1. Stephen Schneider PA-c, Children’s hospital of Philadelphia
The Advance Practice Provider’s Role in the Diagnosis and Management of Pediatric Kidney Stones
Stephen Schneider PA-c, Children’s hospital of Philadelphia

2. Disclosures
None

3. Objectives
Discuss the different types of kidney stones and the physiology behind them
Educate on how to manage and treat common types of pediatric kidney stones
Review education strategies focused on the prevention of kidney stones in the pediatric patient

4. The Basics – What is a kidney stone?
Hard Mass developed from crystals
Various types of chemicals
Accumulation of stone forming substances
Pain
Agony
Misery
Accumulation of stone forming substances
Increase in concentration/Decrease in inhibitors = stone formation
Super-saturation
Urinary pH

5. The Basics – What is a kidney stone?
Size
Range from a grain of sand or golf ball sized
Shape
Smooth or jagged
Color
Yellow/brown/white

6. Pathophysiology Stone growth starts with the formation of crystals
Crystals adhere to the urothelium
Adherence creates the nidus for the later stone growth

7. Incidence Increasingly common among children
Among adolescents, the incidence of nephrolithiasis has increased 6-10% annually over 20 years.
Nephrolithiasis (kidney stones) affect 9% of the United States population.1 The prevalence of nephrolithiasis among adults has increased 70% over the last thirty years. The incidence of nephrolithiasis among children has risen even more rapidly and has increased by 6-10% per year over the last 20 years.2-4 The long term harms of nephrolithiasis are severe and include an increased risk of end-stage renal disease and coronary heart disease.1,5-8

8. Risk Factors Environment Non-modifiable Risk Factors Behavior
Temperature
Sunlight
Behavior
Diet
Fluid intake
Obesity
Non-modifiable Risk Factors
Age
Gender
Genetics
Preexisting medical conditions
The ecological model of human disease can be used to understand an individuals and a population risk of kidney stones. The risk of stones is comprised of the interaction between the environment, non-modifiable risk factors, and behaviors

9. Risk Factors Non-modifiable risk factors Age Gender Genetics
Preexisting medical conditions
Developmental anomalies of urinary tract
Promote stasis/infection
UPJO
Neurogenic bladder

10. Risk Factors Environmental Behavioral Warmer climates/Stone belt
Several days of heat may increase risk
Behavioral
To be discussed in more detail later
High temperatures cause water loss, concentrate urine, low urine volume and pH

11. Risk Factors
Current U.S. ‘stone-belt’ or high-risk kidney stone area in yellow. Computer model predicts expansion of stone-belt over time in orange (2050) and in red (2095). Currently, 41% of the population is within a high-risk zone. Computer model predicts 56% of the population will be in a high-risk zone by 2050 and 70% by Via PNAS 2008.

13. Different Types of Kidney Stones
Calcium Stones
Calcium oxalate
Calcium phosphate
Struvite
Uric Acid
Cystine Stones

14. Pediatric Stone Composition

15. Calcium Stones Most common type of stone made Two major forms
80% of all stones
Two major forms
Calcium Oxalate
Calcium Phosphate

16. Calcium Oxalate Stones
Oxalate is a type of acid with a plant origin
Not essential to life
Excreted through the urine unchanged
Excess of vitamin C is converted to oxalate
Foods high in oxalate
Spinach, rhubarb, nuts, and wheat bran
Calcium Oxalate Monohydrate Stones

17. Calcium Oxalate Stones
Caused by high calcium and high oxalate excretion
Associated with high levels of serum calcium
Parathyroid disorders
Dehydration
Diet
Refined Carbohydrates
Protein
75 % of stones
Refined Carbohydrates
Sugar causes the pancreas to excrete insulin therefor causing the kidney to increase calcium excretion
Protein
Red meat/poultry increases uric acid, calcium, and oxalates in the urine and decreases citrate levels

18. Calcium Oxalate Stones
Calcium intake should NOT be restricted
Calcium binds to oxalate in the intestines therefor decreasing the amount of calcium oxalate that needs to be eliminated from the body in the urine preventing the formation of calcium oxalate stones in the kidneys

