Nephrolithiasis - Kidney Stone Disease

Nephrolithiasis is on the rise throughout the world, and the estimated lifetime risk of developing nephrolithiasis is 6-12% in individuals in the United States.  Kidney stones (renal calculi) present with hematuria, flank pain, or back pain, which can occur in other conditions, including infection and obstruction of the genitourinary tract. Most small stones are passed spontaneously, but sometimes intervention to break up the stone with a laser or sound waves (lithotripsy) or a more invasive surgical removal is needed. Initial evaluation for a suspected urinary calculus may involve urinalysis with microscopy and culture, a complete blood count, and a metabolic panel to include kidney function testing. Further testing is recommended after initial stone formation in individuals at high risk for stone recurrence, in patients with recurrent stone formation, and in all children with stones. A stone analysis and evaluation of a 24-hour urine specimen for stone risk can help identify the cause of stone formation and may help prevent recurrence by targeting risk factors. 

Quick Answers for Clinicians

What role does laboratory testing play in kidney stone disease?

Laboratory testing can be used to aid in the diagnosis of a kidney stone, to evaluate risk factors for kidney stones, and to analyze the components of kidney stones. This information can help healthcare providers understand why a patient developed kidney stones and may provide guidance to reduce the risk of future stones.  

When is testing for kidney stone disease recommended?

Basic testing, including urinalysis and culture, may be performed to aid in diagnosis when there is clinical suspicion for kidney stones. If the diagnosis is confirmed, serum chemistries should be performed as a screening evaluation. The first kidney stone in a child, recurrent kidney stones in adults, or a stone in an adult who is at high risk for recurrent stones should prompt further testing. Extensive testing is generally not performed in adults with their first kidney stone who are at low risk for recurrence.  

What factors contribute to a higher risk for kidney stone recurrence?

Individuals with anatomic abnormalities of the genitourinary tract, early onset of stone formation, family history of stone formation, infection-associated stones, some genetic syndromes, certain gastrointestinal and metabolic diseases, history of bariatric surgery, and those who are taking particular medications are at a higher risk for kidney stone recurrence. 

What role does imaging play in kidney stone disease evaluation?

Clinical diagnosis of kidney stones is generally supported by imaging. Imaging may be used to confirm the presence of a stone and determine whether intervention might be required for removal. Ultrasound, the most common type of imaging used in stone assessment, can identify stones in the kidney or ureters and clarify indirect signs of a stone, including dilation of the ureter proximal to the stone. A computed tomography (CT) scan is more sensitive and specific than an ultrasound; however, ultrasound offers acceptable performance and is more cost-effective. Generally, ultrasound should be used as first-line imaging, especially in otherwise healthy patients younger than 50 years with a history of kidney stones who present with symptoms of uncomplicated nephrolithiasis. 

What are the different types of kidney stones?

Stones that contain calcium in the form of calcium oxalate and calcium phosphate are the most common, representing more than 80% of stones in the U.S. population, followed by uric acid, struvite, and cystine stones.  Calcium stones can be seen in adults with hypercalciuria, hyperoxaluria, and hypocitraturia. Uric acid stones tend to be found in individuals with features of metabolic syndrome, including high blood glucose, low concentrations of high-density lipoproteins (HDLs), high triglycerides, a large waist circumference, and high blood pressure. Struvite (magnesium ammonium phosphate) stones are associated with urinary tract infections, particularly those caused by Proteus, Klebsiella, or other urease-producing organisms. Cystine stones are found in patients with an autosomal recessive mutation in the cystine renal transporter protein.  

Which testing algorithms are related to this topic?

Indications for Testing

Testing should be considered when an individual presents with signs and symptoms of nephrolithiasis, is diagnosed with a kidney stone, or has a recurrence of stones. Patients tend to present with pain in the back, abdomen, or groin, nausea and/or vomiting, fever and chills, or other symptoms of a urinary tract infection, including blood in the urine, cloudy urine, a frequent urge or inability to urinate, or pain with urination.  In younger children, the signs may be more subtle and include irritability and changes in urinary habits. 

Criteria for Diagnosis

Diagnosis of nephrolithiasis is confirmed when a stone has passed, has been extracted or destroyed, or has been identified by imaging studies. Urinalysis that demonstrates hematuria can also help to confirm the diagnosis if the rest of the clinical picture is consistent with nephrolithiasis. 

Laboratory Testing

Metabolic evaluation and stone composition analysis are recommended for patients with recurrent stones or patients with an initial stone who are at high risk of recurrence, including those with a family history, pediatric patients, and young adult patients.  Other tests may be performed as part of an initial workup in patients with a first stone to narrow the differential diagnosis, evaluate for concomitant infection, or assess renal function.    

