Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kidney plays an important role in calcium homeostasis. In this review we discuss new concepts in tubular calcium transport, related proteins and the clinical implications of these new findings. Most calcium reabsorption occurs in the proximal tubules via the passive paracellular pathway, but calcium reabsorption also occurs in the thick ascending limb of Henle's loop (50% via the transcellular pathway). Finally, at the level of the distal convoluted tubule and connecting tubule calcium is reabsorbed via the active transcellular route. The Calcium-sensing receptor, localised along the thick ascending limb of Henle's loop, regulates the urinary calcium excretion in response to changes in extracellular calcium concentration. The Epithelial Calcium Channel 1 is a highly Ca2+-sensitive channel that is predominantly present in the connecting tubule. The Calbindin D(28k) is a cytoplasmatic protein expressed in the distal tubule, it is involved both in transcellular calcium diffusion and in the control of intracellular calcium concentration. Heterozygous mutations in the gene for the calcium sensing receptor, which result in a loss of function by the receptor, are associated with familial hypocalciuric hypercalcaemia. Mutations involving a gain of function have been associated with hypocalcaemia with normal serum parathyroid hormone concentration. Bartter's syndrome, caused by a dysfunction of thick ascending limb cells, is associated with calcium wasting. On the contrary, Gitelman's syndrome, caused by a dysfunction of the distal tubule, is characterised by hypocalciuria and hypomagnesemia.
 ...
PMID:[New concepts of tubular calcium transport in the kidney: clinical implications]. 1535 41

Although acute nonoliguric renal failure is a well-known nephrotoxic effect of aminoglycoside antibiotics, less recognized is acquired Bartter-like syndrome. Herein, we describe four female patients who presented with marked paresthesia, muscle weakness, and tetany following gentamicin therapy with total dose ranging from 1.2 g to 2.6 g. All were normotensive. Biochemical abnormalities included hypokalemia (K+ 1.8-2.3 mmol/L), metabolic alkalosis (HCO(3-) 31.9-34.2 mmol/L), hypomagnesemia (Mg2+ 0.9-1.2 mg/dL), hypermagnesiuria (fractional excretion of Mg 3-6%), hypocalcemia (free Ca2+ 2.0-4.1 mg/dL), and hypercalciuria (molar ratio of Ca2+/creatinine 0.23-0.53), all consistent with Bartter-like syndrome. Serum immunoreactive parathyroid hormone concentration was low despite the hypocalcemia. The Bartter-like syndrome lasted for 2 to 6 weeks after cessation of gentamicin, coupled with supplementation of K+, Ca2+, and Mg2+. These biochemical abnormalities resembled those seen in patients with gain-of-function mutations in the calcium-sensing receptor. We hypothesize that gentamicin, a polyvalent cationic molecule, induces the action of calcium-sensing receptor on the thick ascending loop of Henle and distal convoluted tubule to cause renal wasting of Na+, K+, Cl-, Ca2+, and Mg2+.
 ...
PMID:Acquired bartter-like syndrome associated with gentamicin administration. 1576 21

The hormones currently believe to influence inorganic phosphate (Pi) metabolism are parathyroid hormone (PTH) and the active metabolite to vitamin D. A new class of phosphate-regulating factors, collectively known as the phosphatonins have been shown to be associated with the hypophosphatemic diseases. The reabsorption of Pi in the kidney is a major determinant of the plasma Pi level. Reabsorption is largely regulated by the type II a sodium-dependent Pi cotransporter (NPT2a) that is expressed in renal proximal tubular cells. Phosphatonins cause Pi wasting by controlling the amount of NPT2a on the apical surface of the proximal tubular cell. A recent finding indicates that mutations in NPT2a can contribute to nephrolithiasis and osteoporosis in humans and suggests that changes in NPT2a levels may also cause other human disease. We discuss the roles of phosphatonins and NPT2a in bone formation.
 ...
PMID:[Novel phosphate regulating genes and osteoporosis]. 1587 40