19. Calcium Phosphate Stones
Caused by the combination of high urine calcium and alkaline urine
Often associated with renal tubular acidosis and hyperparathyroidism
Most often occurs in combination with calcium oxalate stones
5-10% of all stones
Meaning the urine has a high pH – ph is greater than 7.2
The presence of an underlying condition should be considered n patients with pure calcium phosphate stones
Calcium Phosphate Stone

20. Struvite (staghorn) Stone
Infectious stone
Produced by the bacterial waste products formed during the UTI
Composed of magnesium, ammonium, phosphate
Urea- Splitting Bacteria
Bacteria splits urea into ammonia which decreases the acidity of the urine and forms struvite stones
Proteus mirabilis, Klebsiella, Serratia Pseudomonas
10-20%
An enzyme called urease is produced by the infection causing bacteria that causes chemical decomposition of urea into ammonium and hydroxyl ions.  In a situation where there is an increase in the above mentioned compounds and the urine is of a high alkaline quality, it provides the right environment for the formation of struvite stone.  This kidney stone type can grow rapidly and become quite large but with little or no symptoms.
Struvite Stones

21. Uric Acid Stone
The end product of purine metabolism which causes urate to crystallize in the kidney
The urine is often excessively acidic
Presence of an underlying condition should be considered in patients with uric acid stones
gout
Radiolucent stones
Low PH
5-10% of stones
Meat/fish/chicken
High fructose intake
Uric Acid Stones

22. Cystine Stones Autosomal recessive pattern of inheritance
Cystinuria results in the excessive excretion of four basic amino acids
Cystine, ornithine, lysine, arginine (COLA)
Cystine is insoluble in acidic urine
Inborn error of metabolism
1-2% of stones
Cystine kidney stones are due to cystinuria, an inherited (genetic) disorder of the transport of an amino acid (a building block of protein) called cystine that results in an excess of cystine in the urine (cystinuria) and the formation of cystine stones.
Amino acids are the building blocks of muscles and nerves
Cystine Stones

24. Clinical Presentation
Abdominal pain (often confused with appendicitis)
Young children: generalized (abdominal pain)
Adolescents: localized (flank pain)
colicky
Nausea
Hematuria
Dysuria
Urinary frequency
Flank pain in adolescents moves to the lower quadrant, penis or vagina as the stone travels down the ureter
Macroscopic or microscopic hematuria can occur in up to 90% of children with urolithiasis

25. Physical exam CVA tenderness Patient can not get comfortable
Absence of peritoneal signs

26. Pathway/ Algorithms

27. Pathway/ Algorithms www.chop.edu/pathways
A clinical pathway is a task-oriented care plan that details essential steps in the care of patients with a specific clinical problem and describes the patients expected clinical course.
Goals of clinical pathway
standardize care
improve outcomes
reduce cost

28. Pathway/ Algorithms 2 nephrolithiasis pathways at CHOP
Nephrolithiasis, suspected, emergent care - clinical-pathway
Nephrolithiasis, outpatient specialty care -

29. Pathway/ Algorithms Kidney Stone Pathway Goals Metrics
Reduce recurrence
Reduce associated burden of the disease
Set the international standard for care
Metrics
% of patients appropriately referred to nephrology from urology
% of patients who keep clinic referral appointment
Decrease in emergency department visits
Recurrence of stones

30. Emergent stone pathway and work up
Diagnostic imaging
Only 10-25% of children with suspected nephrolithiasis actually have stones (Persaud et al., Pediatrics, 2009)
72% of children who underwent CT for suspected nephrolithiasis did not have stones.
9% had clinically important alternative diagnoses identified by CT
Use ultrasound as the initial imaging study for children with suspected kidney stones
American Urological Association (2012)
European Association of Urology (2009)
Limit radiation where possible
Image Gently (2007)

31. Imaging Renal and bladder ultrasound Advantages: Limitations:
Accessible
Can detected obstruction by showing dilation - *
Can also detect radiolucent stones that are frequently missed on plain abdominal x-ray
Requires no ionizing radiating
Limitations:
Poor visualization of ureteral stones
Measurement of stone size less reproducible by ultrasound than by CT
Good test
Sensitivity = 70%
Specificity = 100%
Most stones not visualized are not clinically important
Secondary signs of obstruction usually present
Hydronephrosis
No ureteral jet

