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.

The impact of C-reactive protein on the efficacy of roxadustat in managing anemia in chronic kidney disease

A recent study demonstrated that roxadustat displays similar efficacy across different blood C-reactive protein (CRP) levels. Additionally, in the CRP ≥ upper limit of normal (ULN) group, roxadustat can uphold efficacy comparable to erythropoiesis-stimulating agents (ESA) without the need for dose escalation. The study's results were recorded in the publication BMC Nephrology. 
A comprehensive search was conducted across electronic databases, including Web of Science, Pubmed, Embase, Cochrane Library, Wanfang, International Clinical Trials Registry Platform (ICTRP), and CNKI from their inception until 19thMay, 2022. A systematic review was performed on evidence from randomized controlled trials that used hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) for treating renal anemia. The meta-analysis findings were derived from the mean difference (MD) in changes in hemoglobin concentration (∆Hb) pre- and post-treatment, utilizing a random-effects model. Groups with CRP levels at or above the upper limit of normal (ULN) were compared with those below the ULN. Further analysis was conducted within the CRP ≥ ULN group, comparing erythropoiesis-stimulating agents (ESA) and HIF-PHIs.
This analysis included a total of seven studies from six publications. When comparing the CRP ≥ ULN group with the CRP < ULN group, 524 patients from four studies were analyzed. All patients were administered roxadustat as the primary intervention. The pooled results showed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (MD: 0.00, 95% CI: -0.32 to 0.33, P value= 0.99). The effectiveness of roxadustat and erythropoiesis-stimulating agents was compared in three studies involving 1399 patients within the CRP ≥ ULN group. The findings revealed no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (MD: 0.24, 95% CI: -0.08 to 0.56, P value = 0.14). Regarding medication dosage, an increase in ESA dose over time was observed in various studies, particularly noticeable in the CRP ≥ ULN group, while the roxadustat dose remained constant over time and was not affected by the baseline CRP levels.
Therefore, roxadustat exhibited similar efficacy regardless of the CRP levels. Additionally, in the CRP ≥ ULN group, roxadustat can sustain effectiveness comparable to erythropoiesis-stimulating agents without the necessity for dose escalation.