ROXADUSTAT : Magic Oral Drug for Managing CKD Anaemia

A very common problem faced by most Chronic Kidney Disease (CKD) patients is Anaemia. What is Anaemia? Anaemia happens when your Red Blood Cells are in short supply. Red Blood Cells carry oxygen from your lungs to all other parts of your body, Giving you the energy you require for our daily activities. So how is anaemia and chronic kidney disease related? Your kidneys are responsible for producing an important hormone called Erythropoietin (EPO). EPO tells your body to make red blood cells. When you have kidney disease, your kidneys do not produce enough EPO. Low EPO levels cause your red blood cell count to drop an anaemia to develop. Most people with kidney disease will develop anaemia. Anaemia can happen early in the course of kidney disease and grow worse as kidneys fail and can no longer make EPO.

To combat anaemia in chronic kidney disease a very new and innovative solution has come to the forefront. A new oral drug has been introduced in the market, and will be introduced for clinical treatment in the coming future. Anaemia in Chronic Kidney Disease is an age old issue and was first recognized by Robert Bright approximately 200 years ago. It is one of the most common findings among chronic kidney disease patients. It has been seen that more than 45% of people suffering from chronic kidney disease, also had anaemia. The health of a chronic kidney disease patient is greatly influenced by the existence of  anaemia in the patient; not only kidney health, but also the cardiovascular (heart) health and the mortality of the patient.

The causes of anaemia in chronic kidney disease patients are many, but the most common cause is Erythropoietin (EPO) deficiency. EPO is produced by the kidney, it is a hormone which stimulates the bone marrow to produce RBC (Red Blood Cells); which in turn keeps a healthy balance of haemoglobin in our blood. The malfunction of our kidneys lead to efficiency in the EPO levels in our blood, which leads to a diminished stimulation for the bone marrow to produce RBC. There are a few other factors like – Iron deficiency, Inflammation of the kidneys, etc. Inflammation of kidneys lead to the body being unable to utilize the iron properly and also a resistance to the utilization of EPO. There are some other factors apart from these three, which are the main causes; they are as follows:

  • Restricted diet, leading to a vitamin B12 deficiency.
  • Platelet dysfunctions.

Till now anaemia was being treated by administering an EPO shot to the patient, twice a week or thrice a week as per the requirement of the patient, and by giving iron supplements either orally or by injection, and to stop the bleeding of the GI tract via an endoscopy. These were the three main methods of treatment of anemia. These injections were administered to dialysis patients during dialysis or had to be administered at home for non-dialysis patients. Sometimes, the patients face some problems like EPO resistance, blood-bound infections, iron-deplete state. No patient had the same reaction.Thus, many studies were being conducted keeping these in mind.

Roxadustat has been a new discovery in this regard quite recently by researchers. In order to understand the function of Roxadustat, we must understand Hypoxia and Hypoxia Inducing Factor (HIF). Hypoxia is the state of absence of oxygen in the tissues to sustain normal body functions. When the body and the tissues are in an hypoxic state, the cells produce a specific inducer called Hypoxia Inducing Factor (HIF). It is a magic molecule, it was discovered that whenever the body is in hypoxia , HIF is produced. HIF has many benefits; it leads to the production of EPO, which leads to raised haemoglobin levels in the blood, which in turn reduces hypoxia. It also stimulates Vascular endothelial growth factor, this specific inducer generates new blood vessels in our boy. It helps in the reduction of hypoxia and in blood glucose metabolism.

In Chronic kidney Disease patients who have deficient EPO, scientists thought of increasing the HIF in the body, which is an indirect stimulant for EPO. This would reduce the external need for EPO injections. This was the basic principle of Roxadustat production. The HIF, as seen by scientists, does  not stay in the body for a long time; as it gets metabolised by hydroxylous enzyme called HIF alpha prolyl hydroxylase. The scientists wanted to increase the duration of HIF in our body, Roxadustat is an inhibitor for HIF alpha prolyl hydroxylase. This helps in the production of EPO indirectly. Roxadustat increases the duration of action time of the HIF.