32. Imaging Renal ultrasound Good test Sensitivity = 70%
Specificity = 100%

33. Imaging Renal ultrasound Good test Sensitivity = 70%
Specificity = 100%

34. Imaging CT scan Advantages Disadvantages
Most sensitive and specific radiology test
Fast
Definitive diagnosis
Disadvantages
Less accessible
Relatively expensive
Cancer risk
Indicated in children with persistent symptoms of urolithiasis and a non-diagnostic ultrasound.
Sensitivity:
95-100%
Specificity:
94-96%
Provides info on non-genitourinary conditions
attributable risk of cancer from 1 CT ≅ % (Kuhns et al., Ped Emer Care, 2011)
Higher risk for children
Risk is cumulative (Smith-Bindman, Arch Int Med, 2009)

35. Imaging
CT Scan

36. Imaging KUB Abdominal radiograph of the kidneys, ureter, and bladder
Gives size, shape, location
90% or more of urinary-tract stones are radio-opaque
10% of stones there is not enough Ca to be seen
Uric acid stones are radio-lucent
The degree of opacity varies depending upon the composition of stone, size of the stone, position of the stone, and constipation

37. Imaging
KUB

38. Emergent Stone Pathway
Hydronephrosis
Hydroureter
Increase in renal size
Uroepithelial thickening
Significant pain
Hematuria
History of:Nephrolithiasis
Hypercalcuria
Hyperoxaluria
Hyperuricosuria
Cystinuria
Multiple urinary tract infections
Reassess patient
Consider broader differential for abdominal pain
May refer to possible appendicitis and abdominal pain in post pubertal females if indicated

40. Outpatient Stone Pathway
To help evaluate, diagnose, treat, and prevent stone disease

41. Preparation for the Office Visit

42. Serum Labs
BMP
Magnesium, phosphate, and uric acid
Urinalysis

43. Detailed H&P

44. Indications for Surgery

45. Medical Expulsion Therapy
Dilate smooth muscle of the distal third of ureter
Use on passing/ureteral stone

46. Medical Expulsion Therapy
Alpha blockers (Tamsulosin)
Advantages
Increase spontaneous passage rates of ureteral stones
Decrease time for stone passage
Decrease analgesic requirements
Cost effective
Disadvantages
Few studies have assessed the efficacy of MET for ureteral stones
Decrease blood pressure which can lead to dizziness and orthostatic hypotension
Take at night

47. Surgical treatments Shock wave lithotripsy Ureteroscopy
Falling out of favor
Ureteroscopy
Percutaneous Nephrolithotomy
Stones greater than 1.5 cm
Lower pole stones >8 mm
Infected stones
Multiple stones
Reason why ESWL is not great - Poor stone free rates
High re-intervention rates
Long term safety in children not demonstrated
Still needs GA
We have better interventions
Advantage to PCNL – better stone free rates with one procedure, disadvantage – riskier operation, increased bleeding, inpatient procedure

49. Outpatient Stone Pathway

50. Metabolic Evaluation

51. 24 hour urine test
Analyzes urine to help determine the cause of the kidney stones
Helps to guide the treatment
Aids in prevention of kidney stones in the future
70% of children with nephrolithiasis will have abnormalities in the urine that increase the risk of stone formation
targets for dietary and pharmacological interventions
Patient obtains the 24 hour urine at home and then the coorelating blood work
Determines
How much urine is being produced
The acidity (pH) of the urine
The amount of certain substances in the urine, such as calcium, sodium, uric acid, oxalate, citrate, and creatinine

52. 24 hour urine test

53. 24 hour urine test
Creatinine clearance – first thing to look at this helps to tell us if this was an adequate sample. Unfortunately the normal are values set are only for adults, but most teenagers will fit into these normal. Normal male is and normal female is 15 – 20.

