Harvey's Garden

Nephrolithiasis

6 min read

Etiology

Classifications

Mnemonic

PH

Elevated: Struvite stones, Calcium phosphate stones Decreased: Else

Calcium stones

Calcium oxalate stones

Etiology

  • Hypercalciuria
  • Hyperoxaluria
  • Hypocitraturia
    • Citrate inhibits stone formation by forming a soluble complex with calcium in the renal tubule, which reduces the amount of free calcium in the urine to bind with oxalate or phosphate. Citrate excretion in the kidney is strongly influenced by pH (systemic, tubular, and intracellular). Alkalosis increases renal citrate excretion, whereas acidosis decreases it.

Tip

Individuals with higher (but not excessive) calcium intake paradoxically have a lower risk of calcium oxalate stone formation.  Dietary calcium binds oxalate in the gut to form insoluble calcium oxalate, which is eliminated in the feces.  This reduces the amount of oxalate absorbed into the body and excreted in the urine, reducing stone formation.

Diagnosis

  • Urine microscopy: dumbbell-shaped or octahedron-shaped crystals
    • The monohydrate calcium oxalate crystal is described as the “picket fence” form. These dumbbells shaped crystals are common in ethylene glycol toxicity. The dihydrate form is octahedral or “envelope” shaped.
  • X-ray (or CT): radiopaque stones

Tip

Serum calcium can be normal or elevated.

Treatment

  • Hydration
  • Dietary modification
    • Reduced intake of salt (mainly sodium) and animal protein (Low sodium enhances renal tubular reabsorption of sodium and calcium, decreasing urinary calcium levels. Animal protein consumption increases calcium excretion in urine.)
    • Reduced intake of oxalate-rich foods and supplemental vitamin C
    • Calcium intake should not be restricted (restriction increases risk of hyperoxaluria, and thereby, the risk for osteoporosis)
  • Thiazide diuretics for recurrent calcium-containing stones with idiopathic hypercalciuria (i.e., no hypercalcemia)
  • Urine alkalinization (e.g., with potassium citrate)
  • Possibly citrate supplementation

Calcium phosphate stones

Etiology

Diagnosis

  • Urine microscopy: wedge-shaped crystals
  • X-ray (or CT): radiopaque stones

Prevention

  • Hydration
  • Thiazide diuretics
  • Diet low in sodium

Uric acid stones

Etiology

Diagnosis

  • Urine microscopy: rhomboid/needle-shaped crystals
  • X-ray: radiolucent stones
  • CT: can be visible but are usually only minimally visible (not as visible as calcium stones)

Treatment

  • Hydration
  • Oral chemolitholysis (e.g., potassium citrate) via urine alkalinization
    • Uric acid (pKa = 5.4) is soluble at physiologic pH, but precipitates in an acidic environment. The lowest pH along the nephron is found in the distal tubules and collecting ducts; so these are the segments of the nephron that become obstructed by uric acid crystals. Obstructive uropathy and acute renal failure follow.
    • Uric acid stones are unique in that they can usually be dissolved by alkalizing the urine. In other stones, urine alkalinization is used for prophylaxis rather than treatment.
  • Low-purine diet
  • Allopurinol

Mnemonic

Uric acid stones are radiolUcent (x-ray negative).

Warning

Uricosuric agents (e.g., probenecid) increase the excretion of uric acid, which can accelerate the formation of stones.

Cystine stones

Etiology

  • Autosomal recessive defect in cystine-reabsorbing PCT transporter → impaired proximal renal tubular absorption of dibasic amino acids → Cystinuria → cystine stone formation (as cystine is poorly soluble)
  • Develop in persistently acidic urine

Clinical features

Recurrent kidney stones (manifesting with e.g., flank pain) starting in childhood

Diagnosis

  • Urine microscopy: hexagonal crystals
  • X-ray (or CT)
    • Weakly radiopaque stones
    • Possibly staghorn calculi
  • Positive cyanide nitroprusside test

Struvite stones (magnesium ammonium phosphate stones)

Etiology

  • Upper UTI with urease-producing bacteria such as Proteus mirabilis, Klebsiella, Staphylococcus saprophyticus, and/or Pseudomonas
    • These bacteria convert urea to ammonia → elevated ammonia causing alkaline urine → precipitation of the ammonium magnesium phosphate salt → crystal and stone formation
      • Urea → 2 NH3 + CO2
      • NH3 + H2O → NH4+ + OH−
    • Grow rapidly into a branched staghorn calculus that fills the renal calyces and pelvis.
    • Over time, the affected kidney can atrophy due to recurrent infection and chronic obstructive nephropathy.

Treatment

Pathophysiology

Clinical features

Diagnostics

Treatment

Acute Management (Renal Colic)

  • Pain/Inflammation: NSAIDs (e.g., Ketorolac) are first-line. Opioids are second-line.
  • Hydration: PO or IV fluids.
  • Facilitate Passage: For stones 5-10 mm, use Medical Expulsive Therapy (MET) with an alpha-blocker (e.g., Tamsulosin).

Intervention Thresholds

  • < 5 mm: Conservative Tx (hydration, analgesia); likely to pass.
  • > 10 mm or urosepsis, AKI, refractory pain: Urologic intervention required.

Procedural Interventions

  • ESWL (Extracorporeal Shock Wave Lithotripsy): For stones < 2 cm in renal pelvis/upper ureter.
    • Effectiveness: It works best when the stone is in a large, fluid-filled space like the renal pelvis, allowing for effective fragmentation. Stones in the narrow, muscular ureter are harder to target and fragment.
    • Limitations: It is less effective for larger, harder stones (>2 cm) which may not fragment completely. The fragments must still pass down the ureter, which can cause obstruction (“steinstrasse” or “street of stones”) if the initial stone burden is too large.
  • Ureteroscopy (URS): For mid-to-distal ureteral stones.
    • Direct Visualization & Treatment: It provides direct visualization, allowing the urologist to use a laser to precisely break the stone into tiny pieces or a basket to retrieve it. This ensures clearance.
    • Anatomical Suitability: The scope can easily reach the lower and middle parts of the ureter. It is the most effective and least invasive option for stones that are “stuck” in this location and unlikely to pass on their own.
  • PCNL (Percutaneous Nephrolithotomy): For large stones (> 2 cm) or staghorn calculi.
    • Efficiency for Large Volume: It allows for the use of larger, more powerful instruments to break up and suction out stone fragments in a single setting. Trying to manage a >2 cm stone with ESWL would require multiple sessions and risk ureteral obstruction, while URS would be a very long and difficult procedure.
    • Highest Stone-Free Rate: For large and complex stones (like staghorn calculi that fill the renal collecting system), PCNL offers the highest probability of rendering the patient completely stone-free after one procedure.

Stone-Specific Prevention

  • General (All Types): ↑ Fluid intake (>2L/day urine), ↓ Na+ diet.
  • Calcium Oxalate (most common): Thiazide diuretics, Potassium Citrate.
  • Uric Acid (radiolucent): Allopurinol, Potassium Citrate (alkalinize urine).
  • Struvite (infection stones, Proteus): Eradicate infection (antibiotics) & surgically remove stone.

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