Primary hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder characterized by profound hypomagnesemia associated with hypocalcemia. Pathophysiology is related to impaired intestinal absorption of magnesium accompanied by renal magnesium wasting as a result of a reabsorption defect in the distal convoluted tubule. Recently, mutations in the TRPM6 gene coding for TRPM6, a member of the transient receptor potential (TRP) family of cation channels, were identified as the underlying genetic defect. Here, the results of a TRPM6 mutational analysis of 21 families with 28 affected individuals are presented. In this large patient cohort, a retrospective clinical evaluation based on a standardized questionnaire was also performed. Genotype analysis revealed TRPM6 mutations in 37 of 42 expected mutant alleles. Sixteen new TRPM6 mutations were identified, including stop mutations, frame-shift mutations, splice-site mutations, and deletions of exons. Electrophysiologic analysis of mutated ion channels after heterologous expression in Xenopus oocytes proved complete loss of function of TRPM6. Clinical evaluation revealed a homogeneous clinical picture at manifestation with onset in early infancy with generalized cerebral convulsions. Initial laboratory evaluation yielded extremely low serum magnesium levels, low serum calcium levels, and inadequately low parathyroid hormone levels. Treatment usually consisted of acute intravenous magnesium supplementation leading to relief of clinical symptoms and normocalcemia, followed by lifelong oral magnesium supplementation. Serum magnesium levels remained in the subnormal range despite adequate therapy. This is best explained by a disturbed magnesium conservation in the distal convoluted tubule, which emerged in all patients upon magnesium supplementation. Delay of diagnosis resulted in permanent neurologic damage in three patients.
 ...
PMID:Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia. 1610 78

Phosphate plays a key role in several biological processes. In recent years, new insights have been obtained into the regulation of the phosphate metabolism, including a growing amount of evidence suggesting that factors other than parathyroid hormone (PTH) and vitamin D are involved in maintaining the phosphate balance. A new class of phosphate-regulating factors, the so-called "phosphatonins," have been shown to be important in phosphate-wasting diseases. However, the role of the phosphatonins in the normal human homeostasis remains to be established. The incidence of hypophosphatemia in selected patient series can be more than 20%, with clinical sequelae ranging from mild to life threatening. Only when combined with phosphate depletion does hypophosphatemia become clinically significant. The factors that are involved in the phosphate homeostasis, the pathophysiology, the relevance in patient care, the clinical manifestations, and an appropriate management of phosphate depletion are discussed in this review.
 ...
PMID:Hypophosphatemia: an update on its etiology and treatment. 1682 19

Phosphate diabetes is defined as inadequate tubular reabsorption. Hypophosphatemia is responsible for most of the clinical manifestations, which vary with the age of the patient and the severity of the phosphate wasting. Vitamin D-resistant rickets in children or osteomalacia in adults, osteoporosis, bone pain including spinal pain, and pain in the joints and periarticular areas are the main manifestations. Several factors are known to affect tubular phosphate reabsorption via the sodium/phosphate cotransporters located on the tubular cell membranes. Factors that decrease phosphate reabsorption include a high intake of dietary phosphate, acidosis, parathyroid hormone (PTH), PTH-related peptide (PTHrp), glucocorticoid therapy, calcitonin, and vitamin D. On the other hand, a low-phosphate diet, alkalosis, growth hormone, insulin, IGF-1, and thyroid hormones increase tubular phosphate reabsorption. Physiological concepts about tubular phosphate reabsorption have been radically changed by the recent identification of phosphaturic factors called phosphatonins. The most extensively studied phosphatonin to date is fibroblast growth factor 23 (FGF23), which was first identified in patients with tumor-induced osteomalacia and shown to be secreted by the neoplastic cells. The FGF23 has also been implicated in autosomal dominant hypophosphatemic rickets, in which a gene mutation results in production of abnormal FGF23 that resists hydrolysis. In healthy individuals, FGF23 contributes to regulate phosphate reabsorption via Na/Pi cotransporters. Other phosphatonins may exist, such as matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein 4 (SFRP4), whose role remains to be defined. The part played by these proteins in idiopathic renal phosphate wasting in adults needs to be investigated.
 ...
PMID:Phosphate diabetes, tubular phosphate reabsorption and phosphatonins. 1621 71

