Chronic Kidney Disease (CKD) and Anemia: The Relationship with Red Blood Cell Survival

1. The Relationship Between CKD and Anemia

Patients with Chronic Kidney Disease (CKD) often experience anemia. When kidney function declines, factors such as decreased erythropoietin (EPO) production, iron metabolism abnormalities, and chronic inflammation lead to shorter red blood cell lifespan, resulting in anemia.

However, recent research has discovered another critical factor contributing to anemia: premature red blood cell death (eryptosis).

2. Research Findings: GFR Decline Determines Red Blood Cell Survival

A recent study found that a decrease in glomerular filtration rate (GFR) is closely linked to a reduction in red blood cell survival time. In other words, as CKD progresses, red blood cells die faster, exacerbating anemia.

Key findings of the study include:

The lifespan of red blood cells in CKD patients is approximately half that of healthy individuals (around 60 days in G5 stage).
As CKD progresses from G1 to G5, red blood cell death rates (measured by Annexin V-binding) significantly increase.
A negative correlation was found between eGFR and red blood cell death (r = -0.45, p < 0.001).
EPO response is insufficient in patients with severe anemia.

✅ What Are the CKD Stages (G1-G5)?

G1: Normal kidney function (eGFR ≥ 90 mL/min/1.73㎡) but with signs of damage.
G2: Mildly decreased kidney function (60 ≤ eGFR < 89).
G3a: Mild to moderate kidney function decline (45 ≤ eGFR < 59).
G3b: Moderate kidney function decline (30 ≤ eGFR < 44).
G4: Severe kidney function decline (15 ≤ eGFR < 29).
G5: End-stage kidney disease (eGFR < 15), requiring dialysis or kidney transplant.

✅ What Did Previous Research Reveal? Previous studies have identified EPO deficiency, iron deficiency, and increased chronic inflammation as primary causes of anemia in CKD patients. However, there was a lack of research directly linking GFR decline with red blood cell survival.

Previous studies observed increased eryptosis in CKD but did not clearly establish a direct relationship between CKD progression (GFR decline) and red blood cell survival.
Most research attributed shortened red blood cell lifespan to chronic inflammation and oxidative stress, with limited evidence pointing to GFR decline as a direct cause.
This study quantitatively analyzed red blood cell death at different CKD stages using Annexin V-binding, confirming that GFR decline is a key determinant.

(Reference: Bissinger R, Schaefer L, Bohnert BN, et al. “GFR is a Key Determinant of Red Blood Cell Survival in Anemia Associated With Progressive CKD.” Kidney Int Rep. 2025;10:730-742. https://doi.org/10.1016/j.ekir.2024.12.023)

3. Annexin V-binding and Red Blood Cell Death (Eryptosis)

📌 What Is Annexin V-binding?

During red blood cell death, phosphatidylserine (PS), which is normally located on the inner membrane, is exposed on the outer membrane. Annexin V is a protein that binds to PS, allowing for the measurement of red blood cell death levels.

In this study, Annexin V-binding levels in CKD patients were about 1.4 times higher than in healthy controls, indicating that increased eryptosis is a major contributor to anemia in CKD patients.

4. Effective Management Strategies for Anemia in CKD Patients

✅ Iron Supplementation Alone Is Not Enough

Traditionally, anemia in CKD was thought to be due to iron deficiency or EPO deficiency. However, this study highlights that shortened red blood cell lifespan is also a key factor. Thus, a more comprehensive treatment approach is required.

✅ Maintaining Kidney Function Is Essential

As GFR declines, red blood cell survival also decreases. Therefore, slowing kidney function deterioration through lifestyle modifications is crucial for CKD patients.

🔹 Low-sodium diet: Reducing sodium intake to relieve kidney burden. 🔹 Proper hydration: Preventing dehydration to protect kidney function. 🔹 Managing blood pressure and diabetes: Hypertension and diabetes accelerate CKD progression. 🔹 Regulating protein intake: Excessive protein consumption can increase kidney workload.

✅ Considering Antioxidant and Anti-inflammatory Treatments

One cause of increased red blood cell death is oxidative stress and inflammation. CKD patients may benefit from antioxidants and anti-inflammatory treatments.

🔹 Vitamin C, Vitamin E intake: Reduces oxidative stress. 🔹 Omega-3 fatty acids: Helps reduce inflammation. 🔹 Diet rich in antioxidants: Fruits, vegetables, and green tea.

5. Case Studies: Anemia Improvement in CKD Patients

📍 Case 1: 55-year-old Male, CKD Stage 3

Diagnosed with anemia (Hb level of 10.8 g/dL).
Did not improve with iron supplementation alone.
After lifestyle modifications and antioxidant supplementation, Hb increased to 11.5 g/dL.

📍 Case 2: 62-year-old Female, CKD Stage 4

Continued anemia despite EPO therapy.
Improved after incorporating omega-3 supplements and adjusting protein intake.

6. Conclusion: A New Approach to Managing Anemia in CKD

This study has clearly demonstrated that premature red blood cell death is a major cause of anemia in CKD patients.

💡 Maintaining GFR is key to preventing anemia → Lifestyle improvements are essential. 💡 Iron supplementation alone is insufficient → Strategies to enhance red blood cell survival are needed. 💡 Consider antioxidant and anti-inflammatory treatments → Reducing oxidative stress can help.

CKD patients should not rely solely on conventional anemia treatments but instead adopt a comprehensive strategy to prevent red blood cell death and protect kidney function. Future research should focus on developing therapies that enhance red blood cell lifespan, rather than just supplementing EPO.

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