Anemia is an inevitable complication during your Chronic Kidney Disease (CKD) Journey and there is no avoiding it. However, intensive medical research on this subject has enabled doctors to prescribe effective treatments to improve your blood counts.
In the course of this “Anemia-in-CKD Series“, we have already provided a comprehensive insight on:
1. Hemoglobin & its relation to Anemia
2. The reasons for Anemia in Chronic Kidney Disease (CKD)
3. The Clinical Protocol that your Doctor needs to follow to “diagnose” Anemia
4. A guide to analyzing your Blood Test Report to see if you are Anemic or not
Today’s article will throw light on the multi-pronged Treatment Approaches used by your doctor to try & keep your Anemia at bay.
TREATMENTS FOR ANEMIA IN CKD
Anemia entails an abnormal drop in red blood corpuscle (RBC) count. The special protein called Hemoglobin that transports Oxygen to all tissues across our body resides within RBCs. So, a fall in RBC count reduces the overall Hemoglobin content within our body. All in all, this jeopardizes our “in-house oxygen transport & delivery system” which in turn, leads to Clinical Signs & symptoms commonly associated with Anemia.
Keeping in sync with the above fact, anemia in CKD is treated using a multi-pronged approach. The plan is to “repair” the components of this “compromised oxygen transport system”.
Before we get into further detail, it is worthwhile that you go through the various causes of Anemia in CKD. In the image below, we have put together a comprehensive list of the same. It will help you better understand the available modalities.
Based on the above reasons, your nephrologist will prescribe you a multi-pronged treatment plan over time, that includes the following:
Measures to boost the RBC production process directly in the bone marrow
■ Injections of RBC-forming hormone — Erythropoietin
■ Supplements for Iron, Folic Acid and Vitamin B12.
Measures to instantly improve RBC numbers in circulation
■ Blood Transfusions.
The image below points-out the specific step of Red Blood Cell production and Circulation at which, anemia treatments work. Following this, find a comprehensive explanation for each modality.
APPROACHES THAT BOOST RBC PRODUCTION PROCESS
1. ERYTHROPOIETIN STIMULATING AGENTS (ESA)
Erythropoietin (pronounced as “erith-row-poy-tin”) or EPO is the hormone that is essential to kick-start the red blood cell formation process. RBC formation takes place in the marrow of our long bones. In good health, erythropoietin or EPO is almost exclusively produced by our kidneys. But when Chronic Kidney Disease hits, our unwell kidneys are not able to produce enough of this hormone to keep up with the normal pace of blood cell production that would allow for a healthy Oxygen transport system in our body. This is the chief reason for anemia in the course of chronic kidney disease.
Hence, injections of chemicals called Erythropoietin Stimulating Agents (ESA) form an important part of Anemia management in CKD. It acts by stimulating the specific blood-forming stem cells in our bone marrow to “start forming” more RBCs. This category includes Synthetic Erythropoietin (EPO) Hormone and “EPO Bio-similars” explained below.
□ Synthetic Erythropoietin (EPO)
Synthetic EPO is an artificially produced chemical in the lab which closely resembles Erythropoietin hormone naturally produced in our body. The time-frame for these injections to start showing clinical improvement is the same as the natural hormone. This stands at approximately 2 weeks. A commonly used Synthetic EPO injection is Injection Epoetin Alfa. Such injections are available in various strengths of 2000, 4000, 10,000 & 40,000 IU/mL. Your doctor will prescribe you a dose best suited to your anemic status.
Click the file below to download a comprehensive guide explaining the Usage, Effects, Side-effects and Contra-indications of Epoetin Alfa injections.
(Source: Janssen Biologics, Leiden, Netherlands)
□ Erythropoietin hormone (EPO) “Bio-similars”
EPO Bio-similars are chemicals which have specific minor but effective changes introduced in their molecular structure without greatly compromising on its broad resemblance with the natural hormone. Such changes in the chemical structure make EPO bio-similars longer-lasting with relatively faster clinical improvement as compared to synthetic EPO. In short, these analogues have enhanced overall blood-producing capabilities.
A commonly used EPO Analogue is “Darbepoietin Alfa” which requires low and less-frequent doses to get better RBC numbers relatively quickly. This formulation is available in various strengths ranging from 10 – 500 micrograms. Your doctor will advise you a dose tailored to your individual requirement.
Click the file below to download a comprehensive guide explaining the Usage, Effects, Side-effects and Contra-indications of Epoetin Alfa injections.
(Source: Amgen Limited, UK)
NOTE:
While Erythropoietin Stimulating Agents (ESA) mentioned above are usually pretty effective in raising your red blood cell counts, it is not free of medical concerns. Research in the past decade has indicated that while these medicines raise the Hematocrit or the proportion of red blood cells in your blood very rapidly, this could promote clot formation and strokes in a subset of patients with heart disease. Keeping in mind, the possibility of these dangerous complications, doctors have turned towards exercising caution with the dosage and frequency of ESA injections.
2. IRON SUPPLEMENTATION
Iron is a mineral that is essential for life to go on. Among the many of its critical functions in our body, the formation of the special Oxygen-transport protein — Hemoglobin within newly forming Red Blood Cells holds special significance.
When CKD patients develop anemia and their Red Blood Cell numbers start going down, there is an overall fall of Hemoglobin levels as well. Our body responds to this situation by initially using up body iron stores to compensate for falling Hemoglobin levels. However, with time, these body iron stores get depleted. Moreover, as CKD progresses, patients are unable to obtain enough Iron from food due to a poor nutritional status. These factors underscore the necessity of Iron Supplementation for anemic CKD patients.
