Metabolic evaluation and medical management of urolithiasis aims to prevent recurrent stone formation and complications. It should be simple, economically viable, and provide targeted treatment. Patients at high risk for recurrence include those with family history, intestinal diseases, or anatomical abnormalities. Evaluation includes history, blood tests, urine tests, imaging and stone analysis to identify metabolic derangements. Treatment is tailored based on stone composition and includes increased fluid intake, dietary modifications, and medications to correct underlying causes and reduce stone risk factors.

1. DETAILED METABOLIC
WORKUP & MEDICAL
MANAGEMENT IN
UROLITHIASIS
Gaurav Nahar
DNB
Urology(Std.)
MMHRC

2. GOALS OF M.E.
Why?
• The main goal of metabolic evaluation is
to prevent recurrent stone formation in
high-risk stone producers,
to prevent further growth of any existing
stones, &
to prevent extrarenal complications in
associated systemic disorders.

3. CHARACTERISTICS
It should be
• simple to perform,
• economically viable,
• provide information that can be applied
toward a selective, rational therapy of
stone disease.

4. Selection of Patients
for Metabolic Evaluation
• First-time “stone formers”-50% risk of recurrence within
subsequent 10 years.
• Stone clinic effect: “single stone formers” placed on a
conservative program of high fluid intake alone or
combined with avoidance of dietary excess revealed a
low incidence of recurrent stone disease.
• Decision to thoroughly investigate a first-time stone
former should ideally be shared by the physician and the
patient.

5. Contd...
• Formation of a first stone may be the harbinger of
a more severe underlying systemic disorder
such as renal tubular acidosis, bone
disease, or hypercalcemia due to
hyperparathyroidism.
• In such patients, metabolic evaluation is justified
solely to make the correct diagnosis in order to
prevent extrarenal complications.

6. TIMING
When?
• At least 1 month after stone passage or
stone removal, allowing the patient to
return to their normal routine.

7. Indications for a Metabolic
Stone Evaluation
Who ?
• Recurrent stone formers
• Strong family history of stones
• Intestinal disease (particularly chronic diarrhea)
• Pathologic skeletal fractures
• Osteoporosis
• History of urinary tract infection with calculi
• Personal history of gout
• Infirm health (unable to tolerate repeat stone episodes)
• Solitary kidney
• Anatomic abnormalities
• Renal insufficiency
• Stones composed of cystine, uric acid, struvite
• Children

8. Abbreviated Protocol for Low-Risk,
Single Stone Formers
History
• Underlying predisposing conditions
• Medications(calcium, vitamin C, vitamin D, acetazolamide, steroids)
• Dietary excesses, inadequate fluid intake or excessive fluid loss
Multichannel blood screen
• Basic metabolic panel (sodium, potassium, chloride, carbon dioxide, blood urea
nitrogen, creatinine)
• Calcium
• Intact parathyroid hormone
• Uric acid
Urine
• Urinalysis
pH > 7.5: infection lithiasis
pH < 5.5: uric acid lithiasis
Sediment for crystalluria
• Urine culture
Urea-splitting organisms: suggestive of infection lithiasis
• Qualitative cystine

9. Contd...
Radiography
• Radiopaque stones: calcium oxalate, calcium phosphate,
magnesium ammonium phosphate (struvite), cystine
• Radiolucent stones: uric acid, xanthine, triamterene
Intravenous pyelography: radiolucent stones, anatomic
abnormalities
Stone analysis

10. CRYSTAL MORPHOLOGY
Scanning electron
micrographs of
various urinary
crystals.
• A, Apatite(Amorphous)
• B, Struvite
(Rectangular,Coffin-lid)
• C, Ca oxalate dihydrate
(Envelope,tetrahedral)
• D, Ca oxalate
monohydrate(Hourglass)
• E, Cystine(Hexagonal)
• F, Ammonium acid urate.
• G, Brushite(Needle-shaped)

11. Extensive Diagnostic
Evaluation
• Should be performed in patients with recurrent
nephrolithiasis, and stone formers at increased
risk for further stone formation.
• To identify underlying physiologic
derangements.
• Pt. to discontinue any medication that interferes
with metabolism of calcium, uric acid, or oxalate.
(vitamin D, calcium supplements, antacids,
diuretics, acetazolamide, & vitamin C) & any
current medication for stone treatment
(thiazides, phosphate, allopurinol, or

12. Contd...
• It involves two outpatient visits.Three 24-hour
urine samples are collected.
• First two 24-hour specimens: on random diet,
reflective of their usual dietary intake.
• Third 24-hour sample: after 1 week, on a
calcium-, sodium-, & oxalate-restricted diet.

