vitamin-k-semiquinone-radical and Nephrotic-Syndrome

Thromboembolism (TE) is a common and serious complication of nephrotic syndrome (NS). NS is associated with hypercoagulability, which may be induced by changes in coagulation, anticoagulant, and fibrinolytic factors. Moreover, accumulating evidence supports the hypothesis that the complex interactions between genetic and acquired risk factors in TE should be considered and that genetic susceptibility should not be ignored. Extracellular vesicles (EVs) also play unique roles. Further research on EVs may provide new insights into the discovery and treatment of TE associated with NS. The occurrence of NS accompanied by TE may be associated with various risk factors. Preventive anticoagulant therapy can not only reduce the risk of TE in patients but also aggravate the risk of bleeding. Heparin and vitamin K antagonists (VKAs), traditional anticoagulant drugs, have been extensively applied in the prevention and treatment of thromboembolic diseases, and emerging direct oral anticoagulants (DOACs) also provide an alternative choice. Owing to the particularity of NS, the safe application of DOACs still needs to be addressed. This review aimed to comprehensively describe the pathophysiology of TE in NS, as well as analyze the associated risk factors, the opportunity for preventive anticoagulation, and current anticoagulant information.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Heparin; Humans; Nephrotic Syndrome; Thromboembolism; Venous Thromboembolism; Vitamin K

Thromboembolic complications are among the most important extrarenal consequences of nephrotic syndrome (NS). In addition to deep vein thrombosis in the legs and pulmonary embolism, NS is very frequently accompanied by renal vein thrombosis. Due to enhanced procoagulatory and antifibrinolytic potential and reduced anticoagulatory potential, multifactor disruption of hemostatic equilibrium leads to hypercoagulability in NS patients, which is aggravated by an increase in blood viscosity and endothelial dysfunction. Circulating antibodies against α-enolase, a plasmin(ogen)-binding protein, and the possibility of certain molecules being renally eliminated in specific manner are discussed as reasons for the particular frequency of thromboembolic complications in patients with idiopathic membranous nephropathy. Serum albumin concentration is an indicator for the risk of thrombosis in NS patients. When applying the current KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for glomerulonephritis to NS patients with a serum albumin concentration of less than 25 g/l and at least one additional thrombogenic risk factor, primary prophylactic anticoagulation ("conditioned prophylaxis") with an orally administered vitamin K antagonist (target INR 2-3) is recommended as long as the serum albumin concentration is less than 30 g/l.

Topics: Anticoagulants; Autoantibodies; Blood Viscosity; Endothelium, Vascular; Hemostasis; Humans; Nephrotic Syndrome; Pulmonary Embolism; Renal Veins; Risk Factors; Serum Albumin; Thromboembolism; Thrombosis; Venous Thrombosis; Vitamin K

Thromboses of abdominal veins outside the iliac-caval axis are rare but clinically relevant. Early deaths after splanchnic vein thrombosis occur in 5-30% of cases. Sequelae can be liver failure or bowel infarction after splanchnic vein thrombosis, renal insufficiency after renal vein thrombosis, ovarian infarction after ovarian vein thrombosis. Local cancer or infections are rare in Budd-Chiari syndrome, and common for other sites. Inherited thrombophilia is detected in 30-50% of patients. Myeloproliferative neoplasms are the main cause of splanchnic vein thrombosis: 20-50% of patients have an overt myeloproliferative neoplasm and/or carry the molecular marker JAK2 V617F. Renal vein thrombosis is closely related to nephrotic syndrome; finally, ovarian vein thrombosis can complicate puerperium. Heparin is used for acute treatment, sometimes in conjunction with systemic or local thrombolysis. Vitamin K-antagonists are recommended for 3-6 months, and long-term in patients with Budd-Chiari syndrome, unprovoked splanchnic vein thrombosis, or renal vein thrombosis with a permanent prothrombotic state such as nephrotic syndrome.