Iron supplementation can either be a formulation that can be taken by mouth or that combined with Iron Infusions.
i. ORAL IRON
Doctors most preferably start Iron supplementation in the form of pills / syrups to be taken by mouth (fancy term: Oral route). However, only a limited portion of Iron taken by mouth is actually absorbed in our bloodstream per day. This means Oral Iron is predominantly beneficial in stable CKD patients with moderately depleted body iron stores.
For optimal benefit, clinical protocols currently suggest taking supplements that provide a total of 200-400 mg of elemental iron daily, taken in 2 or 3 divided doses.
ii. IRON INFUSION
If the bloodwork of Anemic CKD patients suggests low body iron stores or if the patient does not respond to oral iron supplements alone, doctors will advise additional Iron Infusions.
Since Iron Infusions pack-in all the iron directly into the patient’s bloodstream, it ensures faster recovery and restoration of Body Iron Stores. This would, in turn, rapidly boost Hemoglobin production within newly forming Red blood cells. Another benefit of infusions over oral iron supplements is the ability to bypass intestines to reach the bloodstream. This virtually eliminates the prospect of any bouts of constipation or diarrhoea which are otherwise known side-effects of oral iron.
NOTE:
Before starting an infusion, it is imperative for the nurse to conduct an allergy test on the patient with respect to the iron-formulation.
3. VITAMIN B12 & FOLIC ACID SUPPLEMENTATION
Akin to Iron, nutrients such as Folic Acid (Vitamin B9) and Vitamin B12 are also in short supply due to various dietary restrictions & an overall poor nutritional status in CKD patients.
Both these nutrients are essential for “maturation” of newly formed red blood cells. Basically, this helps form RBCs that have elastic membranes that do not rupture at the slightest nudge while ferrying across the body.
While RBCs do not stop forming in the absence of Folate & Vitamin B12, they are abnormally bloated up with thin membranes that rupture before RBCs complete their normal lifespan. What this means is, these “immature” RBCs are spacious enough to carry adequate Hemoglobin levels within them, but they “live for shorter periods” leading to a rapid decline in the “in-house oxygen work-force”.
Hence, monitoring & supplementation (with pills taken by mouth) of Folic Acid & Vitamin B12 (as needed) is a necessary treatment approach for Anemia in CKD.
WORD OF CAUTION
Folate and Vitamin B12 given to CKD patients are in much lower doses than those available in over-the-counter formulations on supermarket shelves. We understand, this sounds counter-productive. Point is, after metabolism, these vitamins normally move out of the body through Urine (via kidneys). Unwell kidneys will be unable to efficiently process the huge residue left after taking high doses of these vitamins. This would, in turn, cause dangerous side-effects due to what we call “Hyper-vitaminosis” (Vitamin Toxicity).
Moral of the story? Stick to the specific doses of Folate & Vitamin B12 advised by your medical team. Steer clear of over-the-counter “Vitamin punch” supplements.
APPROACHES THAT “INSTANTLY” INCREASE RBC NUMBERS
All anemia treatments mentioned in the above segment act directly on the Red Blood Cell (RBC) formation process within the bone marrow as shown in this picture.
This process takes approximately 14 days to supply new RBCs into the bloodstream. Hence, in the absence of other complications, it takes around 2 weeks to show any improvement in RBC count in the patient’s bloodwork.
However, if a CKD patient develops severe anemia due to sudden blood loss or infection, replenishing Red Blood Cell (RBC) numbers becomes a matter of urgency. That is when Blood Transfusion comes to our aid.
BLOOD TRANSFUSION
Blood Transfusion entails a severely anemic CKD patient receiving whole blood or “blood products” from a properly matched (human) blood donor.
Most patients specifically have a low Red Blood Cell count with other blood numbers within normal limits. They are more likely to receive a Packed Red Cell Transfusion. On the other hand, a general drop in the numbers of all blood cell types calls for a Whole Blood Transfusion. Whole Blood contains all cell types present in the human bloodstream.
Benefits:
The obvious benefit that blood transfusion brings with it is the “instant correction” of RBC numbers in the patient’s bloodstream. Infusing an entire army of red blood cells at a time restores near-normal oxygen transport to tissues almost immediately. This helps mitigate any possible complications arising from severe anemia and fast-tracks the way back to normal blood numbers.
Concerns:
If the anemic CKD patient concerned is on a Kidney Transplant wait-list already, it is imperative for them to know one thing. Blood transfusions add blood cells in their body from a separate human. Like all other cells in a human body, blood cells also carry specific “identity proteins” called “Antigens” on their outer surface. These numbers normally help our body to distinguish our own cells from particles from the outside.
You can only donate blood to someone with a similar blood group. This is so that the patient’s body “registers” the proteins on the new red blood cells from “outside” without aggressively attacking them. However, this “sensitizes” the immune system of such patients against any prospective donor kidney that carries some of these identity proteins on them. This may add to the time it takes to find a suitable kidney donor.
Despite these negative implications on a CKD patient’s chances of finding a matched kidney transplant, Blood transfusion stands as an approved modality. This is especially in the backdrop of pressing heart-related concerns with other promising treatments such as Erythropoietin Stimulating Agents (ESAs). However, blood transfusions are always the last resort in treating Anemia in CKD patients.
If you have had a history of blood transfusion during your Chronic Kidney Disease (CKD) journey and have had to change your medical team for some reason, always make it a point to mention this to your new medical team.
NOTE
Transplant candidates who have received blood transfusions can end up being highly sensitized to the “identity proteins” of the local kidney donor pool. In the US, current policy allows patients with >80% sensitization to qualify for extra points under the “Points-based system” of the Kidney Allocation process. This is to expedite the process of finding a matched kidney in such patients. Also, globally, patients who present with this situation have the option to go for something called a “Paired Kidney Donation”. (More on these provisions in a separate article soon!)
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