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

Related Links:

Publication date: Available online 28 March 2019Source: American Journal of Kidney DiseasesAuthor(s): Simon Nusinovici, Charumathi Sabanayagam, Boon Wee Teo, Gavin Siew Wei Tan, Tien Yin WongEyes and kidneys have numerous structural, developmental, physiologic, and pathogenic pathways in common, suggesting that many kidney and eye diseases may be interlinked. Studies suggest that the prevalence of eye diseases and vision impairment are higher among persons with end-stage kidney disease and earlier stages of chronic kidney disease (CKD) than in those without. Ocular morbidity in persons with CKD and end-stage kidney di...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
Discussion: Incomplete septal cirrhosis is an uncommon cause of non-cirrhotic portal hypertension. Its definition is not well known, morphological and pathophysiological. We have not found published cases of post-RT ascites secondary to this pathology, described as possibly associated with drugs, immune alterations, infections, hypercoagulability and genetic predisposition. PMID: 30897191 [PubMed - as supplied by publisher]
Source: Jornal Brasileiro de Nefrologia - Category: Urology & Nephrology Tags: J Bras Nefrol Source Type: research
Publication date: Available online 13 December 2018Source: The Lancet HIVAuthor(s): Joseph J Eron, Jean-Daniel Lelievre, Robert Kalayjian, Jihad Slim, Anson K Wurapa, Jeffrey L Stephens, Cheryl McDonald, Eric Cua, Aimee Wilkin, Brigitte Schmied, Mehri McKellar, Stephanie Cox, Sophia R Majeed, Shuping Jiang, Andrew Cheng, Moupali Das, Devi SenGuptaSummaryBackgroundCurrent treatment for HIV-infected individuals with renal failure on haemodialysis frequently requires complex regimens with multiple pills. A daily single-tablet regimen of coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is approve...
Source: The Lancet HIV - Category: Infectious Diseases Source Type: research
In conclusion, acupuncture is proved to be beneficial for CKD patients. More research, however, is needed to verify the potential mechanisms. PMID: 30286626 [PubMed - in process]
Source: The American Journal of Chinese Medicine - Category: Complementary Medicine Authors: Tags: Am J Chin Med Source Type: research
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 ...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
Abstract Chronic kidney disease (CKD) affects health and life of patients. They confront anemia, hypertension, infections and cardiovascular disease. Due to these health issues, they are at risk of repeated hospitalizations. The risk factors which propel them to hospitalize are important to know, and by controlling these factors, we can impede preventable hospitalization. This case-control study included 1050 adult CKD patients, conducted in two tertiary care hospitals of Karachi. Variables included were age, gender, ethnicity, area of residence, marital status, education smoking status, comorbids, blood pressure,...
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
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
More News: Anemia | Chronic Kidney Disease | Clinical Trials | Dialysis | Drugs & Pharmacology | Hypertension | Iron | Study | Urology & Nephrology