Clinical Features and Diagnosis of Nephrolithiasis in ChildrenUPTODATE NOV 2015

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4/12/2015 Clinical features and diagnosis of nephrolithiasis in children

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Offi cial reprint from UpToDatewww.uptodate.com 2015 UpToDate

AuthorsJodi Smith, MD, MPHF Bruder Stapleton, MD

Section EditorLaurence S Baskin, MD, FAAP

Deputy EditorMelanie S Kim, MD

Clinical features and diagnosis of nephrolithiasis in children

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Nov 2015. | This topic last updated: Jun 09, 2015.

INTRODUCTION Nephrolithiasis is increasingly recognized in children. Its presentation varies, and often

patients, especially young children, do not present with the classic acute onset of flank pain commonly seen in

adults. As a result, children are frequently evaluated for other conditions before the diagnosis of nephrolithiasis is

made. The clinical features and diagnosis of childhood nephrolithiasis will be reviewed here. The epidemiology,

risk factors, acute management, and prevention of recurrent nephrolithiasis in children are discussed separately.

(See "Epidemiology of and risk factors for nephrolithiasis in children" and "Acute management of nephrolithiasis in

children" and "Prevention of recurrent nephrolithiasis in children".)

CLINICAL PRESENTATION Most children with nephrolithiasis present symptomatically, usually with flank or

abdominal pain. Approximately 15 to 20 percent are asymptomatic, primarily young children who are diagnosedbecause of stone detection when abdominal imaging is performed for other purposes [ 1-3].

In those with symptomatic presentation, the most common symptom is pain [1-4]. Other potential manifestations

include gross hematuria, dysuria and urgency, and nausea/vomiting.

Pain Pain can be located either as abdominal or flank pain (referred to as renal colic). In several case series,

pain was the presenting complaint in 50 to 75 percent of patients [ 1-5].

Pain frequency varies with age. In one report, for example, pain was present in 60, 40, and 20 percent of

adolescents, school-aged children, and children below five years of age, respectively [2]. The age-related

difference in pain may be related to stone location at presentation. Younger children (ie, less than five years of

age) are much less likely to have ureteral stones than school-aged children and adolescents (32 versus 64 and 82percent, respectively) [6]. Ureteral stones are generally painful, since they cause ureteral obstruction, whereas

kidney stones are often asymptomatic and may be diagnosed as an incidental finding on abdominal imaging.

Similar to adults with nephrolithiasis, the intensity of pain can vary from a mild ache to severe debilitating pain. In

children below five years of age, the pain, if present, appears to be milder and is nonspecific. In addition, young

children often are unable to articulate the location and sev erity of the pain.As a result, young children are

frequently evaluated for other causes of abdominal pain before the diagnosis of nephrolithiasis is made.

In addition, nephrolithiasis may be the cause ofrecurrent abdominal pain in children, as illustrated by a

retrospective study that included patients that required hospitalization or underwent appendectomy for abdominal

pain [7].

Gross hematuria In pediatric case series, gross hematuria as a presenting symptom for nephrolithiasis varied

from 30 to 55 percent [1-4]. Hematuria can present as the sole symptom or concomitantly with abdominal pain.

Dysuria and urgency Approximately 10 percent of children with nephrolithiasis present with symptoms of

dysuria and urgency suggestive of a urinary tract infection (UTI) [1,4,5]. In some cases, urinary tract infection is

present and is a contributing factor to stone formation, especially in young children [1,2,5]. In other cases, dysuria

and urgency can be seen when the stone is present in the bladder or urethra without an associated UTI. (See

"Epidemiology of and risk factors for nephrolithiasis in children", section on 'Infection' .)

In addition to these symptoms, nausea and vomiting has been described as a presenting symptom in 10 percent of
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patients [1].

