Altered fibrin clot properties are associated with the progression of chronic kidney disease in atrial fibrillation.

INTRODUCTION: Formation of denser and resistant to lysis fibrin clot networks has been shown in chronic kidney disease (CKD) and atrial fibrillation (AF). We investigated whether such prothrombotic fibrin clot properties are associated with faster progression of CKD in AF patients. MATERIAL AND METHODS: We recruited 265 AF patients (men 49.1 %, median age of 64.0 years, median estimated glomerular filtration rate [eGFR] of 77.0 ml/min/1.73 m2), including 137 patients on non-vitamin K antagonist oral anticoagulants (NOACs) (51.7 %) and 109 patients (41.1 %) on vitamin K antagonists (VKAs). At baseline while off anticoagulation, we determined fibrin clot permeability (Ks), and clot lysis time (CLT), along with plasminogen activator inhibitor-1 (PAI-1), endogenous thrombin potential (ETP), and von Willebrand factor (vWF). The kidney function was assessed at baseline and after a median follow-up of 50.0 months. RESULTS: During follow-up, a median eGFR decreased by 8.0 (5.0-11.0) ml/min/1.73 m2, 1.8 ml/min/1.73 m2/year and this change correlated with age (R = 0.19, P = 0.002), Ks (R = 0.46, P < 0.0001), and CLT (R = -0.17, P = 0.005), but not ETP, fibrinogen, PAI-1 or vWF. A decrease in eGFR was lower in patients who used NOACs at baseline but not in those who started NOACs during follow-up (n = 101) as compared to the remaining patients. On multiple linear regression analysis, adjusted for age and fibrinogen, baseline Ks, eGFR, hypertension, and NOACs use independently predicted a decrease in eGFR. CONCLUSIONS: This study is the first to show that more compact fibrin clot networks may contribute to faster progression of CKD in AF, indicating novel kidney-related harmful effects of prothrombotic clot properties in humans.

Effect of COVID-19 on Kidney Graft Function One Year after Onset.

Background and Objectives: Kidney transplant recipients (KTRs) are at a higher risk of severe COVID-19 development. The course of the infection may vary. Long-term consequences for graft function are still being studied. We investigate whether the clinical course of SARS-CoV-2 infection among KTRs had a long-term effect on graft function. Patients and method: 128 KTRs with confirmed SARS-CoV-2 infection were included in the study. They were divided into two groups: mild (without the need for oxygen therapy; n = 91) and severe (with the need for oxygen therapy; n = 21). Baseline characteristics and medical data, especially creatinine level, estimated glomerular filtration rate (eGFR) CKD-EPI, and proteinuria, were analyzed. The main outcomes were the absolute and relative change in eGFR during the one-year follow-up after COVID-19. In the final models, sex, age, smoking, presence of diabetes mellitus (DM), and cardiovascular disease (CVD) were included. Results: KTRs with severe COVID-19 were older, more likely to smoke, and had DM and CVD more frequently. Our analysis reveals that COVID-19 severity was associated with a significantly more pronounced relative eGFR decline one year after recovery only in males [-13.94 (95% CI: -25.13 to -2.76, p = 0.015) percentage points]. One year after the disease onset, males with a severe course of the infection had a higher eGFR decline than those with a mild one. The COVID-19 severity did not affect eGFR loss in females. Conclusions: In KTRs suffering from COVID-19, deterioration of graft function was noticed. The eGFR decline was associated with disease severity and sex. It indicates a need for further research, observation, and preventive actions for KTRs, especially males.

Anticoagulant Treatment in Patients with Atrial Fibrillation and Chronic Kidney Disease: Practical Issues.