Initial Workup

When a patient presents with signs and symptoms of nephrolithiasis, a urinalysis that includes detection of blood should be performed. The presence of hematuria can support the diagnosis of a kidney stone in the appropriate setting. In patients with a new diagnosis of nephrolithiasis, a routine metabolic panel and urinalysis in addition to a detailed medical and dietary history are a good starting point for a basic evaluation. Chemistry tests should include serum/plasma electrolytes, calcium or ionized calcium, creatinine, and uric acid. The results could indicate an underlying medical condition that may be associated with kidney stone disease. Urinalysis should include a dipstick with pH and microscopic evaluation for crystals. If the urinalysis is suggestive of a urinary tract infection, a urine culture should be performed.  

Further Metabolic Evaluation

Additional metabolic testing should be performed in patients at high risk of stone recurrence or who have a personal history of stones. Testing for concentrations of urinary salts can be used to determine risk factors and guide treatment protocols. This evaluation should consist of one or two 24-hour urine collections (two are better) tested for volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine. If a cystine stone is found, urine amino acid analysis should be performed.  

Stone Composition

When a stone is available, particularly in the case of a patient with stone recurrence or an individual at high risk of recurrence, stone analysis should be performed. For those with recurrent stones, analysis may be performed on subsequent stones, especially if the patient is not responding to treatment or there is suspicion of a different type of stone, given that stone composition can change over time.   Stones are analyzed for heterogeneity, and the different components are tested separately. The clinically significant crystalline components identified in the specimens are reported and may guide medical or preventive management of the patient. 

Pediatrics

Comprehensive testing should be pursued in the first episode of a kidney stone in a pediatric patient due to the high risk of a metabolic disorder causing the stone formation. Stone composition analysis is recommended, if possible. Urinalysis and microscopic evaluation for crystals, urine culture, and a basic metabolic panel including calcium, magnesium, phosphorus, uric acid, and creatinine should be performed in any child with kidney stones. Evaluation of a 24-hour urine specimen for urine volume, pH, sodium, calcium, creatinine, citrate, oxalate, magnesium, phosphate, and creatinine should be performed when possible to evaluate for underlying metabolic abnormalities and other risk factors. Testing for cystinuria involves amino acid analysis for cystine, arginine, lysine, and ornithine on a urine sample and should be performed in patients with cystine stones or cystine crystals seen on microscopic evaluation of the urine.  

ARUP Laboratory Tests

Panels

Kidney stone risk assessment

Panel includes calcium, citric acid, creatinine, oxalate, and uric acid

Specimen: 24-hour urine collection

Kidney stone risk assessment and monitoring

Panel includes calcium, chloride, citric acid, creatinine, magnesium, oxalate, pH, phosphorus, potassium, sodium, and uric acid

Specimen: 24-hour urine collection

Kidney stone risk assessment and monitoring; includes interpretation of data

Panel includes calcium, chloride, citric acid, creatinine, magnesium, oxalate, pH, phosphorous, potassium, sodium, sulfate, and uric acid

Specimen: 24-hour urine collection

Use to evaluate for kidney dysfunction in patients with known risk factors

Panel includes albumin, calcium, carbon dioxide, creatinine, chloride, glucose, phosphorous, potassium, sodium, urea nitrogen, and a calculated anion gap value

Specimen: serum or plasma

Initial test to diagnose or rule out cystinuria

Cystinura panel includes arginine, cystine, lysine, and ornithine

Specimen: random urine

Composition Analysis

Use to determine composition of calculi

Specimen: calculus

Use to determine composition of calculi

Includes photograph of submitted specimen

Specimen: calculus

Related Tests

Use to evaluate renal function and to assess for electrolyte abnormalities

Panel includes: calcium, carbon dioxide, chloride, creatinine, glucose, potassium, sodium, and urea nitrogen

Specimen: serum or plasma

Use to detect urinary tract abnormalities, including crystals

Specimen: random urine

Quantitative culture to identify bacterial causes of urinary tract infections

Specimen: random urine

Individual Tests

Medical Experts

Author

Leonard

Picture of Nicole Leonard, MD

 

Nicole Leonard, MD
Anatomic and Clinical Pathology Resident, University of Utah School of Medicine and ARUP Laboratories
Contributor

Frank

Elizabeth L. Frank, PhD, DABCC
Professor of Pathology (Clinical), University of Utah
Medical Director, Analytic Biochemistry, Calculi and Manual Chemistry; Co-Medical Director, Mass Spectrometry, ARUP Laboratories

References

Additional Resources