KIDNEY STONES

I. Management of acute urolithiasis

  1. Diagnosis
    1. Typical pain = acute, colicky flank pain radiating to the groin, with migration of the pain as the stone migrates
    2. Other sx include dysuria, urinary urgency, and increased urinary frequency
    3. Hematuria
      1. Hematuria on dipstick urinalysis had a sensitivity of 80% and specificity of 35% and > 1 RBC/HPF on microscopic urinalysis had a sensitivity of 81% and a specificity of 49% for ureteral stones as assessed by helical CT in a study of 195 patients with acute flank pain seen in the ED (J. Urol. 162:685, 1999--JW)
      2. In a retrospective study of 452 pts presenting with acute flank pain who were eventually diagnosed with ureteral stones, microscopic hematuria (1+ or greater on dipstick) was seen in 94% of those presenting on day 1 of sx, 80% of those on day 2, and 65% of those on day 3 (J. Urol. 170:1093, 2003--JW)
    4. Plain films of abdomen will often show the stone
    5. Non-contast spiral CT is highly sensitive and specific; can also demonstrate if ureteral obstruction is present; greater sensitivity than and similar specificity to IVP in one meta-analysis of 4 studies (Ann. Emerg. Med. 40:280, 2002)
    6. IVP--Carries risk of increased pressure & pain and even urinary tract rupture, if stone is obstructing the tract; also can be slow
  1. Spontaneous stone passage
    1. 75% of upper tract stones pass spontaneously
    2. Stones 0.5 cm. or less in diameter have am 80% chance of spontaneous passage, > 0.5 cm change is 20-50%, so consider urol. referral if > 0.5cm.
    3. In a cohort of 62 pts with ureteral stones followed prospectively, average time to stone passage was 8d for stones < 2mm, 12d for 2-4mm stones, and 22d for 4mm stones (J. Urol. 162:688, 1999--JW)
  1. Treatment
  1. Analgesia
    1. In a meta-analysis of 9 randomized trials comparing opioids with NSAIDs for acute ureteral colic, NSAIDs were ass'd with significantly better control of pain (BMJ 328:1401, 2004--JW)
    2. In a study in 130 pts 18-55yo with acute renal colic randomized to morphine (5mg IV Q20min x 2), ketorolac (15mg IV Q20min x 2), or both, pain scores at 40min were sig. lower in combination-therapy group (2.0) than in either the morphine group (3.7) or the ketorolac group (4.1).  (Ann. Emerg. Med. 48:173, 2006--JW)
  2. Adequate fluids
  3. Strain urine
  4. Close follow-up; Watch for fever or increased pain
  5. Medications to hasten stone passage
    1. Calcium channel blockers
      1. In a meta-analysis of 9 randomized studies in pts with ureteral stones, Ca-blockers vs. no expulsive therapy x 1-6wks was associated with sig. increased likelihood of spontaneous stone passage (RR 1.65). (Lancet 368:1171, 2006--JW)
  6. Interventions to extract stones not likely to pass spontaneously--Indications include stone size (see above), evidence of infection, obstruction for > 4d, uncontrolled pain
  1. Medical treatment
    1. In a study in 210 pts with symptomatic distal ureteral calculi > 4mm diameter randomized to Tamsulosin 0.4mg QD, nifedipine 30mg QD, or phloroglucinol (an anticholinergic); all pts received oral corticosteroids (to reduce putative ureteral edema at site of stone) and diclofenac; spontaneous passage occurred sig. more frequently in tamsulosin recipients than nifedipien or phloroglucinol pts (97% vs. 77% and 64%, respectively); median time to stone passage was 3d in tamsulosin group vs. 5d in other two groups (sig.) (J. Urol. 174:167, 2005--JW)
  2. Extracorporeal shock wave lithotripsy--mostly done for stones in kidney or upper ureter; often accompanied by ureteral stenting
    1. Associated with increased risk of Hypertension and Diabetes Mellitus in non-randomized studies (J. Urol. 175:174, 2006--JW)
  3. Ureteroscopic removal (possibly with fragmentation of stone by laser, electrohydraulic, or u/s)
  4. Percutaneous Nephrostolithotomy--Usually reserved for large stones and stones in areas of stasis (e.g. in calyceal diverticula)
  5. Open surgery--Done in only < 1% of cases
  1. Asymptomatic stones (e.g. incidentally noted on x-ray)
    1. Check urine culture, creatinine, lytes
    2. Only 50% will become symptomatic, so watchful waiting is OK

