URINARY LITHIASIS Etiology, Epidemiology

and Pathogenesis

Urology Division, Surgery DepartmentMedical Faculty,

University of Sumatera Utara

References

EpidemiologyPrevalence of kidney stone 1 – 15 %, and in

hot area such as the mountains, desert & tropical

areas

: = 2 to 3 : 1, peak age onset 40 - 60 yrs

The third most common affliction of the urinary

tract, after UTI and pathologic conditions of the

prostate

Race : Whites > Asian > African

Individual occupations eg. manager and

professional risk of stone (unclear reason)

Epidemiology25% stone formers have a family history

Risk of stone correlates with weight and body mass index

Uric acid and Ca stones more frequent in, infectious stones more common in

The most common kinds of stones are calcium oxalate, uric acid, struvite and cysteine

Etiology1. Definitive causes :

Metabolic

Infection

Anatomic

Functional

2. Idiopathic

Definitive causesDefects in purine metabolism (uric acid related disorders)

Hyperoxaluric states

- Primary hyperoxaluria

- Enteric hyperoxaluria

Hypercalcemic states

- Primary hyperparathyroidism

- Hyperthyroidism

- Vitamin D abuse

Hypercalcemic states (cont.) - Immobilization - Disseminated malignancies

- Sarcoidosis- Renal tubular acidosis

Chronic diarrheal statesCystinuriaUrinary infection with urease producing microorganismsAnatomical and functional abnormalities

Risk factors Genetics : Cystinuria : autosomal recessive RTA (renal tubular acidosis) – type IMedullary sponge kidney

Geography : temperature & humidity

Diet : calcium / oxalate intake >>

Profession : sedentary

ClassificationDefenition

Non Calcium Stones Infection stones:• Magnesium ammonium phosphate• Carbonate apatite• Ammonium urateaUric acidAmmonium urateaSodium urateCystine

Calcium Stones

Stone Composition and Relative Occurrence

Stone Composition Occurrence (%)

Calcium-Containing Stones

Calcium oxalate 60

Hydroxyapatite 20

Brushite 2

Non–Calcium-Containing Stones

Uric acid 7

Struvite 7

Cystine 1–3

Triamterene <1

Silica <1

2,8-Dihyroxyadenine <1

Stone formation

Stone formationCrystallization

Stone salts that precipitate out of urine The point of saturation of a salt in solution is called the

solubility product (Ksp)

When the product of the components of a salt (e.g.

calcium and oxalate) exceeds Ksp, salt crystals will precipitate out of solution Crystallization is based on Ksp, pH, and the presence of stone inhibitors and promoters

Nucleation

- Is the process by which stones form around a

core, or nucleus

- Homogeneous stone nuclei form in solution

- Heterogeneous stone nuclei form around

existing structures, such as cellular debris

Aggregation

- Crystals join together to form larger clumps

Inhibitors and Promoters of Crystal Formation

Inhibitors : Nephrocalcin Uropontin Tamm-Horsfall protein Citrate Magnesium

Promoters : Calcium phospate Calcium oxalate

Urinary tract stone

AgeSexProfessionNutritionClimateRaceInheritance

Abnormal renal morphologyDisturbed urin flow UTIMetabolic abnormalGenetic factors

Increaseexcretion of : 1.Stone

forming constituents2. Crystallization promoters

Decrease :1.Urinary

volume2. Excretion of crystallization inhibitors

SUPERSATURATION

STONE

PathogenesisCALCIUM STONES1. Hipercalciuria : excretion of Ca > 4

mg/kg/day a. Absorptive : increased ca excretion (>0.2

mg/mg creatinine) after an oral calcium load

b. Renal : urinary ca levels >0.11 mg/dL glomerular filtration with a normal serum calcium

c. Resorptive : associated with primary hyperparathyroidism

2. Hyperoxaluria : urinary oxalate greater than 40 mg/day

a. Primary Hyperoxaluria (autosomal recessive disorder )

b. Enteric Hyperoxaluria : associated with chronic diarrheal states

c. Dietary Hyperoxaluria : oxalate-rich foods such as nuts, chocolate, brewed tea, spinach, broccoli, strawberries.

d. Idiopathic Hyperoxaluria

3. Hyperuricosuria

Urinary uric acid exceeding 600 mg/day

The most common cause increase purin intake

4. Hypocitraturia

Urinary citrate level less than 320 mg/day

Correctable abnormality

Associated with nephrolithiasis in up to 10% of

calcium stone

5. Hypomagnesuria

Rare cause, less than 1%

Magnesium complexes with oxalate and calcium,

mg levels decrease reduced inhibitory activity

Poor dietary intake Mg

URIC ACID STONES 5-10% of all stone 3 factors of uric acid stone formation :

1. Low pH, < 5,52. Low urine volume3. Hyperuricosuria urinary uric acid

less than 600 mg/day

Secondary causes : gout (20%),obesity , myeloproliferative cancer and congenital disorder

STRUVITE STONESInfection stones comprise 5% to 15% of all

stones Composed of Mg ammonium phosphate crystals

= infection stones or triple phosphate stoneStaghorn calculi are typically struvite stoneCaused by infection with urease-producing

bacteria :

- proteus is the most common

- urease hydrolized urea to form ammonia

alkalinizes the urine, pH and allows crystals to form

CYSTINE STONES

1% of all stones

Congenital disorders, autosomal recessive

Caused by a defect in cystine reabsorption

in the proximal tubule

Cystine poorly soluble at normal pH (pKa

8.3)

Crystal form benzene ring on microscopy

CALCIUM PHOSPHATE STONE Urine pH > 5.5

Hypocitraturia

70% of adults with type 1 RTA have stones

80% are women

Associated with renal cyst

Medications That directly Promote Stone Formation

Indinavir Stones

Triamterene Stones

Guaifenesin and Ephedrine

Silicate Stones

Anatomic Predisposition Ureteropelvic Junction Obstruction :

20 %

cases

Horseshoe Kidneys

Caliceal Diverticula

SUMMARY

The most common type is calcium oxalate

Uric acid stones form at pH <5.5

The most important determinant of uric acid stone formation is low urinary pH

Struvite stone are composed of magnesium

ammonium phosphate crystals

- They are classically caused by infection with

a urease-producing bacterium

- Urinary pH is >7.2 treatment is surgery &

antibiotics

Cystine stones caused by a congenital

autosomal recessive disorder

Calcium phosphate stones associated with

type 1 RTA