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.

Quick Answers for Clinicians

Which testing algorithms are related to this topic?
Nephrolithiasis Testing Algorithm

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
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

Kidney stone risk assessment and monitoring

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

Kidney stone risk assessment and monitoring; includes interpretation of data

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

Initial test to diagnose or rule out cystinuria

Panel includes arginine, cystine, lysine, and ornithine

Monitor treatment in patients previously diagnosed with cystinuria

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

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

Determine composition of calculi

Determine composition and appearance of calculi

Related Tests

Evaluate for concomitant infection

Evaluate for obstructive pathology

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

Detect urinary tract abnormalities, including crystals

Quantitative culture to identify bacterial causes of urinary tract infections

Screening test to evaluate kidney function

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only when concentrations are at or above those expected during acetaminophen overdose

  

Evaluate individuals with calcium oxalate renal calculi

Assess the body pool size of oxalate

Aid in diagnosis and monitoring of gout or kidney stones

Aid in monitoring uric acid levels in patients at risk for kidney stone development

Assay interference (negative) may be observed when high concentrations of NAC are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only when concentrations are at or above those expected during acetaminophen overdose

Aid in the evaluation of unexplained hypercalcemia, particularly in suspected hypercalcemia, particularly if possible hypercalcemia of malignancy

Aid in the diagnosis of and monitoring of treatment for hypercalcemia

Highly specific test for PTHrP

Amino (N)- and carboxy (C)-terminus PTHrP fragments, such as those produced by some patients with renal insufficiency, do not interfere with this assay

   

Medical Experts

Contributor

De Biase

 

Irene De Biase, MD, PhD

Assistant Professor of Clinical Pathology, University of Utah

Assistant Medical Director, Biochemical Genetics and Newborn Screening at ARUP Laboratories

Contributor

Frank

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

Longo

Nicola Longo, MD, PhD

Nicola Longo, MD, PhD

Professor, Pediatrics, and Adjunct Professor of Clinical Pathology, University of Utah

Medical Director, Biochemical Genetics at ARUP Laboratories

Contributor

Pasquali

Marzia Pasquali, PhD

Marzia Pasquali, PhD

Professor of Clinical Pathology and Co-Director, Fellowship Training Program in Biochemical Genetics, University of Utah

Laboratory Section Chief, Biochemical Genetics, and Medical Director, Biochemical Genetics and Newborn Screening, at ARUP Laboratories

References

Additional Resources

  • 22896859

    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

    Generic

  • 27188687

    Khan SR

    Pearle MS

    Robertson WG

    Gambaro G

    Canales BK

    Doizi S

    Traxer O

    Tiselius HG

    Kidney stones.

    Nat Rev Dis Primers

    2016
    2
    16008
    PubMed
    • Resources from the ARUP Institute for Clinical and Experimental Pathology®

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