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.
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

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Purpose of review Iron deficiency is a major contributory cause to the development of anaemia in chronic kidney disease (CKD), and thus, iron replacement therapy plays a critical role in the management of this condition. The two main routes for administering iron are oral and intravenous, and there have been a number of new publications relevant to both routes of administration. Recent findings Recent developments on the topic of iron management in CKD include the introduction of new oral iron preparations, as well as two recent meta-analyses on iron therapy in CKD (one on oral versus intravenous iron, and one on high...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research
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 ...
Source: Contributions to Nephrology - Category: Urology & Nephrology Tags: Contrib Nephrol Source Type: research
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
Source: Nephron - Category: Urology & Nephrology Source Type: research
This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify ...
Source: Brazilian Journal of Medical and Biological Research - Category: Research Tags: Braz J Med Biol Res Source Type: research
H Suresh, BS Arun, V Moger, PB Vijayalaxmi, K. T. K Murali MohanIndian Journal of Nephrology 2018 28(2):127-134 Pulmonary hypertension (PH) is a recently recognized complication of chronic kidney disease (CKD), especially in end-stage renal disease. It has prevalence estimates of 30%–50% and is an independent predictor of increased mortality in CKD patients. The aim of this study is to analyze the prevalence of PH in patients with CKD, its severity in different stages of CKD, and risk factors for it. One hundred and eight patients with CKD treated at Karnataka Institute of Medical Sciences, Hubli, Karnataka,...
Source: Indian Journal of Nephrology - Category: Urology & Nephrology Authors: Source Type: research
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...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
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.
Source: Nigerian Journal of Clinical Practice - Category: Rural Health Authors: Source Type: research
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.
Source: CEN Case Reports - Category: Urology & Nephrology Source Type: research
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.
Source: Hypertension - Category: Cardiology Authors: Tags: Poster Abstract Presentations Source Type: research
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]
Source: South African Medical Journal - Category: African Health Tags: S Afr Med J Source Type: research
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