13. Fast and Calcium Load Test:
• discriminate b/w various forms of hypercalciuria.
• no longer performed by most clinicians.
• essential if plan to place a patient with absorptive
hypercalciuria on a calcium binding resin.
 Normal fasting urinary calcium < 0.11 mg/dL GF
 Normal postload urinary calcium < 0.2 mg calcium/mg
creatinine

14. Simplified Metabolic
Evaluation
• All patients: basic metabolic screening,
searching for systemic disorders.
• High-risk stone patients: more extensive
metabolic evaluation based on two 24-hour urine
samples.
• Cornerstone of these simplified protocols-
development of a urine preservation method that
allows collection of urine without refrigeration.
• Urinary constituents most commonly assayed:
calcium, oxalate, citrate, total volume, sodium,
magnesium, potassium, pH, uric acid, and
sulfate.

15. STONE ANALYSIS TO DETERMINE
METABOLIC
ABNORMALITIES
• Most stones are a mixture of more than one component,
relative ratios or predominance of any particular
molecule has predictive value.
• Ca apatite & mixed Ca oxalate-Ca apatite stones: RTA &
1° hyperparathyroidism
• Pure & Mixed Uric acid stones: Gouty diathesis
• Brushite stones: RTA
• Infection stones: Infection
• Cystine stones: Cystinuria
• Pure uric acid, pure infection & pure cystine stones- start
treatment; no further testing required.

16. IMAGING IN DETERMINING STONE
COMPOSITION
• Hounsfield unit (HU)measurement to
determine stone composition- significant
variation for diff.stone types.
• DECT technology: to distinguish b/w uric
acid, Ca phosphate & Ca oxalate calculi.
HU ratios
DECT Slope algorithm
DECT attenuation values.

17. Classification of
Nephrolithiasis
1. Absorptive hypercalciuria (i)Type I (ii)Type II
2. Renal hypercalciuria
3. Primary hyperparathyroidism
4. Unclassified calcium nephrolithiasis
5. Hyperoxaluric calcium nephrolithiasis (i)Enteric hyperoxaluria (ii)Primary
hyperoxaluria (iii)Dietary hyperoxaluria
6. Hypocitraturic calcium nephrolithiasis (i)Distal renal tubular acidosis
(ii)Chronic diarrheal syndrome (iii)Thiazide-induced (iv)Idiopathic
7. Hypomagnesiuric calcium nephrolithiasis
8. Gouty diathesis
9. Cystinuria
10.Infection stones
11.Low urine volume
12.No disturbance and miscellaneous

18. Diagnostic criteria

19. CONSERVATIVE
MEDICAL M/M
1.Fluid recommendations
2.Dietary recommendations
3.Obesity

20. 1. Fluid recommendations
VOLUME:
• Forced increase in fluid intake to achieve
a urine output of 2L.
• Two effects:
1.Mechanical diuresis that ensues may
prevent urinary stagnation & formation of
symptomatic calculi.
2.Creation of dilute urine alters
supersaturation of stone components.

21. Contd...
WATER HARDNESS:
• Although water hardness can alter urinary
parameters, it does not play a significant
role in recurrence risk.

22. Contd...
CARBONATED BEVERAGES:
• Carbonated water offers increased protection
against recurrent stone formation, by increasing
urinary citrate levels.
• Soda flavored with phosphoric acid may
increase stone risk, whereas those with citric
acid may decrease risk.
• Caffeine intake may increase the risk of stone
recurrence in calcium stone formers by
increasing the excretion of calcium.

23. Contd...
CITRUS JUICES:
• Citrus juices (particularly lemonlemon and
orange juices) may be a useful adjunct to
stone prevention.

24. 2. Dietary Recommendations
PROTEIN RESTRICTION:
• Incidence of renal stones is higher with
increased animal protein intake.
• Protein intake increases urinary calcium,
oxalate, & uric acid excretion and probability of
stone formation even in normal subjects.
• Diets high in fruits and vegetables impart a
significantly reduced risk of stone formation than
diets high in animal protein.

