calcitriol and Communicable-Diseases

There is evidence from both observational studies and clinical trials that calcium malnutrition and hypovitaminosis D are predisposing conditions for various common chronic diseases. In addition to skeletal disorders, calcium and vitamin D deficits increase the risk of malignancies, particularly of colon, breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g. insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension). The aim of the present review was to provide improved understanding of the molecular and cellular processes by which deficits in calcium and vitamin D cause specific changes in cell and organ functions and thereby increase the risk for chronic diseases of different aetiology. 1,25-Dihydroxyvitamin D(3) and extracellular Ca(++) are both key regulators of proliferation, differentiation and function at the cellular level. However, the efficiency of vitamin D receptor-mediated intracellular signalling is limited by the negative effects of hypovitaminosis D on extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase activity and thus on the production of 1,25-dihydroxyvitamin D(3). Calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific modulation of calcium-sensing receptor activity. Hence, attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism by which calcium and vitamin D insufficiencies cause perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system. The wide range of diseases associated with deficits in calcium and vitamin D in combination with the high prevalence of these conditions represents a special challenge for preventive medicine.

Topics: Autoimmune Diseases; Calcium; Calcium, Dietary; Chronic Disease; Communicable Diseases; Humans; Hypertension; Musculoskeletal Diseases; Neoplasms; Osteoporosis; Prevalence; Vitamin D; Vitamin D Deficiency

Human cathelicidin antimicrobial protein (hCAP18) is an antimicrobial and immunomodulatory peptide that has pleiotropic effects and is transcriptionally regulated by vitamin D. Because the administration of vitamin D analogues has been linked to decreased mortality among patients with end-stage renal disease, we hypothesized that low hCAP18 levels would identify those who are at increased risk of death attributable to infection while undergoing hemodialysis.. We performed a case-control study nested in a prospective cohort of patients (n = 10,044) initiating incident hemodialysis. Case patients (n = 81) were those who died of an infectious disease within 1 year; control patients (n = 198) were those who survived at least 1 year while undergoing dialysis.. Mean (+/-SD) baseline levels of hCAP18 in case patients and control patients were 539 +/- 278 ng/mL and 650 +/- 343 ng/mL, respectively (P = .006). hCAP18 levels had a modest correlation with 1,25-dihydroxyvitamin D levels r = 0.23; P = .053) but not with 25-hydroxyvitamin D levels r = -0.06; P = .44). Patients with hCAP18 levels in the lowest tertile had a 2-fold increased risk (odds ratio, 2.1; 95% confidence interval, 1.2-3.5) of death attributable to infection; after multivariable adjustment, this relationship remained statistically significant (odds ratio, 3.7; 95% confidence interval, 1.2-11.2).. In individuals initiating chronic hemodialysis, low baseline levels of hCAP18, a vitamin D-regulated antimicrobial protein, are independently associated with an increased risk of death attributable to infection.

Topics: Aged; Antimicrobial Cationic Peptides; Case-Control Studies; Cathelicidins; Cohort Studies; Communicable Diseases; Female; Humans; Male; Renal Dialysis; Risk Factors; Vitamin D

It is known that vitamin D has many functions besides involvement in calcium metabolism. It has recently been recognized that vitamin D deficiency is associated with mortality, especially in cardiovascular disease (CVD). Vitamin D deficiency is common in end-stage renal disease, but develops from the early stage of chronic kidney disease (CKD). So we investigated whether the serum level of the activated form of vitamin D (1,25-dihydroxyvitamin D) affected mortality in patients with CKD stages 3 and 4.. Between January 1, 1995, and June 30, 2006 we measured serum 1,25-dihydroxyvitamin D In 226 patients with CKD stages 3 and 4 and classified the results into two groups depending on whether the level was below (group I) or above (group II) 20 pg/ml. We ended the follow-up period on December 31, 2006. We compared all-cause and cardiovascular mortality between the two groups. We also examined predictors of mortality by using Cox proportional regression analysis.. Two-hundred and twenty-six patients (67 men and 159 women, mean age 67.0) were registered in this study, and groups 1 and 2 comprised 84 and 142 patients, respectively. During the follow-up period 43 patients died. CVD was the major cause of death, followed by infectious disease. The Kaplan-Meier survival curve revealed that all-cause mortality was significantly higher in group I, but a significant difference between CVD mortality in the two groups was not demonstrated. By Cox proportional regression analysis, group I was related to all-cause mortality, but this was not proved to be an independent predictor.. The results suggested that serum level of 1,25-dihydroxyvitamin D was associated with all-cause mortality in patients with CKD stages 3 and 4.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Communicable Diseases; Disease Progression; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Assessment; Severity of Illness Index; Time Factors; Vitamin D; Vitamin D Deficiency