Early Anemia Treatment in Nondialysis CKD Patients Reduces Cardiovascular Risks and Mortality

A recent retrospective cohort study examined the impact of initiating anemia treatment at different hemoglobin levels on renal and cardiovascular outcomes in patients with nondialysis-dependent chronic kidney disease (NDD-CKD). 
Using data from two large Japanese databases, the study evaluated patients treated with long-acting erythropoiesis-stimulating agents (ESAs), dividing them into early treatment (hemoglobin ≥9.0 g/dl) and delayed treatment (<9.0 g/dl) groups. 
The primary outcome was a renal composite, including renal replacement therapy, significant reduction in estimated glomerular filtration rate (eGFR), and all-cause mortality. Secondary outcomes focused on cardiovascular events such as heart failure, stroke, and cardiovascular death. 
After propensity score matching, results from 1472 (MDV) and 1264 (RWD) patients revealed that delayed treatment did not significantly raise the risk of renal events (MDV HR: 1.15; RWD HR: 1.08). However, delayed anemia treatment was associated with a substantial increase in cardiovascular risks, including heart failure (MDV HR: 1.50; RWD HR: 1.53), as well as higher all-cause mortality (MDV HR: 1.83; RWD HR: 1.64).
The findings suggest that while renal outcomes may remain unaffected, delaying anemia treatment in NDD-CKD patients can significantly increase cardiovascular risks and mortality, highlighting the importance of early intervention before hemoglobin drops below 9.0 g/dl.
 

Anemia and Renal Dysfunction Have Negative Impact on Long-Term Survival After Acute Myocardial Infarction

Anemia and chronic kidney disease (CKD) are known to worsen outcomes following acute myocardial infarction (AMI). This retrospective, single-center study evaluated the interaction between anemia and CKD in predicting 10-year survival among AMI survivors. The cohort consisted of 11,395 patients (69.1% male, mean age 65.8 years), stratified by anemia and CKD grade based on admission hemoglobin and creatinine levels.

Among participants, 29.9% had anemia and 15.9% had CKD grade 3b or higher. Anemia prevalence increased with advancing CKD grade (p < 0.001), and CKD was more severe in anemic patients. After a decade, 47.8% of the cohort had died. Despite varying baseline characteristics and treatment approaches, both anemia (HR 1.40, 95% CI 1.32-1.49, p < 0.001) and higher CKD grades (HR 1.10, 95% CI 1.02-1.20, p < 0.001) independently predicted increased mortality risk. 
The mortality risk due to anemia or worsening CKD was particularly evident in patients with normal renal function to CKD grade 3a in the overall cohort and conservative treatment subgroup, and up to grade 4 in the invasive revascularization subgroup. Notably, higher CKD grades also elevated mortality risk among non-anemic patients across CKD stages.
In conclusion, anemia and advancing CKD independently contribute to reduced long-term survival following AMI, with the combined effect posing the greatest risk in patients with mild to moderate CKD.
 

Factors that affect the response to vadadustat in those with anemia associated with chronic kidney disease

A new study has found several factors that impact the effectiveness of vadadustat. These insights could assist in making informed decisions about dose adjustments for the drug. This study’s findings were presented in the journal Clinical and Experimental Nephrology.

The studies on non-dialysis-dependent chronic kidney disease (NDD-CKD) and hemodialysis-dependent chronic kidney disease (HDD-CKD) began with 151 and 162 patients, respectively. Finally, 136 and 140 patients were included and divided into subgroups for analysis. The resistance index for assessing vadadustat responsiveness was defined as the mean body weight-adjusted dose of vadadustat (mg/kg) at weeks 20 to 24, divided by the mean hemoglobin level (g/dL) during the same period. To investigate the factors that affect the resistance index, a multivariate analysis was conducted.

Factors that were independently linked to a better response to vadadustat included: low baseline eGFR, high baseline hemoglobin, elevated ferritin levels between weeks 20-24, and chronic kidney disease not due to glomerulonephritis, autoimmune diseases, or vasculitis in non-dialysis-dependent chronic kidney disease. In the case of dialysis-dependent chronic kidney disease, the determinants were male sex, a low erythropoiesis-stimulating agent resistance index (ERI), and high baseline C-reactive protein.

The study highlighted several factors influencing the effectiveness of vadadustat in patients with NDD-CKD, including low baseline eGFR, high baseline hemoglobin, elevated ferritin levels, and the presence of chronic kidney disease not linked to glomerulonephritis, autoimmune diseases, or vasculitis. When considering HDD-CKD, factors like a low erythropoiesis-stimulating agent resistance index (ERI), being male, and high baseline C-reactive protein influenced the efficacy of vadadustat. Understanding these factors can help guide appropriate dose adjustments for vadadustat.

The effect of ziltivekimab on hemoglobin levels in individuals with CKD stage 3-5

A recent study has shown that the use of ziltivekimab as an anti-inflammatory treatment led to improvements in anemia markers and iron regulation in individuals with stage 3-5 chronic kidney disease (CKD) and systemic inflammation, indicating a potential role in managing anemia. The Journal of the American Society of Nephrology published the study's findings.

This study analyzed exploratory end points from the RESCUE trial, involving 264 adults with CKD stage 3-5 and high-sensitivity C-reactive protein ≥2 mg/L. The subjects were administered with either a placebo or subcutaneous ziltivekimab (7.5 mg, 15 mg, or 30 mg) in a 1:1:1:1 ratio at four-week intervals for a duration of up to twenty-four weeks. The end points included the biomarkers of iron homeostasis and changes in hemoglobin (Hb) from baseline to twelfth week.

The levels of hemoglobin significantly increased from the starting point to week 12 when administered with ziltivekimab at 7.5 mg, 15 mg, and 30 mg doses. The differences in treatment compared to the placebo were +0.57 g/dl [95% CI, 0.27 to 0.86], +1.05 g/dl [0.76 to 1.33], and +0.99 g/dl [0.70 to 1.28], respectively, all with a P value < 0.001. Ziltivekimab also resulted in significant elevations in total iron-binding capacity, serum iron levels, and transferrin saturation from the baseline to week 12 (P value < 0.05 vs. placebo for all doses and comparisons). Instances of sustained neutropenia, sustained thrombocytopenia, anemia, and iron deficiency anemia were uncommon and similar across all cohorts.

The above study showed that treatment with ziltivekimab, an anti-inflammatory therapy, led to improvements in anemia markers and iron homeostasis in patients with stage 3-5 CKD and systemic inflammation. This indicates a possible role in the treatment of anemia.