25. Contd...
SODIUM RESTRICTION:
• An important element of dietary prevention of
recurrent nephrolithiasis.
• A high sodium intake increases calcium
excretion, urinary pH and decreases citrate
excretion. Net effect- increased propensity for
crystallization of calcium salts in urine.
• Animal protein restriction, moderate calcium
ingestion, & a reduced-sodium diet decreases
stone episodes by roughly 50%.
• Calcium stone formers who ingest large
quantities of daily salt are more likely to suffer
from decreased bone mineral density

26. Contd...
DIETARY CALCIUM:
• Evidence supports maintenance of a
moderate calcium intake in calcareous
nephrolithiasis.
• Dietary calcium restriction may
subsequently increase oxalate absorption,
thereby raising Ca oxalate
supersaturation.
• "Safe" Calcium supplementation: Time &
Type
Time- to be taken with meals.
Ca citrate- "Stone friendly" Ca

27. OXALATE AVOIDANCE:
• Avoidance of excess dietary oxalate is
reasonable & intuitive.
• Vitamin C in large doses(By conversion to
oxalate) may increase the risk of stone
recurrence. Doses should be limited to 2 g/day.
Contd...

28. 3. Obesity
• Increased BMI, larger waist size, & weight
gain correlate with an increased risk of
stone episodes.
• More pronounced for women.

29. Contd...
METABOLIC SYNDROME:
• Hypertension, Hypertriglyceridemia,
Glucose intolerance & Central obesity.
• Obesity & Insulin resistance → impaired
ammonium excretion→ Low urinary pH→
Increased incidence of uric acid stone
formation.

30. Contd...
IMPACT OF WEIGHT-LOSS DIETS:
• a low-carbohydrate, high-protien diet
delivers a marked acid load to kidney,
increases risk for stone formation & bone
loss.

31. Contd...
IMPACT OF BARIATRIC SURGERY:
• Bariatric surgery may significantly
increase the overall risk of stone
formation.
• Jejunoileal bypass(before) & Roux-en-Y
gastric bypass(now) both increase oxalate
nephropathy & nephrolithiasis.

32. SELECTIVE MEDICAL
M/M
• Selective treatment program would be
more effective and safe than “random”
therapy.

33. Rx ALGORITHM FOR
UROLITHIASIS

35. Medications

36. I.Calcium-Based Calculi
HYPERCALCIURIA(>200mg/day):
• Absorptive Hypercalciuria(AH): an
increased amount of Ca absorbed by intestinal
tract.
AH type1- increased urinary excretion of calcium
on both fasting & loading specimens.
AH type2- elevated urinary Ca on regular diet,
normalises on fasting.
a low iPTH due to suppression from a constant
abundance of available serum Ca.

37. Rx: Absorptive Hypercalciuria
AH type1:
• Thiazides(1st
choice)+Pot.citrate +dietary
restriction.(drug holiday in long-term therapy)
• Thiazides do not treat underlying cause of AH
but reduce urinary calcium & manage its
symptoms.
• MoA: Thiazides directly stimulate calcium
resorption in distal nephron while promoting
sodium excretion.
• S/E: Potassium wasting, muscle cramps,
hyperuricosuria, intracellular acidosis,
hypocitraturia

38. Contd...
• Sodium cellulose phosphate (SCP)
effectively decreases absorption of
intestinal Ca but abandoned due to GI
intolerance & side effects.
• S/E: GI distress, hypomagnesemia,
hyperoxaluria, PTH stimulation.

39. Contd...
• Thiazides- limited long-term effectiveness
in AH type1.
Other hypocalciuric agents:
• Hydrochlorthiazide,Indapamide(OD dose)
• Amiloride + thiazide(K.Cit not needed)
• Triamterene(Risk of triamterene stones)

40. Contd...
AH type2:
• No specific drug Rx needed.
• Moderate Ca intake(400 to 600 mg/day) &
high fluid intake(sufficient to achieve a
minimum urine output of >2 L/day).
• Avoidance of excessive sodium intake
further decrease hypercalciuria.

41. Contd...
Orthophosphate:
• MoA- inhibit 1,25-(OH)2vitamin D
synthesis; reduces urinary Ca by binding
Ca in intestinal tract.
• Has a role when other methods are
ineffective.
• S/E: GI upset,soft tissue calcification.
• UroPhos-K: a slow-release, neutral
potassium phosphate prepared in wax
matrix limits GI upset.

42. Contd...
Dietary Bran:
• Rice bran binds intestinal Ca & increases
urinary pyrophosphate.
• Thiazide + bran superior to bran alone.

43. Contd...
• Renal Hypercalciuria: due to a wasting
of calcium by functioning nephron.
• constant loss of Ca from distal tubules.
• hypercalciuria during all phases of fasting,
loading, or restriction of dietary calcium.
• mild elevation of iPTH.

44. Rx:Renal Hypercalciuria
• Thiazides(Rx of choice) + Pot.citrate(correct
hypokalemia, increase urinary citrate)
• Thiazides correct renal leak of Ca by
augmenting calcium reabsorption in distal tubule
and by causing ECV depletion and stimulating
proximal tubular reabsorption of Ca.
• Correction of 2°
hyperparathyroidism restores
normal serum 1,25-dihydroxyvitamin D
concentration & intestinal Ca absorption.
• Sustained correction for upto 10 yrs.

