Anemia in Kidney Disease & EPO too

Anemia in Kidney Disease & EPO too thumbnail
By admin
Published: September 23, 2009

Anemia for the normal population is defined as having less than the normal quantity of red blood cells within the blood. Each individual red cell contains within it the substance hemoglobin. This substance carries oxygen within the cell and releases it in organs where it is needed most. Oxygen is derived from the lung and the process of taking up oxygen into the red cell from the lung is known as oxygenation. Patients with chronic kidney disease are usually anemic for various reasons some of which are specific to kidney disease.

Anemia in CKD

Anemia in CKD


Creative Commons License photo credit: Andrew Mason

Patients with anemia have symptoms such as weakness and general lethargy, poor appetite, decreased capacity to exercise and usually describe themselves as generally unwell. The hormone responsible for the production of red blood cells is erythropoietin or epo. It is produced by the kidney, it then travels to the bone marrow where it stimulates the cells there to change into red blood cells and enter the circulation.

Patients with kidney disease may have anemia because the damaged kidney is unable to produce epo. The presence of toxins which accumulate in kidney disease also have a negative impact on the bone marrow to produce cells. Because of the depressed appetite present in patients with kidney disease there may be inadequate intake of the nutrients required to form the building blocks for the production of red blood cells. Patients with kidney disease are also deficient in iron due to slow leaks of iron from the gut due to the build up of toxins within the blood. When on dialysis there is blood lost in the dialysis tubing that further compounds this iron deficiency. Because of decreased levels of vitamin D there maybe elevated levels of another hormone known as PTH which can lead to damage of the bone marrow and decreased ability to produce red blood cells.

Treatment of anemia in kidney disease therefore relies on first determining the cause of the anemia. In addition to the usual causes detailed above, patients may also have anemia due to the preexisting diseases that cause anemia of which there are many. The evaluation to determine the cause never assumes that the anemia is only due to kidney disease.

If it is established that anemia is entirely due to kidney disease then treatment may commence by replacing the nutrients required for generation of red blood cells, iron and vitamins usually. Provision of adequate dialysis where necessary and the administration injectable of synthetic epo.

Epo is administered in such a manner as to maintain your blood count in the region of 11 to 12 grams of hemoglobin (Hb). Any higher and there is a risk of adverse events such as stroke or heart attack any lower and the benefits in terms of well being may be less than ideal.

Recently studies have suggested that there may be benefits of higher doses of epo. The authors of one study found that targeting a higher Hb around 12 g/dl was more beneficial than targeting conventional Hb in terms of reduction of the size of the heart and quality of life. Enlargement of the heart is a very serious complication of hypertension and anemia which can lead to early death in patients on dialysis. The fact that epo at higher doses may reduce the occurrence of this is exciting. In fact epo has recently been found to have a possible regulatory role in the function of the heart where studies have shown that administration of epo has direct effects on the muscle cells of the heart improving their function this study suggests that erythropoietin may have a direct positive effect on the heart and brain unrelated to correction of the anemia by reducing cell death and by increasing new blood vessel growth, both of which could prevent tissue damage. This could have profound therapeutic implications not only in heart failure but in the future treatment of myocardial infarction, coronary heart disease, strokes, and renal failure. These effects are independent of the effect of epo on the bone marrow.

However the current guidelines are based on very well done studies which have demonstrated increased mortality in patients with hemoglobin levels of greater than 12 g/dl. Other authors however are of the opinion that the increased mortality may not be due to the actual level of the hemoglobin but the dose of epo and iron required to get you there. These same authors are usually of the opinion that slowly increasing the levels of Hb over a longer period of time may be beneficial.

Erythropoietin currently is the best therapy available for anemia of chronic kidney disease. The exact dose and rate of increase in hemoglobin is likely to be revealed in upcoming studies.

