eMedicine Specialties > Urology > Stones

Hypocitraturia: Differential Diagnoses & Workup

Author: George Bennett Stackhouse IV, MD, Clinical Fellow in Endourology, Urology, University of California, San Francisco
Coauthor(s): Howard H Woo, MD, Consulting Staff, Clinical Instructor, Department of Urology, Ochsner Urology Institute
Contributor Information and Disclosures

Updated: Jun 16, 2006

Differential Diagnoses

Bariatric Surgery
Hyperparathyroidism
Medullary Sponge Kidney
Short-Bowel Syndrome
Struvite and Staghorn Calculi

Other Problems to Be Considered

Hypomagnesuria is another metabolic abnormality contributing to nephrolithiasis.

Workup

Laboratory Studies

  • Hypocitraturia, defined as less than 320 mg of citrate excreted per 24-hour urine collection, is diagnosed by 24-hour urine collection for metabolic stone risk analysis. Many laboratories have their own definitions of normal citrate levels. Other laboratory studies for stone workups may include urine analysis and culture, Sequential Multiple Analysis of 20 chemical constituents (SMA-20), serum uric acid, and parathyroid hormone (PTH) if the serum calcium is elevated.
  • 24-hour urine collection
    • The collection should be undertaken in recurrent stone formers, children, patients with solitary kidneys, and selectively in first-time stone formers with either increased risk (eg, family history of stones, bone or bowel disease, gout, chronic UTI, nephrocalcinosis) or who are sufficiently motivated to follow long-term therapy for stone prophylaxis.
    • A 24-hour urine sample is obtained for analysis of a full stone risk profile while patients maintain their customary activity level, diets and fluid intakes. Some practitioners always use 2 separate 24-hour urine collections for initial evaluation to avoid clinical confusion due to spurious variations in diet or activity. Patients should not have a metabolic stone risk profile while on a controlled diet in the hospital or while they are experiencing an acute renal colic attack.
    • Several commercial laboratories provide metabolic kidney stone prevention profiles, including Dianon, LabCorp, Litholink, Mission, Nichols, and Urocor. Some analyze only 24-hour urine data, while others include serum data and/or patient-reported clinical history and medications in their analysis. They calculate the total volume from the dilution of the volume marker and analyze metabolic risk factors (eg, calcium, oxalate, uric acid, citrate, pH) as well as total volume, sodium, phosphorus, and magnesium. Supersaturation ratios are calculated, and the risk of specific stone types is presented.
    • The 24-hour urine collection usually is deferred for several weeks after stone passage, although several studies have suggested that this may be unnecessary as long as the patient is following the regular routine diet and activity.
    • If the evaluation results are normal, the 24-hour collection may be repeated twice. If the evaluation results of metabolic stone workups remain normal after 2 separate 24-hour urine collections, idiopathic nephrolithiasis is suspected. False-positive 24-hour urine collection results can be caused by the patient altering the usual diet while being tested. The issue of defining what may be within the reference range versus what is optimal for a stone former also may exist. Increased fluid output almost always is recommended for recurrent stone formers regardless of the measured amount on a 24-hour urine testing.
    • In a large database of over 20,000 stone-forming patients with computerized analysis of the urinary and serum laboratory data, less than 1% demonstrated no urinary or serum chemistry abnormality related to possible kidney stone disease.
  • Urine analysis and culture
  • Sequential Multiple Analysis of 20 chemical constituents - Serum calcium, phosphorus, electrolyte, uric acid, and creatinine levels
  • Parathyroid hormone
  • Clinical examples
    • Complete type I RTA - Urine pH greater than 6.9, high serum chloride, low serum potassium, low bicarbonate levels, hypercalciuria (may be present)
    • Incomplete type I RTA - Normal electrolytes but poor response to acid load (NH4Cl 100 mg/kg administered PO, and urine pH does not fall below 5.3), hypercalciuria (may be present)
    • Chronic diarrhea - Urine pH less than 5.5, low urine volume, hypokalemia, hypomagnesemia, hypocalciuria, hypomagnesuria
    • Uric acid lithiasis - Some patients with uric acid stones may demonstrate unusually acidic urine and normal or near-normal uric acid excretion levels. In these cases, appropriate levels of potassium citrate should be used to alkalinize the urine sufficiently to prevent uric acid stone formation. Allopurinol is reserved for cases where potassium citrate supplementation is insufficient to stop uric acid stone formation or not tolerated for some reason. It also can be used in cases of calcium nephrolithiasis, gout, hyperuricemia, and hyperuricosuria, particularly where alkalinization alone has been inadequate to stop stone formation.

