Nephrolithiasis - Kidney Stone

Nephrolithiasis is a worldwide problem that accounts for significant morbidity and expense. Initial testing includes CBC, electrolytes, BUN/creatinine, and urinalysis. 24-hour urine evaluation is not usually performed with first stone, except in children.

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Patient with symptoms of a stone

Laboratory Testing

Initial testing
- CBC – evaluate for concomitant infection
- Electrolytes – evaluate for electrolyte abnormalities
- Blood urea nitrogen (BUN)/creatinine – evaluate for obstructive renal pathology
- Urinalysis with possible urine culture – evaluate for concomitant urinary tract infection

24-hour urine evaluation – use panel testing for most patients

Not usually performed with first stone (exception with children)
- Usually includes electrolyte analysis (eg, sodium) and metabolic analysis (eg, oxalate and calcium)
May delay risk assessment until stone disease recurs
Two different specimens recommended

Urine metabolic studies at ARUP

Urine Metabolic Studies at ARUP
Component	Kidney Stone Risk Panel	Calculi Risk Assessment	Supersaturation Profile
Total volume	X	X	X
pH		X	X
Calcium	X	X	X
Creatinine	X	X	X
Oxalate	X	X	X
Uric Acid	X	X	X
Chloride		X	X
Citric acid	X	X	X
Magnesium		X	X
Phosphorus		X	X
Potassium		X	X
Sodium		X	X
Sulfate			X
Calcium oxalate Supersaturation			X
Calcium phosphate supersaturation			X
Uric acid supersaturation			X

Serum – uric acid, ionized calcium, and parathyroid hormone-related peptide (PTH)
- PTH testing may be reserved for recurrent disease unless primary hypoparathyroidism is suspected
Amino acids analysis – evaluate when cystinuria is suspected or for those with cystine stones
Stone analysis
- Repeat if lack of response to therapy since stone composition may change

Imaging Studies

Helical CT scan can confirm presence and location of stones
- May help assess stone burden and risk of recurrence

Differential Diagnosis

Urinary tract infection
Ectopic pregnancy
Musculoskeletal pain
Ovarian cyst rupture
Ovarian torsion
Peritonitis
Prostatitis
Acute pyelonephritis
Interstitial cystitis
Groin hernia

Screening

There is no evidence to support screening for stones in asymptomatic patients.

Monitoring

Usually unnecessary in first-time stone former
If performed, usually includes a minimum of the following
- Assessment within 6 months after treatment begins or changes; thereafter annually, depending on stone activity (American Urological Association, 2014)
- 24-hour urine – kidney stone panel testing
  - Should include testing for calcium oxalate sodium, uric acid, citric acid, phosphorus, creatinine
  - Quantitative cystine in patients with cystinuria
- Serum – urea nitrogen, creatinine, and ionized calcium

Background

Epidemiology

Prevalence – 1-5/1,000
- 1/11 affected during lifetime (Pearle, 2014)
Age – peaks in 20s
Sex – M>F, 2-3:1
Ethnicity – Caucasian men have highest incidence
Geographic – hotter and drier climates

Risk Factors

Risk factors for kidney stones

Risk Factors for Kidney Stones
Type of Stone	Percentage of Stones	Risk Factors
Calcium oxalate/calcium phosphate	Most common (70-90%)	Dehydration Thiazide diuretics Increased intestinal absorption Pregnancy Primary hyperparathyroidism Chronic bowel malabsorption Chronic use of calcium-containing products Excessive consumption of Oxalate Phosphoric acid (cola products) Sugar-sweetened beverages
Magnesium ammonium phosphate Also referred to as struvite stones (staghorn calculi)	10-15%	Frequent urinary tract infections Presence of alkaline urine
Uric acid	5-15%	Gout Family history of gout or stones Malignancy treated with chemotherapy Diet high in purines
Cystine	1-2%	Hereditary cystinuria

