eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Uric Acid Stones

Author: Sahar Fathallah-Shaykh, MD, Assistant Professor in Pediatric Nephrology, Northwestern University Feinberg School of Medicine; Consulting Staff, Division of Kidney Diseases, Children's Memorial Hospital
Coauthor(s): Richard Neiberger, MD, PhD, Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital
Contributor Information and Disclosures

Updated: Jul 8, 2008

Introduction

Open table in new window

Table
Clinical Image Atlas

Click to view clinical images on the features, causes, epidemiology, diagnosis, and treatment of Gout.

Clinical Image Atlas

Click to view clinical images on the features, causes, epidemiology, diagnosis, and treatment of Gout.

Background

Uric acid stones are the most common cause of radiolucent kidney stones in children. Several products of purine metabolism are relatively insoluble and can precipitate when urinary pH is low. These include 2- or 8-dihydroxyadenine, adenine, xanthine, and uric acid. The crystals of uric acid may initiate calcium oxylate precipitation in metastable urine concentrates (see Xanthinuria).

The terms gouty nephropathy, urate nephropathy, and uric acid nephropathy are used to describe renal insufficiency due to uric acid precipitation within the renal tubules.

Uric acid urolithiasis or uric acid kidney stones refer to development of a stone or calculus composed of significant amounts of urate in the renal pelvis, ureter, or bladder.

Pathophysiology

Uric acid is a weak acid, with an ionization constant of acid (pK) of 5.8. At pH levels below the pK, uric acid is predominately found in a nonionized form. The urate ion is more soluble than the nonionized molecule. Urate ions (predominate form at a pH level of 7.4) are about 5% protein bound. Urate is filtered at the glomerulus. The renal tubule can reabsorb (movement of urate from tubule lumen to peritubular fluid) or secrete (movement of urate from peritubular fluid into tubular lumen) urate. Typically, net reabsorption occurs in infants and children. The fractional excretion of urate in infants and children ranges from about 0.1-0.6 (see the table below). 

Serum Uric Acid Levels and Urinary Acid Excretion in Neonates, Children, and Adults1

Open table in new window

Table

Neonates*ChildrenAdults
29-33 wk34-37 wk38-40 wk3-4 y5-9 y10-14 y40-44 y
MaleFemaleMaleFemaleMaleFemaleMaleFemale
Serum uric acid
(mg/dL)
7.71±2.656.04±2.195.19±1.573.45±1.013.44±0.83.63±1.043.71±0.924.28±1.194.09±1.25.134±1.254.25±1.1
Uric acid excretion
(mg/dL GFR)
4.8±2.232.81±0.931.69±0.840.34±0.110.403±0.095
Uric acid excretion
(mg/kg/d)
N/AN/A19.613.5±3.75
(3 y)
11.5±3.75
(7 y)
9±3.75
(12 y)
10
Fractional excretion of uric acid
(%)
61.24±12.2144.52±15.2338.19±13.6112±3.75
(3 y)
10±3
(7 y)
7.6±3.75
(12 y)
7±1.6

Neonates*ChildrenAdults
29-33 wk34-37 wk38-40 wk3-4 y5-9 y10-14 y40-44 y
MaleFemaleMaleFemaleMaleFemaleMaleFemale
Serum uric acid
(mg/dL)
7.71±2.656.04±2.195.19±1.573.45±1.013.44±0.83.63±1.043.71±0.924.28±1.194.09±1.25.134±1.254.25±1.1
Uric acid excretion
(mg/dL GFR)
4.8±2.232.81±0.931.69±0.840.34±0.110.403±0.095
Uric acid excretion
(mg/kg/d)
N/AN/A19.613.5±3.75
(3 y)
11.5±3.75
(7 y)
9±3.75
(12 y)
10
Fractional excretion of uric acid
(%)
61.24±12.2144.52±15.2338.19±13.6112±3.75
(3 y)
10±3
(7 y)
7.6±3.75
(12 y)
7±1.6

*Gestational ages

Glomerular filtration rate

For a printable version of this table see Media file 2.

The fractional excretion of urate can exceed 1, indicating net urate secretion.

When the concentration of uric acid in urine exceeds its solubility at the urine pH, uric acid changes from a compound dissolved in solution to an insoluble precipitate. Urate stones are formed by 1 of 3 general mechanisms: overproduction, increased tubular secretion, or decreased tubular reabsorption.

Uric acid results as a relatively insoluble end-product of purine metabolism. The concentration of uric acid in plasma depends on dietary ingestion, de novo purine synthesis, and uric acid elimination by the kidneys and intestine. Normal uric acid excretion is shown in the table above.