II. Pathophysiology

  1. Supersaturation of the stone substrate in urine (thus, hypovolemia is a risk factor for all types of stones)
  2. Reduced concentrations of inhibitors of stone formation will tend to promote stone formation
  3. Urine pH can affect likelihood of precipitation of stone substrate and thus, stone formation (citrate, magnesium, pyrophosphate, glycosaminoglycan, other complex organic molecules)

III. Stone types

  1. Calcium oxalate
    1. 70-80% of kidney stones
    2. Caused by hypercalciuria, hyperoxaluria, or hypocitraturia (see below)
  1. Calcium phosphate
    1. 5-10% of kidney stones
    2. Caused by hypercalciuria or hypocitraturia (see below)
  1. Uric acid
  1. 5-10% of kidney stones
  2. More likely to form in highly acid urine (pH < 5.5)
  3. Caused by hyperuricosuria (see below)
  4. Radiolucent!
  1. Struvite
  1. 5-10% of kidney stones
  2. aka "infection stones" or "triple phosphate stones"
  3. Composed of Magnesium-, Ammonium-, and Calcium phosphate
  4. Almost always found in association with UTI (urease produced by bacteria catalyze breakdown of urea into Ammonia + CO2; ammonia forms ammonium ions which bind PO4 and create the nidus for the stone)
  5. The most common causes of "staghorn" calculi
  1. Cystine
  1. 1-5% of kidney stones
  2. Caused by cystinuria (see below)

IV. Metabolic factors predisposing to formation of kidney stones:

  1. Hypercalciuria (> 200mg/24h per one reference, 300mg/24 in men or 250mg/24h in women per another reference)
  1. Predisposes to calcium oxalate and calcium phosphate stones
  2. Calcium is filtered by the glomeruli and reabsorbed in the tubules
  3. Hypercalciuria can be subcategorized as:
  1. Absorptive: Increased intestinal absorption causing increased serum [Ca], resulting in decreased PTH and decrease in renal tubular reabsorption, thus increased renal Ca excretion. Root cause is usually either excess synthesis of 1,25-vit. D or increase # of intestinal vit. D receptors
  2. Renal: Defective reabsorption of Ca by renal tubules; serum [Ca] is low or normal; PTH is high
  3. Primary hyperparathyroidism (note some neoplasms can produce PTH or PTH-like petidfes that don't show up on standard PTH assay!)--serum [Ca] will be normal or high; serum PO4 will be low
  4. Other causes of hypercalciuria
    1. Renal tubular acidosis type I
    2. Addison's
    3. Sarcoidosis
    4. Paget's disease or other osteolytic/osteoclastic bone conditions, e.g. chronically immobilized pts
    5. Hyperthyroidism
    6. Vit. D intoxication
    7. Milk-alkali syndrome
    8. Neoplasms, including Multiple Myeloma, lymphomas, or leukemia
    9. Lithium tx
  1. Hyperuricosuria (> 800mg/24h in men, > 750mg/24h in women)
    1. Predisposes to calcium oxalate stones (form around uric acid crystal--can see calcium oxalate stones in hyperuricosuric pts witn normal serum and urinary Ca levels!) as well as uric acid stones
    2. Main cause is high serum uric acid levels, in turn caused by:
      1. High dietary ingestion of purines (meats esp. organ meats; meat extracts & gravies; seafood; yeast; beer; legumes; oatmeal; spinach; asparagus; cauliflower; mushrooms)
      2. Meds (probenecid, high-dose salicylates)
      3. Increased WBC turnover, e.g. myeloproliferative disorders
      4. "Tumor lysis syndrome" after chemotherapy
  1. Hyperoxaluria (> 45mg/24h)
    1. Predisposes to Calcium Oxalate stones
    2. Causes
      1. Any intestinal problem resulting in fat malabsorption (IBD, GI bypass, etc.) This is because of increased amounts of intraluminal free oxalate resulting from binding of non-absorbed bile acids with divalent cations (e.g. Ca, Mg).
      2. High dietary consumption of oxalate (spinach, rhubarb, beets, tea, strawberries, chocolate, wheat bran, nuts)
      3. High consumption of vitamin C (metabolized to oxalate)
      4. There is an autosomal recessive genetic defect that causes hyperoxaluria
      5. Ethylene glycol ingestion
  1. Hypocitraturia (< 640mg/24h)
    1. Predisposes to all types of urinary stones, particularly calcium-based
    2. Citrate inhibits formation of urinary stones by binding calcium
    3. Usually idiopathy. Also can be caused by:
      1. Acidosis
      2. Thiazide diuretics
      3. High dietary protein consumption
  1. Hypomagnesuria (< 50mg/24h)
    1. Magnesium is a stone-formation inhibitor
  1. Cystinuria (> 50mg/24h)
  1. Predisposes to formation of Cystine stones
  2. Caused by a genetic defect in renal tubular reabsorption of cystine, lysine, arginine, & ornithine; Heterozygotes as well as homozygotes have increased risk for urinary stones
  3. Cystine is less soluble than others so more prone to stone formation; more soluble at higher pH