Clinical Presentation

Acute, colicky flank pain radiating into the pelvis and genitalia
Nausea and vomiting
Urinary urgency, frequency, and dysuria may develop with stone passage
Hematuria – present in 90% of patients

Prevention

All stones – maintain urine volume ≥2.5 L/day
Uric acid stones – limit intake of nondairy protein, allopurinol (Agency for Healthcare Research and Quality [AHRQ], 2013)
Cystine stones – limit intake of protein and salt
Calcium oxalate stones (AHRQ, 2013; American Urological Association, 2014)
- Increase intake of fluid
- Reduce consumption of soft drinks
- Thiazide diuretics
- Citrate pharmacotherapy if urinary citrate is low
- Reduce sodium and animal protein
- If oxalate is relatively high – limit oxalate and use dairy products at mealtime to enhance binding of oxalate and calcium in gastrointestinal tract

Pediatrics

Clinical Background

Epidemiology

Incidence – 4.7/100,000 hospitalized
Lower than in adults

Clinical Presentation

Flank pain, abdominal pain
<5 years of age – nonspecific; nausea, emesis
Blood in urine, dysuria, urgency

Diagnosis

Indications for Testing

Patient with suspicion for stone

Laboratory Testing

Initial testing
- CBC – evaluate for concomitant infection
- Electrolytes – evaluate for electrolyte abnormalities
- Blood urea nitrogen (BUN)/creatinine – evaluate for obstructive renal pathology
- Urinalysis with possible urine culture – evaluate for concomitant urinary tract infection
24-hour urine evaluation
- May delay this risk assessment until stone disease recurs
- Initial testing should include 2 different specimens
- Recommended in first episode due to high risk of metabolic problems underlying stone
Amino acids analysis
- Evaluate for cystinuria in patients with elevated urine cystine – more common in children with nephrolithiasis

Monitoring

More important in children, even with first-time stone former
- >75% of stones in children are secondary to metabolic problems
Usually includes the following
- Assessment within 6 months after treatment begins or changes
- 24-hour urine evaluation – kidney stone panels to assess
  - Should include testing for calcium oxalate, sodium, uric acid, citric acid, phosphorus, creatinine
  - Quantitative urine cystine or urine amino acids analysis in patients with cystinuria
- Serum – urea nitrogen, creatinine, and ionized calcium

ARUP Lab Tests

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Calculi Risk Assessment, Urine 2008708
Method: Quantitative Spectrophotometry/Quantitative Enzymatic/Quantitative Ion-Selective Electrode

Recommended Use

Acceptable initial urine test for kidney stone risk assessment and monitoring

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

Supersaturation Profile, Urine 2008771
Method: Quantitative Spectrophotometry/Quantitative Enzymatic/Quantitative Ion-Selective Electrode

Recommended Use

Acceptable initial urine test for kidney stone risk assessment and monitoring; includes interpretation of data

Panel includes calcium, magnesium, sodium, sulfate, citric acid, oxalate, uric acid, potassium, creatinine (24-hour) chloride, and phosphorous

Limitations

Assessment for risk of magnesium ammonium phosphate (struvite) calculi is not included in this profile

Does not test for urine cystine

Follow-up

If magnesium ammonium phosphate calculi are suspected, order plasma ammonia testing

If cystine calculi are suspected, order cystinuria panel, cystine quantitative urine or amino acids quantitative urine tests

Kidney Stone Risk Panel, Urine 0020843
Method: Quantitative Spectrophotometry/Quantitative Enzymatic

Recommended Use

May be used to monitor kidney stone formation

Preferred test is urine supersaturation profile or urinary calculi risk assessment, depending on calculation need

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

Cystinuria Panel 0081105
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Recommended Use

Evaluate for cystinuria

Panel includes arginine, cystine, lysine, and ornithine

Cystine Quantitative, Urine 0081106
Method: Liquid Chromatography/Tandem Mass Spectrometry

Recommended Use

Monitor treatment in patients with cystinuria

Amino Acids Quantitative by LC-MS/MS, Urine 2009419
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Recommended Use