Diseases that produce uric acid nephropathy or pure uric acid stones in children are rare. They may be considered in 5 basic groups. The evaluation should be directed at identifying one of the following:

  • Group 1: The patient may have deficiencies in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase, or xanthine dehydrogenase enzymes. Mutations for these gene products occur as autosomal recessive, spontaneous, or X-linked. Assess for a history of deficiency of these enzymes, family history of gout at a young age, renal stones with uric acid in other family members, or glycogen-storage disease. A previous history of painful gross hematuria is requested in the proband.
  • Group 2: The patient may have tissue breakdown, which can produce large amounts of uric acid that precipitate in the nephron. This group includes children with primary leukemia and lymphoma. Other malignancies may produce uric acid nephropathy such as lung cancer, breast cancer, and pancreatic cancer; however, these conditions are very rare in children.
  • Group 3: These children have genetic defects in renal tubular urate reabsorption. The defects are X-linked or sporadic, and these patients have hyperuricosuria with hypouricemia. The high urinary urate concentration in the scenario of low urine volume and low urine pH tends to promote crystallization. Uricosuric drugs (eg, cellulose sodium phosphate, colchicine, probenecid, sulfinpyrazone) inhibit renal tubular urate reabsorption, producing hyperuricosuria.
  • Group 4: These children have hyperuricemia and hypouricosuria secondary to decreased renal excretion. This is due to decreased tubular secretion of uric acid rather than decreased filtered load. Children with familial juvenile gouty nephropathy are in this group. This condition is inherited in an autosomal dominant fashion. Several other children with similar pathology, which occurs in an isolated sporadic fashion, are reported. Glycogen-storage disease type I is also in this category.
  • Group 5: These children develop hyperuricosuria with or without hyperuricemia secondary to oral purine intake. Although unusual, this may occur with a diet rich in purines (eg, children with cystic fibrosis who take enzymes rich in purines). It may occur in children on ketogenic diets because the increase in ketoacids probably competes with uric acid via organic anion secretory transporters. Several drugs, such as hydrochlorothiazide (HCTZ), inhibit uric acid excretion in a similar manner.

Frequency

United States

The formation of uric acid stones in US children is infrequent. No population-based studies are available. A review of several reports shows the incidence of uric acid stones to be between 4 per 100 children and 4 per 1000 children with renal stones presenting to academic medical centers.

International

The incidence of uric acid stones in most parts of the world is not known. Uric acid stones tend to be more frequently reported in urban societies than rural societies. Persons with higher dietary protein intake are more likely to develop uric acid stones. Variation in incidence among different parts of the world is likely.

Mortality/Morbidity

Complications of renal stone diseases include renal failure, infection, pain, urinary tract obstruction, renal colic, gross hematuria, pallor, vomiting, sweating, nausea, and insomnia. In addition, if surgical intervention is necessary, surgical complications may occur.

  • Mortality and morbidity are not increased with uric acid stones compared with other stones; however, the process that leads to excess uric acid production (eg, malignancy, Lesch-Nyhan syndrome) may cause death.
  • Children may experience frequent bouts of pain and gross hematuria due to frequent uric acid stones.

Race

Uric acid stones are more frequent in white children.

Sex

Uric acid stones are more frequent in boys than in girls.

Age

With Lesch-Nyhan syndrome, the HGPRT defect is greater than 95%. A severe disease occurs. Numerous individuals have been reported with 20-50% of normal HGPRT function who develop uric acid stones as their primary manifestation.

  • Uric acid nephropathy (precipitation of urate crystals in renal tubules) and uric acid stones develop in people of any age (even infants or children). Occasionally, acute renal failure occurs secondary to crystal nephropathy in infants or children with inherited abnormalities of purine salvage enzymes. Renal failure produced by uric acid also occurs in children with leukemia and lymphoma as a component of tumor lysis disease. Children with Lesch-Nyhan disease may develop uric acid stones or nephropathy.
  • Remember that prepubertal children have relatively high uric acid clearance; therefore, hyperuricosuria rather than hyperuricemia may be the primary manifestation of uric acid overproduction in high-risk children.
  • Specific enzyme defects (ie, xanthine oxidase, phosphoribosyl pyrophosphate [PRPP] synthetase, adenine phosphoribosyltransferase, HGPRT) should be suspected if gout develops at an early age, if a family history of early gout is present, and if uric acid lithiasis is the first sign of excessive uric acid production.

Clinical

History

  • When obtaining the history, attempt to identify factors associated with hyperuricosuria such as the following:
  • Infants with urate crystalluria may have pink-to-orange areas in their diapers after urination. If Serratia marcescens is also present, the diaper may appear red.

Physical

Renal stones, particularly in the upper urinary tract, cause pain, costovertebral angle tenderness, or both. The manifestations of pain are expressed differently in infants than in teenagers. Hematuria is most often present. Fever, nausea, and vomiting occur. Urinary tract infection may be present.

