urolithiasis
UROLITHIASIS

Urolithiasis is the formation of urinary stones in the kidney, bladder and/or urethra.

The hallmark of obstruction in the ureter and renal pelvis is the sudden onset of excruciating, intermittent pain that radiates from the flank to the groin or to the genital area and inner thigh.

It is a painful urologic disorder that occurs in 12% of the global population and has a high recurrence rate among male patients.

Lower urinary tract symptoms that are associated with urolithiasis are urgency, frequency, urge incontinence and dysuria.

 

Classification

Classification of urinary stones

Size

  • Usually given in one or two dimensions & is stratified to those measuring up to 5, 5-10, 10-20 & 20 mm in largest diameter

Location

  • Classified according to anatomical position: upper, middle or lower calyx, renal pelvis, upper, middle or distal ureters & urinary bladder

X-ray characteristics

  • Classified according to plain X-ray appearance (eg kidney-ureters-bladder (KUB) radiography), according to mineral composition
  • Non-contrast computed tomography (NCCT) scan is used to classify stones according to density, structure & composition

Etiology of formation

  • Non-Infectious (eg calcium oxalate, calcium phosphate, uric acid)
  • Infectious (eg magnesium ammonium phosphate, carbonate apatite, ammonium urate)
  • Genetic causes (eg cystine, xanthine, 2,8 dihydroxyadenine)
  • Further diagnostic tests & management depends on the composition of the stone
  • Risk status of the stone formers should be assessed because it will define the probability of recurrence or regrowth & is imperative for the choice of pharmacological treatment
Analysis of stone composition
  • Preferred analytical procedures are infrared spectroscopy (IRS) & X-ray diffraction analysis of urinary stones
  • Repeat stone analysis is needed in cases of:
    • Recurrence after pharmacological intervention
    • Early recurrence after interventional therapy w/ complete stone clearance
    • Late recurrence after a prolonged stone-free period since stone composition may change overtime

Stone types

Calcium stones (oxalate & phosphate)

  • Most common type of kidney stone
  • Formed when there is high level of calcium in the urine
  • Characterized as either large & smooth or rough & spiky
  • Diseases & disorders related to calcium stones:
    • Hypercalciuria (inherited condition)
    • Renal tubular acidosis
    • Nephrocalcinosis
    • Primary hyperparathyroidism
    • Kidney disease
    • Sarcoidosis (granulomatous disease)
    • Primary hyperoxaluria
    • Enteric hyperoxaluria

Struvite or infection stones

  • May originate de novo or grow on pre-existing stones infected w/urea-splitting bacteria
  • Predisposing factors for stone formation:
    • Neurogenic bladder
    • Spinal cord injury or paralysis
    • Continent urinary diversion
    • Ileal conduit
    • Foreign body
    • Stone disease
    • Indwelling urinary catheter
    • Urethral stricture
    • Benign prostatic hyperplasia
    • Bladder diverticulum
    • Cystocele
    • Caliceal diverticulum
    • Uteropelvic junction (UPJ) obstruction

Uric acid & ammonium urate stones

  • Associated w/ hyperuricosuria or low urinary pH
  • Hyperuricosuria may be due to dietary excess, endogenous overproduction (enzyme defects), myeloproliferative disorders, tumor lysis syndrome, drugs, gout & catabolism
    • Ammonium urate stones are rare & are associated w/ inflammatory bowel disease (IBD), ileostomy diversion, laxative abuse, potassium deficiency, hypokalemia & malnutrition
    • Forms in the urine at pH <6.5 (ammonium urate crystals) & <5.5 (uric acid stones)

Cystine stones

  • Poorly soluble in urine & crystallizes spontaneously w/in the physiological urinary pH at 6.0
  • Clinical manifestations are the same for patients who are genotypic or phenotypic type of cystinuria

Other stone types

2,8-Dihydroxyandenine stones & xanthine stones

  • Both stone types were rare & the diagnosis is similar to that of uric acid
  • Genetically determined defect of adenine phosphoribosyl transferase that causes high urinary excretion
  • Decreased levels of serum uric acid are seen in patients who forms xanthine stones

Drug stones

  • These are induced by pharmacological treatment & exists as:
    • Stones formed due to unfavorable changes in urine composition under drug therapy & by the crystallized compounds of the drug
  • Compounds that causes drug stones:
    • Allopurinol/oxypurinol
    • Amoxicillin/ampicillin
    • Ceftriaxone
    • Quinolones
    • Ephedrine
    • Indinavir
    • Magnesium trisilicate
    • Sulphonamides
    • Triamterene
    • Zonisamide
  • Substances impairing urine composition:
    • Acetazolamide
    • Allopurinol
    • Aluminium magnesium hydroxide
    • Ascorbic acid
    • Calcium
    • Furosemide
    • Laxatives
    • Methoxyflurane
    • Vitamin D
    • Topiramate

Matrix stones

  • Pure matrix stones are extremely rare
  • More prevalent among females
  • Main risk factors are:
    • Urinary tract infections (UTIs) due to Proteus mirabilis or Escherichia coli
    • Previous surgery for stone disease
    • Chronic renal failure
    • Hemodialysis