Young children As noted above, young children with nephrolithiasis are less likely to display the classical

presentation of abdominal/flank pain commonly seen in older children and adults [2,6,8]. Younger children are also

more likely than older children to have a renal rather than a ureteral stone [ 6,8]. In one of the largest case series,

abdominal pain and gross hematuria were the presenting symptoms in about one-half of the children below six

years of age [2]. The other half of patients presented with a urinary tract infection and/or incidental finding of

stones on abdominal imaging.

INITIAL EVALUATION Because renal stones can cause urinary obstruction, and are often associated withurinary tract infection, children who present with symptoms suggestive of nephrolithiasis should be evaluated

promptly.

History The evaluation begins with a history that identifies any of the following factors that are associated with

an increased likelihood for nephrolithiasis:

Physical examination The physical examination in the child with suspected nephrolithiasis should include:

Laboratory evaluation The initial laboratory evaluation for the child with suspected nephrolithiasis includes:

History of previous renal stone.

Family history of nephrolithiasis. In one case series, 16 percent of children had a first-degree relative and 17

percent had a second-degree relative with renal stones [3]. (See "Epidemiology of and risk factors for

nephrolithiasis in children".)

History of underlying renal and urinary tract structural abnormalities. (See "Epidemiology of and risk factors

for nephrolithiasis in children", section on 'Congenital/structural abnormalities'.)

History of underlying metabolic conditions associated with nephrolithiasis, such as malabsorption leading to

enhanced enteric absorption of oxalate and hyperoxaluria, or the use of a ketogenic diet to treat epilepsy.

(See "Epidemiology of and risk factors for nephrolithiasis in children".)

History of medications associated with stone formation, such as indinavir or sulfadiazine [9]. (See

"Epidemiology of and risk factors for nephrolithiasis in children", section on 'Other metabolic causes'.)

History of recurrent urinary tract infection, especially with a urease-producing organism, such as Proteus or

Klebsiella. (See "Epidemiology of and risk factors for nephrolithiasis in children", section on 'Infection' .)

An abdominal examination for tenderness or mass (eg, evidence of urinary obstruction or another cause of

abdominal pain, such as appendicitis).

Growth measurements, as poor weight gain and/or failure to thrive may be an indication of a congenital or

chronic condition that may be associated with nephrolithiasis, such as renal tubular acidosis or Dent's

syndrome. (See "Epidemiology of and risk factors for nephrolithiasis in children".)

Blood pressure measurement and assessment for edema. The presence of hypertension and/or edema in a

child with hematuria suggests an alternative diagnosis to nephrolithiasis, such as glomerular disease. (See

'Differential diagnosis' below.)

Documentation of temperature. The presence of fever may represent a urinary tract infection.

Urinalysis Examination of the urine sediment may be useful if crystals are present. As an example, cystine

crystals, which are colorless, flat, and hexagonal, are diagnostic of cystinuria (picture 1). Other crystals that

can be seen in the sediment include calcium oxalate (picture 2A-B), calcium phosphate, uric acid (picture 3A-

B), and phosphate (picture 4). Drugs, such as sulfadiazine and indinavir, can also crystallize in the urine

(picture 5 and picture 6).
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Further evaluation for metabolic risk factors, such as hypercalciuria or hyperuricosuria, is important, but should be

performed once the acute episode is over, while the patient is at home, fully ambulatory, consuming a regular diet,

and free of infection. (See "Prevention of recurrent nephrolithiasis in children".)

DIAGNOSIS The diagnosis of nephrolithiasis is initially suspected by the presentation and initial clinical

evaluation [10]. It is confirmed by the detection of a stone on imaging studies or retrieval of a passed stone. As

previously mentioned, the diagnosis is made as an incidental finding in about 15 to 20 percent of pediatric cases

when abdominal imaging is performed for other purposes [1-3].

Imaging The three imaging modalities currently used to diagnosis nephrolithiasis in children are non-contrast

helical computed tomography (CT), ultrasonography, and plain abdominal radiography. CT is the most sensitive for

the detection of renal stones, followed by ultrasonography and plain radiography [ 11]. In small children, there are

concerns about radiation exposure from CT [12].

