of treating SHPT in hemodialysis patients range from $80.20 per patient per week ($4,170 per year) for generic calcitriol (IV) to $278.46 per patient per week ($14,480 per year) for oral cinacalcet.. SHPT causes skeletal and cardiovascular complications in CKD patients. Calcitriol therapy is effective in managing PTH levels, but efforts to reduce the associated hypercalcemia and hyperphosphatemia have led to the development of newer, yet more expensive, vitamin D analogs. With the lack of evidence to support comparative superior outcomes in end-organ disease among SHPT therapy alternatives, future research is still needed to clearly identify which newer agents are most competitive with the historical gold standard of calcitriol therapy.

Topics: Calcitriol; Cardiovascular Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Cinacalcet; Cost-Benefit Analysis; Drug Costs; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Naphthalenes; Parathyroid Hormone; Parathyroidectomy; Renal Insufficiency, Chronic; Vitamin D; Vitamins

Progression of chronic kidney disease is associated with an early reduction in serum calcitriol levels; thus, therapy with calcitriol should be initiated early in the course of chronic kidney disease to prevent the development of secondary hyperparathyroidism. Initial studies demonstrated a potential role of calcitriol in the prevention of growth retardation in children with chronic kidney disease prior to dialysis. But the optimal parathyroid hormone (PTH) levels that will maximize growth response during calcitriol treatment remain to be defined. Therapy with calcitriol has been shown to control the biochemical and skeletal manifestations of secondary hyperparathyroidism, but patients developed hypercalcemia, hyperphosphatemia and adynamic osteodystrophy. Thus, new vitamin D analogues with a lower hypercalcemic response have been developed. Although comparative studies are lacking, current evidence indicates that these new active vitamin D sterols (19-nor-paracalcitol and doxercalciferol) adequately control secondary hyperparathyroidism with minimal changes in serum calcium and phosphorus levels during treatment with calcium-containing binders. The long-term effect of such therapies on the skeleton and the process of vascular calcifications remain to be evaluated.

Topics: Calcitriol; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Kidney Failure, Chronic; Parathyroid Hormone

Bone metabolism is very frequently disturbed in end stage renal failure hemodialyzed, with secondary hyperparathyroidism development but also serious potential cardiovascular consequences. New treatments will be available very soon in Europe such as new phosphate binders, vitamin D2 analogues or calcimimetics to fight against such medical diseases, with the hope of less risk for vascular complications. The real place of such new medical opportunities needs to be determined. Moreover, studies with morbidity and mortality end-points are waited before estimating the real importance of these new therapeutic tools.

Topics: Calcium; Chelation Therapy; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Phosphorus; Renal Dialysis

Vitamin D deficiency/insufficiency, which is clinically represented by low 25(OH)D concentration, is frequently seen in patients with CKD stage 3 and 4. Although its cause is unknown, hypovitaminosis D is partly associated with low 1,25(OH)2D in these patients, possibly leading to advancement of renal osteodystrophy. Recently, in United States, K/DOQI (Kidney disease outcomes quality initiative) guideline indicated that vitamin D deficiency/insufficiency of 25(OH)D concentration less than 30 ng/mL should be treated by supplementation of ergocalciferol. A Japanese guideline to treat vitamin D deficiency/insufficiency should be urgently established.

Topics: Biomarkers; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Severity of Illness Index; Vitamin D; Vitamin D Deficiency

Secondary hyperparathyroidism (2HPT), a common disorder in patients with chronic renal failure, develops in response to phosphate retention and low serum 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol). Replacement therapy with calcitriol or its precursor 1alpha-hydroxyvitamin D(3) (1alphaOHD(3), alfacalcidol) often produces hypercalcaemia, especially when combined with calcium-based phosphate binders. In addition, these vitamin D compounds can aggravate the hyperphosphataemia in these patients. Several vitamin D analogues have been developed that retain the direct suppressive action of 1,25(OH)(2)D(3) on the parathyroid glands but have less calcaemic activity, thereby offering a safer and more effective means of controlling 2HPT. 1,25-Dihydroxy-19-norvitamin D(2) (19-norD(2)) and 1alpha-hydroxyvitamin D(2) (1alphaOHD(2)) are available in the US and 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) and 1,25-dihydroxy-26,26,26,27,27,27-hexafluorovitamin D(3) (1,25(OH)(2)26,27F6 D(3), falecalcitriol) have been approved for use in Japan. Animal studies have demonstrated that OCT and 19-norD(2) have a wider therapeutic window for suppression of parathyroid hormone (PTH) because of their lower calcaemic and phosphataemic activities. The low calcaemic activity of OCT has been attributed to its rapid clearance, which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression and parathyroid cell growth. The calcaemic activity of 19-norD(2) diminishes with the duration of treatment by as yet unknown mechanisms. The lower toxicity of 1alphaOHD(2), compared with 1alphaOHD(3), has also been noted with chronic, but not acute administration, perhaps due to differential metabolism. The unique actions of falecalcitriol may also result from an altered metabolism. A clear understanding of the molecular basis for the selectivity of vitamin D analogues on parathyroid function may allow the design of even more effective analogues.