Use for risk assessment if cystine stone is found

Calculi (Stone) Analysis 0099460
Method: Quantitative Reflectance Fourier Transform Infrared Spectroscopy/Quantitative Polarizing Microscopy

Recommended Use

Determine composition of calculi

Determine causative agent of calculi

Calculi (Stone) Analysis with Photo 2005231
Method: Quantitative Reflectance Fourier Transform Infrared Spectroscopy/Quantitative Polarizing Microscopy

Recommended Use

Determine composition of calculi

Determine causative agent of calculi

For specimens smaller than 2 mg, refer to Calculi (Stone) Analysis

Medical Reviewers

De Biase, Irene, MD, PhD, Assistant Medical Director, Biochemical Genetics and Newborn Screening at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

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

Longo, Nicola, MD, PhD, Medical Director, Biochemical Genetics at ARUP Laboratories; Professor, Pediatrics and Associate Professor of Clinical Pathology, University of Utah

Openshaw, Amanda, MS, Genetic Counselor, Biochemical Genetics at ARUP Laboratories

Pasquali, Marzia, PhD, Laboratory Section Chief, Biochemical Genetics, and Medical Director, Biochemical Genetics and Newborn Screening, at ARUP Laboratories; Professor of Clinical Pathology and Co-Director, Fellowship Training Program in Biochemical Genetics, University of Utah

References

Guidelines

Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, Brasure M, Kane RL, Monga M. Recurrent Nephrolithiasis in Adults: Comparative Effectiveness of Preventive Medical Strategies [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US) 2012; :PubMed

Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, Brasure M, Kane RL, Ouellette J, Monga M. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann Intern Med. 2013; 158(7): 535-43. PubMed

Pearle MS, Goldfarb DS, Assimos DG, Curhan G, Denu-Ciocca CJ, Matlaga BR, Monga M, Penniston KL, Preminger GM, Turk TM, White JR, American Urological Assocation. Medical management of kidney stones: AUA guideline. J Urol. 2014; 192(2): 316-24. PubMed

General References

Brener ZZ, Winchester JF, Salman H, Bergman M. Nephrolithiasis: evaluation and management. South Med J. 2011; 104(2): 133-9. PubMed

Frassetto L, Kohlstadt I. Treatment and prevention of kidney stones: an update. Am Fam Physician. 2011; 84(11): 1234-42. PubMed

Goldfarb DS. In the clinic. Nephrolithiasis. Ann Intern Med. 2009; 151(3): ITC2. PubMed

Sakhaee K, Maalouf NM, Sinnott B. Clinical review. Kidney stones 2012: pathogenesis, diagnosis, and management. J Clin Endocrinol Metab. 2012; 97(6): 1847-60. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology^®

Gabrielsen S, Laciak RJ, Frank EL, McFadden M, Bates CS, Oottamasathien S, Hamilton BD, Wallis C. Pediatric urinary stone composition in the United States. J Urol. 2012; 187(6): 2182-7. PubMed

Testing Algorithms

Nephrolithiasis Testing Algorithm

Read more about Nephrolithiasis Testing Algorithm

Educational Videos

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Last Update: March 2018


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	Nephrolithiasis - Kidney Stone. ARUP Consult^©. Retrieved April 18, 2018, from: https://arupconsult.com/content/nephrolithiasis

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Nephrolithiasis - Kidney Stone

Tabs Content

Diagnosis

Indications for Testing

Laboratory Testing

Imaging Studies

Differential Diagnosis

Screening

Monitoring

Background

Epidemiology

Risk Factors

Clinical Presentation

Prevention

Pediatrics

Clinical Background

Epidemiology

Clinical Presentation

Diagnosis

Indications for Testing

Laboratory Testing

Monitoring

ARUP Lab Tests

Medical Reviewers

References

Guidelines

General References

References from the ARUP Institute for Clinical and Experimental Pathology®

Nephrolithiasis Testing Algorithm

References from the ARUP Institute for Clinical and Experimental Pathology^®