Ultrasonography Ultrasonography is an effective modality for diagnosis in many cases and avoids the

concern of radiation [13]. It is the modality of choice when radiation should be avoided, as in pregnant girls, orwhen the radiation dose from CT cannot be reduced to safe levels. Ultrasonography can detect radiolucent stones,

such as uric acid stones, and urinary obstruction [14]. However, it is limited in its ability to uncover small stones

(eg, less than 5 mm), papillary or calyceal stones, or ureteral stones [15].

The experience and expertise of the ultrasonographer is an important factor in the sensitivity of the study,

especially in the accurate detection of small stones or ureteral stones.

In one case series of 50 consecutive patients with suspected nephrolithiasis from a tertiary center,

ultrasonography failed to detect stones seen on CT in eight patients and missed bilateral stone disease in six

patients, resulting in a 76 percent sensitivity and 100 percent specificity [ 16]. The mean size of missed stones

was 2.3 mm. In four cases, clinical management decisions would have changed if CT was not performed. These

results suggest that ultrasonography is a reasonable alternative to CT to detect nephrolithiasis, especially when

there are concerns about radiation exposure from CT.

Non-contrast helical CT Similar to in adults, non-contrast helical CT is the most sensitive modality to

detect renal or ureteral stones in children (image 1A-B) [10,11,17]. CT can detect stones in the following

conditions, which may not be detected by the other modalities:

CT also provides more detailed anatomic information including detection of obstruction or a structural abnormality[18].

CT is a rapid procedure requiring less than two minutes to be performed. Patients who undergo CT generally do

not require anesthesia. If necessary, contrast can be given after non-contrast images have been obtained to

provide additional anatomic detail, such as subtle signs of urinary obstruction or increased detail of an anatomic

abnormality.

The radiation exposure during CT varies with different equipment and institutional protocols. Concerns have been

raised that small children can be exposed to excessive radiation, if conventional adult radiation doses are used

during the procedure [12,19]. However, radiation doses can be significantly reduced through adjusting scanning

parameters to the size and weight of the child while still maintaining adequate imaging quality [20,21]. In

Urine culture A urine culture should be obtained because urinary tract infection (UTI) can be present in a

child with nephrolithiasis. A UTI is also the most common condition in the differential diagnosis of pediatric

nephrolithiasis. (See 'Differential diagnosis' below.)

Serum creatinine Measuring serum creatinine to determine initial renal function.

Ureteral stones, which may not be detected by ultrasonography

Radiolucent stones (eg, pure uric acid stones), which are not detected by plain radiography

Small (ie, 1 mm in diameter) stones, which are not detected by ultrasonography or plain radiography
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institutions that provide care for children, protocols to ensure effective and safe radiation doses for CT should be

implemented as outlined by guidelines from the National Cancer Institute [19,22]. If this is not feasible, another

imaging modality, such as ultrasonography, should be used [ 23].

Abdominal plain radiography A plain abdominal radiograph will detect radiopaque stones (eg, calcium,

struvite, and cystine stones) (image 2), but will miss radiolucent stones (eg, uric acid stones), may miss small

stones or those that overlay bony structures, and will not detect urinary obstruction. In settings where renal

ultrasonography and CT are not available in children, plain abdominal radiography remains a reasonable alternative,

recognizing that the reported sensitivity of this study is about 60 percent [11].

Our approach We recommend non-contrast helical CT in the diagnostic evaluation of pediatric

nephrolithiasis. Radiation doses are adjusted to the size and weight of the child to reduce the radiation exposure.

Abdominal ultrasonography or plain film can be used if appropriate CT imaging for children is not available.

Ultrasonography is preferred to plain film since it is a more sensitive test and can also detect radiolucent stones

and urinary tract obstruction.

