Urinary Tract Stones

Metabolic drivers (supersaturation)

• Hypercalciuria: the single most common metabolic abnormality — idiopathic (absorptive, renal-leak, resorptive), primary hyperparathyroidism, granulomatous disease (sarcoidosis, calcitriol excess), immobilization, and Paget disease.
• Enteric hyperoxaluria: fat malabsorption (Crohn disease, celiac disease, chronic pancreatitis, Roux-en-Y gastric bypass) leaves free luminal calcium bound to fatty acids, so oxalate is absorbed unopposed. A high-oxalate, low-calcium diet does the same thing through a different route.
• Hypocitraturia: distal (type 1) renal tubular acidosis, chronic diarrhea, and metabolic acidosis increase proximal tubular citrate reabsorption; type 1 RTA also alkalinizes urine, favoring calcium phosphate stones.
• Persistently acidic urine: obesity, type 2 diabetes/insulin resistance, and chronic diarrhea impair renal ammoniagenesis, dropping urine pH and precipitating uric acid.

Non-metabolic mechanisms

• Urease-producing infection: Proteus mirabilis and relatives alkalinize urine and drive struvite staghorn formation — a chronically catheterized or neurogenic bladder is the classic stem.
• Urinary stasis/anatomy: UPJ obstruction, horseshoe or transplanted kidney, medullary sponge kidney, calyceal diverticula.
• Drug-induced stones: protease inhibitors (indinavir, atazanavir), sulfadiazine, triamterene, and the carbonic anhydrase inhibitors topiramate and acetazolamide (alkaline urine plus hypocitraturia → calcium phosphate).

Modifiable risk factors

• Low fluid intake with urine volume under roughly 2 L/day; high dietary sodium (obligates calciuria); high animal-protein/purine load (acid, uric acid, and calcium load with citrate loss); sucrose and fructose excess; obesity; vitamin C megadoses (oxalate precursor); prolonged immobility.

Non-modifiable risk factors

• Male sex, white ancestry, peak incidence in the third to fifth decades, prior stone (roughly half recur within a decade, per the AUA medical management guideline), family history, and monogenic disease — cystinuria, primary hyperoxaluria, Dent disease, adenine phosphoribosyltransferase deficiency. Hot climates and outdoor occupations are the semi-modifiable middle ground.

Crystal Formation and Supersaturation

• Nucleation occurs when urine becomes supersaturated with stone-forming solutes (calcium, oxalate, uric acid, phosphate, cystine). Supersaturation is the thermodynamic driving force for all stone formation
• Crystal growth and aggregation require that urine remains supersaturated long enough for crystals to enlarge and bind together; reduced urine flow rates and concentrated urine increase dwell time
• Inhibitors of crystallization (citrate, magnesium, pyrophosphate, glycosaminoglycans, nephrocalcin, Tamm-Horsfall protein) normally prevent stone formation; their deficiency increases stone risk

Calcium Oxalate Stones (75-80% of stones)

• Occur in hypercalciuria (elevated urinary calcium >200 mg/day in women, >250 mg/day in men) from hyperparathyroidism, vitamin D excess, sarcoidosis, hyperthyroidism, or idiopathic causes
• Associated with hyperoxaluria (elevated urinary oxalate >45 mg/day) from dietary sources (nuts, chocolate, spinach, beets), inflammatory bowel disease, malabsorption, or primary hyperoxaluria (genetic enzyme defects)
• Hypocitraturia (low urinary citrate <320 mg/day) is a major risk factor since citrate complexes calcium and inhibits crystal formation; seen in renal tubular acidosis, chronic diarrhea, and certain medications

Uric Acid Stones (5-10% of stones)

• Form in acidic urine (pH <5.5); uric acid is a weak acid and precipitates in acidic conditions rather than its soluble form (urate)
• Associated with hyperuricemia from gout, malignancy (especially tumor lysis syndrome), high purine diet, or genetic disorders
• More common in men and those with chronic diarrhea

Struvite Stones (10-15% of stones)

• Caused by chronic urinary tract infections with urease-producing organisms (Proteus mirabilis most common; also Klebsiella, Pseudomonas, Morganella)
• Urease enzyme splits urea into ammonia, alkalinizing urine to pH >7.5, precipitating magnesium ammonium phosphate (struvite) and calcium phosphate
• Staghorn calculi (branching stones filling renal pelvis and calyces) are frequently struvite stones and can cause chronic infection and renal damage

Cystine Stones (1-2% of stones)

• Result from autosomal recessive cystinuria causing defective renal tubular reabsorption of cystine and other dibasic amino acids
• Cystine is poorly soluble; elevated urinary cystine (>600 mg/day diagnostic) exceeds solubility threshold, especially in acidic urine
• Often present in childhood or young adulthood