Topics: Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Parathyroid Hormone; Vitamin D

The skeletal disorders associated with renal insufficiency result from alterations in calcium, phosphorus, and vitamin D metabolism. Each requires intervention to prevent and control the problem. Hyperparathyroidism and its treatment can also result in extraskeletal complications. To prevent the development of parathyroid hyperplasia and the skeletal complications of chronic kidney disease, it is desirable to initiate interventions early in the course of kidney disease; however, many patients present with established hyperparathyroidism and additional strategies are necessary to suppress hyperparathyroidism. Mainstays of this approach are the control of phosphorus and the use of vitamin D analogs. Phosphorus control requires the use of phosphate binders, preferably non-calcium-containing binders, to prevent intestinal phosphorus absorption. Vitamin D analogs are used to suppress hyperparathyroidism and have the potential to have lesser toxicity than calcitriol. Paricalcitol is the most widely used vitamin D analog in this country and it effectively suppresses hyperparathyroidism with only minimal effects on calcium and phosphorus. A substantial body of data in experimental animals supports the use of paricalcitol as a preferential therapeutic agent. Recently, an additional vitamin D sterol, doxercalciferol, has been introduced, which is metabolized to 1,25-dihydroxyvitamin D(2). Although initially thought to have lesser toxicity than its vitamin D(3) counterpart, recent studies have not provided support for a major difference in this regard. Doxercalciferol is also effective in lowering parathyroid hormone (PTH), though hypercalcemia in hyperphosphatemic episodes occurred relatively frequently during the clinical studies. As these therapeutic strategies are undertaken, it is important not to oversuppress PTH and decrease bone turnover to abnormally low levels because of the risk for adynamic renal bone disease. It is possible that when bone turnover is abnormally low, the extraskeletal deposition of calcium in blood vessels and other tissues is enhanced. Accordingly, constant monitoring is required during treatment, with emphasis on minimizing the calcium load, and, if monitored correctly, a satisfactory control of hyperparathyroidism may be achieved with the agents currently available.

Topics: Animals; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hyperparathyroidism; Osteoporosis; Parathyroid Hormone; Phosphorus; Renal Dialysis; Renal Insufficiency; Vitamin D

Studies in rats with renal ablation indicate that anemia lessens, whereas its vigorous correction with recombinant human erythropoietin (r-HuEPO) worsens systemic and glomerular hypertension, factors known to promote progression of chronic renal failure (CRF). However, in human studies, use of r-HuEPO in predialysis patients has not been associated with worsening renal function, provided blood pressure control is achieved. Histological evidence of bone disease is common in early renal failure, and deficits in calcitriol synthesis seem to be an important factor in the pathogenesis of secondary hyperparathyroidism (HPTH) in early CRF. Reports to data, on the use of low dose active vitamin D metabolites in predialysis patients, indicate either a reversible decline or no decline in renal function. Adynamic bone disease, however, may ensure during such therapy if excessive reductions in serum intact parathyroid hormone concentrations occur. Recent data suggest that chronic metabolic acidosis decreases albumin synthesis, increases muscle proteolysis, and induces negative nitrogen balance in patients with CRF. Despite these experimental data, the clinical relevance of correction of metabolic acidosis in end-stage renal disease (ESRD) is still not defined. Even though therapy of metabolic acidosis in the adult patient with CRF remains conjectural at this time, reports indicate that its correction might lead to healing of osteomalacia and osteopenia, and possibly may decrease protein degradation and improve growth in children with CRF.

Topics: Acidosis; Adult; Anemia; Animals; Calcitriol; Calcium Compounds; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Erythropoietin; Humans; Kidney Failure, Chronic; Rats; Recombinant Proteins; Renal Dialysis

Topics: 25-Hydroxyvitamin D 2; Calcitriol; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Ergocalciferols; Humans; Intestinal Absorption; Osteomalacia; Parathyroid Hormone; Vitamin D