DIFFERENTIAL DIAGNOSIS The differential diagnosis in a child with suspected nephrolithiasis depends upon

the presenting symptoms. Nephrolithiasis is differentiated from the other conditions by demonstration by imaging

of a stone within the kidney or urinary tract.

Abdominal or flank pain Abdominal pain is one of the most common complaints in children and the differential

is extensive. Infections, such as gastroenteritis, urinary tract infections (UTI), appendicitis, and pneumonia, are

the most common cause of abdominal or flank pain. Other signs and symptoms, most commonly fever, usually

distinguish them from nephrolithiasis. (See "Causes of acute abdominal pain in children and adolescents" and

"Emergent evaluation of the child with acute abdominal pain".)

Gross hematuria In children, the most commonly identified causes for gross hematuria include UTI, irritation of

the meatus or perineum, and trauma. These are differentiated from nephrolithiasis by the history and physical

examination. Glomerular disease, such as postinfectious glomerulonephritis, is a less common cause of gross

hematuria that is distinguished from nephrolithiasis by cola-colored urine instead of red urine, examination of the

urinary sediment, and the possible presence of hypertension and/or edema. (See "Evaluation of gross hematuria in

children".)

Urinary tract infection Many of the symptoms associated with nephrolithiasis (eg, abdominal/flank pain, gross

hematuria, dysuria, and urgency) can also be seen in children with UTI. In addition, the two conditions can present

concomitantly with the UTI contributing to the process of stone formation.

Children with UTI diagnosed by urine culture usually begin to show clinical improvement within 24 to 48 hours of

initiation of appropriate antibiotic therapy. If the clinical condition worsens or fails to improve as expected within 24

to 48 hours of the start of antimicrobial therapy, imaging should be performed to determine if the failed or slow

response to therapy is due to the presence of renal stone, renal abscess, or underlying anatomic abnormalities or

obstruction. (See "Urinary tract infections in infants older than one month and young children: Acute management,

imaging, and prognosis", section on 'Clinical response'.)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and

Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5 to 6 grade

reading level, and they answer the four or five key questions a patient might have about a given condition. These

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the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written

at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable

with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these

topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on

th th

th th
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patient info and the keyword(s) of interest.)

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REFERENCES

1. Gearhart JP, Herzberg GZ, Jeffs RD. Childhood urolithiasis: experiences and advances. Pediatrics 199187:445.

2. Milliner DS, Murphy ME. Urolithiasis in pediatric patients. Mayo Clin Proc 1993 68:241.

3. Coward RJ, Peters CJ, Duffy PG, et al. Epidemiology of paediatric renal stone disease in the UK. Arch DisChild 2003 88:962.

4. VanDervoort K, Wiesen J, Frank R, et al. Urolithiasis in pediatric patients: a single center study ofincidence, clinical presentation and outcome. J Urol 2007 177:2300.

5. Sternberg K, Greenfield SP, Williot P, Wan J. Pediatric stone disease: an evolving experience. J Urol 2005174:1711.

Basics topics (see "Patient information: Kidney stones in children (The Basics)")

Beyond the Basics topics (see "Patient information: Kidney stones in children (Beyond the Basics)" )

Childhood nephrolithiasis usually presents with symptoms that most commonly include abdominal or flank

pain, and/or gross hematuria. However, 15 to 20 percent of children are asymptomatic and are diagnosed

because of stone detection when abdominal imaging is performed for other purposes. (See 'Clinicalpresentation'above.)

Abdominal or flank pain as a presenting symptom varies in intensity from a mild ache to severe debilitating

pain. Pain is a common feature in adolescents and school-aged children with nephrolithiasis, but is only

present in about half of the children below six years of age. Urinary tract infection and/or an incidental finding

of a stone on imaging are the presenting findings in almost half of the children below six years of age. (See

'Clinical presentation'above.)