Up to 20% of patients with chronic kidney disease have atrial fibrillation, and 40%-50% of atrial fibrillation patients suffer from chronic kidney disease. The 2 diseases share several risk factors and frequently coincide with each other. Both entities are associ ated with a prothrombotic state, which contributes to increased thromboembolic risk. Atrial fibrillation patients with chronic kidney disease have elevated risk of stroke, major bleeding, and mortality. Clinical risk scores, including CHA2DS2-VASc score, HAS-BLED score, or ORBIT score have a limited value in adverse clinical outcome risk stratification in patients with severe chronic kidney disease. However, the inclusion of renal function in the R(2)-CHA2DS2-VASc score does not improve significantly thromboembolic risk predic tion in atrial fibrillation. There is growing evidence suggesting that biomarkers, including N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin, cystatin C, or growth differentiation factor-15, might be helpful in the assessment of thromboembolic, bleeding, and/or mortality risk in atrial fibrillation patients with chronic kidney disease. The first-choice anticoagulant therapy is based on direct oral anticoagulants in this subgroup. The highest risk of adverse events is observed in end-stage renal disease, and in Europe, in contrast to the USA, solely warfarin is recommended in such atrial fibrillation patients. Treatment of atrial fibrillation patients with chronic kidney disease should be closely moni tored with the selection of right anticoagulant agents at the appropriate dose. The current review paper summarizes available evidence and the challenges of the management of atrial fibrillation patients with chronic kidney disease with practical implications.

Thromboembolism and bleeding in patients with atrial fibrillation and stage 4 chronic kidney disease: impact of biomarkers.

BACKGROUND: Chronic kidney disease (CKD) is considered a risk factor for thromboembolic and bleeding events in patients with atrial fibrillation (AF). AIMS: We sought to assess predictors of clinical outcomes among AF patients with advanced CKD. METHODS: In a prospective cohort study, we enrolled 180 AF patients with stage 4 CKD, defined as estimated glomerular filtration rate of 15-29 ml/min/1.73 m2, on vitamin K antagonists (n = 90), and non-vitamin K antagonists oral anticoagulants (n = 90). We assessed biomarkers, including growth differentiation factor-15, cystatin C, and high-sensitivity cardiac troponin T, and prothrombotic state parameters, including plasma fibrin clot permeability (Ks). RESULTS: The median age of the patients was 71.0 (64.0-75.0) years (men 65.0%). The median estimated glomerular filtration rate was 24.0 (21.0-25.0) ml/min/1.73 m2 while the median CHA2DS2-VASc score was 3.0 (2.0-4.0). Age (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.02-1.20) and decreased Ks (HR, 0.55; 95% CI, 0.34-0.90) were associated with thromboembolic events (n = 18; 4.7% per year). Previous bleeding (HR, 3.21; 95% CI, 1.22-8.45), growth differentiation factor-15 (HR, 1.48; 95% CI, 1.29-1.69), cystatin C (HR, 9.24; 95% CI, 2.15-39.67), and high-sensitivity cardiac troponin T (HR, 1.30; 95% CI, 1.14-1.48) were independent predictors of major or clinically relevant non-major bleeding (n = 27; 7.1% per year). After adjustment for age and comorbidities, only cystatin C (HR, 3.95; 95% CI, 1.08-14.37) predicted mortality (n = 25; 6.5% per year). CONCLUSIONS: Novel biomarkers might be useful in risk stratification of thromboembolic and bleeding events in AF patients with stage 4 CKD receiving oral anticoagulants.

Protein-energy wasting and asymmetric dimethylarginine in peritoneal dialysis patients.

Cardiovascular (CVS) morbidity and mortality in the peritoneal dialysis patients (PD) is 10-30-fold higher than in the general population. A relatively low level of adiponectin and a higher level of leptin are important predictors of vascular complications as well as CVS events in PD patients. The asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is an important risk factor of CVS morbidity and mortality. It is very important to establish all CVS risk factors in the PD patients to prevent CVS morbidity and mortality in this population. The aim of the study was to determine the plasma concentration of ADMA and adipokines in relation to the protein-energy wasting (PEW) in PD patients. The study was performed in 30 PD patients and in the control group which consisted of 23 healthy volunteers. Plasma levels of hsC-reactive protein, TNF, IL-6, leptin, adiponectin, oxyLDL and ADMA were measured by ELISA method in both groups. The nutritional status was determined by measuring the albumin, body mass index (BMI), the percentage of body fat (%F), lean body mass (LBM) and Subjective Global Assessment Score (SGA). The adequacy of dialysis was estimated by weekly Kt/V. In all PD patients, significantly higher levels of ADMA, leptin, oxyLDL, hsCRP and TNF in comparison to controls were observed. In contrast to well-nourished subjects, patients with PEW, in addition to increased hsCRP, showed significantly higher ADMA. PEW was associated with high levels of ADMA and hsCRP and this could probably be responsible for increased CVS risk in PD patients.