primary hyperparathyroidism, hyperoxaluria, gouty diathesis, and low urinary volumes. It should be noted that gouty diathesis may also predispose patients to uric acid stone formation, while low urinary volumes may contribute to all causes of calcium stone formation in addition to patients with uric acid stones, cystinuria, and infectious stones.

Uric Acid Urolithiasis

Patients with pure uric acid urolithiasis generally have a low urinary pH (<5.5) and are therefore defined as having gouty diathesis. As previously mentioned, patients with the diagnosis of gouty diathesis (urine pH < 5.5) may form either calcium or uric acid stones.

Infectious Urolithiasis

High urinary pH (>7.5) is associated with the presence of urinary tract infection and the formation of infectious urolithiasis. The presence of urea splitting organisms leads to an increase in the ammonia concentration, which further promotes struvite stone formation.9,10

Struvite stones compose the majority of staghorn calculi.

Cystine-Based Urolithiasis

Cystine urolithiasis is the result of an autosomal recessive trait, which disrupts the transepithelial transport of cystine, ornithine, lysine, and arginine. The concentration of cystine rises to levels above the saturation point,and as a consequence, cystine crystals precipitate.11,12 Of note, even though cystine stone formers all have definitive genetic derangements, they have been found to have a number of other metabolic risk factors, which can contribute to their stone formation.13

Metabolic Evaluation of

Stone Disease

Aims

The main goal of metabolic evaluation is to prevent recurrent stone formation in high-risk stone producers, as well as to prevent further growth of any existing stones, to help limit the need for surgical intervention. Stone recurrence rate among first time stone formers is as high as 50% in a period of 5–10 years, while remission rates under appropriate treatment can reach as high as 80–90% with appropriate medical stone management.14-17

Who Deserves Metabolic Evaluation?

As a rule, any patient with a history of stone disease will benefit from a metabolic evaluation.18 However, two studies suggest that medical management, which includes metabolic evaluation, may not be cost-effective in the first time stone formers. One study determined that only at a recurrence rate of 0.3–4 stones per year does medical evaluation and treatment become equivalent to management of recurrent episodes.19

The same conclusion was reached by a second study group that performed an international cost comparison analysis utilizing urologic literature to support their assumptions.20 For first time stone formers, the recurrence rate on conservative therapy was determined to be 0.07 stones/patient/year. Conservative therapy was also found to be the least costly for recurrent stone formers but was associated with the highest rate of recurrence (0.3 stones/patient/year) compared to empiric and directed medical therapy (0.06 and 0.084 stones/patient/year, respectively). These authors suggest that first time stone formers should initially be treated conservatively.

Additional studies also support the role of conservative measures to manage initial stoneformers. Dietary modification alone has been shown to decrease the overall rate of recurrence in 58% of patients with a variety of metabolic risk factors.21 More specifically, a 71% and 47% reduction was demonstrated in stone formation for patients with hypercalciuria and

hyperuricosuria, while on high fluid intake and avoidance of dietary excesses, respectively.

There are, however, two studies which support the role of metabolic evaluation in first time stone formers. Both groups found that the incidence and severity of stone formation, including the number of underlying metabolic abnormalities, was identical in recurrent and solitary stone formers.22,23

Most would also agree that another group that should undergo a thorough metabolic evaluation is the first time stone producers, who are at a high risk for recurrence. This includes those patients with a family history of stones, intestinal disease/chronic diarrhea,urinary tract infections, history of gout, osteoporosis or skeletal fractures.

Some authors argue that patients with stones composed of uric acid, cystine, and struvite should undergo metabolic evaluation as well.18,24 However, this same subset of stone compositions has been used to identify patients which may not benefit from further evaluation.25 Additionally, it is recommended that metabolic evaluation of calcium stone formers should be performed in patients with difficult to treat stones, patients with stones in a solitary kidney, or those individuals with nephrocalcinosis.18

Children with nephrolithiasis would clearly benefit from a metabolic evaluation. Young patients with urolithiasis are at similar risk of metabolicdisturbancesasadults.26 Theincreased risk of detrimental effects of repeated episodes of obstruction, urinary tract infections, and the need for surgical intervention strengthen the recommendation for metabolic evaluation and management of children with nephrolithiasis.

When Should Metabolic Evaluation

Be Performed?

The first obligation in managing of urolithiasis is treating the offending stone. Apart from relieving obstruction and alleviating accompanying symptoms, stone retrieval enables chemical analysis that by itself provides clues for the underlying pathology that originally caused the problem. Moreover, most suggest that one should wait at least 1 month after stone passage or stone removal, allowing the patient to return to their normal routine, before a metabolic evaluation is initiated. Obtaining urine or blood