What Is Crystalline Nephropathy?
Crystalline nephropathy is characterized by the presence of intrarenal crystal deposition. These crystals form due to the nature of specific molecules and ions and the favorable tubular fluid physiology that encourages their precipitation and deposition within the tubular lumens. The resulting crystal deposition causes kidney injury by obstructing the tubules and causing direct and indirect cytotoxicity. Additionally, inflammation triggered by the crystals can cause further kidney damage.
Crystalline nephropathy is associated with urinary sediment findings, tubulopathies, acute kidney injury (AKI), and chronic kidney disease (CKD). Analysis of urine sediment is often useful in detecting crystal-related kidney injury. Pathologists can confirm the presence of crystals in kidney biopsy samples, which prompts clinicians to investigate potential causes such as medication-related kidney injury, dysproteinemia-related malignancies, and certain inherited disorders.
What Causes Crystalline Nephropathy?
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The deposition of crystals within the kidneys occurs primarily due to the high concentration of ions and molecules that pass through the tubules, increasing the likelihood of substrate supersaturation and crystal nucleation.
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These crystals have innate characteristics that cause them to aggregate in a symmetrical, fixed distance and form ordered 3-dimensional structures.
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The combination of injured cell membranes and urinary supersaturation of molecules with crystal-forming potential creates a basis for crystal deposition. Injured cells regulate cellular surface molecules, creating a local environment that favors crystal nucleation and adhesion, which provides a foundation for further crystal growth.
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Crystal deposition causes tubular obstruction and both direct and indirect kidney injuries related to crystals. Crystals that are phagocytosed destabilize lysosomes, leading to the release of their contents, which induces cellular stress and autophagic cell death.
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Renal tubular cell necroptosis occurs when various crystals damage lysosomes or phagolysosomes, causing cathepsin-B to be released, which cleaves key regulators of the cell death pathway such as RIPK3 (receptor-interacting protein kinase 3) and pseudokinase MLKL.
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Additionally, crystal-triggered cellular necrosis promotes the release of various substances into the extracellular compartment, including danger-associated molecular patterns, histones, double-stranded DNA, mitochondrial DNA, demethylated DNA and RNA, adenosine triphosphate, and uric acid. One or more of these substances engage the death receptors on neighboring cells, further amplifying cell necrosis.
What Are the Symptoms of Crystalline Nephropathy?
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Crystalline nephropathy can be acute or chronic.
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The disease is mainly characterized by the worsening of kidney function leading to renal insufficiency, which is irreversible.
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The presence of protein in the urine (proteinuria) is generally present.
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Hematuria (presence of blood in urine) is not accompanied by the disease progression.
What Are the Types of Crystalline Nephropathy?
Crystalline nephropathy can be divided into four categories based on the following:
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Clinical setting in which they are formed.
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The composition of the crystals.
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Drug-induced.
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Metabolic and genetic forms of crystalline nephropathy.
How Is Crystalline Nephropathy Diagnosed?
Crystalline nephropathy can be diagnosed through a combination of urine sediment examination and kidney biopsy.
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Urine Sediment Examination - Urine sediment examination is a diagnostic procedure that involves examining a urine sample under a microscope to detect abnormalities such as the presence of crystals, red blood cells, white blood cells, or other substances. In the case of crystalline nephropathy, urine sediment examination can aid in identifying the presence of crystals in the urine, which may suggest crystal-related kidney injury. Urine sediment examination may reveal the presence of crystals, which can indicate crystal-related kidney injury.
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Kidney Biopsy - Kidney biopsy is considered the gold standard for diagnosis as it can confirm the presence of intrarenal crystals and help identify the underlying cause of the disease. Pathologists can examine the crystal morphology and composition to determine the type of crystal present, which can provide clues about the underlying cause of the disease.
In addition to monitoring serum creatinine and urine sediment, other tests may be necessary to rule out kidney injury, depending on the patient's symptoms and medical history.
Some of these tests may include:
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Blood Tests: Blood tests such as electrolyte levels, complete blood count (CBC), and blood urea nitrogen (BUN) can provide valuable information about kidney function.
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Imaging Tests: Imaging tests such as ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can help visualize the kidneys and detect any abnormalities.
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Urine Tests: Additional urine tests such as urinary protein, creatinine clearance, and microalbuminuria can help diagnose kidney injury and monitor its progression.
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Renal Function Tests: Renal function tests measure the ability of the kidneys to filter waste products from the blood and include tests such as glomerular filtration rate (GFR) and creatinine clearance. These tests can help assess the severity of kidney injury and guide treatment.
How Is Crystalline Nephropathy Treated?
The treatment of crystalline nephropathy depends on the underlying cause and severity of the condition.
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Mild Cases - In some cases, if the condition is mild, the recommended treatment includes increased fluid intake to help flush out the crystals from the kidneys. This may be enough to alleviate the symptoms and prevent further damage to the kidneys.
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Severe Cases - If the condition is severe or if the crystals are causing significant damage to the kidneys, more aggressive treatment may be necessary. This may involve medications to help dissolve the crystals, or procedures such as extracorporeal shock wave lithotripsy (ESWL) or percutaneous nephrolithotomy (PCNL) to remove the crystals from the kidneys. If crystalline nephropathy is caused by an underlying medical condition, such as gout or hyperuricemia (an excess level of uric acid in the blood), treating that condition may help alleviate the symptoms of crystalline nephropathy.
To avoid crystalline nephropathy, it is recommended to regularly check the urine sediment and serum creatinine levels of high-risk patients, taking into account factors such as volume depletion, the use of nonsteroidal anti-inflammatory drugs, and acidic urine. To prevent the formation of urinary crystals and casts, alkalinization of the urine can be effective. The key to preventing and treating suspected crystalline nephropathy is to discontinue the suspected medication and rehydrate the patient. In cases of acute kidney injury (AKI), a kidney biopsy may be necessary to distinguish between acute interstitial nephritis (AIN) and crystalline nephropathy. If AIN is confirmed, corticosteroids may be helpful, while Amoxicillin should be avoided in the future. Urine alkalinization can also be helpful in preventing urinary crystal precipitation in the tubules for patients with urine pH levels below 6.0.
Conclusion:
Crystalline nephropathy is a distinct type of kidney disease that results from both direct and indirect injuries related to crystals, including inflammation and necroinflammation pathways. Clinicians and pathologists should be knowledgeable about the potential causes of crystalline nephropathies, such as medications, dysproteinemia, and inherited disorders. Diagnosis is reliant on the results of urine sediment examination and kidney biopsy, which can reveal the presence of intrarenal crystals.