The effect of 1 alpha OHD2 and 1 alpha OHD3 have been studied in rachitic, normal, and prednisolone-treated male rats. The healing of rickets, the stimulation of intestinal Ca and P transport, the effect on bone mineral, and the induction of renal calcifications have been examined. The two 1-hydroxylated compounds are equally potent in healing rickets, and by comparison with previous data are equivalent to 100-200 IU/micrograms. 1 alpha OHD2 and 1 alpha OHD3 stimulated intestinal Ca and P transport to the same extent and were antagonistic to prednisolone in this respect. 1 alpha OHD2 reduced the number of osteoclasts and increased bone mineral in normal rats in contrast to 1 alpha OHD3, which increased osteoclasts and slightly reduced bone mineral. Prednisolone-induced osteopenia was more effectively counteracted by 1 alpha OHD2 than by 1 alpha OHD3. Mortality rate was higher in rats intoxicated with 1 alpha OHD3 than for rats given 1 alpha OHD2. LD50 was estimated to be five to fifteen times higher for 1 alpha OHD2. Renal calcification were more pronounced after dosing with 1 alpha OHD3 than after treatment with 1 alpha OHD2. When prednisolone was given together with 1 alpha OHD2 or 1 alpha OHD3, renal calcifications were further increased. These observations demonstrate physiological dissimilarities between vitamin D2 and vitamin D3 in rats which are in accordance with a different metabolism of the two vitamins. The findings, in particular that 1 alpha OHD2 is less toxic than 1 alpha OHD3, are of potential clinical importance.

Topics: Animals; Biological Transport; Bone and Bones; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Intestinal Absorption; Intestines; Kidney; Liver; Osteomalacia; Osteoporosis; Phosphorus; Prednisolone; Rats; Rickets; Skin; Vitamin D

Topics: Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Genes, Dominant; Genetic Linkage; Humans; Hypophosphatemia, Familial; Kidney Tubules, Proximal; Male; Phosphates; X Chromosome

Current status of our understanding of the metabolism of vitamin D and its implications in metabolic bone disease is reviewed. The details of metabolism of vitamin D3 to 25-hydroxyvitamin D3 in the liver and its further conversion in the kidneys to either 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 are presented. The latter conversions are regulated by the vitamin D status, serum calcium through the parathyroid gland system, and serum inorganic phosphorus concentration. The 1,25-dihydroxyvitamin D3 can now be regarded as a calcium- and a phosphate-mobilizing hormone and must be considered as one of the most important serum calcium-regulating hormones. Disruption of the vitamin D metabolic sequence or the signal system for 1,25-dihydroxyvitamin D3 results in several bone and calcium metabolism disorders such as renal osteodystrophy, hypoparathyroidism, pseudohypoparathyroidism, and vitamin D-dependency rickets. The use of the synthetic analogs of 1,25-dihydroxyvitamin D3 as well as 1,25-dihydroxyvitamin D3 itself in the management of these disease states is discussed.

Topics: Animals; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Endocrine Glands; Ergocalciferols; Homeostasis; Humans; Hyperparathyroidism, Secondary; Intestinal Absorption; Kidney; Phosphates; Vitamin D

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: Aluminum; Bone Regeneration; Calcium; Calcium Carbonate; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Intestinal Absorption; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Glands; Phosphorus; Secretory Rate; Vitamin D

Topics: Bone Diseases; Calcinosis; Chronic Kidney Disease-Mineral and Bone Disorder; Diet Therapy; Ergocalciferols; Fibrous Dysplasia of Bone; Fractures, Spontaneous; Humans; Hyperparathyroidism, Secondary; Hypocalcemia; Kidney Transplantation; Metabolic Diseases; Osteomalacia; Osteosclerosis; Parathyroid Glands; Phosphates; Renal Dialysis; Tendon Injuries; Vitamin D

The parathyroid glands are endowed both with receptors responsive to FGF23 and to 1,25 vitamin D. Vitamin D receptor (VDR) activation, besides lowering PTH, also raises serum FGF23. FGF23 has been implicated in parathyroid resistance to VDR activation but the issue has never been investigated in predialysis CKD patients.. In the Paricalcitol and Endothelial Functio in Chronic Kidney Disease (PENNY) study (NCT01680198), a 12-week randomized trial in stage G3-4 CKD patients (placebo n = 44 and paricalcitol n = 44), we measured PTH and the active form of FGF23 with no missing value across the trial.. At baseline, serum FGF23 and PTH were inter-related (r = .54, P < .01). Paricalcitol reduced serum PTH (-75.1 pg/mL, 95% CI: -90.4 to -59.8; P < .001) and increased FGF23 (+107 pg/mL, 95% CI: 44-170 pg/mL, P = .001). Changes in the Ca × P product in response to paricalcitol were closely related to simultaneous FGF23 changes in an analysis adjusted for changes in serum calcium and phosphate (P < .001). Of note, baseline FGF23, appropriately adjusted for baseline PTH, was unrelated with the PTH response to paricalcitol (r = -.06, P = .72). Placebo did not change neither PTH nor FGF23.. Serum FGF23 and PTH are inter-related and changes in the Ca × P product induced by paricalcitol per se correlate with the FGF23 response to this drug. Independently of serum FGF23, the parathyroid glands of patients with moderate to severe CKD maintain an intact ability to respond to VDR activation.

