Nephrolithiasis - Kidney Stone

Nephrolithiasis accounts for significant morbidity and expense and is increasing in prevalence in the U.S.; an estimated 7% of females and 11% of males are affected during their lifetimes (Ingimarsson, 2016). Initial testing is usually a point-of-care urinalysis, followed by urinalysis with microscopy and/or culture, CBC, and basic metabolic panel to evaluate electrolytes and kidney function. Imaging is used to confirm presence of a stone and to determine whether intervention might be required for removal. A stone analysis and a 24-hour urine evaluation can help identify the cause of stone formation, although these are not often performed in adults experiencing a first stone. The first kidney stone in a child prompts a more complete workup.

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Clinical Overview

Diagnosis

Indications for Testing

Hematuria
Flank pain
Colicky back pain

Laboratory Testing

Initial testing
- Urinalysis
  - Point-of-care testing for hematuria
  - Urine microscopic testing
    - Blood indicates injury due to crystal passage
    - Crystals indicate the possibility of a stone
- Urine culture – consider to evaluate for concomitant urinary tract infection
- CBC – especially if symptoms of concomitant infection are present
- Serum electrolytes – evaluate for electrolyte abnormalities
- Blood urea nitrogen (BUN)/creatinine – evaluate for obstructive renal pathology

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

Not usually performed with first stone, except in children (refer to Pediatrics)
Usually includes electrolyte analysis (eg, sodium) and metabolic analysis (eg, oxalate and calcium)
Collection of two different urine specimens is recommended

Urine metabolic studies at ARUP

Urine Metabolic Studies at ARUP
Component	Kidney Stone Risk Panel, 0020843 (Basic Urine Panel)	Calculi Risk Assessment, 2008708 (Extended Urine Panel)	Supersaturation Profile, 2008771 Extended Urine Panel with Supersaturation Tests)
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 (PTH)-related peptide (PTHrP)
- PTH testing may be reserved for recurrent disease unless primary hypoparathyroidism is a concern
Amino acids analysis – evaluate when cystinuria is a concern or in those with cystine stones
Stone collection and analysis
- Repeat if there is lack of response to therapy, since stone composition may change

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 patients experiencing first stone
If performed, usually includes a minimum of the following
- Assessment within 6 months after treatment begins or changes; annually thereafter, 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)
Sex – M>F, 1.3:1
Ethnicity – Caucasian men have highest incidence
Geography – greater incidence in hotter and drier climates

Risk Factors

Risk Factors for Kidney Stones
Type of Stone	Percentage of Stones	Risk Factors
Calcium oxalate/calcium phosphate	70-90% (most common)	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), or 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
Hematuria – present in 90% of patients
Nausea and vomiting
Urinary urgency, frequency, and dysuria with stone passage

Pediatrics

Epidemiology

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

Clinical Presentation

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

Indications for Testing

Refer to Diagnosis

Laboratory Testing

Refer to Diagnosis
Differences in pediatric testing
- 24-hour urine evaluation recommended in the first episode due to high risk of metabolic problems underlying stone formation
- Amino acid analysis recommended
  - Evaluate for cystinuria in patients with elevated urine cystine – more common in children with nephrolithiasis

Monitoring

More important in children, even in those with first stone
- >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 panel testing
  - 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, 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

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

Kidney stone risk assessment and monitoring; includes interpretation of data

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

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

Recommended Use

May use 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

Initial test to diagnose or rule out cystinuria

Panel includes arginine, cystine, lysine, and ornithine

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

Recommended Use

Monitor treatment in patients previously diagnosed with cystinuria

To diagnose or rule out cystinuria, refer to the cystinuria panel or amino acids quantitative, urine

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

Recommended Use

Screen for disorders of amino acids transport (eg, cystinuria, lysinuric protein intolerance, hyperornithinemia-hyperammonemia-homocitrullinuria [HHH] syndrome)

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

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

Recommended Use

Determine composition and appearance of calculi

Medical Experts

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 Adjunct Professor of Clinical Pathology, University of Utah

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, 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
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

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

Ingimarsson JP, Krambeck AE, Pais VM. Diagnosis and Management of Nephrolithiasis. Surg Clin North Am. 2016; 96(3): 517-32. PubMed

Khan SR, Pearle MS, Robertson WG, Gambaro G, Canales BK, Doizi S, Traxer O, Tiselius H. Kidney stones. Nat Rev Dis Primers. 2016; 2: 16008. 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

Resources 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

Last Update: August 2019

Nephrolithiasis - Kidney Stone

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Screening

Monitoring

Background

Epidemiology

Risk Factors

Clinical Presentation

Pediatrics

Epidemiology

Clinical Presentation

Indications for Testing

Laboratory Testing

Monitoring

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Nephrolithiasis Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult


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	Nephrolithiasis - Kidney Stone. ARUP Consult^©. Retrieved October 15, 2019, from: https://arupconsult.com/content/nephrolithiasis

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Nephrolithiasis - Kidney Stone

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Screening

Monitoring

Background

Epidemiology

Risk Factors

Clinical Presentation

Pediatrics

Epidemiology

Clinical Presentation

Indications for Testing

Laboratory Testing

Monitoring

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Nephrolithiasis Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult