What Are the Common Metabolic Causes of Urolithiasis?

A 21-year-old male came to the emergency room with acute onset of severe back pain and emesis for 3 hours.
He was awoken with the pain which he described as starting in his left costovertebral angle (CVA) and radiating across the flank and toward the pelvis.
The pain was most intense in the CVA and diminished as it radiated. He had one episode of emesis of a small amount of stomach contents that was non-bilious.
He also had a small amount of concentrated urine.
The day previous, he had drunk very little because of being busy with his classes and had worked outside in a hot environment as a landscaper.
The family history was positive for kidney stones in his father x 2 that resolved spontaneously.
The past medical history and review of systems were otherwise negative.
The pertinent physical exam showed a male in moderate distress secondary to pain with an elevated blood pressure. He was slightly diaphoretic but was afebrile.
He had dry mucous membranes and skin turgor.
He had exquisite tenderness in the left CVA that radiated around the left flank and toward the pelvis. He had no abdominal masses and his genitourinary examination was normal.
The laboratory evaluation showed an urinalysis with a specific gravity of > 1.030, 50 red blood cells, no white blood cells, no casts, and some crystals.
A complete blood count and a basic metabolic profile were normal including a blood urea nitrogen, creatine, calcium and phosphorus.
The diagnosis of urolithiasis was made. He was given intravenous morphine for the pain and 2.5 liters of normal saline fluid.
At that point he started to be able to drink fluids but was still nauseated. His blood pressure had also returned to normal.
He was discharged with instructions to drink small amounts of fluid almost continuously to maintain a copious urine output.
Codeine was given for pain control and he was given a sieve to screen his urine.
He was also instructed on the necessity to drink throughout his day especially when he was performing manual labor or in a hot environment to maintain hydration and try to prevent another stone.
The patient’s clinical course two days later showed he went to the student health service at his university with the stone that was later identified as a calcium urate stone.
The urine culture from the emergency room was negative. A repeated urinalysis was normal.
The physician re-emphasized the need to maintain adequate or increased hydration as a way to help prevent future stone formation.
Further metabolic testing was deferred to his primary care physician in his hometown because of medical insurance.

Discussion
Metabolic causes of urolithiasis are increasing.
The common metabolic causes of urolithiasis in children are below along with their percentages:

  • Hypercalciuria – 30-50%, these are radiopaque on radiographs
  • Hyperoxaluria – 20%, these are radiopaque on radiographs
  • Hyperuricosuria – 2-10%, these are not radiopaque on radiographs
  • Cystinuria – <1%, these are not radiopaque on radiographs
  • Xanthinuria – <1%, these are not radiopaque on radiographs

Patients presenting with urolithiasis should have a metabolic evaluation to help determine the etiology and possible treatments.
Metabolic evaluation may include the following:

  • Serum – electrolytes, creatinine, calcium, phosphorus, uric acid, and alkaline phosphatase.
    Parathyroid hormone in patients with hypercalciuria, hypercalcemia or hypophosphatemia.

  • 24-hour urine collection – creatine, calcium, sodium, urate, oxalate, citrate and cystine.
  • Urine culture

Learning Point
Urolithiasis is uncommon in children compared to adults. Children are only ~2-3% of all cases of urolithiasis and have about 1/50th the rate of hospital admission for urolithiasis compared to adults.
Boys have urolithiasis more commonly than girls. There are also geographical differences. The southeastern area of the United States has a higher incidence.
Globally, areas around the Balkans, Turkey, Pakistan and India have a higher rate of urolithiasis and bladder stones, presumably because of dietary and hydration differences.
In a United Kingdom study in 2003, the underlying causes of urolithiasis were metabolic (44%), infectious (30%) and idiopathic (26%).

Factors that are involved in urolithiasis formation include:

  • Metabolic
    • Urine
      • Concentration
      • Ionic activity
      • Solubility
      • Abnormal metabolites present
      • Elevated concentration of normal metabolites
  • Infectious
    • Klebsiella
    • Proteus
    • Pseudomonas
  • Other
    • Anatomic abnormalities of the urinary tract
    • Foreign bodies – stents, sutures
    • Prematurity – infants < 32 weeks gestation have a higher risk for developing urolithiasis

Questions for Further Discussion
1. What radiological modalities can be used to image urolithiasis?
2. What are the indications for lithotripsy or surgery for urolithiaisis?
3. Where are the most common anatomic places for urolithiasis to lodge?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Kidney Stone.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Nicoletta JA, Lande MB. Medical evaluation and treatment of urolithiasis.
Pediatr Clin North Am. 2006 Jun;53(3):479-91, vii.