Topics: Aged; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphates; Receptors, Calcitriol; Renal Insufficiency, Chronic

1,25(OH). VDRA by paricalcitol causes a moderate increase in serum sclerostin in CKD patients. Such an effect is abolished by adjustment for PTH, suggesting that it may serve to counter PTH suppression. The sclerostin rise by PCT is attenuated by pentosidine, an observation in keeping with in vitro studies showing that AGEs alter the functioning of the VDRA.

Topics: Adaptor Proteins, Signal Transducing; Aged; Arginine; Biomarkers; Bone Morphogenetic Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Double-Blind Method; Ergocalciferols; Female; Fibroblast Growth Factor-23; Genetic Markers; Humans; Italy; Lysine; Male; Middle Aged; Receptors, Calcitriol; Renal Insufficiency, Chronic; Time Factors; Treatment Outcome; Up-Regulation; Vitamins

To compare the efficacy and safety of ergocalciferol and calcitriol in stage 3 to 5 chronic kidney disease (CKD) patients, a randomized, prospective, controlled, open-labeled study was designed. 204 patients were enrolled into the present study with following-up duration of 33.2±3.8 months. Patients in Group VitD2 (n=104) and Group aVitD3 (n=100) were treated by ergocalciferol and calcitriol, respectively. The 25-hydroxyvitamin D levels of group VitD2 increased significantly from 15.14±7.46 to 37.32±10.49ng/ml (P<0.001, t=-19.692) and increased more (P<0.001, t=-14.982) than those of group aVitD3, which increased from 14.90±6.15 to 18.08±7.55ng/ml. Maintenance target levels of serum calcium, phosphorus, and intact parathyroid hormone as the primary outcome measure did not show significant difference in frequencies between two groups. In summary, treatment of CKD-mineral and bone disorders in CKD patients at stages 3 to 5 using ergocalciferol has a similar long-term efficacy and safety profile as calcitriol.

Topics: Biomarkers; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Humans; Male; Middle Aged; Safety; Treatment Outcome

We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized to 8 months of therapy with either oral calcitriol or doxercalciferol, combined with either calcium carbonate or sevelamer. Bone formation rates decreased during therapy and final values were within the normal range in 72% of patients. A greater improvement in eroded surface was found in patients treated with doxercalciferol than in those given calcitriol. On initial bone biopsy, a mineralization defect was identified in the majority of patients which did not normalize with therapy. Serum phosphate concentrations were controlled equally well by both binders, but serum calcium levels increased during treatment with calcium carbonate, and serum parathyroid hormone levels were decreased by 35% in all groups. Baseline plasma FGF-23 values were significantly elevated and rose over fourfold with calcitriol and doxercalciferol, irrespective of phosphate binder. Thus, doxercalciferol is as effective as calcitriol in controlling serum parathyroid hormone levels and suppressing the bone formation rate. Sevelamer allows the use of higher doses of vitamin D. Implications of these changes on bone and cardiovascular biology remain to be established.

Topics: Adolescent; Bone and Bones; Bone Density Conservation Agents; Calcitriol; Calcium Carbonate; Chronic Kidney Disease-Mineral and Bone Disorder; Drug Therapy, Combination; Ergocalciferols; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Failure, Chronic; Longitudinal Studies; Male; Osteogenesis; Parathyroid Hormone; Polyamines; Sevelamer

Comparative assessment of the action of vitamin D2 in high doses, of oxydevit and rocaltrol applied in renal osteopathies has demonstrated that they are equally effective in elevating the calcium concentration in blood serum occurring at the expense of its increased absorption by the intestine. At the same time certain differences have been discovered in the action of these agents on endocrine regulation. The data obtained provide evidence in favour of the use of vitamin D2 in high doses or of its metabolites not only in renal osteopathies at the stage of chronic renal failure but also in the management of the disorders of phosphorus-calcium metabolism in patients with the nephrotic syndrome in the functional-compensation stage after continuous use of corticosteroids, heparin and diuretics.