Epo News

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4 Sep 2010 at 9:02am


EPO a No-go in Post-MI Patients: HEBE III

by Medscape Today Headlines
29 Aug 2010 at 2:40pm
While the trial missed its primary end point, investigators report that erythropoietin did reduce major adverse cardiovascular events, a reduction driven primarily by a lower incidence of heart failure. They caution against making too much of this secondary finding, however, and say that larger phase 3 studies are still needed. Heartwire (Source: Medscape Today Headlines)


Hospira Begins Phase I U.S. Clinical Trial Of Biosimilar Erythropoietin In Re…

by Health News from Medical News Today
28 Jul 2010 at 6:00pm
Hospira, Inc. (NYSE: HSP), the world leader in generic injectable pharmaceuticals, announced the start of a U.S. Phase I clinical trial of its biosimilar erythropoietin (EPO) in patients with renal (kidney) dysfunction who have anemia, an important step on the road toward introducing a biosimilar product in the United States. Erythropoietin is a treatment for anemia associated with chronic renal failure and chemotherapy… (Source: Health News from Medical News Today)


Akebia Announces Initiation Of Phase 2a Clinical Study Of AKB-6548

by Health News from Medical News Today
23 Jul 2010 at 8:00am
Akebia Therapeutics, Inc., a pharmaceutical discovery and development company focused on anemia and vascular disorders, announced that it has initiated dosing in patients for a phase 2a single dose clinical trial of AKB-6548, an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) in development for anemia. Akebia recently completed a phase 1b study of AKB-6548 which demonstrated a dose-dependent increase in erythropoietin (EPO), reticulocytes (immature red blood cells) and hemoglobin with no significant adverse events… (Source: Health News from Medical News Today)


Stopping EPO Bests Dose Reduction for ESRD Patients (CME/CE)

by MedPage Today Nephrology
22 Jul 2010 at 10:01pm
Hemodialysis patients had better hemoglobin profiles when the erythropoiesis-stimulating drug was stopped rather than dose reduced, data from a large cohort study showed. (Source: MedPage Today Nephrology)


ArmaGen® Re-engineers Erythropoietin For Brain Penetration

by Health News from Medical News Today
17 Jul 2010 at 7:00am
Human erythropoietin (EPO) is a potent neuroprotective agent for multiple brain disorders, including stroke, brain and spinal cord injury, and Parkinson’s disease. However, EPO drug development for the brain is limited, because EPO does not cross the blood-brain barrier (BBB). In acute stroke or brain injury, the BBB is intact in the early hours after the insult when neuroprotection is still possible. Therefore, large molecule biopharmaceuticals such as EPO must be re-engineered to enable BBB transport… (Source: Health News from Medical News Today)

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Akebia Announces Positive Results For AKB-6548 Phase 1b Clinical Study And Co…

by Health News from Medical News Today
17 Jun 2010 at 10:00am
Akebia Therapeutics, Inc., a pharmaceutical discovery and development company focused on anemia and vascular disorders, announced that it has successfully completed a phase 1b study for AKB-6548 in healthy volunteers. AKB-6548 is an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor designed to increase the natural production of erythropoietin (EPO) in anemic patients. In the clinical study, healthy volunteers were orally dosed once daily with AKB-6548 for 10 days… (Source: Health News from Medical News Today)

Epo News

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4 Sep 2010 at 9:02am


approval……….

by Carin’ For Karen
17 Aug 2010 at 12:08pm
Karen gets approval for aranesp injections…..she will get one shot every 3 weeks…..here is a little ditty on aranesp…
How Does It Work?
It belongs to a group of medications known as erythropoiesis-stimulating agents (ESAs). Aranesp is a man-made version of erythropoietin, a human protein that is produced in the kidneys. Aranesp works by stimulating the production [...] (Source: Carin’ For Karen)


