fibrin and Renal-Insufficiency--Chronic

The outcome of surgical treatment of renal cancer depends not only on cancer-specific survival, but also on the degree of loss of renal function, which often develops after surgery, especially radical nephrectomy.. To study the features of functional changes in a solitary kidney as a compensation mechanism after radical nephrectomy for renal cancer.. The functional state of a solitary kidney in 36 patients with renal cancer who undergone to radical nephrectomy was evaluated. There were 20 and 16 women. The mean age was 59.0+/-10.8 years (from 39 to 76 years). The size of the tumor was in the range of 7.0-12.0 cm. All patients with a solitary kidney underwent a follow-up examination 3 months after surgery, including measurement of peripheral blood pressure with calculation of mean dynamic pressure, renal ultrasound, calculation of glomerular filtration rate (GFR), renal doppler ultrasound, determination of serum fibrinogen and fibrin monomers, and microscopy of the bulbar conjunctiva. Patients who had pathological abnormalities during the examination were prescribed reno-cardioprotective drugs, including perindopril in a titrated dose, apixaban 5 mg a day as thromboprophylaxis and for improvement of the flow properties of blood for a period of 3 months with re-evaluation of the above parameters.. In 61.1% of patients after radical nephrectomy, on 2-4 postoperative days, there was a tendency to increase blood pressure compared to baseline values (p<0.05). By the seventh day after the procedure, the volume of the contralateral kidney increased on average by 16% (from 110.4+/-11.2 cm3 to 132.4+/-4.8 cm3, p<0.05). After radical nephrectomy, a decrease in GFR was detected in 33 cases (91.7%; p<0.05). Renal doppler ultrasound showed a moderate increase in linear blood flow, the resistance index in the main renal artery, and a decrease in the pulse index in the segmental and arcuate arteries. The microscopy of the bulbar conjunctiva in 83.3% of patients revealed changes in the microcirculatory bed, including narrowing of arterioles, dilation of venules, a decrease in venular and capillary blood flow. After 3 months of reno-cardioprotective therapy, it was revealed that the target values of blood pressure (<130/85 mm Hg) were achieved with an average dynamic blood pressure of 93.4+/-2.6 mm Hg. In addition, a decrease in creatinine to an average of 106.2+/-6.4, fibrinogen and fibrin monomers to subnormal values of 3.2+/-0.2 g/l and up to 8.1+/-0.5x10-2 g/l, respectively were seen. Renal hypertrophy according to ultrasound examination was preserved with a mean kidney volume 119.7+/-3.6 cm3. Disturbances in peripheral microcirculation according to the microscopy of the bulbar conjunctiva was assessed as moderate.. The development of CKD in patients with a solitary kidney is accompanied by a structural reorganization of the organ with an increase in blood pressure, an increase in its volume, a decrease in function, microcirculatory disorders and hypertensive nephropathy. Considering the prognostic significance of changes in the solitary kidney, it is important not only to control the functional parameters, but also to include reno- cardioprotective therapy as a standard, since it contributes to the preservation of the renal function and prevents the rapid progression of CKD. Thus, medical and social rehabilitation of patients with a solitary kidney is required. However, it is currently cannot be considered comprehensive.

Topics: Aged; Anticoagulants; Carcinoma, Renal Cell; Female; Fibrin; Fibrinogen; Glomerular Filtration Rate; Humans; Kidney; Kidney Neoplasms; Microcirculation; Middle Aged; Nephrectomy; Renal Insufficiency, Chronic; Retrospective Studies; Solitary Kidney; Venous Thromboembolism

Thrombin converts fibrinogen to fibrin and activates blood and vascular cells in thrombo-inflammatory diseases. Platelets are amplifiers of thrombin formation when activated by leukocyte- and vascular cell-derived thrombin. CD36 on platelets acts as sensitizer for molecules with damage-associated molecular patterns, thereby increasing platelet reactivity. Here, we investigated the role of CD36 in thrombin-generation on human platelets, including selected patients with advanced chronic kidney disease (CKD). Platelets deficient in CD36 or blocked by anti-CD36 antibody FA6.152 showed impaired thrombin generation triggered by thrombin in calibrated automated thrombography. Using platelets with congenital function defects, blocking antibodies, pharmacological inhibitors, and factor-depleted plasma, CD36-sensitive thrombin generation was dependent on FXI, fibrin, and platelet signaling via GPIbα and SFKs. CD36-deficiency or blocking suppressed thrombin-induced platelet αIIbβ3 activation, granule exocytosis, binding of adhesion proteins and FV, FVIII, FIX, FX, but not anionic phospholipid exposure determined by flow cytometry. CD36 ligated specifically soluble fibrin, which recruited distinct coagulation factors via thiols. Selected patients with CKD showed elevated soluble fibrin plasma levels and enhanced thrombin-induced thrombin generation, which was normalized by CD36 blocking. Thus, CD36 is an important amplifier of platelet-dependent thrombin generation when exposure of anionic phospholipids is limited. This pathway might contribute to hypercoagulability in CKD.