Topics: Adolescent; Calcitriol; Calcium; Child; Child, Preschool; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Trials as Topic; Ergocalciferols; Glomerulonephritis; Humans; Hydroxycholecalciferols; Phosphorus

In the United States, intravenous vitamin D analogs are the first-line therapy for management of secondary hyperparathyroidism in hemodialysis patients. Outside the United States, oral calcitriol (1,25-dihydroxyvitamin D. We conducted a retrospective cohort study of adult patients treated within Fresenius Kidney Care clinics. During a 6-month period (December 2013 to May 2014), we identified patients on an intravenous vitamin D analog (doxercalciferol or paricalcitol) who switched to oral calcitriol and matched them to patients receiving an intravenous vitamin D analog. Mean serum calcium, phosphate, and intact parathyroid hormone (iPTH) concentrations were examined for up to 12 months of follow-up. We used Poisson and Cox proportional hazards regression models to examine hospitalization and survival rates. The primary analysis was conducted as intention-to-treat; secondary analyses included an as-treated evaluation.. A total of 2280 patients who switched to oral calcitriol were matched to 2280 patients receiving intravenous vitamin D. Compared with patients on intravenous vitamin D, mean calcium and phosphate levels in the oral calcitriol group were lower after the change to oral calcitriol. In contrast, iPTH levels were higher in the oral calcitriol group. At 12 months, the percentage of patients with composite laboratories in target range (calcium <10 mg/dl, phosphate 3.0-5.5 mg/dl, and iPTH 150-600 pg/ml) were comparable between groups (45% versus 45%;. Among patients receiving in-center hemodialysis who were switched to oral calcitriol versus those on an intravenous vitamin D analog, the aggregate of all mineral and bone laboratory parameters in range was largely similar between groups.

Topics: Administration, Intravenous; Administration, Oral; Aged; Biomarkers; Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Drug Substitution; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphates; Renal Dialysis; Retrospective Studies; Time Factors; Treatment Outcome; United States; Vitamins

Vitamin D deficiency has been linked to many different pathologies, especially with morbimortality in patients with chronic kidney disease. The progressive loss of renal function leads to calcitriol deficiency and homeostatic changes in calcium, phosphorus, FGF-23 and PTH, among others. All these changes can also influence vitamin D receptor (VDR) activation and the development of secondary hyperparathyroidism (SHPT). The biologic actions of both vitamin D and its synthetic analogues are mediated by binding to the same VDR, acting on different genes. There is a narrow relationship between low levels of calcitriol and SHPT. The combined approach of VDR activation and phosphate restriction, among others, plays an important role in the early treatment of the chronic kidney disease-mineral and bone disorder (CKD-MBD). The Spanish Society of Nephrology, in order to reduce the uniform and significant association with CKD-associated mortality, calcidiol and high phosphate levels suggests normalization of phosphate as well as calcidiol levels in both CKD and dialysis patients. Moreover, it considers that, in addition to selective/non selective activation of VDR for the prevention and treatment of SHPT, VDR could be activated in dialysis patients by native vitamin D or even low paricalcitol doses, independently of PTH levels, as some cohort studies and a recent metaanalysis have found an association between treatment with active vitamin D and decreased mortality in patients with CKD. In general it is considered reasonable to use all this information to individualise decision making.

Topics: Animals; Calcifediol; Calcimimetic Agents; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Substitution; Ergocalciferols; Fibroblast Growth Factor-23; Humans; Hyperparathyroidism, Secondary; Phosphates; Rats; Receptors, Calcitriol; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D

To assess the level of compliance and variability of mineral metabolism parameters over time in a sample of haemodialysis patients for the different ranges proposed (KDIGO guidelines/S.E.N recommendations) in both groups and individuals continuously.. Every four months, we collected data on calcium, phosphorus, PTH and treatment in a sample of 44 patients followed up continuously for 32 months. We established the percentages of patients who complied with the objectives set for each parameter in both ranges: optimal (KDIGO) and acceptable (S.E.N.) in each control and the percentage that individually complied with the objectives in at least 75% of the determinations.. Compliance with the objective using the optimal range improved, although PTH did not exceed 50%. Using the acceptable range, the objective was achieved in the three parameters in over 70% and over 50% of patients achieved the three simultaneously while using the optimal range, 30% was never achieved. Individually, compliance with the optimal range was continuously achieved in 52.3% (calcium), 45.5% (phosphorus) and in only one patient in PTH, while when using the acceptable range, compliance was achieved in 84.1% (calcium) and 70.5% (phosphorus and PTH).. The use of less stringent criteria than the KDIGO guidelines in calcium, phosphorus and PTH objectives allows patients to remain continuously within appropriate ranges with less intervention and less individual variability.

