A new insight into the treatment of renal anemia with HIF stabilizer

The long-term clinical experiences with recombinant human erythropoietin (rHuEPO) and its analog derivatives have clearly proven that correction of anemia with erythropoiesis stimulating agent (ESA) not only reduces blood transfusion and improves patients’ QOL but has multiple benefits for the concurrent complications of CKD such as Cardio-Renal–Anemia (CRA) syndrome and/or malnutrition-inflammation-atherosclerosis (MIA) syndrome.Unlike ESA, the newly available agent, hypoxia-inducible factor (HIF) stabilizer, stimulates endogenous erythropoietin (EPO) by mimicking hypoxia with HIF prolyl hydroxylase domain enzyme (HIF-PHD) inhibition. The phase 2 and 3 clinical studies have shown that HIF stabilizers are as efficacious as ESA in ameliorating renal anemia. Whether the same clinical benefits on CRA and MIA syndrome hold true in patients given HIF stabilizers is a matter for future debate. Given that HIF stabilizers act on the multiple target genes, the use of this novel agent may lead to unwanted adverse events.Launching HIF stabilizers into the treatment of renal anemia provokes a concern about how this alternative treatment will be taken up in the daily clinical practice. However, guideline-oriented strategies on how to use HIF stabilizer is not available at this limited point due to scant clinical information. Nevertheless, this opinion-based review provides a future insight into the management of renal anemia with HIF stabilizer by reference to the past experiences with ESA. HIF stabilizers can preferably be indicated for CRA syndrome at pre-dialysis stage, ESA resistant anemia at advanced CKD stage, and perhaps for dysregulated iron metabolism akin to MIA syndrome in patients on dialysis.

MALNUTRITION-INFLAMMATION-ATHEROSCLEROSIS (MIA) SYNDROME IN HEMODIALYSIS PATIENTS

Background: Mortality resulting from cardiovascular disease in patients with end-stage renal disease (ESRD) is high. In this study we study characteristics of the malnutrition, inflammation, atherosclerosis (MIA) syndrome; relationship between MIA syndrome and the cardiovascular events in hemodialysis patients. Subjects and methods: A total of 61 hemodialysis patients were enrolled. Inflammatory marker (hs CRP) and nutritional parameters (albumin, prealbumin, BMI) were determined. Carotid atherosclerosis was investigated by ultrasonographically evaluated carotid intima-media thickness (cIMT). Results: -The characteristics of the malnutrition, inflammation, atherosclerosis(MIA) syndrome in in peritoneal dialysis patients: + MIA2-3 group had an average age lower than MIA0 group + MIA2-3 group had lower albumin levels and BMI than MIA0 group. + The prevalence of malnutrition (50.8%), inflammation (27.9%), and atherosclerosis (52.5%); 24 (39.3%) of the patients had one risk factor; 22 (36.1%) of the patients had two risk factors; 4 (6.6%) of the patients had all three risk factors. No signs of either malnutrition, inflammation or atherosclerosis were seen in 11 (18.0%) of patients. Note that a considerable number of patients with malnutrition (23/31 patients) had signs of inflammation or atherosclerosis or both; 12/32 patients with atherosclerosis had signs of inflammation or malnutrition or both. - The relationship between MIA syndrome and the cardiovascular events in peritoneal dialysis patients: We have found the relationship between component M (malnutrition) and the cardiovascular events in syndrome MIA (HR: 4.23 95% CI: 1.89-9.50). Our study suggests that high risk cardiovascular events in patients with 2 or more elements in MIA syndrome (HR: 2.40 95% CI: 1.16-5.00). Conclusion: We had demonstrated an association between malnutrition, inflammation and atherosclerosis; component M (malnutrition) and the cardiovascular events in hemodialysis patients; high risk cardiovascular events in patients with 2 or more elements in MIA syndrome. Key words: Malnutrition-inflammation-atherosclerosis syndrome, hemodialysis

Cardiorenal Syndrome in End-Stage Kidney Disease

Background: Cardiorenal syndrome (CRS) in patients with end-stage kidney disease (ESKD) represents mainly cardiovascular disease (CVD) due to various complications associated with renal dysfunction—defined as type 4 CRS by Ronco et al.—because the effect of cardiac dysfunction on the kidneys does not need to be taken into consideration, unlike in non-dialysis dependent chronic kidney disease (CKD). Summary: Patients with ESKD are often in a state of chronic inflammation due to the upregulation of proinflammatory cytokines. Chronic inflammation leads to malnutrition and consequently to vascular endothelial dysfunction and vascular calcification, which is referred to as malnutrition-inflammation-atherosclerosis (MIA) syndrome and acts as a major risk factor for CVD. Anemia also plays a crucial role in CVD, and individuals with erythropoietin-resistant anemia have a particularly high risk of CVD. However, caution is emphasized because not only anemia itself, but also the overtreatment of anemia with erythropoiesis-stimulating agents aimed at elevating hemoglobin to ≥13 g/dl can also increase the risk of CVD. In CKD-mineral and bone disorder (CKD-MBD), phosphate load triggers the interactions between various factors such as calcium, parathyroid hormone, vitamin D, and fibroblast growth factor 23, promoting vascular calcification and thus becoming a risk factor for CVD. Key Messages: In addition to traditional atherosclerosis risk factors such as hypertension, diabetes, and dyslipidemia, the involvement of MIA syndrome, anemia, and CKD-MBD accompanying CKD have also become a focus for investigation as major players in CRS in patients with ESKD.