Table of Contents
Introduction:
The kidneys are involved in several conditions that affect humans. One such rare disease that causes manifestations in the renal system is Erdheim-Chester disease. Understanding the pathophysiology of renal involvement in Erdheim-Chester disease is important for prompt treatment and a better prognosis.
What Is Erdheim-Chester Disease?
Erdheim-Chester disease is an infrequent expression of non-Langerhan cell histiocytosis. In this disease, there will be a pathological buildup of a type of immune cells called histiocytes. There is an accumulation of these histiocytes in various bones, muscles, and internal organs. Generally, the systems involved are the cardiovascular system, the nervous system, and the retroperitoneal area. Long bones and skeletons are also involved. The common cause for this abnormal deposition of histiocytes is the genetic mutation of genes like BRAF and MAP2K1. This disease is also considered a cause of generalized inflammation in the body. So, the clinical manifestations of this rare disease include generalized fatigue and pain secondary to the inflammatory processes, fever, and weight loss.
What Are the Renal Manifestations of Erdheim-Chester Disease?
The involvement of kidneys is a crucial part of the progression of Erdheim-Chester disease. In advanced cases, some of these manifestations become the reason for the mortality of the affected patients. Common renal features noted are:
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Renal masses are the most common manifestations seen in Erdheim-Chester disease. This is because the depositing histiocytes (immune cells) tend to infiltrate the parenchyma of the kidney and accumulate within the renal tissues. This leads to the enlargement and distortion of the kidneys. This can cause continuous flank pain in the affected people and thus can only be diagnosed incidentally. The incidence of renal masses in Erdheim-Chester disease is always bilateral and symmetrical. Multiple renal masses are generally noted.
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As the histiocytes continue to infiltrate the parenchymal portion of the kidneys, the normal functioning of the kidneys gets disturbed. So, there may be differences in the body's glomerular filtration rate and electrolyte imbalance. This further causes edema (usually swelling of the limbs) and altered urine output.
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When the size of the renal masses advances, the adjacent structures can be obstructed. This leads to obstructive uropathy in patients with Erdheim-Chester disease. The urine flow becomes impaired due to obstruction of the duct. It can also cause hydronephrosis, where the renal pelvis dilates due to compression. The ureter can also dilate, resulting in a hydroureter. Obstructive uropathy causes a dull or sharp pain in the flanks, and patients may also complain of a change in the frequency of urination.
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As the obstruction continues and worsens, urine flow becomes increasingly compromised, leading to a buildup of urine in the affected kidney and ureter. This stasis of urine creates a favorable environment for bacterial or other microbial growth, thus increasing the risk of recurrent urinary tract infections. Additionally, the impaired drainage of urine from the affected kidney can lead to renal impairment and compromised kidney function over time.
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Involvement of blood vessels is a common component of Erdheim-Chester disease. This is also applicable to the renal arteries. Renal arteries will be involved in later stages. There will be stenosis or occlusion of the renal arteries supplying the kidneys. This is also the major cause of the incidence of renovascular hypertension (hypertension secondary to renal artery involvement) in patients with Erdheim-Chester disease.
How to Diagnose Erdheim-Chester Disease and Associated Renal Manifestations?
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The first step in diagnosing Erdheim-Chester disease is a general physical, systemic, and localized systemic examination. The involvement of the skeletal system, neurological deficits associated with the disease, and other associated cardiovascular symptoms should be noted.
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Magnetic resonance imaging shows the presence of masses in vital organs like the heart, kidneys, and lungs due to the buildup of histiocytes for a prolonged period. The involvement of kidneys can be characterized by the presence of nodular masses within the parenchyma of the kidneys. The renal masses have a peculiar appearance on radiographs, and they resemble the surface of a "hairy" kidney due to multiple small nodules or linear densities scattered throughout the renal cortex and medulla. The term "hairy kidney" is descriptive and does not imply the presence of actual hair or follicular structures within the kidneys but rather refers to the characteristic radiological appearance associated with Erdheim-Chester disease-related renal involvement.
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Positron emission tomography shows lesions of Erdheim-Chester disease as hypermetabolic areas or niches when seen through the maximal intensity projection.
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Positron emission tomography and contrast-enhanced computed tomography can also show Erdheim-Chester disease lesions as perinephric infiltrates (surrounding the kidneys). They are seen as hypermetabolic lesions.
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Percutaneous renal biopsy or biopsy obtained from the surgical sample can help diagnose Erdheim-Chester disease and its associated renal involvement. The histopathological examination of such samples would show abundant histiocytes with a frothy cytoplasm, Touton-type giant cells, and associated fibrosis seen as fibroblast infiltration.
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Immunohistochemical staining can help differentiate Erdheim-Chester disease from other histiocytic disorders and malignancies.
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Routine hematological laboratory investigations and urinalysis can also show evidence of renal involvement in Erdheim-Chester disease. Proteinuria and reduced urine output are these investigations' most common abnormalities.
All such investigations will help diagnose Erdheim-Chester disease according to the diagnostic criteria established by the Histiocyte Society. This will guide the doctors in making decisions regarding the appropriate treatment plan.
How to Manage Renal Manifestations of Erdheim-Chester Disease?
Rheumatologists, nephrologists, and oncologists are vital in deciding the most suitable treatment plan for individuals with Erdheim-Chester disease. The common strategies employed in the treatment plan are:
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Systemic therapies will be given to curb the chronic inflammatory process associated with Erdheim-Chester disease. Corticosteroids will be used as a part of the initial therapy. The use of immunomodulators and interferon-alpha will continue in the later stages.
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Recently, drugs like BRAF inhibitors (Vemurafenib) and MEK inhibitors (Trametinib) have been used for Erdheim-Chester disease.
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In advanced cases, localized renal masses will be surgically removed. Nephron-sparing surgeries will be considered to remove the masses while preserving the integrity of the functional units (nephrons).
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External beam radiation therapy may be an adjunctive treatment modality for unresectable or symptomatic renal masses, thus providing local disease control. This can also be helpful in patients with other comorbidities and anatomical limitations.
Conclusion:
Supportive renal care is the key to improving the condition in patients with renal involvement in Erdheim-Chester disease. Continuous monitoring of electrolyte imbalances, urine output range and frequency, and the incidence of renal masses is essential for a better prognosis.