Topics: Aged; Calcium; Chelating Agents; Chronic Kidney Disease-Mineral and Bone Disorder; Cinacalcet; Ergocalciferols; Female; Follow-Up Studies; Goals; Guideline Adherence; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Naphthalenes; Parathyroid Hormone; Parathyroidectomy; Peritoneal Dialysis; Phosphorus; Postoperative Complications; Practice Guidelines as Topic; Renal Dialysis; Retrospective Studies

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is the term used to describe the abnormalities of bone and mineral metabolism that occur in the setting of kidney disease. The spectrum of these abnormalities is wide, ranging from severe high-turnover bone disease on one end to marked low bone turnover bone disease on the other. Similarly, some patients have severe vascular calcifications while others do not, and the values for biochemistry determinations, including calcium, phosphorus, and parathyroid hormone, also may vary widely among patients. This variability may be influenced by such things as the chronicity of the particular kidney disease, effects of therapies such as corticosteroids on modifying the course of kidney disease, and comorbid conditions, such as diabetes, heart disease, age, and osteoporosis. The heterogeneity of CKD-MBD makes strict protocol-driven therapeutic approaches difficult; accordingly, considerable individualized therapy is required. Using a case history, we explore several of the variables and difficulties involved in patient management.

Topics: Bone Density Conservation Agents; Chronic Kidney Disease-Mineral and Bone Disorder; Comorbidity; Diabetes Mellitus; Ergocalciferols; Female; Heart Diseases; Humans; Hyperparathyroidism; Middle Aged; Parathyroid Hormone; Renal Insufficiency, Chronic; Vitamin D

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

Topics: Aged; Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Humans; Kidney Diseases; Male; Middle Aged; Multivariate Analysis; Parathyroid Hormone; Phosphorus; Predictive Value of Tests; Proportional Hazards Models; Renal Dialysis; Risk Factors; Survival Analysis; Time Factors

Elevated calcium and phosphorus levels after therapy with injectable vitamin D for secondary hyperparathyroidism may accelerate vascular disease and hasten death in patients undergoing long-term hemodialysis. Paricalcitol, a new vitamin D analogue, appears to lessen the elevations in serum calcium and phosphorus levels, as compared with calcitriol, the standard form of injectable vitamin D.. We conducted a historical cohort study to compare the 36-month survival rate among patients undergoing long-term hemodialysis who started to receive treatment with paricalcitol (29,021 patients) or calcitriol (38,378 patients) between 1999 and 2001. Crude and adjusted survival rates were calculated and stratified analyses were performed. A subgroup of 16,483 patients who switched regimens was also evaluated.. The mortality rate among patients receiving paricalcitol was 3417 per 19,031 person-years (0.180 per person-year), as compared with 6805 per 30,471 person-years (0.223 per person-year) among those receiving calcitriol (P<0.001). The difference in survival was significant at 12 months and increased with time (P<0.001). In the adjusted analysis, the mortality rate was 16 percent lower (95 percent confidence interval, 10 to 21 percent) among paricalcitol-treated patients than among calcitriol-treated patients. A significant survival benefit was evident in 28 of 42 strata examined, and in no stratum was calcitriol favored. At 12 months, calcium and phosphorus levels had increased by 6.7 and 11.9 percent, respectively, in the paricalcitol group, as compared with 8.2 and 13.9 percent, respectively, in the calcitriol group (P<0.001). The two-year survival rate among patients who switched from calcitriol to paricalcitol was 73 percent, as compared with 64 percent among those who switched from paricalcitol to calcitriol (P=0.04).. Patients who receive paricalcitol while undergoing long-term hemodialysis appear to have a significant survival advantage over those who receive calcitriol. A prospective, randomized study is critical to confirm these findings.

Topics: Adult; Aged; Aged, 80 and over; Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Cohort Studies; Ergocalciferols; Female; Follow-Up Studies; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Renal Dialysis; Retrospective Studies; Survival Rate

A marked improvement of renal osteodystrophy was achieved after a combined treatment with keto acids and vitamin D in patients with chronic renal failure. Results were checked by histological investigations. The biochemical background of the successful treatment was analysed. A regression of hyperparathyroidism and improvement in vitamin D status are the cause of this phenomenon.

Topics: Amino Acids; Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dietary Proteins; Ergocalciferols; Food, Fortified; Humans; Hyperparathyroidism, Secondary; Keto Acids; Kidney Failure, Chronic; Parathyroid Hormone; Phosphorus

Quantitative bone histology, biochemistry and height velocities were studied in 18 children suffering from chronic renal failure. Eight received calcitriol, 7 ergocalciferol and 3, though alloted to a treatment group, failed to comply with therapy. A histochemical stain for aluminum showed heavy deposition at the calcification front in 3 patients; 2, in the calcitriol group had severe osteomalacia which worsened during treatment, and 1 in the ergocalciferol group had osteomalacia which did not improve. One had never undergone hemodialysis. Bone histology improved markedly in the remaining 12 patients, whichever vitamin D preparation was used; it was unchanged in 3 non-compliant children. Plasma calcium levels rose while parathyroid hormone and alkaline phosphatase levels fell following both treatments, and were unchanged in non-compliant children. Hypercalcemia occurred more frequently following calcitriol therapy (11 episodes) than following ergocalciferol therapy (3 episodes). Height velocities, studied in 11 children, increased in 5 (3 on ergocalciferol and 2 on calcitriol) and were unchanged in 6 (1 on ergocalciferol, 5 on calcitriol). Improved bone histology did not correlate with increase in height velocity. As ergocalciferol and calcitriol had similar therapeutic effects and as side-effects were more common with calcitriol, it is concluded that calcitriol provides no advantage over ergocalciferol in the treatment of renal bone disease in children.

