This document summarizes a lecture on metabolic stone work-up with a focus on 24-hour urine evaluation. It discusses guidelines for metabolic testing, specific abnormalities found on 24-hour urine tests like hypercalciuria and hyperoxaluria, and how to interpret results and guide treatment. Case examples from a litholink database are also reviewed to demonstrate real-world applications of 24-hour urine testing and metabolic stone work-up.

1. Metabolic Stone Work-Up: Focus on
the 24-hr Urine Evaluation
Kevan M. Sternberg
Associate Professor, Division of Urology
University of Vermont
@kevanms42

2. • Nothing to disclose
• Content from:
o AUA Core Curriculum
o AUA Guidelines
o Dr. John Asplin Stone Camp
Disclosures
2

3. • Background
• Guidelines and basics
• Specific diagnoses/metabolic abnormalities
• Litholink case- reviews
Objectives
3

4. • Prevalence= 1:11 (8.8%) adults in the U.S
o Likely underestimated
• Stone disease is increasing
o With children as well, particularly adolescents
• Resulting increase cost associated with nephrolithiasis
o $ 4.5 Billion
• Gender gap narrowing
Background
4

5. • Chronic, systemic condition w/multiple contributing
factors:
o Genetics
o Diet
o Lifestyle
o Medical comorbidities
• Associated systemic conditions:
o Obesity
o Metabolic syndrome
o Type 2 DM
o HTN
Nephrolithiasis
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6. • For all newly diagnosed stone patients
o Detailed medical history
• medications
o Dietary history
o Serum chemistries
• Electrolytes, calcium, creatinine, uric acid
o Obtain PTH if high/ high normal serum calcium
Metabolic Testing- AUA Guidelines
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7. Medications Mechanism
Carbonic anhydrase inhibitors
(topiramate, acetazolimide, zonisamide)
Metabolic Acidosis
Vitamin C Hyperoxaluria
Probenecid Hyperuricosuria
Ca/Vit D Hypercalciuria
Triamterene, Guafenacin, Ephedrine,
Indinivir
Stone from med crystalization
Pertinent Medications
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8. • Urinalysis/ Urine culture
o Urine pH, signs of infection
o Urease producing bacteria:
• Gram –; Proteus mirabilis, Klebsiella Pneumonae, Pseudomanas
• Gram +; Corynebacterium, Staphylococcus aureus,
Staphylococcus epidermidis
• Obtain a stone composition at least once
o Uric acid, cystine, calcium phosphate, struvite- important in
identifying etiology
• Review imaging if available
o Stone burden and distribution
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9. • High risk
o Family history
o Malabsorptive bowel disease
o Bowel surgery- resection, bypass
o Gout
o Met-S
o Osteoporosis
o Young age
• Recurrent
• Interested first timers
Who requires metabolic testing/ 24-h Urine?
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10. • Goal- To help guide medical and dietary intervention to
decrease risk of stone recurrence
• 1 vs. 2 tests- no clear answer
• Patients should be instructed to do what they were doing
at the time the stone was formed
(diet/medication/supplement/etc.)
• Collections likely differ when done at home vs. work.
o Most do their test on a weekend/Sunday for convenience.
o May be best to have 2 tests/patient- one home and on work?
24-hr Urine Testing
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11. 11

12. • Volume
o > 2.5L
• Calcium
o < 200 mg/day
• Oxalate
o < 40 mg/day
• Uric acid
o < 800 for men, < 750 for women
• pH
o 5.8-6.2
• Citrate
o > 450 for men, > 550 for women
24-h Urine Parameters
12

13. • Creatinine- accuracy of collection
o Weight-base values for men (20-25 mg/kg) and
o Women (15-20 mg/kg)
• Sodium
• Potassium
• Protein parameters:
o PCR (protein catabolic rate)
o UUN (reflects total protein intake)
o Sulfate (sulfa containing Amino Acids/net acid load =
methionine)
• Super saturation indices
o monitor effectiveness of tx
13

14. • Hypercalciuria
• Hyperoxaluria
• Hyperuricosuria
• Hypocitraturia
• Low Urine pH
• Low urine volume
Specific 24-h Urine Abnormalities
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15. • >4 mg/kg/day or > 200 mg/day (ca, Na restricted diet)
• Improper ca handling (GI tract, kidney, bone)
• Increases risk of bone disease and osteoporosis
o Bone mineral density is important
• Absorptive- increased absorption from intestine
o PTH normal or suppressed
• Renal- impaired reabsorption from prox and distal
tubules
o PTH increased and 1,25 vit D synthesis à increased intestinal
ca absorption and bone resorption
• Resorptive- primary hyperparathyroidism
Hypercalciuria
15

16. • Main players- Calcium, Sodium, and animal protein.
• Stone formers- more Na sensitive
• Na goal should be 120
• When patients are instructed to drink more fluids, often
there is a tendency to increase salt intake à
hypercalciuria.
• Sugar and caffeine can also affect calcium output.
• Protein loading/protein shakes à significant
hypercalciuria
Hypercalciuria and Diet
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17. • Consider primary HPT even if high normal PTH
• If borderline results, have blood work done fasting-
accounts for the diurnal variation.
• Draw Ca at same time as PTH
• Take patient off of thiazide (~2 weeks) if working up
Primary HPT
o Thiazides can cause hypercalcemia
Hypercalcemia
17

18. • High serum Ca, low/suppressed PTH à
o Consider malignancy (PTHrp, bony metastasis),
o Granulomatous disease-
• sarcoid (extrarenal source of 1,25 Vit D from alveolar
macrophages/granulomas)
• Tuberculosis
• Silicosis
o thiazides, Ca supplements
o Thyrotosicosis
o Vit D intoxication
o 24-hydroxylase deficiency (can’t metabolize 1-25 Vit D resulting
in hypercalcemia)
Additional Hypercalcemia Causes
18