The initial evaluation of a child with suspected nephrolithiasis includes the following:

History focusing on underlying risk factors for stone formation (eg, family history, renal and urinary tract

structural abnormalities, metabolic disorders, or recurrent urinary tract infection). (See "Epidemiology of

and risk factors for nephrolithiasis in children".)

Physical examination that includes measurement of blood pressure and growth parameters, and

abdominal examination for signs of urinary obstruction or another cause of abdominal pain.

Urinalysis, urine culture, and measurement of serum creatinine. (See 'Initial evaluation'above.)

The diagnosis of nephrolithiasis is made by the detection of a renal stone by imaging studies or retrieval of a

passed stone.

We recommend abdominal imaging for any child suspected to have nephrolithiasis. In most patients, we

recommend ultrasound or non-contrast helical computed tomography.

Computed tomography does provide the greatest sensitivity of the available imaging modalities, but

consideration of radiation exposure is important. Radiation doses can be adjusted to the size and

weight of the child to reduce radiation exposure.

Ultrasonography detects radiolucent stones and urinary obstruction, and remains the overall imaging

choice when radiation should be avoided, such as in pregnant adolescents. (See 'Imaging'above.)
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7. Polito C, La Manna A, Signoriello G, Marte A. Recurrent abdominal pain in childhood urolithiasis. Pediatrics2009 124:e1088.

8. Kalorin CM, Zabinski A, Okpareke I, et al. Pediatric urinary stone disease--does age matter? J Urol 2009181:2267.

9. Catalano-Pons C, Bargy S, Schlecht D, et al. Sulfadiazine-induced nephrolithiasis in children. PediatrNephrol 2004 19:928.

10. Persaud AC, Stevenson MD, McMahon DR, Christopher NC. Pediatric urolithiasis: clinical predictors in theemergency department. Pediatrics 2009 124:888.

11. Nimkin K, Lebowitz RL, Share JC, Teele RL. Urolithiasis in a children's hospital: 1985-1990. Urol Radiol1992 14:139.

12. Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of radiation-induced fatal cancer from pediatric CT.AJR Am J Roentgenol 2001 176:289.

13. Penido MG, Srivastava T, Alon US. Pediatric primary urolithiasis: 12-year experience at a MidwesternChildren's Hospital. J Urol 2013 189:1493.

14. Smith SL, Somers JM, Broderick N, Halliday K. The role of the plain radiograph and renal tract ultrasound inthe management of children with renal tract calculi. Clin Radiol 2000 55:708.

15. Diament MJ, Malekzadeh M. Ultrasound and the diagnosis of renal and ureteral calculi. J Pediatr 1986

109:980.

16. Passerotti C, Chow JS, Silva A, et al. Ultrasound versus computerized tomography for evaluatingurolithiasis. J Urol 2009 182:1829.

17. Palmer JS, Donaher ER, O'Riordan MA, Dell KM. Diagnosis of pediatric urolithiasis: role of ultrasound andcomputerized tomography. J Urol 2005 174:1413.

18. Smergel E, Greenberg SB, Crisci KL, Salwen JK. CT urograms in pediatric patients with ureteral calculi: doadult criteria work? Pediatr Radiol 2001 31:720.

19. Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med2007 357:2277.

20. Donnelly LF, Emery KH, Brody AS, et al. Minimizing radiation dose for pediatric body applications of single-detector helical CT: strategies at a large Children's Hospital. AJR Am J Roentgenol 2001 176:303.

21. Karmazyn B, Frush DP, Applegate KE, et al. CT with a computer-simulated dose reduction technique fordetection of pediatric nephroureterolithiasis: comparison of standard and reduced radiation doses. AJR Am JRoentgenol 2009 192:143.

22. Radiation risks and pediatric computed tomography (CT): A guide for health care providers. Available at:www.nci.nih.gov/cancertopics/causes/radiation-risks-pediatric-CT (Accessed on April 29, 2009).

23. Ng C, Tsung JW. Avoiding Computed Tomography Scans By Using Point-Of-Care Ultrasound WhenEvaluating Suspected Pediatric Renal Colic. J Emerg Med 2015 49:165.

