Risk factors for thromboembolic events in individuals with dialysis-dependent chronic kidney disease

A recent study has shown that it is reasonable to avoid sudden fluctuations in hemoglobin levels and maintain transferrin saturation (TSAT) levels at or above 30%, rather than escalating the dosage of roxadustat. The findings of the study were published in the journal Advances in Therapy.

Thromboembolic events in patients receiving roxadustat were investigated through a combined analysis of four phase 3 trials, including PYRENEES, HIMALAYAS, SIERRAS, and ROCKIES, both prior to and following the twelfth week. Cox regression analyses were used to explore the baseline risk factors for thromboembolic events. The association between thromboembolic events and laboratory parameters that were last known before the event was explored through nested case-control studies using matched case-control pairs.

Among the 2354 patients studied, 1026 thromboembolic events were observed in 568 patients. Baseline risk factors identified included hemodialysis versus peritoneal dialysis, race, high high-sensitivity C-reactive protein, advanced age ≥ 65 years, a history of thromboembolism, cardiovascular disease, or diabetes. Univariate case-control analyses indicated that a high hemoglobin rate of rise (≥ 0.5 g/dL/week; OR 2.09; 95% CI 0.98-4.46) showed a potential increase in the risk of thromboembolic events before week twelve, while a high rate of hemoglobin decline was linked to events after week 12 (< - 0.5 g/dL/week; OR 3.73; 95% CI 1.68-8.27) in comparison to steady levels of hemoglobin (ranging from ≥ - 0.1– < 0.1 g/dL/week).

Multivariate case-control analyses demonstrated that a low last known hemoglobin level (< 10 g/dL: adjusted OR 1.91; 95% CI 1.04-3.50; versus ≥ 12 g/dL) and low last known transferrin saturation (TSAT < 10%: adjusted OR 3.78; 95% CI 1.71-8.39; versus ≥ 30%) before event onset were associated with events after week twelve. An increased dose of roxadustat was correlated with thromboembolic events in patients whose last known transferrin saturation was less than 30%, while no correlation was observed in patients with transferrin saturation of 30% or higher.

The above study demonstrated that among several risk factors associated with thromboembolic events, it is suitable to avoid abrupt changes in hemoglobin levels and keep TSAT levels at or above 30% instead of increasing the dosage of roxadustat.

The relation between diabetic retinopathy and diabetic nephropathy in individuals with type 2 diabetes

According to a recent study, diabetic retinopathy (DR) proved to be a reliable predictor of diabetic nephropathy (DN). Among individuals with DN, the DR severity correlated with glomerular damage, while the existence of KW nodules, reduced hemoglobin levels, and younger age were identified as independent risk factors linked to more severe DR. This research findings were published in the journal, Frontiers in Endocrinology.

A total of 272 patients diagnosed with type 2 diabetes mellitus (T2DM) who underwent a renal biopsy were eligible for this study. The severity of DR was categorized as: non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). The aim of this research was to investigate the association between DN and DR, as well as to assess the diagnostic effectiveness of DR in detecting DN.

DN patients had a higher prevalence of DR (86.4%). Additionally, the severity of DR was higher in DN patients. The specificity and sensitivity of DR in DN were 78.8% and 86.4%, while that of PDR was 98.5% and 26.4%, respectively. In DN patients, it was observed that the severity of glomerular lesions increased significantly (p = 0.001), along with the prevalence of KW nodules (p<0.001), as the severity of DR increased. Independent risk factors associated with more severe DR in DN patients included the presence of KW nodules, lower hemoglobin levels, and younger age.

The above study showed that DR is a reliable marker for DN. Among those with DN, the severity of DR was found to be correlated with damage to the glomeruli. Additionally, the presence of KW nodules, lower hemoglobin levels, and younger age were recognized as independent risk factors that were associated with more severe DR.

Reduction of cardiovascular risk with icosapent ethyl

According to a recent study the baseline lipoprotein(a) (Lp[a]) concentration was found to have prognostic value for major adverse cardiovascular events (MACE) in individuals with elevated triglyceride levels receiving statin therapy. Icosapent ethyl (IPE) demonstrated a consistent reduction in MACE occurrence across various levels of Lp(a), even in cases where clinically relevant elevations were present. This study’s findings were published in the Journal of the American College of Cardiology.

The post hoc analysis study involved 8,179 individuals receiving statin therapy for established cardiovascular disease or were aged ≥50 years with diabetes and had ≥1 one additional risk factor, had fasting triglyceride levels ranging from 1.69 to 5.63 mmol/L and had low-density lipoprotein cholesterol levels ranging from 1.06 to 2.59 mmol/L. Participants were randomly assigned to receive either 2 g of IPE twice daily or a placebo that matched the appearance of IPE. This study analyzed the relationship between the continuous baseline Lp(a) mass concentration, and the risk of experiencing the first and total MACE. Additionally, the effects of IPE on the occurrence of the first MACE event were analyzed in participants with Lp(a) concentrations either ≥50 or <50 mg/dL.

Among the 7,026 participants (86% randomized) had their baseline Lp(a) levels assessed. The median concentration of Lp(a) was found to be 11.6 mg/dL. The analysis revealed significant relationships between Lp(a) levels and both first and total MACE (P < 0.0001). IPE showed a significant reduction in first MACE among subgroups with Lp(a) concentrations ≥50 and <50 mg/dL.

The above study demonstrated the prognostic value of the baseline Lp(a) concentration for MACE in individuals with elevated triglyceride levels who were receiving statin therapy. IPE consistently reduced the occurrence of MACE across different levels of Lp(a), even in instances where clinically relevant elevations were present.

Safety and efficacy of dapagliflozin in acute heart failure patients

According to a recent study, the early administration of dapagliflozin during hospitalization for acute heart failure (AHF) is considered safe and fulfills a component of guideline-directed medical therapy (GDMT) optimization. Additionally, dapagliflozin has been associated with evidence indicating enhanced diuresis in individuals with AHF. This study’s findings were published in the Journal of the American College of Cardiology.

In this open-label, multicenter trial, 240 patients were randomly assigned within one day of hospital presentation for hypervolemic AHF to either structured usual care with the protocol of diuretic titration until the 5^th day or dapagliflozin 10 mg once daily or discharge from hospital. The primary outcome of the study, diuretic efficiency indicated by cumulative weight change per cumulative loop diuretic dose, was compared between treatment groups using a proportional odds model adjusted for initial weight.

There was no difference observed in terms of diuretic efficiency between dapagliflozin and standard care. Dapagliflozin resulted in lower loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] compared with 800 mg [Q1-Q3: 380-1,715 mg]) and fewer intravenous diuretic up-titrations to achieve similar weight loss compared to standard care. Initiating dapagliflozin early did not lead to an increase in adverse events related to diabetes, heart health, or kidney function. Additionally, dapagliflozin was linked to enhanced median 24-hour natriuresis and urine output, facilitating quicker hospital discharge during the study period.

Thus, it can be concluded that the administration of dapagliflozin at an early stage during hospitalization for AHF is regarded as a safe practice and fulfills a component of optimizing GDMT. Additionally, there is evidence indicating that dapagliflozin promotes enhanced diuresis in individuals with AHF.