Hiorns MP.
Imaging of urinary tract lithiasis: who, when and how?

Pediatr Radiol. 2008 Jun;38 Suppl 3:S497-500

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    January 19, 2009

  • What is Mauriac Syndrome?

    Patient Presentation
    A 12.5-year-old female was referred to endocrinology for short stature.
    She has been followed intermittently by the endocrinologists for type 1 diabetes melitis for 4 years.
    Her last visit was 1 year ago and she was showing some growth slowing at that time.
    Laboratory testing at that time showed normal thyroid and insulin- like growth factors (IGF) tests, a hemoglobin A1c of 9%, and a bone age that was 16 months delayed.
    Her father states that she checks her blood sugars several times a day and they generally run “low.”The patient does not have any signs of puberty yet.
    The past medical history shows difficult control of the diabetes.
    The patient is on a standard insulin regimen with meals and a sliding scale for corrections. Parents and patient do not know the sliding scale.
    The family history showed the Mother is 5’1″. Father and brother are 5’6″. Sister is 5’2″ and maternal grandmother is 4’10”.
    Brother and sister are adults and menarche in the maternal family occurs at ~11-12 years of age.
    The review of systems was negative.
    The pertinent physical exam showed normal vital signs with a weight of 29.8 kg (50% for a 9.5 year old) and a height of 129.3 cm (50% for a 8.5 year old).
    She had no dysmorphic features, but a rounded, moonish face.
    She had a protuberant abdomen that revealed a liver edge to the umbilicus without splenomegaly or other masses.
    She was Tanner stage I for pubic hair and breasts. She had extra nuchal fat.
    A working diagnosis of Mauriac syndrome was made but other testing for other diseases was done.
    The laboratory evaluation included
    thyroid testing, celiac disease testing, leutenizing hormone and follicle stimulating hormone, insulin-like growth factors, hepatitis screening, and a complete blood count were all negative.
    The liver function tests were elevated with aspartate aminotrassferase 1538 U/L (normal 10-40), alanine aminotransferase 782 U/L (normal 5-20) and a normal albumin.
    The radiologic evaluation of a right upper quadrant ultrasound revealed a liver span of 16 cm that was homogeneous without focal lesions.
    She was seen by the gastroenterologists and was admitted for a liver biopsy which showed homogeneous glycogen deposition in the hepatocytes.
    The diagnosis of Mauriac syndrome was made and the patient was begun on strict diabetes control initiated in the hospital.

    Discussion
    Patients with type 1 diabetes mellitus may have growth failure for many reasons including insulin deficiency, poor glycemic control, concurrent autoimmune diseases, and decreased caloric intake and/or eating disorders.
    Autoimmune diseases that are more common include Addison’s disease, autoimmune gastritis, celiac disease and hypothyroidism.
    Prior to treatment with long-acting insulin, delays in growth and sexual maturity were common but generally modest.
    Even today with good treatment, patients may have subtle abnormalities of growth (both weight and height) due to abnormalities of the IGF-1 and growth hormone axis.

    Learning Point
    Mauriac syndrome is a severe form of growth retardation seen in patients with poorly controlled type 1 diabetes mellitus.
    It is characterized by growth failure, delayed puberty, hepatomegaly and Cushingoid features.
    It is often referred to as diabetic dwarfism.
    The actual cause is unknown but is probably a combination of factors including inadequate glucose in the tissues, decreased IGF-1 and growth hormone levels, impaired bioactivity of the hormones, a circulating hormone inhibitor, or resistant or defective hormone receptors.
    The hepatomegaly seen in Mauriac syndrome is not seen in newly diagnosed patients who have been severely insulin deficient because it appears that periods of supraphysiologic insulin levels are associated with the hepatomegaly.