As with all new drugs, Roxadustat also has a few side effects. It stimulates the production of Vascular Endothelial Growth Factor, this generates new blood vessels in our body. People who have tumors may want to steer clear of Roxadustat; as higher supply of blood in an area with a tumor may make the tumor grow faster. It can also lead to Pulmonary Hypertension, hyperkalemia and metabolic acidosis., but people who are undergoing diabetes are in the clear.

Roxadustat also helps with iron metabolism through hepcidin. Hepcidin is responsible for iron metabolism in the body; but that is a discussion for a different day. Till then, stay safe and healthy.

Published by Dr.Pratim Sengupta

Dr. Pratim Sengupta thinks of himself as conscious, living, soulful being with an inner urge to break the inertia of life. He feels that life is nothing but a material expression of the Supreme Almighty Consciousness. His conscious existence empowered him to see, to hear, to talk, to interact, to feel, to dream, to ask questions, and to seek solutions to every problem. In the flow of life, as he grew up, he understood that knowledge of life is the only way to understand the scientific basis of conscious existence. Hence Dr. Sengupta felt the urge to study the science of life – i.e. Medicine. After he completed his higher secondary education from the Ramakrishna Mission Vidyamandira in Belurmath, he joined the MBBS (Bachelor of Medicine, Bachelor of Surgery) course at RG Kar Medical College, Kolkata. The professional packaging of knowledge in terms of a time-bound, goal-oriented syllabus frustrated him a bit, but nevertheless ignited the urge within him to study further. He thus went on to his post-graduation (MD) in Medicine from IPGMER and SSKM Hospital, Kolkata. During his MD training, he got a glimpse of the vastness of knowledge, and the quest to learn precisely the facts of life narrowed down his area of interest to the functioning of the kidneys and the specialisation of Nephrology – a discipline that is complex, yet relatively new and still evolving in terms of complete understanding of renal physiology and pathology. So, Dr. Sengupta decided to study and train for the DM (Doctorate of Medicine) degree in Nephrology. Right from the start of his career, Dr. Sengupta was passionate about Research. During the MD programme he worked on Cirrhotic Cardiomyopathy, Autonomic Neuropathy of Lupus, and Insulin resistance in Diabetics. All these research studies were published in national journals. During his postdoctoral study in Nephrology, he worked on Hemodialysis efficiency, and suggested an angular placement of the Dialyser in order to increase efficiency. This innovative concept was accepted for presentation at the World Congress of Nephrology, Milan, in 2009, and also published in Hemodialysis International. Dr. Sengupta also worked on Plasmapheresis – a blood filtering technique by which toxic and pathogenic immunoglobulins can be removed from the body. He studied the role of Prethymectomy Plasmapheresis in Myasthenia Gravis patients, and his findings were published in the journal Interactive Cardiovascular and Thoracic Surgery. The patient-empowered nutritional model for nutritional care of kidney patients is another interesting and innovative area in which Dr. Sengupta has worked for quite a long time. Dr.Pratim Sengupta won the Bharat Jyoti award for his excellency in the field of medicine. He is also the president of our non-governmental organization, The Kidney Care Society. His tireless contribution to provide quality living for his patients is worth mentioning. He introduced Mukti, blending ancient Indian yoga with modern medicine for well being of every patient. He has also introduced an unique online course "Art of Living with diabetes" which is a complete solution to diabetes management. He has authored many books, blogs, for the patients. Searching and researching for solutions to problems in the field of Nephrology remains the passion and dream of Dr. Pratim Sengupta, and he intends to persist on this journey as long as he is conscious. Meanwhile, even as he pursues his dreams, Dr. Sengupta diligently puts into practice all he has learned about Nephrology over the years, at the Belle Vue Clinic in Kolkata and ILS hospital,Dumdum where he is available for his patient

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