Risk Factors for Stone Formation

• Dehydration and low urine volume (<1.5 L/day) dramatically increase supersaturation
• Immobility and prolonged bed rest reduce urine flow and increase urinary stasis
• Genetic predisposition and family history
• Anatomic abnormalities (ureteropelvic junction obstruction, medullary sponge kidney, horseshoe kidney)

Acute Renal Colic (Classic Presentation)

• Sudden-onset severe flank pain radiating to lower abdomen/groin, often described as "worst pain of life," with restlessness and inability to find comfortable position (distinguishes from peritonitis where patients lie still)
• Pain follows the stone's path from renal pelvis through ureter to bladder; lower ureteral stones cause lower abdominal/groin pain and dysuria
• Associated nausea and vomiting (often from visceral innervation of ureter and reflex GI symptoms)
• Hematuria (gross or microscopic) in 85-90% of cases from mucosal trauma

Associated Symptoms Depend on Stone Location

• Upper ureteral stones: Flank pain with CVA tenderness
• Mid-ureteral stones: Lower abdominal pain
• Lower ureteral stones: Groin pain, dysuria, urinary frequency, testicular pain in men, labial pain in women (mimics UTI or gynecologic pathology)

Asymptomatic Stones

• Discovered incidentally on imaging for other reasons; approximately 10-15% of stone formers are asymptomatic
• Require monitoring for growth and complications

Chronic Presentations (Recurrent or Staghorn Stones)

• Chronic flank/back pain
• Recurrent UTIs (especially struvite stones)
• Progressive renal insufficiency from obstruction
• Nephrolithiasis-induced CKD from recurrent obstruction and pyelonephritis

Important Clinical Pearls

• Fever with renal colic = infected obstructed kidney (pyelonephritis with obstruction), a MEDICAL EMERGENCY requiring urgent imaging, blood cultures, antibiotics, and often percutaneous nephrostomy or ureteral stent
• Absence of hematuria does NOT exclude stones (occurs in ~10-15% of cases)
• Painless hematuria is rare with stones; consider other diagnoses (malignancy, glomerulonephritis)

Non-Contrast CT (CT KUB - Gold Standard)

• Sensitivity 95-98% and specificity 98-99% for detecting stones regardless of composition; can detect radiolucent uric acid and cystine stones missed on plain X-ray
• Provides information on stone size, location, density (helps predict composition), degree of obstruction, and complications
• Single "scout" image or full CT depending on clinical context; full CT provides additional information for complications
• No radiation concerns relative to diagnostic benefit in acute setting

Ultrasound

• First-line imaging in pregnant patients and children to avoid radiation; sensitivity 95% when performed by experienced sonographer
• Shows hydronephrosis (indirect evidence of obstruction) but cannot reliably visualize stones <4 mm or in lower ureter
• Useful for follow-up monitoring of known stones

Plain Radiography (KUB)

• Detects only radiopaque stones (calcium oxalate/phosphate, struvite, cystine stones are visible; uric acid stones are radiolucent)
• Low sensitivity (60%) and specificity (low) due to overlapping bowel gas; useful only if stone suspected radiopaque on prior imaging
• Not recommended as first-line imaging for suspected acute stones

Laboratory Findings

• Hematuria (gross or microscopic, RBCs on urinalysis) in 85-90%
• Pyuria may be present without UTI from mucosal irritation
• Leukocytosis if infection present
• Elevated creatinine if bilateral obstruction, solitary kidney with obstruction, or chronic kidney disease
• BUN/creatinine ratio elevated if dehydration present

Stone Analysis (After Passage/Removal)

• Definitive diagnosis of stone composition; should be performed on all available stones
• Guides specific preventive therapy and dietary modifications
• Infrared spectroscopy or X-ray diffraction most accurate

Metabolic Evaluation (for Recurrent Stone Formers)

• 24-hour urine for calcium, oxalate, uric acid, citrate, phosphate, sodium
• Serum calcium, phosphate, uric acid, creatinine
• Parathyroid hormone if hypercalcemia present
• Urine pH and culture
• Genetic testing (cystinuria) if indicated

Important Diagnostic Considerations

• **Diagnosis

Immediate stabilization — rule out the emergency first

• Infected obstructed kidney: fever, leukocytosis, or hemodynamic instability with obstruction requires blood/urine cultures, broad-spectrum IV antibiotics, and urgent decompression by ureteral stent or percutaneous nephrostomy. The AUA surgical management guideline is explicit that definitive stone treatment must be deferred until the infection is drained and controlled — lithotripsy or primary ureteroscopy at that moment can precipitate urosepsis.
• Other indications for urgent urology involvement: acute kidney injury, bilateral obstruction, obstructed solitary or transplanted kidney, intractable pain or vomiting.