45. Contd...
• Resorptive Hyperclaciuria
(1°hyperparathyroidism): overproduction
of PTH from dominant adenoma or diffuse
hyperplasia.
• Hypercalcemia,hypercalciuria in all
phases, & raised iPTH.

46. Rx: 1°hyperparathyroidism
• Parathyroidectomy: resection of dominant
adenoma or all four glands.
• No established medical Rx.
• Orthophosphates used only when Sx
cannot be undertaken.

47. Contd...
• HYPERURICOSURIC CA OXALATE
NEPHROLITHIASIS (HUCN):
(>800mg/day) Heterogeneous
nucleation/Epitaxy.
• Hyperuricosuria + pH> 5.5.
• Causes: increased dietary purine intake,
Gout, MPD/LPD,MM, neoplastic states,
pernicious anemia, 2°polycythemia,
Hbpathies, thalassemia etc.

48. Rx: HUCN
• Decreased dietary protein intake.
• Allopurinol decreases uric acid production
by inhibiting Xanthine oxidase( which
converts xanthine to uric acid).
• Potassium citrate alters the urinary milieu
in hyperuricosuria by decreasing
supersaturation of uric acid & calcium
oxalate.

49. Contd...
HYPEROXALURIA: (>40mg/day)
• Enteric Hyperoxaluria: fat malabsorption
results in saponification of fatty acids with
divalent cations such as Ca and Mg, thereby
reducing Ca oxalate complexation and
increasing the pool of available oxalate for
reabsorption.
• Diarrhoea,dehydration,HCO3
-
losses.
• A/w chronic diarrheal syndrome, small bowel
resection, jejunoilleal bypass, intrinsic disease.

50. Rx: Enteric Hyperoxaluria
• Oxalate-restricted diet.
• High fluid intake (to ensure adequate urine
volume).
• Anti-diarrhoeal agent.
• Probiotics & gut flora correction (O.formigenes).
• Pot.Citrate (correct hypokalemia, metabolic
acidosis, increase urinary citrate).
• Oral Ca citrate or Mg gluconate(ileal disease)
• Cholestyramine(binds bile salts in bowel lumen).
• Replace dietary fat with MCT(correct
malabsorption).

51. • Primary Hyperoxaluria: rare AR disorder of
glyoxylate metabolism, normal glyoxylate to
glycine conversion is prevented, preferential
oxidative conversion to oxalate.
• Two types; PH1 & PH2.
Contd...

52. Rx: Primary Hyperoxaluria
• Present during childhood with early stone
formation, tissue deposition of oxalate
(oxalosis), & renal failure due to
nephrocalcinosis.
• Death before age 20 in untreated patients
• Early Dx & Combined liver-kidney
transplant.

53. Contd...
• Dietary Hyperoxaluria:
1.Oxalate rich foods.
2.Increased animal protein.
3.Severe Ca restriction
4.Ascorbic acid supplementation
5.Reduced levels/absent colonisation of
O.formigenes.
6.Cystic fibrosis pts.(prolonged antibiotics;
absent O.formigenes.)

54. Contd...
HYPOCITRATURIC CA OXALATE
NEPHROLITHIASIS: (<550mg/day in F; <450mg/day
in M)
• Distal RTA(Type1): Hypokalemic,hyperchloremic,non-
AG metabolic acidosis.
• Abnormal collecting duct function; inability to acidify urine
in systemic acidosis.(pH>5.5).
• Ca phosphate stones m.c.
• Two-thirds pts.adults-nephrolithiasis, nephrocalcinosis.
• Infants- Vomiting or diarrhoea, FTT & growth retardation.
• Children- Renal stones & metabolic bone disease.

55. Rx: Distal RTA Hypocitraturia
• Potassium citrate
correct the metabolic
acidosis & hypokalemia
in distal RTA.
• Large doses(up to 120
mEq/day) may be
required in severe
acidotic states.
• Target dose in children:
3-4mEq/kg/day in
divided doses.

56. Contd...
• Chronic Diarrhoeal states: Lab
findings like enteric hyperoxaluria; except
for bowel inflammation.
• moderate decreases in urinary citrate
excretion with associated low urine
volumes.
• Rx: Pot.Citrate(60-120mEq in 3-4 doses;
liquid prepn preferred due to rapid
intestinal transit time).