54. 24 hour urine test
This is the amount of urine that the patient is putting out. Ideally you want them to put out 2 liters of urine.
A Low urine volume increases supersaturation of Ca, oxalate
50% reduction in recurrence with increased water

55. Treatment for low urine output
The single most important determinant of stone formation is low fluid intake.
A low fluid intake results in the production of concentrated urine causing a supersaturation and crystallization of stone forming compounds
Low urine flow rates promote crystal deposition on the urothelium

56. Treatment for low urine output
Tips:
Ask the kids to look at the color of their urine. Most kids think their urine should be yellow, rather we want more clear urine.
Encourage the parents to buy the kid a “cool” water bottle and remind the child to fill it often
Keep a glass of water on your desk at school
Keep another glass next to your bed. Many of us wake up dehydrated first thing in the morning
Decrease sugary drinks as well
Fructose increases calciuria

57. 24 hour urine test Hypocitraturia
Normal for males is greater than 450 and females is >550

58. hypocitraturia
Citrate is a molecule that binds to calcium in the urine
Citrate inhibits calcium stone formation
Prevents calcium from binding to oxalate or phosphate
Treatment
Add Lemonade to the diet
Potassium citrate
Hypocitraturia
Citrate is a molecule that binds to calcium in the urine

59. hypocitraturia Potassium Citrate
Alkalinizing agent
Start with 10mEq (1080mg) TID, max 100mEq daily
Take with full glass water
Relatively safe with minor GI side effects
Nausea
Long- term compliance with therapy and the effect on decreasing stone recurrence in children remain unknown

60. 24 hour urine test Normal sodium level is considered 50-150
Normal calcium for males is <250 and females <200

61. High sodium level
Industrialized countries (food processing) consume far more Na than our recommended daily allowance.
Decrease sodium to <2 grams/day
Direct link between increased sodium level and increasing calcium level
DO NOT DECREASE CALCIUM INTAKE
Low calcium diets INCREASE risk of kidney stones)
children 1-3 yrs 1.0 g
children 4-8 yrs 1.2 g
children 9-13 yrs 1.5 g
males yrs 1.5 g
females yrs 1.5 g

62. Hypercalciuria Treatment
Medication use to be considered after maximizing urine calcium reduction by limiting the dietary sodium intake.
Thiazides – hydrochlorothiazide (not potassium sparing)
Increase calcium absorption in the proximal tubule
Decrease urine calcium

63. 24 hour urine test
Normal oxalate level is between 20-40

64. hyperoxaluria
Only 10-20% of urinary oxalate excretion is derived from diet.
Berries, Greens, Chocolate, Tea (Ice-), and nuts
We used to restrict oxalate intake, but this has fallen out of favor because of the high Magnesium content of these food.
Magnesium can also help prevent kidney stone formation
Vitamin C supplements also associated with increased risk of CaOx stones, as oxalate is a byproduct of ascorbic acid metabolism

66. Metabolic Evaluation
Recommendation if to follow up in either urology, nephrology , or joint uro/nephrology clinci based on metatbolic evaluation. Typical follow up in every 6 months wit ha repeat RBUS and 24 hour urine

67. Children are at Higher Risk
Longer lifetime over which recurrent stones may occur
Longer lifetime over which diseases associated with nephrolithiasis may develop

68. Associated Disease
Loss of Kidney Function (Alexander et al., BMJ 2013)
Women <50 years with ≥1 kidney stone had a 3.6 times greater risk of ESRD
Increased but lesser risk present among men and older women
Coronary Heart Disease (Ferraro et al., JAMA, 2013)
Highest risk of MI observed among younger women
Bone fracture (Denburg et al., CJASN, 2014)
Among women in 30s, kidney stones were associated with a 55% increased risk of fracture
Among boys years old, kidney stones associated with a 13% increase risk of fracture

69. In Conclusion The incidence of kidney stones is increasing in children
Ultrasound should be the first line study
24 hour urine test will help to target dietary and pharmacological intervention
There are behavioral risk factors that can be modified to help reduce the risk of reoccurrence
Increase water and lemonade
Decrease sodium intake
Risk of recurrence ~ 50% in 3 years

70. Questions?