What Is Radiation Nephropathy?
Radiation nephropathy is caused when the renal tissues are exposed to ionizing radiation to a limit greater than they are sensitive for. The intensity of radiation therapy is very limited to the normal tissues, which, when exceeded, causes damage and kidney toxicity. The damage to the renal tissues depends upon the different thresholds of radiation therapy. The presence of clinical radiation nephropathy is due to the use of total body irradiation (TBI).
Total body radiation is used as a preparative method for bone marrow transplantation and as a series of radionuclide therapies. The ionizing radiation breaks the double-stranded DNA damage, which causes direct cell death and also involves necrosis of glomerular, interstitial, and tubular cells.
Further, activation of the renin-angiotensin-aldosterone-system and vascular dysfunction might occur. Inflammation and oxidative changes in the renal tissues have also been noted due to radiation nephropathy.
What Is Radiation Therapy?
Radiation therapy, along with chemotherapy, is used as a treatment modality for treating various types of cancer. Radiotherapy can be given by the following-
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External Beam Radiotherapy - It is administered externally to the affected area. This is the most common form of radiation therapy.
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Brachytherapy - It is administered internally where the source of radiation is implanted inside the body.
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Radionuclide Therapy - Radionuclides are injected inside the body parenterally.
Radiation therapy is very effective in controlling the growth of tumors and increasing the lifespan of an organ affected by cancer. Despite all this, it has adverse effects on normal and healthy tissues of the body, which are within the field of radiation.
What Are the Effects of Radiation on Renal Tissues?
Radiation therapy is used to control the growth of tumors, but it has adverse effects on the normal healthy tissues under the radiation field. Exposure to a dose of 4 Gy can lead to kidney injury.It is difficult to selectively reach the tumor cells without affecting the normal tissues. The ionizing radiation targets mainly DNA by breaking the double-stranded DNA structure and destroying the chemical bonds that are removing the electrons. This radiation also causes damage by generating oxygen molecules called reactive oxygen species ROS. This leads to the formation of oxidative series.
The damage to the DNA causes cell death and instability. When the tumor cells are irradiated, the double-stranded break causes sella proptosis and changes in the mitotic division leading to cell death, thus killing the tumor cells. When the radiation therapy is exposed to the normal tissues, it leads to acute toxicity, which is marked by acute cell death, fibrogenesis, and extracellular matrix deposition. Fibrotic changes cause degeneration of the renal tissues.
What Are the Symptoms of Radiation Nephropathy?
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Azotemia - It is the increase in blood urea nitrogen (BUN) and serum creatinine levels. It occurs due to the damage to the renal tissues caused by ionizing radiation. The kidneys become incapable of filtering the nitrogen into the urine.
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Hypertension - Due to the disturbances in the renin-angiotensin-aldosterone system, there is an elevation in blood pressure.
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Anemia - Radiation to the hematopoietic organs causes abnormal production of RBCs or destruction of them, leading to severe anemia, which, when left untreated, causes renal failure.
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Other Symptoms - It includes shortness of breath, proteinuria, confusion or difficulty in concentration, cardiovascular diseases, and swelling in the arms and legs.
How to Diagnose Nephropathy Caused by Radiation Therapy?
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Kidney Biopsy - Fine needle aspiration cytology can be done to remove a piece of renal tissue by inserting a needle inside it. Biopsy indicates the necrosis and damage caused by radiation and also the presence of hypercellularity.
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Urine Test - This test provides results for the presence of azotemia, the presence of blood urea nitrogen (BUN), protein and red blood cells, creatinine clearance, urine specific gravity, total urine protein, and uric acid in the urine.
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Blood Test - This test measures the high level of serum creatinine, a decrease in the number of RBCs, abnormal albumin levels, abnormal blood urea nitrogen, and serum electrolytes- like potassium levels may be raised in patients with severe renal disease.
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Imaging Test - Computed tomography (CT scan).
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Kidney Ultrasound - Kidney ultrasound is used to check the size of a kidney or for the presence of any blockages.
How to Treat Radiation Nephropathy?
The renal injury cannot be reversed, but the disease progression can be slowed by using drugs like - anti-apoptotic drugs (anti-cell lysis), antioxidants, renin-angiotensin-aldosterone-system blockades, and statins.
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Anti-apoptotic Drugs -These are the drugs used to prevent cell suicide. For example- Caspase inhibitors are used for cell apoptosis.
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Anti-inflammatory Drugs - To reduce inflammation caused during nephrotoxicity, such as Montelukast.
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Antioxidants - Deferiprone, Genistein, and Apocynin reduce oxidation stress on the kidneys.
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Statins - Statins have effects on lipid metabolism and also have anti-inflammatory, anti-apoptotic, and antioxidant effects. Daily treatment with Atorvastatin seven days before 2 grays (Gy) radiation decreases lipid peroxidation and improves kidney function.
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Renin-Angiotensin-Aldosterone-System Blockade - RAAS-inhibition has a protective effect by reducing intraglomerular pressure and renal fibrosis. The nephroprotective effect of RAAS blockade is caused by the reduction of intraglomerular pressure and, as a result, reduced proteinuria with subsequently less tubulointerstitial damage. RAAS inhibition is also used in radiation injuries in the brain and lungs.
Conclusion :
The radiation therapy to treat tumors should be under the minimal tolerance level. Under this level that damage to the tissues is minimal and can be reversed. Doses ranging from 4 to 7Gy can be tolerated by the body. Radiation changes occurring in these ranges are minimal and can be brought to normal. High doses causing nephrotoxicity should be controlled by chemotherapy. Complete screening weeks and years after radiation therapy is very necessary to diagnose any changes occurring inside the irradiated regions.
