Hypoxia-inducible factor stabilizers for treating anemia of chronic kidney disease
Purpose of review Small-molecule inhibitors of prolyl hydroxylase domain enzymes (PHD inhibitors) are novel renal anemia therapies that increase endogenous erythropoietin (EPO) production by stabilizing hypoxia-inducible factor (HIF). This review summarizes recent findings and future perspectives of PHD inhibitors (HIF stabilizers) in chronic kidney disease (CKD)-associated anemia. Recent findings Clinical trials have demonstrated that HIF stabilizers effectively increase hemoglobin levels of both nondialysis and dialysis CKD patients without causing serious adverse effects. HIF stabilizers not only restore EPO production but also optimize iron metabolism by reducing hepcidin levels. Considering the pleiotropic roles of the PHD–HIF pathway, HIF stabilizers might have both advantageous and disadvantageous effects in humans, in addition to erythropoiesis. Results of studies in animal models have suggested that HIF stabilizers alleviate ischemia–reperfusion injury and play protective roles against metabolic diseases. In contrast, a theoretical concern exists regarding the potential for tumorigenesis due to HIF stabilization. Summary At least five HIF stabilizers are now in phase III trials and may appear on the market in 1–2 years. The long-term effects and safety of HIF stabilization should be carefully examined in future basic and clinical studies.
Publication date: October 2018Source: American Journal of Kidney Diseases, Volume 72, Issue 4Author(s): Yoshio N. HallThere is ongoing recognition that a wide array of social, economic, and environmental factors influence individuals’ opportunities to engage in health care and healthy behaviors. Despite spending $34 billion annually on the care of patients with end-stage renal disease, the American public and nephrology community remain remarkably complacent about addressing “upstream” factors that influence the prevention, progression, and treatment of chronic kidney diseases. Recently, a growing number ...
Authors: Io H, Suzuki Y Abstract BACKGROUND: Currently, left ventricular (LV) hypertrophy and dysfunction are considered the strongest predictors of cardiovascular mortality in chronic kidney disease (CKD) patients. We investigated the factors associated with elevated LV mass index (LVMI) using echocardiography and assessed the strategies used to treat CKD (stages 1-5D) patients. SUMMARY: In study 1, we prospectively determined correlations among biochemical values, physical specimens, and LVMI using echocardiography in hemodialysis (HD) and peritoneal dialysis (PD) patients (stage 5D). In study 2, biochemical ...
Conclusions: This is the first Italian prospective study performed with a large cohort of CKD patients over a 3-year period. Considering the multifactorial burden of diseases associated with CKD patients, the need for greater attention to CKD and related disorders is paramount.Nephron
Publication date: Available online 13 March 2018 Source:American Journal of Kidney Diseases Author(s): Yoshio N. Hall There is ongoing recognition that a wide array of social, economic, and environmental factors influence individuals’ opportunities to engage in health care and healthy behaviors. Despite spending $34 billion annually on the care of patients with end-stage renal disease, the American public and nephrology community remain remarkably complacent about addressing “upstream” factors that influence the prevention, progression, and treatment of chronic kidney diseases. Recently, a growing number...
Conclusion: In contrast to some existing literature, this study has demonstrated that EPO resistance and iron deficiency contributes to anemia in CKD and serum ferritin can be used to assess the iron level of dialysis naïve CKD patients at every stage of the disease.
We report the first biopsy-proven ATN caused by dapagliflozin. Great caution together with continuous monitoring of renal function is advised when implementing SGLT-2 inhibitors in clinical practice.
Conclusions: In the setting of acute heart failure in CRAS patients LV function has no significant role in the incidence of in-hospital stroke, major bleeding and death.
CONCLUSIONS: CVRFs may be present in early CKD, even before the decline in GFR. Routine screening for CVRFs, along with timely intervention, may prevent the progression of CVD and mortality later in life. PMID: 28809621 [PubMed - in process]
CONCLUSIONS: There is low certainty evidence that CERA has little or no effects on patient-centred outcomes compared with placebo, epoetin alfa or beta or darbepoetin alfa for adults with CKD. The effects of CERA among children who have CKD have not studied in RCTs. PMID: 28782299 [PubMed - as supplied by publisher]
In conclusion, the use of iron-based phosphate binders with significant iron absorption properties could represent a novel paradigm for correcting anemia and hyperphosphatemia in CKD patients. PMID: 28717990 [PubMed - as supplied by publisher]