Topics: Blood Coagulation Factors; Blood Platelets; CD36 Antigens; Factor XI; Fibrin; Humans; Platelet Activation; Renal Insufficiency, Chronic; Thrombin

Hypercoagulability is associated with chronic kidney disease (CKD). Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade are known to activate protease-activated receptor 2 (PAR2), and to cause inflammation and tissue injury. Although PAR2 is highly expressed in the kidney, it is unclear whether PAR2 plays a pathogenic role in CKD. To test this, we fed the mice lacking Par2 (F2rl1

Topics: Adenine; Animals; Enzyme-Linked Immunosorbent Assay; Factor V; Factor Xa; Fibrin; Fibrosis; Gene Expression Regulation; Inflammation; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oxidative Stress; Receptor, PAR-2; Renal Insufficiency, Chronic; Thromboplastin

Chronic kidney disease (CKD) is associated with a concurrent increased risk of thrombosis and bleeding. We aimed to investigate whether CKD is associated with increased fibrin formation, impaired fibrin degradation, or both. Twenty-one patients with CKD stage 4 (CKD 4), 15 haemodialysis patients, and 13 controls (C) without kidney disease were studied. We used a global assay to determine fibrin formation and degradation in plasma. Fibrin turbidity was measured over time to obtain a value of the coagulation activation profile (Cp) and the fibrinolysis activation profile (Fp), and the amount of fibrin formed, termed fibrin optical density sum (fibrin OD-sum). We used scanning electron microscopy (SEM) to visualize the fibrin network. Plasminogen activator inhibitor type-1 antigen, thrombin-activatable fibrinolysis inhibitor activity, fibrinogen, von Willebrand factor, antithrombin, albumin, and C-reactive protein were measured in plasma. Fibrin OD-sum was significantly elevated in haemodialysis patients [312 a.u.; 278-435 (median; interquartile range); P < 0.0013] and in CKD 4 (293 a.u.; 169-434; P = 0.0119) compared with controls (115 a.u.; 82-234). SEM showed a tight fibrin network in haemodialysis and CKD 4 patients. Fp was lower in the haemodialysis group than in controls (P = 0.030). Plasminogen activator inhibitor type-1 was lower in haemodialysis patients (P = 0.034). Thrombin-activatable fibrinolysis inhibitor activity, Cp, antithrombin, and C-reactive protein did not differ between groups. Fibrinogen was significantly elevated and albumin decreased in both haemodialysis and CKD 4 patients compared with controls. Von Willebrand factor was elevated in haemodialysis patients compared with controls (P = 0.010). The prothrombotic state in severe CKD is characterized by impaired fibrinolysis in association with increased fibrin formation despite normal levels of endogenous fibrinolysis inhibitors.

Topics: Adult; Aged; Antithrombins; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Kidney; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Renal Dialysis; Renal Insufficiency, Chronic; Serum Albumin; Severity of Illness Index; Thrombosis; von Willebrand Factor

Topics: Atrial Fibrillation; Blood Coagulation; Fibrin; Humans; Microscopy, Electron, Scanning; Renal Insufficiency, Chronic

Chronic kidney disease (CKD), defined as a decreased estimated glomerular filtration rate (eGFR < 60 ml/min), is an independent risk factor for cardiovascular events. Both acute coronary syndrome (ACS) and end-stage renal disease have been shown to be associated with formation of compact fibrin clots relatively resistant to lysis. The aim of the current study was to evaluate the effect of CKD on fibrin clot properties in patients with ACS. In 30 ACS patients, aged 48-72 years, with CKD and 30 ACS patients with eGFR more than 60 ml/min, we investigated plasma fibrin clot properties using permeation and turbidity assays, including three different clot lysis assays. The ACS patients with eGFR less than 60 ml/min and those with normal filtration rate did not differ with regard to demographics, risk factors, medications and routine laboratory tests, including fibrinogen. The former group had higher plasminogen activator inhibitor-1 (P = 0.002) and tissue-type plasminogen activator (tPA) (P = 0.008). Compared with ACS patients with eGFR more than 60 ml/min, the ACS patients with CKD formed less porous fibrin clots (P = 0.004) and susceptible to fibrinolysis (P < 0.001), had thicker overall fibrin fibers (P = 0.007), earlier onset of fibrin clot formation (P = 0.004) and increased clot mass (P < 0.001). By multiple regression analysis, clot permeability was independently predicted by eGFR (P = 0.0005) and fibrinogen (P = 0.001), whereas the only predictors of lysis time were eGFR (P = 0.006) and tPA (P = 0.002). This study indicates that ACS patients with CKD display unfavorable fibrin clot properties including impaired fibrinolysis, which might contribute to worse outcome in this population.

Topics: Acute Coronary Syndrome; Aged; Blood Coagulation; Blood Coagulation Tests; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Renal Insufficiency, Chronic