A. Introduction
- Majority of stones form in the kidneys (rather than in the urinary bladder)
- In USA and Europe, 0.1-0.4% of population has kidney stones (nephrolithiasis)
- Also referred to as urinary tract stones (urolithiasis)
- Lifetime risk in USA and Europe is ~12% for men, 6% for women
- Some 50-75% of renal stones recur over 20 years
- Stones are composed of inorganic and organic crystals amalgamated with proteins
B. Types of Stones
- Calcium Stones
- Account for >75% of all renal stones (85% in men, 70% in women)
- Usually combined with oxalate (as monohydrate or dehydrate)
- Calcium phosphate (as apatite or brushite) stones are next most common
- Calcium oxalate or phosphate stones are black, grey or white
- Typically small (<1cm diameter)
- Opaque on radiography
- Uric Acid Stones
- Represent ~8% of kidney stones
- Associated with hyperuricosuria ~25%: high urine uric acid and normal urine pH
- Gouty diathesis ~10%: normal urine uric acid and low urine pH<5.5
- Most persons with uric acid stones have acquired abnormalities
- In persons with gouty diathesis, calcium oxalate stones may also be present
- Stones are smooth, round, yellow-orange
- Nearly radiographically transparent unless mixed with struvite or calcium stones
- Types I and II primary hyperoxaluria are rare genetic defects that can cause urate stones
- Stones Associated with Infection
- Urea-splitting organisms convert urea to ammonium and hydroxyl ions
- This leads to alkaline pH of urine, increasing formation of trivalent phosphate
- Struvite (magnesium-ammonium phosphate) and carbonate apatite stones form
- Proteus, Haemophilus, Ureaplasma urealyticum, and Klebsiella can split urea
- E. coli does not split urea
- Cystine stones comprise about 1% of all kidney stoneste
- Multiple metabolic abnormalities appear to be present in ~30% of patients
- Drugs that precipitate to stones
- Indinavir
- Acyclovir can precipitate in renal ducts, form crystals, block urine drainage
- Triampterene
- Indinavir [4]
- Nephrolithiasis occurs ~4% and is reduced by drinking >48 ounces of water daily
- Unique urinary indinavir crystals: plate-like rectangles, fan-shaped or starburst forms
- These crystals have been associated with stones, flank pain, and dysuria
C. Summary of Types of Kidney Stones
Type | %stones | Size | Causes | Treatment |
---|
Ca Oxalate | 75% | <2cm | Hyper-PTH,high Ca,Hyperoxaluria | Thiazide, citrate, PO4 |
Uric Acid | 5% | any | Hyperuricosuria, Low Urine pH | Allopurinol, oral Ca, base |
Struvite | 15% | any | Urease producing bacteria | Shock wave, acetohydrxamate |
Phosphates | 5% | any | Renal Tubular Acidosis | Potassium Citrate / HCO3- |
Cystine | <1% | any | Cystinuria | Penicillamine, Tiopronin |
Indinavir | -- | | Indinavir (protease inhibitor) | Increased fluids, stop drug |
D. Etiology [1,2]- Promoters of Urinary Stones
- Minerals: calcium, sodium
- Acids: oxalate, urate, cystine
- Low urine pH
- Low urine flow
- Bacterial products
- Primary hyperparathyroidism
- Renal tubular acidosis
- Other Risk Factors for Calcium Oxalate Stones [1]
- Elevated animal protein intake
- Family history
- Primary hyperoxaluria
- Gout
- Obesity
- Hypertension
- Inflammatory bowel disease, other malabsorption syndromes
- Abnormal Calcium Metabolism
- Overall, etiologic in 65-80% of patients with stones
- Hypercalciuria - overall, present in ~50% of persons with stones
- Hyperparathyroidism
- Hypocitriuria calcium nephrolithiasis (abnormally low citric acid)
- Familial idiopathic hypercalciuria - increased stone risk with age, duration, increased urinary calcium and urate concentrations [6]
- Hyperoxaluria can also precipitate stone formation with normal calcium metabolism
- Calcium Source and Stone Formation [5]
- High dietary calcium inversely associated with kidney stones
- High exogenous calcium intake positively associated with kidney stones
- However, low calcium diet does not reduce recurrent calcium oxalate stone formation [7]
- Restricted intake of animal protein and salt reduces recurrent calcium oxalate stone episodes in men [7]
- Likely that dietary calcium complexes with oxalate and reduces absorption of both
- Tamm-Horsfall Protein (THP)
- Most abundant protein in human urine
- Synthesized and secreted by epithelial of Thick Ascending Limb (Loop of Henle)
- Mainly affects aggregation of preformed crystals
- Controversy exists as to whether THP is a promoter or inhibitor of renal stones