New blog feature

by The A and P Professor
26 May 2010 at 10:00pm
This blog now has a new feature . . . AnswerTips. If you double-click any word or phrase in this blog, a floating box will appear with additional information.You can use this handy feature to:look up the meaning of an unfamiliar termfind the acronym or abbreviation of a term (or, conversely, find the meaning of the acronym)get a written and audio pronunciation guide for a termfind the word origin and word parts of a termfind related linksTry it right now by clicking this term . . . erythropoietin (used in a recent blog posting).Now try it on ANY other word in this or any other post on this blog.Yes . . . I’ve also added this feature to The A&P Professor website that serves as a resource-rich companion to this blog.Oh, and another thing . . .YOU can add this feature to your online sylla…


Latest in blood doping

by The A and P Professor
21 May 2010 at 10:00pm
The subject of blood doping has come up a few times in this blog.  Recently, we heard the latest in the Floyd Landis blood doping story . . . now, after years of vigorous (and costly) denials, cycling champion Landis has now admitted that he DID dope to prepare for competitions.Landis states the he used EPO (erythropoietin) to increase his hematocrit to improve performance during cycling events.(EPO is pictured here.)He has also stated that Lance Armstrong, another champion cyclist, gave him EPO and discussed his own blood doping experiences with Landis.  Armstrong denies these claims.Listen to the story from NPR:Cyclist Floyd Landis Admits Doping, Accuses ArmstrongI have an article on doping at The A&P Professor website that includes a lot of resources, as well as tips on us…


Biosimilars: Not So Dang Easy

by In the Pipeline
18 May 2010 at 3:26pm
This post drew a lot of comments here about how the big companies are going after follow-on biologic drugs. As a late-2008 article put it:

Merck already has one FOB in clinical development: a pegylated erythropoietin for anemia similar to Amgen’s Aranesp (darbapoetin alfa) called MK-2578, which is being developed using a sugar-modification technology the pharma obtained via its 2006 purchase of GlycoFi. The company hopes to launch its EPO product in dialysis and pre-dialysis patients with chronic kidney disease in 2012.

Clyburn declined to offer any sales projections for that product or the MBV unit in general, nor would he identify any of the other products or therapeutic areas Merck will attempt to develop. He said MBV will identify product candidates by looking at their value in the m…


Endocrine Today: Benefits of Collaboration to Create Cures

by Policy and Medicine
12 May 2010 at 10:00pm
Conclusion
In the end, patients derive benefits from collaboration between physicians and industry because without collaboration, advances in medical devices and drugs would be significantly stunted. Some commonly used drugs that came about as a result of industry-physician collaborations include calcium channel blockers, angiotensin-converting enzyme inhibitors, various statins, erythropoietin and phosphodiesterase type 5 inhibitors, vaccines, antibiotics, pacemakers, defibrillators, stents, cancer therapy, artificial hips and knees, and HIV medications. Clearly then, the benefits of the collaborations often outweigh the negatives.
Ultimately, for this progress to continue in the future, this framing bias must be eliminated, and relationships with physicians and industry must be acknowle…


I like Don Berwick, but …

by DB’s Medical Rants
29 Mar 2010 at 11:33am
So apparently Don Berwick is the nominee for CMS head.  I know and like Don Berwick.  No one can argue that he has done much to advance the fields of quality and safety.  But …
Don Berwick has the strengths and weaknesses of a zealot and proselytizer.  He believes a bit too strongly, and is unwilling to await data on his beliefs.  Bob Wachter wrote a brilliant piece about this in 2008 – The Great Quality Debate: Berwick’s Plea for Action vs. Evidence-Based Medicine
We must change how we deliver health care, but we must test our hypotheses.  We know too well that Robert Burns was right –

The best-laid plans o' mice an' men
Gang aft a-gley,
An' lea'e us nought but grief an' pain
For promised joy.

We see the …

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About Roger:
Dr. Roger Smith is a nephrologist currently employed to the government of Jamaica. He is the Nephrologist in charge of Spanish Town Dialysis Unit. His interests are lupus nephritis and other glomerulopathies. He was previously a lecturer in Nephrology at the University of the West Indies in the Department of Internal Medicine and Coordinator of the Urogenital Module before moving into private and government practice.

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