V. Workup in a pt with kidney stones

  1. Controversy exists as to when to initiate full vs. limited workup, i.e. how many stone episodes or how many risk factors for recurrence, etc. are necessary
    1. 25y recurrence rate in population studies has been 30-40%
    2. Highest risk of recurrence seen in children, men between the ages of 20 to 50, and patients with a strong family history of urolithiasis. Because of scarcity of urolithiasis among women of African descent, some recommend doing metabolic evaluation in that population.
  1. Serum studies: Na, Cl, K, HCO3, Ca, Mg, PO4, Uric acid, Cr, (PTH, vit. D if indicated)
  1. Urine studies:
    1. pH
    2. 24h collection (for volume, Ca, phosphate, uric acid, Cr, oxalate, Na, citrate)
      1. Before doing 24h urine, stop: Antacids, thiazides, allopurinol, vit. C or D, Ca or Mg supplements
    3. Culture if indicated
    4. Consider sodium nitroprusside test (to r/o presence of cystine)
  1. Stone analysis (if can get the stone)
  1. For recurrent stone formers with hypercalciuria, consider > 1 24h urine collection (after the first, with limited Ca intake or fasting)

 

VI. Prevention

  1. At least 2l of H2O/day (unless contraindicated)
  2. If hypercalciuric:
    1. Thiazide diuretics (e.g. HCTZ 50mg/d or indapamide 2.5mg/d) to reduce calcium excretion (increase reabsorption in prox. & distal renal tubules)
    2. Don't limit Ca intake (ass'd with almost 100% increase in incidence of Ca-oxalate stones in a 5y randomized trial--NEJM 346:77, 2002--JW)
    3. May need to supplement with potassium citrate
      1. This is because thiazides cause both potassium-wasting and decreased citruria.
      2. Potassium citrate increases urinary pH, which leads to increased citruria which in turn incrases solubility of stone-forming salts
      3. Avoid in pts with renal failure b/c of potasium load
    4. Sodium Cellulose Phosphate, a calcium-binding resin, has been used for absorptive hypercalciuria b/c it reduces Ca absorption, but not recc'd as of 1997 b/c may increase oxaluria and also increase risk for osteoporosis; may also reduce magnesium absorption from the gut to the point where hypomagnesemia occurs
  3. If hypocitraturic, consider:
    1. Protein restriction'
    2. Potassium citrate supplementation, and/or
    3. Alkalinizing urine e.g. with potassium bicarbonate
  4. If hyperoxaluric due to any cause, consider limiting dietary oxalate intake (see list of specific foods above)
  5. If hyperoxaluric due to intestinal disease, increase dietary Ca (helps to bind oxalate in the gut) and consider cholestyramine to bind bile acids and decrease oxalate absorption (target pH 6.0-7.0)
  6. If hyperuricosuric, consider allopurinol 300mg/d (if using in a pt with gout, consider colchicine for first 6mos to reduce risk of precipitating acute gout) and/or limitation of dietary purines; urinary alkalinization e.g. with KHCO3 or K-citrate (or, if necessary, acetazolamide) is also used (target pH 6.0-7.0)
  7. If cystinuric, increase H2O intake and consider alkalinizing urine, e.g. with KHCO3, K-Citrate, or acetazolamide; in some cases, chelating agents (e.g., d-penicillamine, mercaptopropionylglycine, bucillamine)

(Sources: Urol. Clin. N. Am. 24:97, 1997; J. Am. Soc. Nephrol. 9:917, 1998; Med. Clin. N. Am. 81:785, 1997)