  • No physical findings are sensitive or specific for uric acid urolithiasis.
  • Children with inherited disorders such as trisomy 21, glycogen-storage disease, or Lesch-Nyhan syndrome may have physical findings consistent with their inherited disease.
  • Children with malignancy may have findings such as lymphadenopathy, hepatosplenomegaly, or paleness secondary to anemia.
  • Tophi (urate deposits) may be present.

Causes

Uric acid stones are produced when the urinary uric acid concentration is increased secondary to overproduction, increased renal tubular urinary uric acid secretion, decreased renal tubular urinary uric acid reabsorption, decreased urinary water content, or increased hydrogen ion concentration.

  • Specific causes include the following purine enzyme defects, which lead to overproduction and increased urinary uric acid concentration:
    • HGPRT deficiency
    • PRPP synthetase overactivity
    • Glucose-6-phosphatase deficiency
  • Other causes include increased nucleotide turnover secondary to cell death.
    • Myeloproliferative and lymphoproliferative disorders
    • Hemolytic anemia
    • Cytotoxic drugs
  • Other causes include the following:
    • Excessive dietary purine intake producing increased urinary uric acid concentration
    • Decreased glomerular filtration, renal tubular uric acid reabsorption, or both producing increased uric acid concentration in urine (eg, renal failure, acidosis, drugs, lead nephropathy)
    • Dehydration produces decreased urine water content (ie, increased urine solute concentration) and increases urinary uric acid concentration.

More on Uric Acid Stones

Overview: Uric Acid Stones
Differential Diagnoses & Workup: Uric Acid Stones
Treatment & Medication: Uric Acid Stones
Follow-up: Uric Acid Stones
Multimedia: Uric Acid Stones
References

References

  1. Baldree LA, Stapleton FB. Uric acid metabolism in children. Pediatr Clin North Am. Apr 1990;37(2):391-418. [Medline].

  2. Kato K, Sai S, Hirata T, et al. Two cases of ammonium acid urate urinary stones related to anorexia nervosa and laxative abuse. Hinyokika Kiyo.Mar. 2004;50(3):181-5. [Medline].

  3. Sakhaee K, Maalouf NM. Metabolic syndrome and uric acid nephrolithiasis. Semin Nephrol. Mar 2008;28(2):174-80. [Medline].

  4. Raj GV, Auge BK, Assimos D, Preminger GM. Metabolic abnormalities associated with renal calculi in patients with horseshoe kidneys. J Endourol. Mar 2004;18(2):157-61. [Medline].

  5. Barrat TM, PG Duffy. Nephrocalcinosis and Urolithiasis. In: Pediatric Nephrology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:933-46.

  6. Camron JS, F Moro. Gout, Uric Acid, and Purine Metabolism in Pediatric Nephrology. In: Pediatric Nephrology. Vol 7. 1993:105-18.

  7. Johnson RJ, Kivlighn SD, Kim YG, et al. Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis. Feb 1999;33(2):225-34. [Medline].

Further Reading

Keywords

uric acid stones, radiolucent kidney stones, gouty nephropathy, urate nephropathy, uric acid urolithiasis, uric acid kidney stones, renal insufficiency, uric acid urolithiasis, renal stones, glycogen-storage disease, gross hematuria, leukemia, lymphoma, lung cancer, breast cancer, pancreatic cancer, hyperuricosuria, hypouricemia, familial juvenile gouty nephropathy, renal failure, urinary tract obstruction, insomnia, Lesch-Nyhan syndrome, tumor lysis disease, gout, polycythemia, lead exposure, congestive heart failure, sarcoidosis, purine disorder, laxative abuse, hypoxanthine-guanine phosphoribosyltransferase deficiency, HGPRT deficiency, phosphoribosyl pyrophosphate synthetase, PRPP synthetase, glucose-6-phosphatase deficiency, myeloproliferative disorder, lymphoproliferative disorder

Contributor Information and Disclosures

Author

Sahar Fathallah-Shaykh, MD, Assistant Professor in Pediatric Nephrology, Northwestern University Feinberg School of Medicine; Consulting Staff, Division of Kidney Diseases, Children's Memorial Hospital
Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology
Disclosure: emedecine Honoraria Other

Coauthor(s)

Richard Neiberger, MD, PhD, Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital
Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group
Disclosure: The Osler Institute Honoraria Speaking and teaching

Medical Editor

Uri S Alon, MD, Director of Research and Education, Department of Pediatrics, Division of Pediatric Nephrology, Children's Mercy Hospital of Kansas City; Professor, University of Missouri at Kansas City
Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Frederick J Kaskel, MD, PhD, Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine
Frederick J Kaskel, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.