- Inhibitors of Stones
- Magnesium
- Pyrophosphate
- Citrate
- Nephrocalcin
- Urinary prothrombin fragment 1
- Glycosaminoglycans
- High urine flow
E. Symptoms
- Renal Colic
- Increasing, often severe pain, writhing, very uncomfortable
- Joint pain may be prominant
- Typically followed by nausea, vomiting
- Obstruction
- Increased frequency of urination
- Dysuria
- Hematuria - microscopic or macroscopic
- Sudden Cessation of Pain (stone is passed)
- Recurrence of Stones
- ~14% at 1 year
- ~35% at 5 years
- ~52% at 10 years
- In women, the incidence of kidney stones is 1 per 1000 person-years [5]
F. Evaluation [3]
- Urinalysis for crystals and pH
- Abdominal radiographs detect ~80% for stones (most stones contain calcium)
- Ultrasound: sensitivity 60%, specificity 100%
- Helical computerized tomographic (CT)
- Preferred modality as is most sensitive and specific
- Sensitivity 96%, specificity 100%
- Improved localization of stone compared with other methods
- Complete serum electrolytes including Ca2+, phosphate, uric acid
- Urine collection, 24 hours
- Creatinine (for determining creatinine clearance and normal urine values)
- Calcium and Phosphorus
- Uric acid
- Citrate
- Oxalate
- Magnesium (for Struvite stones)
- Cysteine if indicated
- Normal Values for urine
- Normal 24 hour urine creatinine 15-25 mg/kg
- Normal 24 hour calcium <200 mg/day
- Normal 24 hour citrate <320 mg/day
- Normal 24 hour cysteine <200 mg/day
- Normal 24 hour oxalate <44 mg/day
- Normal 24 hour uric acid <600 mg/day
- Normal volume 2-2.5 Liters
- pH 5.5-7.0
G. Passage of Ureteral Stones (Table 2, Ref [2])
Stone | Mean Number Days | % Eventual |
---|
Size | to Passage | Intervention |
<3mm | 8 | 3 |
3mm | 12 | 14 |
4-6mm | 22 | 50 |
>6mm | do not pass | 99 |
H. Treatment [1,2]- Indications for Urgent Intervention
- Obstruction
- Infection - usually treated with ampicillin+gentamicin (or consider oral fluoroquinolone)
- Impending renal deterioration
- Intractable pain or vomiting
- Anuria
- Stone >6mm (relatively urgent)
- Pain Control
- Goal is pain free and encouragement of good urine flow
- NSAIDs are very effective for pain relief, probably moreso than opioids [8]
- Opioids usually given, usually meperidine (Demerol®) with hydroxyzine IM
- Ketorolac (Toradol®) IV may be as effective as opiates
- Concern with use of high doses of NSAIDs in renal insufficiency
- Nausea / Vomiting
- Commonly associated with renal pain
- Prochlorperazine (Compazine®) 5-10mg IV (or PO), or 25mg per rectum
- Promethazine (Phenergan®) - 25mg IV
- Serotonin 5HT3 Antagonists - several highly effective agents available
- Ondansetron (Zofran®) - 8-12mg IV q8-12 hours
- Granisetron (Kytril®) - 3mg IV q 24 hours
- Dolasetron (Anzemet®) - 100mg IV x 1; 100mg po x 1
- Stone Removal
- Stones 5mm or smaller can usually pass on their own
- Extracorporeal Lithotripsy (see below)
- Cystoscopic Basketing or Fragmentation - can remove stones even in kidney
- Surgery - percutaneous nephrolithostomy, open ureterolithotomy or nephrolithotomy
- Stones should be removed if indication for urgent intervention needed
- Extracorporeal Shock Wave Lithotripsy [1]
- Least invasive, uses shock wave to shatter stone
- Used for stones <2cm (20mm) located in renal pelvis
- Composed of calcium oxalate, apatite, uric acid or struvite
- Reduces morbidity associated with stone passage
- Good Urine Flow
- Hydration to insure urine volume 2-3L per day
- Alkalinization of urine as Indicated (including for calcium oxalate stones)
- Medical Therapy [9]
- Calcium blockers or alpha-adrenergic blockers increase stone passage
- Pooled analysis suggests that treated patients have 65% increased stone passage
- Consider use of these agents in patients with prolonged pain
- Chronic Treatment / Prevention
- Hypercalciuria - potassium citrate ± thiazide diuretic; low salt/animal protein diet [7]
- Gouty Diathesis - potassium citrate
- Dietary Hyperoxaluria - restrict dietary oxalate; avoid severe calcium restriction
- Enteric Hyperoxaluria - potassium citrate, calcium or magnesium citrate
- Hypocitraturic Calcium - potassium citrate
- Infection stones - antibiotic and acetohydroxamic acid
- Mild Cystinuria - chelating agent, potassium citrate, high fluid intake
- Moderate to Severe Cystinuria - >500mg/day, potassium citrate and tiopronin
- Reduced calcium intake does not reduce calcium oxalate stone recurrence in men [7]
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