Topics: Alkaline Phosphatase; Aluminum; Bone and Bones; Calcitriol; Calcium; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Growth; Humans; Male; Parathyroid Hormone; Patient Compliance

Topics: Body Height; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Infant; Kidney; Male; Urethra

Starting from the results of former investigations the influence of the long-term treatment with the KA of the essential amino acids on the renal osteopathy is investigated. For this purpose we compared 27 patients with renal insufficiency (serum creatinine 981 +/- 354 mumol/l), who besides vitamin D had been treated with KA for at least 12 months, to a group of 50 patients (serum creatinine 778 +/- 273 mumol/l), who had received vitamin D over 19 +/- 9 months, and to a control group of 27 patients (serum creatinine 928 +/- mumol/l) without an adequate conservative therapy. While the control group showed the typical constellation in advanced renal insufficiency with hypocalcaemia, hyperphosphataemia, clearly increased PTH levels, clearly increased CT values and normal 25-OH-D concentrations, during the diettherapy and the vitamin D substitution a significant increase of the serum levels of calcium, 25-OH-D and CT as well as a significant decrease of the PTH and the anorganic phosphate in the serum developed. Under the combination therapy with KA and vitamin D despite the reduction of the phosphate binders another significant decrease of the PTH and the anorganic phosphate was observed. The mineral content of the bones was within the normal in the two therapy groups. The percentage of the normal histological findings of the bones was with 40.7% highest despite the advanced renal insufficiency in the simultaneous substitution with KA. While in the vitamin D group during the control biopsy after 12 months in 20.5% of the cases an improvement of the histological findings developed, this effect occurred under additional KA-therapy in 51.9% of the cases. The results allow the conclusion that by means of the long-term treatment with KA a favourable influence on the renal osteopathy develops.

Topics: Adult; Aged; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Combined Modality Therapy; Ergocalciferols; Humans; Keto Acids; Kidney Failure, Chronic; Middle Aged; Tablets

Topics: Bone and Bones; Calcifediol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Keto Acids; Kidney Failure, Chronic; Minerals; Parathyroid Hormone; Phosphates

Topics: Bone and Bones; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Kidney Failure, Chronic; Minerals; Phosphates

In 25 (33.8%) of 74 chronically haemodialysed patients a distinct osteopathy with bone pain, spontaneous fractures, arthralgias and weakness of the muscles due to dialysis was present. In comparison to a group without complaints the duration of the dialysis was longer by 6 months, the mineral contents of the bones was decreased in 38%, in the comparative group in 22%. A progressive demineralisation was found in 46%, in the comparative group in 20%. Hypercalcaemias under vitamin D2 caused a therapy resistance. In 1 exemplary case (type IIc, PTH 0.3 micrograms/l) in the 3rd year of dialysis a fracture of the neck of the femur took place and an endoprosthesis was implanted. There was a progressive demineralisation of about 16%. The suspicion of a typical combination with an encephalopathy due to dialysis did not confirm itself. A pseudocyst in the brain was found. The differential diagnosis to the hypercalcaemia-induced psychosis in the osteopathy due to dialysis is discussed. In a prophylactic application dihydrotachysterine proved favourable for avoidance of an osteopathy due to dialysis. Parallel to the clinical progressing of the osteopathy due to dialysis a progressive demineralisation could be demonstrated at the peripheral mineral contents of the bones. Extreme losses of minerals appeared from the 4th to the 59th month of dialysis from - 16% to - 37% and from the 22nd to the 87th month from plus 11% to minus 14% of the age-and-sex-specific normal values. Successful transplantations led to the stagnation of the progressive demineralisation, unsucessful transplantations increase them. The influence of the non-refined water for the production of dialysate by possible aluminium intoxications on the development of the osteopathy due to dialysis is discussed.

