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Common Urological Problems

NonCalcium Calculi -Stone Varieties

  • - General Urology - Common Urological Problems - Urinary Stone Disease
  • Jul 25, 2010
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Tags: | ascorbic acid | cystine | cystine lithiasis | glutamine |

1. Struvite -Struvite stones are composed of magnesium, ammonium, and phosphate (MAP). They are found most commonly in women and may recur rapidly. They frequently present as renal staghorn calculi and rarely present as ureteral stones except after surgical intervention (Figure 16–5). Struvite stones are infection stones associated with urea-splitting organisms,  including Proteus, Pseudomonas,  Providencia,  Klebsiella,  Staphylococci,  and Mycoplasma. The high ammonium concentration derived from the urea-splitting organisms results in an alkaline urinary pH. The urinary pH of a patient with a MAP stone rarely is <7.2 (normal urinary pH is 5.85). It is only at this elevated urinary pH (>7.19) that MAP crystals precipitate.

MAP crystals are soluble in the normal urinary pH range of 5–7.  Preoperative bladder cultures do not necessarily reflect the bacteriologic composition found in calculi. Foreign bodies and neurogenic bladders may predispose patients to urinary infections and subsequent struvite stone formation. Massive diuresis does not prevent struvite calculi.

Women with recurrent infections despite apparently appropriate antibiotic therapy should be evaluated for struvite calculi with a conventional kidney-ureter-bladder (KUB) film or renal ultrasound, or both. It is impossible to sterilize such calculi with antibiotics. Culture-specific antibiotics can reduce urease levels by 99% and help reduce stone recurrence. Stone removal is therapeutic.

Long-term management is optimized with the removal of all foreign bodies, including catheters of all varieties. A short ileal loop helps decrease the risk of stones in those with supravesical urinary diversion.  All stone fragments should be removed with or without the aid of follow-up irrigations. Hemiacidrin (Renacidin) irrigations should be used with caution if at all. Rapid magnesium toxicity can result in death even with a low-pressure irrigation setup (<20 cm water pressure), negative daily urine cultures, and no evidence of upper-tract extravasation. Acetohydroxamic acid inhibits the action of bacterial urease, thereby reducing the urinary pH and decreasing the likelihood of precipitation. Most patients have a difficult time tolerating this medication.

image Figure 16–4.  Scout abdominal radiograph demonstrating bilateral, multiple renal calculi in a patient with renal tubular acidosis, type I.

2. Uric acid-
Uric acid stones compose <5% of all urinary calculi and are usually found in men.  Patients with gout, myeloproliferative diseases, or rapid weight loss, and those treated for malignant conditions with cytotoxic drugs have a high incidence of uric acid lithiasis. Most patients with uric acid calculi, however, do not have hyperuricemia.

Elevated uric acid levels are frequently due to dehydration and excessive purine intake. Patients present with a urinary pH consistently <5.5, in contrast to patients with hyperuricosuric calcium nephrolithiasis,  who have a urinary pH >5.5.  As the urinary pH increases above the dissociation constant pKa of 5.75, it dissociates into a relatively soluble urate ion. 

Urinary Stone Disease

Urinary Stone Disease

Treatment is centered on maintaining a urine volume >2 L/day and a urinary pH >6. Reducing dietary purines or the administration of allopurinol also helps reduce uric acid excretion. Alkalinization (with oral sodium bicarbonate,  potassium bicarbonate,  potassium citrate,  or intravenous one-sixth normal sodium lactate) may dissolve calculi and is dependent on the stone surface area. Stone fragments after lithotripsy have a dramatically increased surface area and will dissolve more rapidly.  Dissolution proceeds at approximately 1 cm of stone (as seen on KUB) per month, with compliant alkalinization.

image Figure 16–5.  Scout abdominal radiograph demonstrating large bilateral struvite staghorn calculi. Patient was treated for many years with numerous antibiotics for recurrent urinary tract infections. Only after this radiograph were calculi identified and removed and the infections resolved.

3. Cystine-
Cystine lithiasis is secondary to an inborn error of metabolism resulting in abnormal intestinal (small bowel) mucosal absorption and renal tubular absorption of dibasic amino acids,  including cystine,  ornithine,  lysine, and arginine. The genetic defects associated with cystinuria have now been mapped to chromosome 2p.16 and more recently to 19q13.1.  Cystine lithiasis is the only clinical manifestation of this defect. Classic cystinuria is inherited in an autosomal recessive fashion. Homozygous expression has a prevalence of 1:20,000,  while the heterozygous expression is 1:2000.  It represents 1–2%  of all urinary stones,  with a peak incidence in the second or third decade. 

Homozygous cystinurics excrete more than 250 mg/day,  resulting in constant supersaturation.  Heterozygous patients usually excrete 100–150 mg/day. Unaffected patients typically excrete <40 mg/day. Approximately 400 mg/L of cystine can remain in solution at a urinary pH of 7. As the urinary pH increases >7, the amount of soluble cystine increases exponentially.

image Figure 16–6.  Scout radiograph demonstrating a right cystine calculus. Note ground-glass appearance with smooth edges.

The solubility of cystine is pH-dependent, with a pK of approximately 8.1. There is no difference in the solubility curves in normal versus cystinuric patients.  There is no known inhibitor for cystine calculi, and cystine stone formation is completely dependent on excessive cystine excretion. Cystine stones are frequently associated with calcium calculi and their related metabolic abnormalities.  They may present as single,  multiple,  or staghorn stones.  The diagnosis is suspected in patients with a family history of urinary stones and the radiographic appearance of a faintly opaque, ground-glass, smooth-edged stone (Figure 16–6).

Urinalysis frequently reveals hexagonal crystals. Stone analysis confirms the diagnosis.  Quantitative urinary cystine evaluation helps confirm the diagnosis and differentiate heterozygous from homozygous states. It is also important to titrate medical therapy.

Medical therapy includes high fluid intake (>3 L/day) and urinary alkalinization.  Patients should monitor their pH with nitrazine indicator paper and keep their pH values >7.5. It is difficult or impossible to maintain levels >8.

A low-methionine (precursor to cystine)  diet has limited impact, as most of the cystine is endogenous and most of the ingested methionine is incorporated into protein.

Glutamine,  ascorbic acid,  and captopril are effective in some patients.  Penicillamine can reduce urinary cystine levels. It complexes with the amino acid, and this complex is dramatically more soluble. Treatment should be titrated with quantitative urinary cystine values.  Many patients poorly tolerate penicillamine,  reporting skin rashes (discrete or confluent macules with occasional itching), loss of taste, nausea, vomiting, and anorexia. It may inhibit pyridoxine, which should be supplemented during treatment (50 mg/day).  Mercaptopropionylglycine (Thiola),  300–1200 mg in divided doses, forms a soluble complex with cystine and can reduce stone formation.  Side effects and frequent dosing decrease patient compliance rates. It is better tolerated than penicillamine and is now the first drug of choice in these difficult cases.

Surgical treatment is similar to that for other stones except that most stones are recalcitrant to extracorporeal (outside the body)  shock wave lithotripsy (ESWL).  One should have a low threshold to proceed with percutaneous stone extraction in symptomatic patients. Two populations of cystine stones have been described, including the rough and smooth varieties,  and may reflect subpopulations: those that are effectively treated with ESWL and those that require more invasive therapy. Despite optimum medical therapy, a high stone recurrence rate frequently frustrates both patient and physician. Minimally invasive techniques and optimum medical therapy are paramount.

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