Struvite Nephrolithiasis

Struvite (infection) stones are composed of magnesium ammonium phosphate hexahydrate (struvite) and carbonate apatite. They form only when urine is persistently alkaline (pH above 7.2) and rich in ammonium. This occurs in infection with urease producing bacteria.

Urease producers include Proteus (most common), Klebsiella, Pseudomonas, Providencia, Serratia, Enterobacter, Staphylococcus, Ureaplasma urealyticum, Corynebacterium urealyticum and Mycoplasma hominis.

Urease hydrolyses urea into two molecules of ammonia and carbon dioxide. This raises pH and increases ammonium and carbonate, which supersaturates urine with struvite.

Struvite stones account for 10 to 15 percent of all stones. They are more frequent in:

• Women (2 to 3:1).
• The elderly.
• Patients with neurogenic bladder, urinary diversion or spinal injury.
• Chronic catheterisation and indwelling stents.
• Urinary stasis and anatomic abnormalities.

They grow rapidly (weeks to months) and fill the collecting system as staghorn calculi. They incorporate bacteria within the matrix, which protects them from antibiotics, so cure requires complete stone removal. Untreated, they lead to chronic pyelonephritis, renal scarring, abscess and loss of renal function.

• Recurrent or persistent urinary tract infections (including with the same organism), flank pain, fever and haematuria.
• Strong ammoniacal urine odour, alkaline urine with cloudy sediment.
• Chronic pyelonephritis: fatigue, weight loss, hypertension, impaired renal function.
• Septic complications: pyonephrosis, perinephric abscess, emphysematous infection, and urosepsis with shock.
• Often silent in elderly or neurogenic patients.
• Signs of risk factors: spinal cord injury, indwelling catheter, urinary diversion, and diabetes.

• Urinalysis: pH above 7.0 to 7.5, pyuria, bacteriuria, characteristic coffin lid struvite crystals; urine culture shows urease producing organisms (pH-dependent), with culture of stone fragments or renal pelvic urine at surgery.
• Imaging: non-contrast CT (the best method, density about 600 to 1,000 Hounsfield units, with associated hydronephrosis and renal scarring); X-ray radio opaque stone with a layered appearance; ultrasound for hydronephrosis, and for pregnant patients.
• Stone analysis (infrared spectroscopy, X-ray diffraction): struvite with carbonate apatite; any mixed stones must be classified.
• Blood: complete blood count, creatinine, C-reactive protein, serum calcium, uric acid and bicarbonate to exclude metabolic stones; 24-hour urine metabolic evaluation after treatment (as underlying metabolic stones can be infected).
• Renography (DMSA) for split function.
• Look for the cause of persistent infection: structural abnormalities, residual urine and voiding dysfunction (bladder scan, urodynamics, cystoscopy), neurological assessment.

Management is surgical removal of all fragments combined with antimicrobial therapy and control of urinary tract infection.

• Surgery: percutaneous nephrolithotomy is the first line procedure for large struvite stones, with the aim of complete stone clearance. The 'sandwich' approach combines it with shock wave lithotripsy. Flexible ureteroscopy or open surgery treats residual fragments.
• Small stones (below 2 cm) can be treated with ureteroscopy and laser lithotripsy or shock wave lithotripsy if the urine is sterile. Perform nephrectomy if the kidney is non-functioning.
• Antibiotics: preoperative culture directed therapy for 7 to 14 days, perioperative coverage and 1 to 2 weeks after surgery.
• Choices: ciprofloxacin 500 mg twice daily, levofloxacin 500 mg daily, trimethoprim-sulfamethoxazole 160/800 mg twice daily, amoxicillin clavulanate 625 mg three times a day, or cefuroxime 500 mg twice daily.
• For sepsis, use intravenous ceftriaxone 1 to 2 g daily, gentamicin 5 mg/kg daily, or piperacillin tazobactam 4.5 g every 8 hours.
• Antibiotic therapy alone cannot sterilise a struvite stone.
• Urgent decompression by percutaneous nephrostomy or stent when there is infected obstruction.
• Long term suppression after incomplete clearance: low dose antibiotic (nitrofurantoin 50 to 100 mg nightly or trimethoprim 100 mg nightly) with regular urine cultures.
• Acetohydroxamic acid 250 mg three times a day (up to 15 mg/kg/day) is a urease inhibitor. Use it for patients with recurrence after surgery, residual stone or those not suitable for surgery. It prevents stone growth in about 70 percent.
• Monitor acetohydroxamic acid for haemolytic anaemia, deep vein thrombosis, tremor and rash. It is contraindicated in pregnancy and with a creatinine clearance below 30 mL/min.
• Urinary acidification with L-methionine 500 mg three times daily or ascorbic acid has limited effect and is not reliable.
• Prevent recurrence: eradicate infection, and correct anatomical abnormality or stasis (relieve obstruction, bladder drainage, clean intermittent catheterisation with regular bladder washouts). Minimise catheter use and replace catheters regularly. Ensure hydration with at least 2.5 L per day.
• Surveillance imaging (ultrasound or low dose CT) at 3 to 6 months and then yearly.
• Complications are renal failure and sepsis. Untreated mortality is about 25 to 30 percent over 10 years, so early intervention is warranted.