    Mauriac syndrome was much more common before long-acting insulin and knowledge of glycemic control (including monitoring of hemoglobin A1c’s) was available and is relatively rare today because of these treatments.
    It occurs in males and females equally and is most common in adolescence although there are reports in children as young as toddlers and in adults.

    Improved glycemic control helps to reverse the process, but catch-up growth may not be complete.
    Aggressive insulin treatment also may cause rapid advancement of retinopathy and nephropathy so a delicate balance in strict control but not over control is necessary.

    Questions for Further Discussion
    1. How long after diagnosis of type 1 diabetes mellitus, should screening for retinopathy and nephropathy occur?
    2. How common are eating disorders and suicidal gestures in patients with type 1 diabetes mellitus?
    3. What is the role of mental health professionals in the treatment of poorly-controlled diabetics?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Type 1 Diabetes Mellitus

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Lehman RM. Poorly Controlled Diabetes?
    Adolesc Med. 1996 Oct;7(3):405-408.

    Franzese A, Iorio R, Buono P, Mascolo M, Mozzillo E, Valerio G. Mauriac syndrome still exists.
    Diabetes Res Clin Pract. 2001 Dec;54(3):219-21.

    Kim MS, Quintos JB. Mauriac syndrome: growth failure and type 1 diabetes mellitus.
    Pediatr Endocrinol Rev. 2008 Aug;5 Suppl 4:989-93.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    January 12, 2009

  • When Can an Infant See Color?

    Patient Presentation

    A 5-day-old male came to clinic for his health supervision visit. He was breastfeeding and eliminating well. His parents noted that he was more alert than they remembered his older sister at the same age.. The past medical history showed a full-term infant with no prenatal or natal complications. He received all his normal newborn care including passing his hearing screening. His neonatal screen was negative also. The family history and review of systems were negative including no history of visual problems other than older family members needing reading glasses.

    The pertinent physical exam showed an alert male infant who was 3.468 kg (down 5% from birth weight) with normal vital signs and growth parameters. He was mildly jaundiced in the face and sclera only and the rest of his examination was normal. The diagnosis of a healthy male infant was made. During the interview his parents said they had a mobile that had black and white cards for a newborn and colored cards for an older infant and they wanted to know when to switch the cards. The pediatrician said that infants were born with relatively clear vision of only a few inches (distance between holding the newborn in a cradled elbow to parent face) and that they developed the ability to see red colors within a couple of weeks. He did not know when the other colors became clear, but said he would try to look it up and tell them at the next visit. The pediatrician also discussed safety issues including using a mobile in the infant’s crib and when to take it out of the crib.

    Discussion
    Infants are hyperopic (farsighted) at birth because of the relatively short axial length of the globe and ocular optics. Astigmatism occurs in 15-30%. These refractive errors are gone for most infants by 9-12 months. Newborns can fixate at birth but accurate visual fixation occurs by 6-9 weeks. Accommodation (fixating on near objects) is also evident at birth but is not accurate until about 2-3 months. Visual acuity (defining fine details) is normal by 6-8 months. Stereopsis (3-D vision) has a rapid onset at 3 months and is normal around 6 months.

    Learning Point
    Contrast sensitivity (the ability to detect brightness differences or shades of grey) occurs by 10 weeks.
    Color vision begins as early as 2 weeks (red) and by 3 months is normal.

    Questions for Further Discussion
    1. List signs that may indicate a serious vision problem.
    2. How common are color vision problems?
    3. How could color blindness affect a child’s education?
    4. What items are considered safe to be in a newborn’s crib and when should they be removed?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Eye Diseases

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Hamer RD, Mirabella G. What Can My Baby See? Smith-Kettlewell Eye Research Institute.
    Available from the Internet at http://www.ski.org/Vision/babyvision.html (1990, cited 11/30/09).

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:491.

    Monitoring Visual Development. Texas School for the Blind and Visually Impaired.
    Available from the Internet at http://www.tsbvi.edu/Education/infant/page7.htm (rev. 9/4/2007, cited 11/30/09).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

  • How Much Vitamin D is in Milk?