Topics: Anticoagulants; Biomarkers, Tumor; Budd-Chiari Syndrome; Female; Heparin; Humans; Janus Kinase 2; Leukemia; Nephrotic Syndrome; Ovary; Portal Vein; Splanchnic Circulation; Vena Cava, Inferior; Venous Thrombosis; Vitamin K

Disturbances in hemostasis are common complications of kidney diseases. Both bleeding diathesis and thromboembolism may complicate the course of chronic uremia. As far as we know, there is a limited data about protein Z in kidney disease.. The aim of our work was to examine plasma protein Z and vitamin K concentrations in nephrotic syndrome (n = 34), glomerulonephritis (n = 48), kidney transplant recipients (n = 80), peritoneally dialyzed patients (n = 42) and in the healthy volunteers (n = 27).. Vitamin K was significantly lower in nephrotic syndrome when compared to non-nephrotic patients, CAPD and healthy volunteers (p < 0.05). Protein Z was the highest in CAPD and kidney transplant recipients when compared to any other group. In nephrotic syndrome protein Z was significantly lower when compared to the healthy volunteers, but it did not differ significantly between two groups of patients with chronic renal failure (with and without nephrotic syndrome). Protein Z correlated only with fibrinogen in CAPD, glomerulonephritis and nephrotic patients. Vitamin K correlated with age and albumin in patients with glomerulonephritis, nephrotic syndrome as well as with albumin in CAPD.. Alterations in protein Z might contribute to the enhanced risk of thromboembolic complications in nephrotic syndrome, CAPD and Tx via different and unknown mechanisms. This phenomenon seems to be unrelated to vitamin K status in these patients.

Topics: Adult; Blood Proteins; Case-Control Studies; Female; Glomerulonephritis; Hemorrhagic Disorders; Humans; Kidney Transplantation; Male; Middle Aged; Nephrotic Syndrome; Peritoneal Dialysis; Risk Factors; Thromboembolism; Vitamin K

Topics: Amyloid; Amyloidosis; Antifibrinolytic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Blood Coagulation; Blood Coagulation Factors; Dexamethasone; Disseminated Intravascular Coagulation; Female; Humans; Immunoglobulin kappa-Chains; International Normalized Ratio; Melphalan; Middle Aged; Nephrotic Syndrome; Partial Thromboplastin Time; Vitamin K

Topics: Biomarkers; Blood Proteins; Glomerulonephritis; Humans; Nephrotic Syndrome; Peritoneal Dialysis; Vitamin K

The behavior of warfarin, a drug tightly bound to albumin, was studied in patients with nephrotic syndrome (NS) to assess the influence of hypoalbuminemia on its pharmacokinetics and its effect on vitamin K-dependent coagulation factors. A single dose of warfarin (8 mg) was given orally to 11 nephrotic patients with normal or nearly normal renal function and to 11 controls. In every subject the following measurements were performed: albuminemia before (t0) warfarin administration; plasma warfarin and vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) levels, before and at time intervals from 0 to 48 h after drug administration; warfarin urinary excretion from 0 to 24 h. Urinary warfarin excretion was null in 19 out of the 22 subjects and very low in two nephrotic patients and in one control. Low serum albumin in NS patients induced a twofold increase of unbound warfarin vs controls (3.5% vs 1.8%, p less than 0.001) which led to a threefold increase in plasma clearance of warfarin (9.70 vs 3.26 ml X min-1, p less than 0.001); as warfarin distribution volume showed only a slight (non significant) increase in NS patients, the elimination half-life was thus markedly shortened in NS patients vs controls (18 vs 36 h, p less than 0.01). Maximum warfarin effect on vitamin K-dependent factor levels occurred at 18 h in controls and 24 h in nephrotics, and these lowest values were similar, in spite of a higher level at 0 in NS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Blood Coagulation Factors; Factor IX; Factor VII; Factor X; Female; Humans; Kinetics; Male; Middle Aged; Nephrotic Syndrome; Prothrombin; Serum Albumin; Vitamin K; Warfarin

In a 7 year-old girl presenting with nephrotic syndrome and repeated episodes of thrombosis, a decrease in antithrombin III and in vitro inactivity of heparin were observed. Treatment by vitamin K antagonists prevented further thromboembolic episodes.

Topics: Antithrombin III Deficiency; Child; Female; Humans; Nephrotic Syndrome; Recurrence; Thrombosis; Vitamin K

A patient manifesting acquired factor IX deficiency in association with the nephrotic syndrome received prothrombin complex concentrate and demonstrated an accelerated plasma disappearance rate of factors II, IX and X. Amelioration of proteinuria and the plasma coagulation defect followed therapy with corticosteroids and azathioprine.

Topics: Azathioprine; Coagulants; Factor X; Female; Hemophilia B; Humans; Hypertension; Middle Aged; Nephrotic Syndrome; Prednisone; Proteinuria; Prothrombin; Vitamin K

Topics: Adult; Antibodies, Anti-Idiotypic; Anticoagulants; Antigen-Antibody Reactions; Biopsy; Female; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immune Sera; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Kidney; Kidney Diseases; Kidney Glomerulus; Male; Nephrotic Syndrome; Pregnancy; Vitamin K