Gene/Protein Disease Symptom Drug Enzyme Compound
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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25-dihydroxyvitamin D) by the 25-hydroxy vitamin D 1-hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin-angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD-MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD-MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients.
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PMID:The vitamin D system: a crosstalk between the heart and kidney. 2060 45

Chronic kidney disease (CKD) is one of the major health care burdens worldwide, with a significant increase in the number of patients and a huge increase in the financial demands in recent years. Patients with CKD usually progress through different stages before they reach end-stage renal disease. The rate and speed of renal function deterioration are variable, but uncontrolled hypertension and diabetes mellitus are major risk factors. Pre-dialysis care, with change of life style, blood pressure and glycemic control, the use of angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, lipid-lowering agents and management of anemia and mineral bone disorder can improve quality of life, preserve functioning nephrons and reduce cardiovascular morbidity and mortality with significant reduction in management costs. Early referral of patients with CKD to the nephrologist allows for adequate exposure to educational programs, psychosocial preparation, participation in the decision of type of renal replacement therapy (RRT), pre-emptive kidney transplantation, early creation of dialysis access and adequate training in selected modality of RRT. The degree of involvement and interaction must be individualized according to the needs of the patient and the type of RRT planned. A multi-disciplinary team is crucial for the implementation of a variety of strategies and to intervene more effectively in meeting the health care needs of CKD patients.
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PMID:The value of pre-dialysis care. 2156 94

Nephrolithiasis research and care have been focused on biochemical changes in urinary solute excretion leading to stone formation, but abnormalities in urine chemistry alone do not explain many aspects of the condition of patients with kidney stone disease. Evidence exists of an association with metabolic syndrome, obesity, diabetes and hypertension, and of enhanced risk of chronic kidney disease and metabolic bone disease. Very recently also a higher risk of cardiovascular events and damage has been reported in kidney stone formers when compared with non-stone formers. It is time to view nephrolithiasis as a condition predictive of chronic kidney disease and cardiovascular damage, which deserves full metabolic evaluation together with an early prevention care strategy, mainly consisting of dietary and lifestyle changes, in a multidisciplinary approach. Kidney stone disease should be considered as a systemic disorder with clinical relevance beyond symptomatic urinary tract obstruction.
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PMID:Update on nephrolithiasis: beyond symptomatic urinary tract obstruction. 2162 79

Craniometaphyseal dysplasia (CMD) is a very rare bone disorder characterized by abnormally developed metaphyses in long bones and sclerosis of the craniofacial bones. In this paper, the authors report 2 cases of children diagnosed with CMD and chronic intracranial hypertension with deletion in exon 9 of the human ANK gene (ANKH). After intracranial monitoring, a different treatment was chosen for each patient. One of the patients was treated using CSF shunting because ventriculomegaly in the absence of a Chiari malformation was also observed on cerebral MR imaging. The other patient underwent cranial expansion and decompressive craniotomy of the posterior fossa, because ventriculomegaly was excluded after cerebral MR imaging and cervical MR imaging showed a Chiari malformation Type I. The origin of intracranial hypertension in CMD is multifactorial. Previous intracranial pressure monitoring and a thorough understanding of neuroimaging studies are essential to achieve an accurate diagnosis and effective treatment.
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PMID:Intracranial hypertension in two cases of craniometaphyseal dysplasia: differing surgical options. 2180 45

The observation that renal failure leads to 'uraemia' through retention of solutes that would otherwise be excreted by healthy kidneys, has been formulated as early as the first half of 19th century. The discovery of osmosis and a colloid membrane facilitated the first testing ofdialysis, originally in animals and in the first quarter of 20th century also in humans. In the mid 1940s, dialysis became the method of choice for the treatment of acute renal failure. At the beginning of 1960s, the development of long-term venous access made programmes of chronic haemodialysis possible in many countries. These achievements, together with kidney transplantation, saved or significantly extended life of millions of patients with chronic renal failure. The last 50 years saw a dramatic increase in the number of chronically dialyzed patients; the safety and efficacy of haemodialysis methods improved and effective treatments have been introduced of a number of complications associated with chronic renal failure (e.g. hypertension, anaemia or bone disease). Despite this, mortality of, particularly older chronically dialyzed patients, is very high and their quality of life sometimes low. High cardiovascular mortality, frequently due to chronic heart failure and sudden death (unlike ischemic heart disease in healthy population), is a dominating problem. However, it is difficult to reduce the high cardiovascular morbidity and mortality of haemodialyzed patients. Patient prognosis might probably be improved by more frequent use of convective methods of blood purification and frequent haemodialysis as well as effective management ofdyslipidemia. Nevertheless, early diagnosis of patients with chronic renal insufficiency and early management of all general as well as renal failure-specific risk factors in patients with mild to moderate chronic renal insufficiency is essential if the prognosis ofhaemodialyzed patients is to be improved. Future developments of renal replacement therapies are difficult to predict. The treatment should be individualized; early transplantation, peritoneal or home (frequent) haemodialysis should be performed in younger patients and conservative treatment, in addition to chronic haemodialysis, should be used in older patients. Miniaturization as one of the potential future trends could facilitate the use of portable artificial kidney. Artificial membranes coated with proximal tubule cells and ex vivo kidney cultivation represent another interesting perspective.
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PMID:[The past, the present and the future of renal replacement therapy]. 2187 92

