vitamin-k-semiquinone-radical and Hyperparathyroidism--Secondary

This review presents a closer look at four diseases which are probably closely related to one another pathophysiologically: (a) calciphylaxis (distal pattern); (b) calciphylaxis (proximal pattern); (c) Martorell hypertensive ischemic leg ulcer; (d) calciphylaxis with normal renal and parathyroid function (synonym: eutrophication). The four diseases have largely the same risk factors: (1) arterial hypertension, (2) diabetes mellitus (types 1 and 2), (3) secondary or tertiary hyperparathyroidism (in end-stage kidney disease) and (4) oral anticoagulation with vitamin K antagonists. They share the same clinical patterns: necrotizing livedo, skin infarctions at typical locations and acral gangrene in calciphylaxis. They also share the same histopathology: ischemic subcutaneous arteriolosclerosis and small-artery disease and 'miniaturizing' Mönckeberg medial calcinosis. The treatment concept for the acute phase of the diseases is also broadly similar. In addition to an optimized control of the cardiovascular risk factors, a proactive wound approach (necrosectomy, negative pressure wound treatment with vacuum dressings, and early skin grafts supported by systemic antibiotic therapy) leads most rapidly and effectively to a reduction of the initially severe wound pain, and finally to complete healing of the wound. Oral anticoagulation with vitamin K antagonists should be stopped. In extensive cases, the use of intravenous sodium thiosulfate is recommended. All four diagnoses are little known in the medical schools of most countries. The need to improve familiarity with these four closely related disorders is therefore great. In particular, the risk of confusion with pyoderma gangrenosum is a major diagnostic problem which can lead to false and even damaging treatment.

Topics: Anticoagulants; Calciphylaxis; Diabetes Complications; Humans; Hyperparathyroidism, Secondary; Hypertension; Infarction; Leg Ulcer; Skin; Vitamin K

Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis).. Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug.. Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%-7% at any one time point in patients in whom CUA was not reported.. Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Calcimimetic Agents; Calciphylaxis; Cinacalcet; Dyslipidemias; Female; Humans; Hyperparathyroidism, Secondary; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Renal Dialysis; Risk Factors; Sex Factors; Vitamin K

This investigation of 68 hemodialysis patients (ages 33 to 91) analyzed the association of biochemical indicators of vitamin K nutriture and bone metabolism, and related both to past bone fracture history and prospective bone fracture risk. Phylloquinone concentrations were significantly lower in the 23 patients with previous fractures compared to those without (0.93 vs. 1.50 nmol/liter, P < 0.003) and a smaller percentage of their serum osteocalcin was carboxylated (48.8 vs. 53.6%, P < 0.03). The 41 patients who never had fractures had nearly three times higher phylloquinone concentrations than the nine patients with fractures during a four-year follow-up period (1.59 vs. 0.55 nmol/liter, P < 0.002) and more carboxylated serum osteocalcin (55.2 vs. 42.0%, P < 0.01). None of the patients with phylloquinone concentrations over 2.2 nmol/liter had elevated intact parathyroid hormone (iPTH) concentrations, and only patients with less than 1 nmol/liter phylloquinone had severe hyperparathyroidism (iPTH > 300 ng/liter). Our data thus indicate that suboptimal vitamin K nutriture in hemodialysis patients is associated both with increased bone fracture risk and with a high prevalence of hyperparathyroidism.

Topics: Adult; Aged; Aged, 80 and over; Bone and Bones; Fractures, Bone; Humans; Hyperparathyroidism, Secondary; Middle Aged; Nutritional Status; Osteocalcin; Parathyroid Hormone; Prospective Studies; Renal Dialysis; Risk Factors; Vitamin K; Vitamin K 1

Topics: Calcium; Calcium, Dietary; Celiac Disease; Diet; Diet Therapy; Drug Therapy; Glutens; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Osteitis Fibrosa Cystica; Potassium; Sprue, Tropical; Vitamin D; Vitamin K; Vitamins