57. Contd...
• Thiazide-Induced & Idiopathic
Hypocitraturia:
• Rx: Pot.citrate therapy.

58. Contd...
HYPOMAGNESURIC CALCIUM
NEPHROLITHIASIS: (<80mg/day)
• Low urinary Mg, hypocitraturia, & low urine
volume.
1.Chronic thiazide therapy.
2.IBD causing malabsorption.
3.Laxative abuse.

59. Rx: Hypomagnesuria
• Magnesium supplementation beneficial in
stone reduction.
• Use of magnesium limited by risk of
diarrhea (Mg oxide, hydroxide).
• Potassium-magnesium citrate(new)may
restore urinary magnesium and citrate
levels with minimal GI side effects.

60. II.Uric acid Calculi
• Uric acid: end product of purine metabolism.
• pKa- 5.35. At more acidic pH, undissociated uric
acid predominates & precipitates; at higher pH
6.5, >90% uric acid is ionised & soluble.
• 3 main determinants: low urine pH, low urine
volume & hyperuricosuria.
• "Gouty diathesis” refers to a stone-forming
propensity characterized by low urine pH of
unknown etiology with or without associated
gouty arthritis.

61. Rx: Gouty Diathesis
• Major goal: to increase urinary pH>5.5,
preferably b/w 6.0 & 6.5.
• Alkalinisation to a pH>7.0 should be
avoided (increased risk of Ca phosphate
stone formation).
• Pot.citrate therapy.
• Allopurinol, if hyperuricemia or
hyperuricosuria present.

62. III. Cystinuria
• AR error of transepithelial transport involving
intestine & kidneys.
• Inability to reabsorb dibasic amino acids cystine,
ornithine, lysine, and arginine (COLA).
• Resultant accumulation of cystine causes
crystallization when concentrations rise above
the saturation point (roughly 250mg/L of urine)
• Young age presentation.

63. Contd...
Object: to reduce urinary concentration of cystine
to below its solubility limit(200 to 300 mg/L).
• High fluid intake to produce 2.5-3L/day of urine.
• Urinary alkalinisation by Pot.citrate.
• Restricted salt/sodium diet.
• Use of cystine binding agents (increase cystine
solubility in urine via formation of a more soluble
mixed-disulfide bond).

64. Contd...
1.α-mercaptopropionylglycine (Thiola,
Tiopronin)- m.c.used.
S/E: asthenia, GI distress, rash, joint aches,
and mental status changes.
2. D-penicillamine (Cuprimine)
S/E: Nephrotic syndrome, dermatitis,
pancytopenia
3. Captopril
S/E: rash,cough,hypotension.

65. IV. INFECTION
CALCULI(STRUVITE)
• Form in alkaline(pH>7.2), infected urine with
urease producing bacteria in an ammonia-rich
environment.
• Women produce more infection calculi than
men.
• Infection calculi most likely produce staghorn
stones.
• Symptoms of UTI may be present.

66. Rx: Struvite stones
• PCNL first-line therapy for managing
complex, renal staghorn calculi.
• Complete elimination of all infected stone
material essential for prevention of
recurrent struvite stone formation.
• Antibiotic prophylaxis.
• Hemiacridin irrigation for residual fragment
dissolution.

67. Contd...
• Acetohydroxamic acid, a urease inhibitor, reduce
urinary saturation of struvite, & retard stone
formation.
• Prevent recurrence of new stones.
• Inhibit the growth of stones in patients with
chronic urea-splitting infections.
• S/E: Thromboembolic phenomena, tremor
headache, palpitations, edema, GI distress, loss
of taste, rash, alopecia, anemia, abdominal pain

68. MEDICATION RELATED
STONES

69. MISCELLANEOUS
MEDICAL M/M OF BLADDER CALCULI:
• Stone dissolution using Suby G or M solution:
beneficial in irrigating indwelling suprapubic or
urethral catheters to decrease and prevent
encrustation and occlusion.
• Twice-or thrice-daily irrigation with 0.25%-0.5%
acetic acid solution beneficial prophylaxis
against recurrent struvite calculi when catheters
must be left indwelling for long periods.
• Uric acid calculi may be dissolved by irrigation
with alkaline solutions

70. Contd...
MEDICAL M/M OF CALCULI DURING
PREGNANCY:
• Due to temporary physiologic changes, a metabolic
evaluation is not undertaken to determine the cause of
the stone disease until delivery & return to baseline
health status.
• Majority of ureteral calculi during pregnancy pass
spontaneously.
• Dx during pregnancy- USG or limited IVP.
• Rx- Hydration, analgesics & antibiotics. Stents, if
required exchange every 4-6 weeks.
• URSL with Holmium laser lithotripsy is safe.

71. Thank You
!!!