Overview of Radiation Nephritis
Radiation nephritis is a chronic interstitial nephritis that occurs after a large amount of radiation exposure, and the amount of radiation exposure that causes the onset of the disease is often more than 2,500 rad (25 Gy). It is a non-inflammatory, slowly progressive renal disease, which was discovered by Kunkler et al. in 1952. Young adults, individuals with renal hypertrophy due to single nephrectomy and other etiologies, and individuals with ectopic kidneys are susceptible to radiation injury. The disease occurs most often after irradiation of testes, ovaries, Wilm’s tumor, retroperitoneal lymphoma, osteogenic sarcoma, neurofibrosarcoma, or intraperitoneal metastases.
Etiology.
Radiation nephritis is most often seen in patients who have been radiologically treated for abdominal or genital tumors and have failed to provide any protection for the kidneys. There is a risk of developing this disease if the kidneys are irradiated with a dose of more than 23 Gy (2300 R) in a 5-week period.
Symptoms
The severity of kidney damage is positively correlated with the size of the irradiation dose. The incubation period is longer for those who have received smaller doses of irradiation, and most of them show asymptomatic proteinuria or mild hypertension and renal function impairment.
1. Acute radiation nephritis
The cause of acute radiation nephritis is not known, and the symptoms of nephritis usually appear 6-12 months after radiation exposure. In the incubation period, there may be mild proteinuria and hypertension, and the onset is often rapid, with shortness of breath, headache, loss of appetite, nausea and vomiting, and extreme fatigue. Thereafter, edema, moderate or severe hypertension, heart failure, anemia, proteinuria (mostly <2 g/day but occasionally as high as 4-5 g/day), tubular urine and microscopic hematuria, and progressive azotemia may occur.
2. Chronic radiation nephritis
Chronic radiation nephritis may develop from acute radiation nephritis, or be found after several years or even 10 years of radiation exposure. In the early stage, there is often no obvious history of acute radiation nephritis, and its clinical manifestations may be similar to chronic nephritis, manifested as asymptomatic proteinuria. In some cases, nephrotic syndrome may occur, with varying degrees of renal function impairment, with or without hypertension. The clinical manifestations of chronic radiation nephritis are similar to those of chronic interstitial nephritis due to other causes, and common symptoms include proteinuria, hypotonic urine, anemia, hypertension, and slowly progressive uremia. Hypertension is usually not severe due to sodium loss and decreased blood volume. Retroperitoneal sclerosis may exacerbate renal failure and salt loss by blocking one or both ureters. Radiation enteritis may coexist, and diarrhea can lead to protein and electrolyte loss.
3. Hypertension
After several years of radiation exposure, unexplained hypertension without renal failure may be benign, or it may be acute and malignant from the beginning. The cause may be due to unilateral renal ischemia alone. The mortality rate of acute and malignant hypertension is high and is mainly related to the severity of hypertension.
4. Simple proteinuria
In some mild cases, there may be only simple proteinuria for several years before slow progression to renal shrinkage and chronic progressive renal failure.
Tests
1. Laboratory tests
(1) Acute radiation nephritis: anemia, proteinuria (mostly <2 g/day, but occasionally as high as 4-5 g/day); tubular urine and microscopic hematuria, and progressive azotemia. Usually there is no erythrocyte tubular pattern in urine.
(2) Chronic radiculonephritis Simple proteinuria, salt-loss hypotonuria, and anemia are common; when the patient presents with chronic interstitial nephritis, mild to moderate proteinuria is present, with a small number of red and white blood cells in the urine sediment, and occasional granular tubular patterns are seen. Concentration function is poor (polyuria), and there may be hyponatremia, hypokalemia, and acidosis. Worsening renal impairment may have increased urea nitrogen and creatinine.