In the last 5 years, there has been a remarkable change in our understanding of the health benefits of vitamin D. The classical actions of vitamin D as a determinant of mineral metabolism and rachitic bone disease have been expanded to include a broader role in skeletal homoeostasis and prevalent bone disorders such as osteoporosis. However, it is the nonskeletal function of vitamin D that has attracted most attention. Although pluripotent responses to vitamin D have been recognized for many years, our new perspective on nonclassical vitamin D function stems from two more recent concepts. The first is that impaired, vitamin D status is common to many populations across the globe. This has prompted studies to explore the health impact of suboptimal circulating levels of vitamin D, with association studies linking vitamin D 'insufficiency' to several chronic health problems including autoimmune and cardiovascular disease, hypertension and common cancers. In support of a broader role for vitamin D in human health, studies in vitro and using animal models have highlighted immunomodulatory and anticancer effects of vitamin D that appear to depend on localized activation of vitamin D. The conclusion from these reports is that many nonclassical actions of vitamin D are independent of conventional vitamin D endocrinology and are therefore more sensitive to variations in vitamin D status. The current review summarizes these developments, with specific reference to the newly identified effects of vitamin D on the immune system, but also highlights the challenges in translating these observations to clinical practice.
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PMID:An update on vitamin D and human immunity. 2199 74

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.
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PMID:Vitamin D receptor activation and prevention of arterial ageing. 2319 45

We evaluated an African American woman referred in 1986 at age 33 years because of renal potassium and calcium wasting and chronic hip pain. She presented normotensive, hypokalemic, hypocalcemic, normophosphatemic, and hypercalciuric. Marked hyperparathyroidism was evident. Urinary cyclic adenosine monophosphate (cAMP) excretion did not increase in response to parathyroid hormone (PTH) infusion, indicating renal resistance to PTH. X-rays and bone biopsy revealed severe osteitis fibrosa cystica, confirming skeletal responsiveness to PTH. Renal potassium wasting, suppressed plasma renin activity, and elevated plasma and urinary aldosterone levels accompanied her hypokalemia, suggesting primary hyperaldosteronism. Hypokalemia resolved with spironolactone and, when combined with dietary sodium restriction, urinary calcium excretion fell and hypocalcemia improved, in accord with the known positive association between sodium intake and calcium excretion. Calcitriol and oral calcium supplements did not suppress the chronic hyperparathyroidism nor did they reduce aldosterone levels. Over time, hyperparathyroid bone disease progressed with pathologic fractures and persistent pain. In 2004, PTH levels increased further in association with worsening chronic kidney disease. Eventually hypercalcemia and hypertension developed. Localizing studies in 2005 suggested a left inferior parathyroid tumor. After having consistently declined, the patient finally agreed to neck exploration in January 2009. Four hyperplastic parathyroid glands were removed, followed immediately by severe hypocalcemia, attributed to "hungry bone syndrome" and hypoparathyroidism, which required prolonged hospitalization, calcium infusions, and oral calcitriol. Although her bone pain resolved, hyperaldosteronism persisted.
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PMID:Severe hypercalcemic hyperparathyroidism developing in a patient with hyperaldosteronism and renal resistance to parathyroid hormone. 2307 96

The complex relationships between cardiovascular, renal, and bone disease are increasingly recognized but not yet clearly understood. Vascular calcification (VC) represents a common end point between these interlinked systems. It is highly prevalent in chronic kidney disease (CKD) and may be responsible for some of the excess cardiovascular events seen in this condition. There is much interest in developing therapeutic agents to stop its development or reverse its progression. Traditionally considered to be due to abnormalities in calcium and phosphate metabolism alone, VC is now known to be the product of active, dynamic processes within the vessel wall. Primary prevention of VC is possible through successful prevention or reversal of progressive renal dysfunction, hypertension and hyperlipidaemia, but is challenging given the increasing global prevalence of these risk factors. Secondary prevention of VC through tight control of calcium and phosphate, can be achieved by dietary or pharmacological means. Both the modification of haemodialysis duration or methods and the use of renal transplantation have an effect. Novel drugs such as cinacalcet were hoped to halt calcification but results have been mixed, and no intervention has yet been shown to reverse calcification reliably. A new range of experimental targets involved in the putative mediatory pathways between bone and vascular disease has emerged. Aiming to manipulate the active mechanisms involved in calcium deposition, these hold hope for reversal of calcification, but are still theoretical or in early animal or human experimentation.
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PMID:Regression of vascular calcification in chronic kidney disease - feasible or fantasy? a review of the clinical evidence. 2311 May 27

Vitamin D plays several roles in the body, influencing bone health as well as serum calcium and phosphate levels. Further, vitamin D may modify immune function, cell proliferation, differentiation, and apoptosis. Vitamin D deficiency has been associated with numerous health outcomes, including bone disease, cancer, autoimmune disease, infectious disease, type 1 and type 2 diabetes, hypertension, and heart disease, although it is unclear whether or not these associations are causal. Various twin and family studies have demonstrated moderate to high heritability for circulating vitamin D levels. Accordingly, many studies have investigated the genetic determinants of this hormone. Recent advances in the methodology of large-scale genetic association studies, including coordinated international collaboration, have identified associations of CG, DHCR1, CYP2R1, VDR, and CYP24A1 with serum levels of vitamin D. Here, we review the genetic determinants of vitamin D levels by focusing on new findings arising from candidate gene and genomewide association studies.
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PMID:Genetic regulation of vitamin D levels. 2311 82


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