First-line therapy for the uncomplicated stone

• NSAIDs (e.g., ketorolac IV) are preferred analgesia over opioids per AUA; they reduce ureteral wall edema and prostaglandin-mediated hyperperistalsis. Hold NSAIDs in AKI, CKD, and before planned shock wave lithotripsy because of bleeding risk.
• Opioids as adjunct only; IV antiemetics as needed. Aggressive IV fluid loading has not been shown to flush stones out — hydrate to euvolemia.
• Medical expulsive therapy — alpha-1 blockers (tamsulosin): AUA supports an offer of alpha blockade for distal ureteral stones ≤10 mm, relaxing ureteral smooth muscle. Stones ≤5 mm largely pass spontaneously; observe up to about 4–6 weeks with strained urine.

Definitive/surgical management

• Ureteroscopy with holmium laser lithotripsy: versatile, works for any composition, and is the preferred approach in pregnancy.
• Shock wave lithotripsy: proximal ureteral and renal stones under ~2 cm; contraindicated in pregnancy, uncorrected coagulopathy, active UTI, and obstruction distal to the stone.
• Percutaneous nephrolithotomy: stones larger than ~2 cm and all staghorn calculi, where complete clearance of infected matrix is the only cure.

Prevention

• Fluids to high urine output; thiazide (chlorthalidone) for hypercalciuria; potassium citrate for hypocitraturia, uric acid, and cystine stones; allopurinol for hyperuricosuric calcium oxalate stones; low sodium, moderate animal protein, and normal — not low — dietary calcium.

Emergencies

• Obstructive pyelonephritis / pyonephrosis with urosepsis: pus trapped behind an obstructing stone cannot be sterilized by antibiotics alone. Signaled by fever, rigors, hypotension, or delirium in a patient with hydronephrosis — decompress immediately. This is the single most lethal complication.
• Acute kidney injury: rising creatinine implies bilateral obstruction, a solitary kidney, or superimposed volume depletion/NSAID use, since one healthy kidney compensates for unilateral obstruction.
• Complete obstruction with forniceal rupture: perinephric urine extravasation on CT; usually managed with drainage, but severe pain plus a urinoma should not be dismissed.

Complications of the disease

• Post-obstructive diuresis: after relief of prolonged bilateral obstruction, loss of the medullary gradient and retained solute cause massive polyuria — watch for hypovolemia, hypokalemia, and hypernatremia.
• Chronic kidney disease: recurrent obstruction and infection cause tubulointerstitial fibrosis; struvite staghorn stones are the classic culprit.
• Xanthogranulomatous pyelonephritis: chronic Proteus infection behind a staghorn stone produces a non-functioning kidney with lipid-laden macrophages and the "bear paw" CT appearance; nephrectomy is usually required.
• Ureteral stricture from chronic impaction, and squamous cell carcinoma of the renal pelvis after decades of struvite-related irritation.

Complications of treatment

• Steinstrasse ("stone street") after shock wave lithotripsy: a column of fragments impacts the distal ureter, causing recurrent colic or silent obstruction.
• Subcapsular/perinephric hematoma after SWL from cavitation injury — flank pain with a falling hematocrit; more likely with uncontrolled hypertension or antiplatelet/anticoagulant use.
• Ureteral perforation or avulsion after ureteroscopy; bleeding, pleural injury, and sepsis after percutaneous nephrolithotomy.
• Stent morbidity: dysuria, frequency, hematuria, and — if forgotten — encrustation and stent-related stone formation.

• Crystal morphology sells the answer: envelope- or dumbbell-shaped = calcium oxalate; rhomboid/rosette = uric acid; coffin-lid = struvite; hexagonal = cystine, confirmed by a positive urinary nitroprusside (cyanide-nitroprusside) test.
• Best next step in an adult with acute flank pain: non-contrast helical CT. In pregnancy or in children, ultrasound first — this is the ACR Appropriateness Criteria distinction examiners love.
• Fever plus obstruction is the trap: the answer is antibiotics plus urgent drainage (stent or nephrostomy), not lithotripsy, not "antibiotics and observe."
• Uric acid stones are radiolucent on KUB but visible on CT, and they are the one stone type that can be dissolved medically — alkalinize urine with potassium citrate to pH >6. Allopurinol is second-line and only for true hyperuricosuria; picking allopurinol before alkalinization is the classic distractor.
• **Staghorn calculus + urine pH >7.5 + *Proteus mirabilis*** = struvite. Cure requires complete surgical clearance (PCNL); antibiotics alone never eradicate the infected stone matrix.
• Do not restrict dietary calcium. Low calcium intake frees intestinal oxalate for absorption and increases stone risk; restrict sodium and animal protein instead, and keep calcium intake normal, per the AUA medical management guideline.
• Thiazides lower urinary calcium; loop diuretics raise it. A patient on furosemide with new stones, or an infant on chronic loop therapy with nephrocalcinosis, is a favorite stem.
• Recurrent stones in a child or young adult → think cystinuria (autosomal recessive) or primary hyperoxaluria; recurrent stones with hypercalcemia and low phosphate → check PTH for primary hyperparathyroidism.
• Restlessness distinguishes colic from peritonitis, and absent hematuria never excludes a stone.