2. Renal biopsy
(1) Acute radiation nephritis: glomerular and tubular degeneration, interstitial edema and hemorrhage. Such as acute nephritis type, kidney size is normal, glomerular basement membrane thickening, fracture, vitreous degeneration, vascular endothelial cell degeneration, intima-media swelling, high dose irradiation of the renal artery and arteriolar wall fibrinoid necrosis, thrombosis; and even crescentic formation can be seen in some cases. There is no immunoglobulin, complement or fibrinogen deposition in immunofluorescence examination, and it is easy to distinguish the affected tissues from normal tissues.
(2) Chronic radiation nephritis In chronic radiation nephritis, the kidneys can be seen with severe vascular sclerosis, glomerular shrinkage and tethering sclerosis, tubular atrophy, interstitial fibrosis with mild inflammatory reaction, obvious fibrosis of the capsule, and necrotizing vasculopathy of malignant hypertension can be seen sometimes. Due to extensive necrosis and thrombosis of the arterial wall, glomerulosclerosis and tubular degenerative necrosis are triggered, which ultimately leads to renal atrophy. If only one kidney is irradiated unilaterally, the same lesions may be seen in the unilateral kidney.
Diagnosis
The diagnosis of the disease is made on the basis of clinical staging, laboratory tests, and history of radiation exposure to the renal region. The clinical staging is as follows:
1. Acute radiation nephritis
(1) Incubation period 6 to 12 months after radiation exposure, but may be shorter than 6 months in pediatric patients.
(2) Prodromal stage Blood pressure rises, anemia, heart enlargement, and proteinuria may be detected on examination.
(3) Clinical stage Once symptoms appear, it rapidly develops into extreme fatigue, loss of appetite, edema, intractable anemia, hypertension; laboratory tests show elevated BUN and Scr; after entering the clinical stage, the laboratory tests may show more than moderate proteinuria, and hematuria is rare.
2. Chronic radiation nephritis
(1) Incubation period may be derived from the acute stage, and some patients may develop the disease only after several years of radiation exposure, which is chronic in nature.
(2) Clinical stage: Main symptoms include anemia, hypertension, edema; proteinuria, tubular urine, hypotonic urine and impaired renal function.
3. Simple (asymptomatic) proteinuria
Patients with mild disease have only slight asymptomatic proteinuria, and renal function can be maintained normal under normal circumstances.
4. Benign hypertension
2.5-5 years after radiation exposure, hypertension with different degree of proteinuria, the prognosis is generally good.
5. Malignant hypertension
According to the time of its occurrence, early malignant hypertension, if it occurs in 18 months after receiving treatment, it is called late malignant hypertension, which is mostly caused by radiation-induced renal artery stenosis.
Treatment
1. General treatment
Including maintenance of renal function, lowering blood pressure and symptomatic treatment.
The treatment of acute radiation nephritis includes controlling hypertension, dealing with congestive heart failure and treating uremia. As the pathological damage of chronic radiation nephritis is irreversible, its treatment is mainly symptomatic and supportive, and the chronic renal failure is treated routinely. Epinephrine drops reduce damage by constricting tissue vasculature, and the lack of tumor vascular responsiveness to this drug makes the effectiveness of radiation therapy unaffected by this drug. Cell proliferation inhibitors protect the skin but not the kidneys. Control of hypertension is important, especially in the acute phase or in cases of malignant hypertension, and vasodilators and diuretics are commonly used. Hypertension may not respond to the aforementioned treatments, and a diagnosis of nephritis and renal ischemia occurring unilaterally or bilaterally (unilateral nephritis and renal ischemia are often not associated with an increase in plasma renin activity) is required to manage the condition symptomatically, if necessary.
For the treatment of heart failure, maintain water and electrolyte balance, ensure nutrition, and treat accordingly when foreign compression obstruction caused by in situ tumor or fibrosis is found, and carry out anti-infective treatment in time when urinary tract infection occurs.
2.Surgical treatment
If there is evidence of unilateral nephritis and renal ischemia, and there is malignant hypertension, unilateral nephrectomy can be considered, which can eliminate the malignant hypertension; there are reports that patients with nephrectomy on the diseased side can be cured of hypertension symptoms.
3.Dialysis treatment
Dialysis treatment is given in case of uremia.