Struvite stones are comprised of magnesium ammonium phosphate. The stone propagates with time, forming staghorn calculi, branched stones that fill a portion or the entirety of the renal collecting system. While staghorn stones usually consist of a combination of struvite and calcium carbonate apatite, other components, such as uric acid and cystine are not uncommon [34, 39]. The development of the struvite stone begins with infection of the upper urinary tract with a urease-producing organism, such as Proteus, Mycoplasma, Providencia, or Staph Aureus. The urease breaks down urea into ammonia and carbon dioxide; ammonia then reacts with water, producing ammonium and subsequently alkalinizing the urine. This high pH decreases the solubility of phosphate in urine and promotes the crystallization of magnesium ammonium phosphate [17, 34].

The formation of struvite stones is gender-specific; women are 1.6× more likely than men to develop struvite stones [8]. Those with functional or anatomic abnormalities of the urinary tract are more prone to struvite calculi. For example, patients with urinary diversion and urinary reservoirs containing intestinal segments are more likely to develop calculi due to increased mucus production, bacterial colonization, and chronic urinary stasis. In one study, struvite calculi were the most common type of calculi found in patients with intestinal and gastric reservoirs at an average of 3.6 years post augmentation cystoplasty [22]. 3.5 % of patients with spinal cord injury (SCI) develop struvite stones, likely due to neurogenic bladder dysfunction involving poor bladder compliance, high detrusor pressures and insufficient bladder emptying. Additionally, Vesico-ureteral reflux (VUR) and indwelling catheters have been associated with increasing the risk of struvite stones in the setting of SCI [10]. Although current urologic techniques and urodynamics have improved the management of voiding dysfunction and chronic UTI, struvite stones present an ongoing challenge for patients with SCI [10, 19]. In SCI patients, struvite stones may present with recurrent UTIs or urosepsis, and struvite stones form staghorns in 30 % of cases. Interestingly, a large portion of these patients do not develop their first stone until many years after spinal cord injury [10].

In the setting of infection stones, the urease-splitting infection itself is the primary derangement promoting the development of the struvite stone, which must be distinguished from stones complicated by infection. In the case of a “stone with infection,” a stone of metabolic origin can lead to UTI by causing obstruction or by providing a nidus for bacterial growth. In this case, a patient may present with pyelonephritis or urosepsis necessitating urgent intervention, and others may be asymptomatic, with their only finding being asymptomatic bacteriuria. In the situation of infection with stones, the impact of stone extraction on the subsequent risk of future urinary tract infections is poorly defined.

Managing the risk of serious infection following stone surgery is a challenging task. Sepsis remains a life-threatening problem following stone surgery even in patients with sterile urine and in the presence of prophylactic antibiotics. In fact, 37 % of patients develop SIRS (systemic inflammatory response syndrome) criteria following PCNL [25]. This can be attributed to a variety of factors, including upper tract manipulation, urinary obstruction, and bacteria or endotoxins (produced by bacteria) present within the stone [42]. Importantly, routine mid-stream bladder culture has not been predictive of this risk of SIRS, and anti-microbial treatment of a positive pre-operative urine culture does not necessarily lessen the risk of sepsis [13, 25]. This may be a result of preoperative treatment targeted at the wrong pathogen. Furthermore, it is important to obtain urine samples for culture from the appropriate sites. In a study by Mariappan et al., patients with positive stone culture or positive renal pelvis culture were four times more likely to develop SIRS following PCNL. Additionally, it was demonstrated that while positive urine cultures from the renal pelvis effectively predict stone infection (defined by positive stone cultures), positive bladder cultures do not [25]. In fact, culture and sensitivities obtained from the bladder may reveal different microbial flora than the upper tract. This may explain why patients re-admitted for sepsis following stone surgery often grow out a different pathogen that the pathogen seen on the preoperative urine culture [11]. In light of these findings, some may recommend obtaining routine pelvic urine and stone cultures at the time of PCNL [25].

In the treatment of patients with struvite stones, the primary, evidence-based therapeutic goal should be that the patient is stone-free. It has been demonstrated that complete elimination of the stones combined with appropriate antimicrobial therapy can decrease the stone recurrence rate to only 10 %; conversely, retention of stone fragments can result in a recurrence rate of up to 85 % [46]. Contemporary surgical interventions, such as PCNL or other endoscopic interventions should be performed as first-line treatment toward this end goal. Conservative, non-operative therapy is not recommended as the sole treatment for staghorn calculi in most patients, as it is highly unsuccessful, and has a well-established risk of renal failure in the long-term [23, 44]. However, medical therapy with urease-inhibitors such as hydroxamic acid is a useful option for the treatment of residual struvite stone material when it cannot be completely eradicated. The most relevant substance, aceto-hydroxamic acid (AHA) serves as a non-competitive inhibitor of urease, lowering the pH and ammonia levels and augmenting the efficacy of some antibiotics [3, 49]. In randomized, placebo-controlled trials, AHA was shown to hinder or prevent further struvite stone growth in patients infected with urease-producing bacteria [15, 16, 47, 49]. However, AHA has several limitations. It is contraindicated in patients with serum Cr > 2.5 mg/dl and it is a known teratogen. Bothersome adverse effects, such as nausea, vomiting, headache, tremulousness, and anxiety are very common and often intolerable for patients, often requiring discontinuation of the drug [47, 49]. Additionally, there is a 15 % risk of deep vein thrombosis [12]. Patient populations with the highest stone recurrence rate, such as those with neurogenic bladder or urinary diversion may be appropriate candidates for AHA [43]. In addition, AHA is a viable option in those who cannot tolerate or refuse operative intervention, or if anatomical variations prevent the stone from being accessed by traditional endoscopic techniques. When indicated, AHA is initiated at 250 mg twice a day, and may be titrated up to 250 mg 3–4 times a day [49]. The long term efficacy in deterring stone growth and long-term safety of AHA are not fully outlined.