scholarly journals Novel Masters of Erythropoiesis: Hypoxia Inducible Factors and Recent Advances in Anemia of Renal Disease

2016 ◽  
Vol 42 (2) ◽  
pp. 160-167 ◽  
Author(s):  
Yalcin Solak ◽  
Mustafa Cetiner ◽  
Dimitrie Siriopol ◽  
Kayhan Tarim ◽  
Baris Afsar ◽  
...  

Anemia seen in patients with chronic kidney disease is a particular form of ‘anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population. Recognizing the pivotal roles of hypoxia inducible factors (HIFs) in orchestrating elements of erythropoiesis opened new avenues in the management of renal anemia. Several phase 1 and 2 studies confirmed the results of early experimental studies supporting the beneficial role of augmenting HIFs for erythropoiesis. In this review, we describe the physiologic functions of HIF in erythropoiesis with special emphasis on interactions with iron and hepcidin metabolism and inflammation.

Author(s):  
Władysław Grzeszczak ◽  
Dariusz Szczyra ◽  
Mirosław Śnit

In patients with chronic kidney disease (CKD), anemia develops gradually, which is primarily due to an inadequate synthesis of erythropoietin by the kidneys, as well as to iron disorders in the body, blood loss, shortened erythrocyte survival and inflammation. The currently accepted treatment employs iron, vitamin B12, folic acid supplementation and the use of erythropoiesis stimulants, which are administered only parenterally. Research is currently underway on the new erythropoiesis drugs that can be orally administered, i.e., hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI) inhibitors which temporarily block propyl hydroxylase [PHD] catalysis and promote a transient increase in the expression of genes regulated by HIF, including kidney and liver erythropoietin [EPO]. Roxadustat is the first oral drug in this class and a potent HIF-PHD inhibitor, exerted to treat anemia in patients with CKD. In phase 1, 2 and 3 studies with CKD-affected patients, roxadustat was more effective to stimulate erythropoiesis for anemia correction than previously used drugs. Roxadustat can be orally given, unlike other erythropoiesis drugs with parenteral administration only, which grants roxadustat a considerable advantage. Our paper presents the results of studies with roxadustat applied for the treatment of anemia in CKD patients with or without dialysis. We are currently not yet able to know the exact role of roxadustat in the treatment of anemia in patients with CKD, but time will tell. It is possible that roxadustat has benefits an iron metabolism and cardiovascular risk.


Author(s):  
Federica Piani ◽  
Fumihiko Sasai ◽  
Petter Bjornstad ◽  
Claudio Borghi ◽  
Ashio Yoshimura ◽  
...  

Abstract Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.


Objective: the present study was aimed to evaluate the role of pharmaceutical services in improving the outcome of mineral bone disorder in patients with advanced chronic kidney disease. Methodology: One hundred and twenty patients with chronic kidney disease-mineral bone disorder (CKD-MBD) screened for eligibility, seventy-six patients enrolled in the study and randomly allocated into two groups: pharmaceutical care and usual care, both groups interviewed by the pharmacist using specific questionnaire for assessing the quality of life (QoL). All the drug related problems (DRPs) including drug-drug interactions (DDIs) were recorded by the pharmacist. Blood samples were collected and utilized for analyzing the levels of vitamin D, phosphorous, calcium, albumin and parathyroid hormone at baseline and three months after. The pharmaceutical care group received all the educations about their medications and how to minimize DRPs; improve the QoL. Additionally, the pharmaceutical intervention included correcting the biochemical parameters. Results: Pharmaceutical care significantly improved patients QoL and minimized DRPs and DDIs. It was also effective in improving the biochemical parameters. Conclusion: Pharmaceutical care has a positive impact on improving the outcome of patients with CKD-MBD through attenuating DRPs, improving the biochemical parameters and the QoL.


2016 ◽  
Vol 23 (17) ◽  
pp. 1698-1707 ◽  
Author(s):  
Domenico Santoro ◽  
Vincenzo Pellicanò ◽  
Valeria Cernaro ◽  
Viviana Lacava ◽  
Antonio Lacquaniti ◽  
...  

2018 ◽  
Vol 32 (10) ◽  
pp. 5215-5226 ◽  
Author(s):  
Benjamin P. Larkin ◽  
Sarah J. Glastras ◽  
Hui Chen ◽  
Carol A. Pollock ◽  
Sonia Saad

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