19. • If elevated serum Ca and low PTH (its not HPT)- check
1-25 Vit D level
• Primary HPT can occur in the setting of normocalcemia
• If PTH elevated and normocalcemic-
o check renal function (PTH increases in CKD) and
o vit D levels (25 OH) -make sure no deficiency (>30) also can
increase PTH
19

20. • Don’t start a thiazide if any level of hypercalcemia
• Thiazides great for hypercalciuria + HTN
o Typical doses of HCTZ or the thiazide component in combo pills
are typically too low to impact Ca excretion.
o Chlorthalidone and Indapamide
• Greater % fall in urine ca
Thiazide Diuretics
20

21. • *** Be mindful of hypokalemic effects of thiazides. Can
place on K immediately or follow BMP.
o Hypokalemia can lead to hypocitraturia
• Hyperglycemia (rare) affecting diabetic management
• Gout
o Increased uric acid
• ED
Thiazide Side Effects
21

22. • >700 mg/day
• Can lead to calcium oxalate stone formation
o Heterogenous nucleation
• Causes:
o Excess purine intake from animal protein
o Gout
o Myeloproliferative disorders
o Chemotherapy/tumor lysis
o Meds- probenecid, losartan, salicylates
o Rare hereditary conditions
Hyperuricosuria
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23. • Types:
o Dietary- oxalate rich foods, vitamin C
o Enteric- malabsorption (IBD, celiac, pancreatitis)
• Mechanism- fatty acid saponification of calcium à increased free
luminal oxalate
• Typical findings- low volume, low pH, low ca/Na/citrate, high Ox
o Primary
• Oxalate absorption impacted by:
o Dietary calcium intake
o Oxalobacter formigenes (oxalate degrading bacterium)
Hyperoxaluria
23

24. • Autosomal recessive genetic disorder of glyoxalate
metabolism
• Endogenous overproduction of oxalate
• Recurrent nephrolithiasis
• Renal damage à renal failure
• 3 types (type 1 most common and most sever)
• Young age of presentation
• Urine oxalate levels > 80-100 mg/day
• Liver/kidney transplant
Primary Hyperoxaluria
24

25. • <320 mg/day
• Citrate excretion depends on systemic acid-base status
• Hypocitraturia occurs with acidosis
• Causes of hypocitraturia-
o RTA type 1 (distal)- impaired H ion secretion in distal tubule à
can’t excrete acid load à systemic acidosis
• Hypokalemia, high urine pH, very low citrate
o Chronic diarrhea- loss of bicarbonate à systemic acidosis
o Medications- thiazides (hypokalemia, intracellular acidosis),
carbonic anhydrase inhibitors (prevent bicarb reabsorption in
nephron)
o Idiopathic
Hypocitraturia
25

26. • Can’t excrete acid load
o NH4 (ammonium) will not be high on 24-h testing
• Treatment with Urocit K
o Ph rises but citrate goes up and ca excretion goes down
• Citrate complexes ca and is a direct crystal inhibitor
• Topiramate, acetazolamide, zonisamide (carbonic
anhydrase inhibitors) à stones
o Hard to get citrate to go up with Urocit-K
RTA and CaP Stones
26

27. • Urine pH <5.5
• Main factor leading to uric acid stone formation
o Low volume and hyperuricosuria also contribute
• Can have heterogenous nucleation à CaOx stones
• Uric acid stones more common in DM type 2
o Insulin resistance à impaired renal ammonium excretion
Low Urine pH
27

28. • Acid production- from methionine/cysteine (sulfate
excretion/H2SO4) and lysine/arginine
o Higher sulfate excretion = higher acid load
• Alkali production- aspartate/glutamate and organic
anions
• Diets are net acid producing
• SO4 (sulfate) and NH4 (ammonium) should travel
together
o Sulfate is our dietary acid load
o Ammonium is our acid excretion/what we pee out
Acid-Base
28

29. • Alkali therapy
o High pH, suppressed NH4 secretion
• Urease activity
o High pH, high NH4
• Met syndrome, hyperkalemia, inadequate alkali tx
o Low pH (can’t get rid of acid as NH4, suppressed NH4 secretion
(insulin resistance)
• GI alkali loss, diarrhea (looses alkali in the gut and
kidneys must secrete acid), hypokalemia
o Low pH, ammonium >> sulfate
• If both sulfate and ammonium are high- that is a normal
response- to a high protein diet (should trend together)
29

30. • Need an alkaline urine to solubilize cystine
• Want SS cystine to be <0.8
• Capacity – Unique parameter to Litholink
o assess risk of further cystine stone formation
o particularly when on a thiol
• Neg capacity= bad (supersaturated);
• Pos capacity= good (undersaturated)
• Cystine stone formers have high pH at baseline
Cystinuria
30

31. • Not all cystine forming pts need meds- do not need to
start Thiola immediately
• Initial management = diet
o Hydration
o Low salt diet
o Low protein diet- not a huge benefit to protein limitation in terms
of cystine excretion
31

32. • Alkalinization- solubility goes up in general with
increasing pH
• Thiol drugs: pH must be high for meds to work
• Thiol binding to cystine occurs quicker with higher pH
• Need pH of 7.5 for thiol drugs to work
• Make sure you test siblings (25% chance)
o Autosomal recessive
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33. • Potassium citrate vs. calcium citrate
o Only 20-30% of ca is absorbed, much more K absorption àget
more alkali
• Thiazides and alkali together- do not get as much of an
increase in citrate vs. alkali alone
Medications- Pearls
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34. Litholink Cases
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44. Questions?
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• Thank you!
• @kevanms42
• @UVMUrology

45. Thank You
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