Topics: Aluminum Hydroxide; Bone and Bones; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Ergocalciferols; Fractures, Spontaneous; Humans; Kidney Transplantation; Minerals; Prognosis; Renal Dialysis; Ultraviolet Therapy

Topics: 24,25-Dihydroxyvitamin D 3; Calcifediol; Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Intestinal Absorption; Osteomalacia; Osteoporosis; Rickets; Tetany; Vitamin D

The incidence, age at onset, and progression of the biochemical, radiographic, and histologic characteristics of renal osteodystrophy were studied in 50 children in whom chronic renal failure had been recently diagnosed. During a ten-year observation period, 19 patients progressed to end-stage renal failure and radiographic signs of renal osteodystrophy developed in 15 of these (79%). Renal osteodystrophy developed in all nine patients whose chronic renal failure was diagnosed before 3 years of age and in six of the ten children with later onset of failure. The mean interval from diagnosis of renal failure to development of osteodystrophy was 1.4 years. Radiographically, growth zone lesions predominated in the younger children, whereas cortical erosions were more prevalent in the older children. Histologic examination, performed in 38 patients, showed both defective mineralization and excessive resorption and was a more sensitive diagnostic index than radiography. Noticeable deformities developed in one third of the patients with osteodystrophy, despite medical treatment including vitamin D2 therapy. Deformities were particularly frequent and severe in patients whose renal failure developed in infancy. In all 13 patients whose growth patterns were studied before and after osteodystrophy developed, the onset of bone lesions was associated with a deterioration of growth, indicating that osteodystrophy plays a major role in causing the growth retardation commonly observed in children with chronic renal failure.

Topics: Adolescent; Aluminum Hydroxide; Bone and Bones; Bone Resorption; Calcium; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Growth Disorders; Humans; Infant; Infant, Newborn; Kidney Failure, Chronic; Male; Minerals; Radiography

Topics: Calcium Metabolism Disorders; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hypoparathyroidism; Osteomalacia; Osteoporosis; Phosphorus Metabolism Disorders; Renal Dialysis; Vitamin D

Hypercalcaemia developed in 21 patients due to vitamin-D poisoning; 2 were poisoned twice and 2 were poisoned three times. All patients had taken milligram doses of vitamin D, which for 5 patients was inappropriate. For the other 16 patients (mainly with hypoparathyroidism) milligram doses of vitamin D were appropriate; the patients were poisoned either early in therapy, trying to correct the plasma-calcium too quickly, or, later, because of failure to follow up patients properly. 2 patients died as a result of their intoxication. Constant vigilance is essential when patients are taking large doses of vitamin D.

Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Follow-Up Studies; Humans; Hypercalcemia; Hyperparathyroidism; Iatrogenic Disease; Osteomalacia; Osteoporosis; Patient Dropouts; Self Administration; Self Medication

Topics: Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hypercalcemia; Male

Topics: Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hydroxycholecalciferols; Kidney Failure, Chronic; Liver; Vitamin D

Results of 1alpha-hydroxyvitamin D3 therapy in twelve children with renal bone disease are described. Nine of the twelve children showed a good response to 0.05--0.08 microgram/kg/day. Hypercalcaemia was the only side effect and proved easy to manage because of the short half-life of 1alpha-OHD3.

Topics: Adolescent; Alkaline Phosphatase; Calcium; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Hand; Humans; Hydroxycholecalciferols; Ilium; Phosphorus; Radiography; Renal Dialysis

Topics: Adult; Aged; Alkaline Phosphatase; Analgesics; Bicarbonates; Bone Diseases; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Hormone; Substance-Related Disorders

Topics: Adult; Alkaline Phosphatase; Calcium; Chemical Phenomena; Chemistry; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxylation; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Phosphorus

Topics: Adult; Alkaline Phosphatase; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Humans; Kidney Failure, Chronic; Male; Parathyroid Glands; Parathyroid Hormone; Phosphorus; Radiography; Renal Dialysis; Vitamin D

Topics: Calcium; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Intestinal Absorption; Male; Radiography; Tuberculosis, Renal

Topics: Adolescent; Calcium; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Congenital Abnormalities; Drug Therapy; Dwarfism; Ear Deformities, Acquired; Ear, External; Ergocalciferols; Fractures, Bone; Humans; Kidney Diseases; Metabolism; Radiography

Topics: Acidosis; Acidosis, Renal Tubular; Adolescent; Age Determination by Skeleton; Alkaline Phosphatase; Blood; Bone Resorption; Calcium; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Cystoscopy; Dwarfism; Ergocalciferols; Humans; Hydronephrosis; Kidney Papillary Necrosis; Kidney Tubules; Pathology; Phosphates; Rickets; Schistosomiasis; Tuberculosis; Tuberculosis, Miliary

Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Chronic Kidney Disease-Mineral and Bone Disorder; Dipeptides; Ergocalciferols; Glycine; Glycosuria; Glycosuria, Renal; Humans; Hydroxyproline; Kidney Function Tests; Osteomalacia; Osteoporosis; Phosphates; Phosphorus; Phosphorus Metabolism Disorders; Radiography; Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Rickets; Rickets, Hypophosphatemic; Urine