Iron plays a critical role in the transport of oxygen and oxidative metabolism. Two important iron-containing proteins involved in these processes are hemoglobin and myoglobin. If stores of iron within the body become depleted, several processes are affected including erythropoiesis. As iron deficiency progresses and requirements for erythropoiesis are not met anemia may occur.
Adapted from Jacinto et al.1
Iron Deficiency Anemia and CKD
Chronic Kidney Disease (CKD) is a progressive disease that gradually impairs kidney function, usually over a period of years. It often progresses to end stage renal disease (ESRD), where the kidneys fail and renal replacement therapy such as dialysis or transplantation is required to sustain life. A significant complication of CKD is iron deficiency anemia, which develops early in the course of the disease and progresses with loss of renal function. Causes of iron deficiency in CKD patients include:
Functional Iron Deficiency vs Absolute Iron Deficiency
Functional iron deficiency is defined as a condition in which there is a failure to release iron rapidly enough to keep pace with the demands of the bone marrow for erythropoiesis, despite adequate total body iron stores. This condition is commonly associated with ESA usage:
Absolute iron deficiency occurs when total body iron stores become depleted. The amount of stored iron is no longer adequate to meet the demands for erythropoiesis.
Lab Values to Differentiate Function and Absolute Iron Deficiency
Hypotension has been reported frequently in non-dialysis dependent-CKD patients receiving IV iron. Hypotension following administration of Venofer® may be related to rate of administration and total dose delivered.
In a multi-dose efficacy study in non-dialysis dependent-CKD patients (N=91), the most frequent adverse events (≥5%) whether or not related to Venofer® administration, were taste disturbance (7.7%), peripheral edema (7.7%), diarrhea (5.5%), constipation (5.5%), nausea (5.5%), dizziness (5.5%), and hypertension (5.5%). In an additional study of Venofer® with varying erythropoietin doses in 96 treated NDD-CKD patients, adverse events, whether or not related to Venofer® reported by ≥5% of Venofer® exposed patients are as follows: diarrhea (16.5%), edema (16.5%), nausea (13.2%), vomiting (12.1%), arthralgia (7.7%), back pain (7.7%), headache (7.7%), hypertension (7.7%), taste disturbance (7.7%), dizziness (6.6%), extremity pain (5.5%), and injection site burning (5.5%).
In multi-dose efficacy studies in HDD-CKD patients (N=231), the most frequent adverse events (> 5%) whether or not related to Venofer® administration, were hypotension (39.4%), muscle cramps (29.4%), nausea (14.7%), headache (12.6%), graft complications (9.5%), vomiting (9.1%), dizziness (6.5%) hypertension (6.5%), chest pain (6.1%), and diarrhea (5.2%). In post-marketing safety studies in HDD-CKD patients (N=1051), the most frequent adverse events reported (>1%), whether or not related to Venofer® administration, were congestive heart failure, sepsis, and taste disturbance. In the study of PDD-CKD patients (N=75), the most frequent adverse events, whether or not related to Venofer®, reported by ≥5% of these patients were diarrhea (8.0%), peritoneal infection (8.0%) vomiting (8.0%), hypertension (8.0%), pharyngitis (6.7%), peripheral edema (5.3%), and nausea (5.3%).
Adapted from Jacinto et al.1
Iron Deficiency Anemia and CKD
Chronic Kidney Disease (CKD) is a progressive disease that gradually impairs kidney function, usually over a period of years. It often progresses to end stage renal disease (ESRD), where the kidneys fail and renal replacement therapy such as dialysis or transplantation is required to sustain life. A significant complication of CKD is iron deficiency anemia, which develops early in the course of the disease and progresses with loss of renal function. Causes of iron deficiency in CKD patients include:
- Use of ESAs
- Restricted diets
- Loss of blood (GI bleed, hemodialysis)
Functional Iron Deficiency vs Absolute Iron Deficiency
Functional iron deficiency is defined as a condition in which there is a failure to release iron rapidly enough to keep pace with the demands of the bone marrow for erythropoiesis, despite adequate total body iron stores. This condition is commonly associated with ESA usage:
- Dramatic increase in RBC production, Hb, and Hct due to ESA
- Iron uptake by erythroid cells is increased to meet demand of increased RBC production.
- Reticuloendothelial cells are unable to release stores of iron fast enough to meet demand.
- Despite adequate levels of stored iron (ferritin), insufficient iron is available for epoetin-stimulated RBC production.
- Eventually iron deficiency erythropoiesis develops; the RBCs produced are small and have low Hb content.
- In time, iron deficiency limits the response to epoetin therapy, and higher doses of epoetin are required to reach target Hb and Hct levels.
Absolute iron deficiency occurs when total body iron stores become depleted. The amount of stored iron is no longer adequate to meet the demands for erythropoiesis.
Lab Values to Differentiate Function and Absolute Iron Deficiency
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Venofer iron sucrose injection, USP. Reinvigorating anemia management
American Regent. Enriching the lives of anemia patients. ™
IMPORTANT SAFETY INFORMATION: Venofer® (iron sucrose injection, USP) is contraindicated in patients with evidence of iron overload, in patients with known hypersensitivity to Venofer® or any of its inactive components, and in patients with anemia not caused by iron deficiency. Serious hypersensitivity reactions have been reported in patients receiving Venofer®. In clinical studies, several patients experienced hypersensitivity reactions presenting with wheezing, dyspnea, hypotension, rashes, or pruritus. The post-marketing spontaneous reporting system includes reports of patients who experienced serious or life-threatening reactions (anaphylactic shock, loss of consciousness or collapse, bronchospasm with dyspnea, or convulsion) associated with Venofer® administration.Hypotension has been reported frequently in non-dialysis dependent-CKD patients receiving IV iron. Hypotension following administration of Venofer® may be related to rate of administration and total dose delivered.
In a multi-dose efficacy study in non-dialysis dependent-CKD patients (N=91), the most frequent adverse events (≥5%) whether or not related to Venofer® administration, were taste disturbance (7.7%), peripheral edema (7.7%), diarrhea (5.5%), constipation (5.5%), nausea (5.5%), dizziness (5.5%), and hypertension (5.5%). In an additional study of Venofer® with varying erythropoietin doses in 96 treated NDD-CKD patients, adverse events, whether or not related to Venofer® reported by ≥5% of Venofer® exposed patients are as follows: diarrhea (16.5%), edema (16.5%), nausea (13.2%), vomiting (12.1%), arthralgia (7.7%), back pain (7.7%), headache (7.7%), hypertension (7.7%), taste disturbance (7.7%), dizziness (6.6%), extremity pain (5.5%), and injection site burning (5.5%).
In multi-dose efficacy studies in HDD-CKD patients (N=231), the most frequent adverse events (> 5%) whether or not related to Venofer® administration, were hypotension (39.4%), muscle cramps (29.4%), nausea (14.7%), headache (12.6%), graft complications (9.5%), vomiting (9.1%), dizziness (6.5%) hypertension (6.5%), chest pain (6.1%), and diarrhea (5.2%). In post-marketing safety studies in HDD-CKD patients (N=1051), the most frequent adverse events reported (>1%), whether or not related to Venofer® administration, were congestive heart failure, sepsis, and taste disturbance. In the study of PDD-CKD patients (N=75), the most frequent adverse events, whether or not related to Venofer®, reported by ≥5% of these patients were diarrhea (8.0%), peritoneal infection (8.0%) vomiting (8.0%), hypertension (8.0%), pharyngitis (6.7%), peripheral edema (5.3%), and nausea (5.3%).
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