Imaging Studies

  • Kidneys, ureters, and bladder (KUB) radiography, intravenous pyelography (IVP), renal ultrasound, and noncontrast spiral CT scans are available to diagnose nephrolithiasis. On plain radiography, radiopaque stones imply the presence of calcium oxalate, calcium phosphate, struvite, or cystine. Radiolucency may implicate uric acid stones. Nephrocalcinosis may lead to consideration of type I RTA. Large branching stones are more likely to be infection stones or cystine stones. No imaging modality is sensitive or specific for hypocitraturia as an etiology for detected stones.
    • KUB radiography: This is the least specific but most available and inexpensive imaging modality for stone detection. KUB radiography is commonly used for follow-up of stone therapies or screening for recurrence.
    • Renal ultrasonography: This operator-dependent modality is widely available, noninvasive, and without ionizing radiation. Renal ultrasonography is typically used in pregnant women, in acute screening, and in follow-up in conjunction with KUB radiography.
    • Intravenous pyelography (IVP) or intravenous urography (IVU): These are widely available. The sensitivity and specificity of these modalities are better than those of plain KUB radiography. IVP and IVU are invasive and entail increased radiation exposure. Contrast allergy and nephropathy are associated risks.
    • Noncontrasted spiral computed tomography: The availability of this is increasing throughout the world. The radiation exposure is increased compared with KUB radiography, but this modality carries the best sensitivity and specificity for stone detection. Cross-sectional imaging also allows for evaluation of non–stone-related causes of flank or abdominal pain. Noncontrasted spiral computed tomography is typically used in the immediate evaluation of patients with colic.

Other Tests

  • Stone analysis: Urinary calculi secondary to hypocitraturia are typically composed of some hydroxyapatite (calcium phosphate) along with calcium oxalate.

More on Hypocitraturia

Overview: Hypocitraturia
Differential Diagnoses & Workup: Hypocitraturia
Treatment & Medication: Hypocitraturia
Follow-up: Hypocitraturia
References
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Further Reading

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Keywords

citrate, citric acid, nephrolithiasis, calcium nephrolithiasis, calcium oxalate, calcium phosphate, alkalinization, uric acid, potassium citrate

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Contributor Information and Disclosures

Author

George Bennett Stackhouse IV, MD, Clinical Fellow in Endourology, Urology, University of California, San Francisco
George Bennett Stackhouse IV, MD is a member of the following medical societies: Alpha Omega Alpha and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Howard H Woo, MD, Consulting Staff, Clinical Instructor, Department of Urology, Ochsner Urology Institute
Howard H Woo, MD is a member of the following medical societies: American Urological Association
Disclosure: Nothing to disclose.

Medical Editor

Leonard Gabriel Gomella, MD, FACS, Director of Urologic Oncology, Bernard W Godwin Associate Professor of Prostate Cancer, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University
Leonard Gabriel Gomella, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Laser Medicine and Surgery, American Urological Association, Sigma Xi, Society for Basic Urologic Research, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf, Jr, MD, FACS, David A Bloom Professor of Urology, Director, Division of Minimally Invasive Urology, Department of Urology, University of Michigan Medical Center
J Stuart Wolf, Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Stephen W Leslie, MD, FACS, Founder and Medical Director of the Lorain Kidney Stone Research Center, Clinical Assistant Professor, Department of Urology, Medical College of Ohio
Stephen W Leslie, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, National Kidney Foundation, and Ohio State Medical Association
Disclosure: Nothing to disclose.

 
 
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