    Patient Presentation
    A 3-year-old female came to clinic for her health supervision visit.
    Her mother had recently been diagnosed with Vitamin D deficiency based on screening tests.
    She wanted to know if her daughter was also Vitamin D deficient particularly as it was currently fall and winter was coming with decreased sunlight.
    The patient ate a general diet including eggs and 1-2 cups/day of milk, plus yogurt and some cheese regularly.
    She also took a general children’s multivitamin.
    Her mother said that she did play outside and they used sunscreen when they remembered to put it on.

    The family history was negative for bone, kidney, or gastrointestinal disease.
    The pertinent physical exam showed a smily preschooler of Middle Eastern descent.
    Her growth parameters were in the 50-90% and her vital signs were normal.
    She had no bony abnormalities including normal wrists, ribs and legs.
    The diagnosis of a healthy 3 year old was made.
    The mother decided that she did not want her child tested for Vitamin D as it appeared that she probably was getting enough from her diet.
    The pediatrician discussed that she needed at least 400 IU (international units) of Vitamin D/day. The mother was also going to check the multivitamin and how much Vitamin D was in it.

    Discussion
    Vitamin D is an important vitamin for bone formation and mineral homeostasis.
    Vitamin D deficiency can cause hypocalcemia, hypophosphatemia, osteomalacia, rickets and tetany.
    Deficiency is caused by inadequate dietary intakes of Vitamin D, inadequate exposure to sunlight or patients with fat malabsorption or renal disease.

    Sunscreen blocks sunlight and an SPF (sun protection factor) of 8 blocks 95% of the sun, so there needs to be a careful balance between over- and under- sun exposure.
    Adequate sunlight exposure for infants is considered 30 minutes/week clothed in a diaper only, or 2 hours/week fully clothed but without a hat.

    25-hydroxy Vitamin D (calcidiol) is the best indicator of Vitamin D status.
    For a review of the production of Vitamin D, click here.

    Learning Point
    Human breast milk is low in Vitamin D. Therefore all infants who are exclusively breastfed need supplementation.
    Infants with darker pigmentation or living in northern climates with less sunlight are particularly susceptible to Vitamin D deficiency.
    This supplementation can be stopped if the infant is taking at least 1 liter or quart/day of formula or Vitamin D fortified whole milk.
    Children taking less than 1 liter/day of Vitamin D fortified milk should also receive supplementation of 400 IU/day. Note that soy milk may or may not be Vitamin D fortified.

    The Vitamin D content of foods rich in Vitamin D is below. All are in IU.

    • Milk
      • Human milk – 22/L
      • Infant formula – 62/100 kcal, usually 5 ounces
      • Cow’s milk, fortified – 100/8 ounces
      • Soy milk – may or may not be Vitamin D fortified, usually 100/8 ounces
      • Rice milk – may or may not be Vitamin D fortified, usually 100/8 ounces
      • Other foods made with milk or soy may or may not be fortified such as yogurt, pudding, tofu, etc.
    • Cereals, fortified – 40-50/8 ounces
    • Egg yolk – 21
    • Fish and Shellfish (3 ounces)
      • Catfish – 425
      • Halibut – 510
      • Herring – 1383
      • Oyster – 272
      • Mackerel – 213
      • Pink salmon – 530
      • Sardine – 231
      • Shrimp – 129
      • Tuna – 200
    • Cod liver oil – 450 / teaspoon
    • Shiitake mushrooms – 249 per 4
    • Orange juice, fortified -100/8 ounces
    • Multivitamins – may or may not be Vitamin D fortified, even within brands there can be differing content so individual bottles need to be checked.

    Questions for Further Discussion
    1. How do you balance the need for adequate sunlight for Vitamin D synthesis versus the risks of sunlight and skin cancer?
    2. What other blood testing may be helpful to evaluate overall Vitamin D metabolism?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Rickets and Vitamins.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    New York State Department of Health. Vitamin D and Healthy Bones.
    Available from the Internet at http://www.health.state.ny.us/diseases/conditions/osteoporosis/vitd.htm (rev. 11/03, cited 11/13/08).

    Linus Pauling Institute. Vitamin D.
    Available from the Internet at http://lpi.oregonstate.edu/infocenter/vitamins/vitaminD/ (rev. 11/7/08, cited 11/13/08).

    American Academy of Pediatrics. Pediatric Nutrition Handbook. Kleinman RE, edit. 6th Edit. 2008;458, 464-66.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    January 5, 2009