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GRAPHICS

Urine sediment showing cystine crystals

Urine sediment showing hexagonal cystine crystals that areessentially pathognomonic of cystinuria.

Courtesy of Harvard Medical School.

Graphic 56834 Version 2.0


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Calcium oxalate crystals in the urine

Urine sediment showing both dumbbell-shaped calcium oxalate

monohydrate (long arrow) and envelope-shaped calcium oxalate

dihydrate (short arrows) crystals. Although not shown, themonohydrate crystals may also have a needle-shaped appearance.

The formation of calcium oxalate crystals is independent of the urine

pH.

Courtesy of Frances Andrus, BA, Victoria Hospital, London, Ontario.



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Urinary calcium oxalate monohydrate crystals

under polarized light

Urine sediment viewed under polarized light showing coarse, needle-

shaped calcium oxalate monohydrate crystals. These crystals have asimilar appearance to hippurate crystals.

Courtesy of W Merrill Hicks, MD.



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http://www.uptodate.com/contents/clinical-features-and-diagnosis- of-nephrolithiasis-i n-children?topicKey=PEDS%2F6123&elapsedTim eMs=0&source=sea 10

Uric acid crystals in the urine

Urine sediment loaded with uric acid crystals. These crystals are

pleomorphic, most often appearing as rhombic plates or rosettes.

They are yellow or reddish-brown and form only in an acid urine (pH

5.5 or less).




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Uric acid crystals under polarized light

Urine sediment showing uric acid crystals viewed under polarized

light.

Courtesy of Frances Andrus, BA, Victoria Hospital, London, Ontario.



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Urine sediment showing struvite (magnesium

ammonium phosphate) crystals

Urine sediment showing multiple "coffin lid" magnesium ammoniumphosphate crystals (struvite) that form only in an alkaline urine (pH

usually above 7.0) caused by an upper urinary tract infection with a

urease-producing bacteria.




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Photomicrograph showing urine sediment of a

patient with sulfonamide crystalluria

Urine sediment showing sulfonamide crystals with a needle-shapedappearance. Other forms that may be seen include rosettes and a

shock of wheat appearance.




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Photomicrographs showing urine sediment of a

patient with indinavir sulfate crystalluria

Light microscopic photographs of a fresh unstained preparation of

urinary sediment showing three different forms of indinavir sulfate

crystals.

(A) Rectangular plates of various sizes containing needle-shaped

crystals. The plates have irregular borders with occasional tapering,

and internal layering evident in the largest forms (arrows). Small,

triangular pieces (arrowheads) represent broken ends of needles.

(B) A sheaf of densely packed indinavir sulfate needles.

(C) Several indinavir crystal groupings are arranged in a rosette.

Reprinted with permission from: Gagnon RF, Tsoukas CM, Watters AK, Ann

Intern Med 1998 128:321.



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CT scan showing ureteral stone

CT scan shows a calculus in the proximal left ureter causing delayed

excretion of contrast material from the left kidney (long arrow). All

the contrast has been excreted from the normal functioning right

kidney and is in the nondilated right ureter (small arrow).

CT scan: computed tomographic scan.

Courtesy of Jonathan Kruskal, MD.



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CT scan showing large renal pelvic stone

CT scan without contrast shows a large calculus in the right renal

pelvis (arrow).

CT scan: computed tomographic scan.

Courtesy of Mark D Aronson, MD.



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KUB showing staghorn calculi

The plain film of the abdomen in the anteroposterior projection reveals a staghorn calculus.

Note calcifications (arrows) in the opposite kidney as well.



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Disclosures:Jodi Smith, MD, MPH Nothing to disclose. F Bruder Stapleton, MD Nothing to disclose. Laurence S Baskin, MD, FAAPNothing to disclose. Melanie S Kim, MD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a

multi-level review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.

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