History

  • A detailed history from the patient should be elicited
  • Thorough review of medical records should include:
    • Number & frequency of episodes
    • Previous imaging studies, interventions, evaluations & treatments
  • Family history that may reveal genetic predisposition:
    • Cystinuria (type A, B & AB)
    • 2,8 Dihydroxyandeninuria
    • Xanthinuria
    • Renal tubular acidosis (RTA type 1)
    • Primary hyperoxaluria
    • Lesch-Nyhan syndrome
    • Cystic fibrosis
  • General factors:
    • Early onset of urolithiasis (especially in children & teenagers)
    • Familial stone formation
    • Brushite-containing stones (calcium hydrogen phosphate)
    • Uric acid & urate-containing stones
    • Infection stones
    • Solitary kidney
  • Dietary history of the patient:
    • Average daily intake of fluids (amount & specific beverages)
    • Eating habits (meals & snacks)
    • Calcium, sodium, high oxalate-containing food
    • Fruits & vegetables
  • Nutritional factors associated w/ stone diseases:
    • Calcium intake that is below or significantly above the recommended dietary allowance (RDA)
    • Low fluid intake
    • High sodium intake
    • Limited intake of fruits
    • Vegetables & high intake of animal-derived purines
  • Complete list of current prescription & over-the-counter drugs, as well as vitamins & supplements should be obtained; stone-provoking medications include:
    • Probenecid
    • Some protease inhibitors
    • Lipase inhibitors
    • Triamterene
    • Chemotherapy
    • Vitamins C & D
    • Carbonic anhydrase inhibitors (eg Topiramate, Acetazolamide, Zonisamide)
  • Conditions associated w/ stone disease:
    • Obesity
    • Gout
    • Hyperparathyroidism
    • Renal tubular acidosis type I
    • Diabetes mellitus type II
    • Bone disease
    • Primary hyperparathyroidism
    • Bariatric surgery
    • Bowel or pancreatic disease
    • Nephrocalcinosis
    • Sarcoidosis
    • Due to jejunoileal bypass & intestinal resection
  • Anatomical abnormalities associated w/ stone formation:
    • Medullary sponge kidney (tubular ectasia)
    • Ureteropelvic junction (UPJ) obstruction
    • Calyceal diverticulum, calyceal cyst
    • Ureteral stricture
    • Vesico-uretero-renal-reflux
    • Horseshoe kidney
    • Ureterocele

Physical Examination

  • Should include the weight, blood pressure, costovertebral angle tenderness & lower extremity edema, as well as signs of primary hyperparathyroidism (HPT) & gout in the assessment

Laboratory Tests

  • Serum chemistries should include electrolytes (eg sodium, potassium, chloride, bicarbonate, calcium, creatinine, & uric acid) to uncover hypokalemia or renal tubular acidosis (RTA)
  • Parathyroid hormone (PTH) level should be measured if there is high normal or elevated serum & urine calcium concentration
  • Level of 25-hydroxy vitamin D should also be investigated to rule out the possibility of vitamin D deficiency in patients w/ elevated PTH
  • Urinalysis should include dipstick, microscopic evaluation (urinary pH, indicators of infection & identification of crystals that are pathognomonic of stone type)
  • 24-hour urine collection/metabolic testing
    • The cornerstone for which the therapeutic recommendations are based
    • At least two samples are collected, while consuming their usual diet & volume of fluid
    • Metabolic testing should analyze total volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium & creatinine
    • Urinary potassium measured at baseline can be compared to urinary potassium obtained during follow-up, to gauge compliance w/ medication regimens
    • Urinary cystine should additionally be measured in stone formers w/ known cystine stones or a family history of cystinuria or for those in whom cystinuria is suspected
    • Primary hyperoxaluria should be suspected when urinary oxalate excretion exceeds 75 mg/day in adults w/o bowel dysfunction
    • These patients should be considered for referral for genetic testing &/or specialized urine testing
Basic laboratory analysis in emergency cases
  • Urine (eg dipstick test of spot urine sample, urine microscopy &/or culture)
  • Serum blood sample (eg creatinine, uric acid, ionized calcium, sodium & potassium)
  • Blood cell count
  • Coagulation test, if intervention is likely or planned

Basic laboratory analysis in non-emergency cases

  • Biochemical work-up is similar for all patients but if there is no planned intervention, then sodium, potassium, C-reactive protein (CRP) & blood coagulation time can be omitted

Imaging

  • Choice of imaging modality will depend on the clinical situation of the patient
  • Indicated for patients w/ fever or solitary kidney & when diagnosis is doubtful
  • Used to differentiate ureteral stones from renal stones

Ultrasound (UTZ)

  • Used as the primary diagnostic tool
  • Identifies presence of stones in the calices, pelvis, pyeloureteric & vesicoureteric junctions, & in patients w/ upper urinary tract dilatation

Kidneys, Ureter & Bladder (KUB) radiography

  • Helpful in differentiating radiolucent & radiopaque stones
  • Used for comparison during follow-up
  • Should not be performed if non-contrast computed tomography scan (NCCT) is being considered

Evaluation of patient w/ acute flank pain

Non-Contrast Computed Tomography (NCCT)

  • First choice in confirming stone diagnosis in patients w/acute flank pain
  • Significantly more accurate than intravenous urethrogram (IVU)/intravenous pyelogram (IVP) in evaluating patients w/ acute urolithiasis
  • Used to determine the diameter, density, inner structure & skin-to-stone distance that affects the outcome of extracorporeal shockwave lithotripsy (SWL)
  • Can detect uric acid & xanthine stone that are radiolucent on plain films

Low-Dose Computed Tomography (CT) Scan

  • Can reduce radiation risk
  • Used to detect ureteric stones in patients w/ a body mass index (BMI) of <30
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