Secondary hyperparathyroidism is sometimes seen in patients with hypophosphatemic osteomalacia after long-term oral phosphate therapy. Parathyroidectomy is sometimes needed for the correction of hypercalcemia in these patients, and is rarely performed in patients without hypercalcemia. A 46-year-old female patient had hypophosphatemic osteomalacia with unknown cause and secondary hyperparathyroidism. A palpable neck mass developed after long-term oral phosphate therapy. An intrathyroid parathyroid gland was confirmed through partial thyroidectomy and parathyroidectomy. Renal phosphate wasting decreased strongly, and serum parathyroid hormone was in the normal range after the operation. A correction of secondary hyperparathyroidism may partially overcome hyperphosphaturia in some patients with hypophosphatemic rickets.
 ...
PMID:Secondary hyperparathyroidism as a palpable intrathyroid parathyroid gland in a patient with hypophosphatemic osteomalacia. 1650 17

Congestive heart failure (CHF) is more than a failing heart and salt-avid state. Also present is a systemic illness which features oxidative stress in diverse tissues, a proinflammatory phenotype, and a wasting of soft tissue and bone. Reactive oxygen and nitrogen species contribute to this illness and the progressive nature of CHF. Aldosteronism, an integral component of the neurohormonal profile found in CHF, plays a permissive role in leading to an altered redox state. Because of augmented urinary and fecal excretion of Ca(2+) and Mg(2+) and consequent decline in plasma-ionized [Ca(2+)](o) and [Mg(2+)](o) that accompanies aldosteronism, parathyroid glands release parathyroid hormone (PTH) in an attempt to restore Ca(2+) and Mg(2+) homeostasis; this includes bone resorption. However, PTH-mediated intracellular Ca(2+) overloading, considered a Ca(2+) paradox, leads to oxidative stress. This can be prevented by: spironolactone, an aldosterone receptor antagonist that rescues urinary and fecal cation losses; parathyroidectomy; amlodipine, a Ca(2+) channel blocker; N-acetylcysteine, an antioxidant. In addition to the role played by aldosteronism in the appearance of secondary hyperparathyroidism is the chronic use of a loop diuretic, which further enhances urinary Ca(2+) and Mg(2+) excretion, and reduced Ca(2+) stores associated with hypovitaminosis D. This broader perspective of CHF and the ever increasing clinical relevance of divalent cations and oxidative stress raise the question of their potential management with macro- and micronutrients. An emerging body of evidence suggests the nutritional management of CHF offers an approach that will be complementary to today's pharmaceutical-based strategies.
 ...
PMID:Oxidative stress in aldosteronism. 1663 Nov 48

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.
 ...
PMID:Impact of kidney bone disease and its management on survival of patients on dialysis. 1719 30

Secondary hyperparathyroidism is highly prevalent in patients with end-stage renal disease. After successful kidney transplantation, however, parathyroid glands gradually involute to normal size with subsequent normalization of intact parathyroid hormone (PTH), serum calcium, and phosphorous concentrations. This report describes a 48-year-old diabetic end-stage renal disease patient who underwent a successful cadaveric kidney transplant. Serum calcium and phosphorous concentrations normalized within 6 months. Three years later, he presented with complaints of proximal muscle weakness that was progressively worsening. Physical examination revealed temporal wasting and proximal muscle weakness. Detailed neurologic examination was unremarkable except for decreased vibratory sensation in both feet. Laboratory data showed stable allograft function (serum creatinine, 1.3 mg/dL), hypocalcemia, and hypophosphatemia with markedly elevated alkaline phosphatase level (726 IU/L) and intact PTH level (947 pg/mL). Further laboratory evaluation revealed poor nutritional status and severe deficiency of 25(OH)D (4.0 ng/mL). Past medical history included remote episodes of acute pancreatitis due to prior alcohol abuse. Computed tomography of the abdomen showed calcific atrophic pancreas, and steatorrhea was confirmed on stool studies. Decreased bone mineral density was noted by computed tomography bone density scan. Secondary hyperparathyroidism and osteomalacia had developed due to severe vitamin D deficiency, occurring as a result of previously unrecognized, minimally symptomatic pancreatic exocrine insufficiency. Treatment with vitamin D, calcium, and pancreatic enzyme replacement led to remarkable resolution of clinical symptoms and secondary hyperparathyroidism (intact PTH, 65 pg/mL after therapy) and resulted in significant improvement in bone mineralization. Factors associated with vitamin D deficiency in the chronic kidney disease and post-transplant patient population are reviewed.
 ...
PMID:Osteomalacia and secondary hyperparathyroidism after kidney transplantation: Relationship to vitamin D deficiency. 1722 Jun 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>