INTRODUCTION — Struvite (magnesium ammonium phosphate) stones are often referred to as "infection stones" since they are strongly associated with urinary tract infections (UTIs) with urea-splitting organisms. They may grow rapidly over a period of weeks to months and, if not adequately treated, can develop into a staghorn or branched calculus that fills the entire kidney collecting system. If left untreated, this can lead to deterioration of kidney function and end-stage kidney disease. In addition, since the stones often remain infected, there is a risk of developing sepsis. Thus, most patients require definitive surgical treatment.
This topic will review the pathogenesis, clinical manifestations, and management of struvite stones. Other aspects of kidney stones in adults are discussed elsewhere:
EPIDEMIOLOGY — The epidemiology of struvite stone formation is, in part, sex dependent . Women are more likely to form pure struvite stones (3:1) because females are more likely to develop an upper urinary tract infection (UTI). Other patients susceptible to UTI, such as those with a neurogenic bladder, urinary diversion, or indwelling Foley catheter, also may form pure struvite stones . In France, the prevalence of stones containing any struvite decreased from 11.1 percent in the 1980s to 6.1 percent in the 2000s . In Rochester, Minnesota, only 1 percent of first stones contained struvite .
Improving care of patients at high risk for UTI has shifted the epidemiology of stones in such patients. As an example, in a cohort of 33 immobile patients with musculoskeletal anomalies (traditionally at high risk for struvite stones), the proportion of stones due to infection was only 18 percent; the rest were calcium or uric acid stones . In addition, a 2011 study of 52 patients with staghorn calculi revealed that just 44 percent were struvite .
PATHOGENESIS — Struvite stones are composed of magnesium ammonium phosphate (struvite) and calcium carbonate-apatite . Normal urine is undersaturated with magnesium ammonium phosphate, and struvite stone formation occurs only when ammonia production is increased and the urine pH is elevated, which decreases the solubility of phosphate. The only situation in which this occurs in humans is with an upper urinary tract infection (UTI) with a urease-producing organism, such as Proteus mirabilis, Klebsiella pneumoniae, Corynebacterium species, or Ureaplasma urealyticum. Urease breaks down urinary urea into ammonia (NH3) plus carbon dioxide (CO2):
Urea → 2NH3 + CO2
The ammonia produced by this reaction then combines with water (H2O):
NH3 + H2O → NH4+ + OH-
The net result is increased availability of ammonium (NH4+) in an alkaline urine. This is the only circumstance in which high levels of urinary ammonium and high urine pH coexist, in contrast to the usual setting of increased ammonium due to increased acid production, systemic acidosis, and low urine pH.
In comparison to those patients with pure struvite stones, many males and some females have mixed calcium oxalate and struvite stones. It is presumed that the primary event in this setting is calcium oxalate stone formation, with secondary upper UTI and struvite deposition. In these patients, a comprehensive medical evaluation will uncover the underlying metabolic defect(s) responsible for calcium stone formation . Patients with pure struvite stones may also benefit from a metabolic evaluation in addition to benefiting from a determination of the cause of the upper tract infection. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Approach to evaluation'.)
CLINICAL MANIFESTATIONS — Symptoms directly attributable to struvite stones are uncommon. More often, patients will present with symptoms of a urinary tract infection (UTI), mild flank pain, or hematuria and will be found to have a persistently alkaline urine pH (>8), often with multiple magnesium ammonium phosphate crystals in the urine sediment (picture 1), and a complex kidney stone on kidney ultrasound or plain film of the abdomen. The stone may grow rapidly over a period of weeks to months and, if not adequately treated (including complete removal and treatment of the infection), can develop into a staghorn or branched calculus filling the entire renal pelvis and calyces (image 1 and image 2).
A persistently infected stone often leads to focal areas of parenchymal scarring with loss of cortex (chronic pyelonephritis). Some patients may develop xanthogranulomatous pyelonephritis, an unusual variant of chronic pyelonephritis in which there is massive destruction of the kidney by granulomatous tissue containing lipid-laden macrophages (see "Xanthogranulomatous pyelonephritis"). Passage of a struvite stone is rare. When passed and collected or removed surgically, chemical analysis of these stones may falsely report the absence of struvite [9,10]. Thus, if the suspicion is high in the appropriate clinical setting, struvite may be present even if not identified by the analyzing laboratory. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Stone analysis'.)
DIAGNOSIS AND EVALUATION
When to suspect struvite stones — Confirmation of the diagnosis of struvite stones requires a stone composition analysis demonstrating the presence of struvite. However, since most patients with struvite stones do not spontaneously pass their stones, a stone analysis is not usually available to the clinician prior to making treatment decisions, except in those with prior documented struvite stones. In patients without a prior history of struvite stones, the diagnosis of struvite stones should be suspected if the patient has one or more of the following features (see 'Clinical manifestations' above):
●History of recurrent or persistent urinary tract infections (UTIs), particularly those involving urease-producing organisms. (See "Recurrent simple cystitis in women".)
●Persistently alkaline urine pH (>8).
●Presence of magnesium ammonium phosphate crystals in the urine sediment (picture 1).
Metabolic evaluation — Patients with confirmed struvite stones should undergo a metabolic evaluation, similar to the evaluation performed in patients who form other types of stones. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Complete metabolic evaluation'.)
The reasons are as follows:
●Reporting of struvite as a component of a kidney stone sent for analysis is unreliable , and it is therefore possible that retrieved stones may have formed in the upper urinary tract due to factors other than infection with urease-producing bacteria.
●In addition, the entire stone is not typically removed as a single piece, so not all components of the stone may be identified if a single piece is sent for analysis. Thus, it is possible that there was a more common type of stone present in the kidney (eg, calcium oxalate) that became secondarily infected with urease-producing bacteria and the struvite stone grew over the original stone. Because struvite stones can grow quickly and become quite large, it is possible that the original stone nidus may not be included in a sample that is sent to the laboratory for analysis.
Approach to therapy — Surgical therapy is usually required to successfully treat struvite stones. Adjunctive medical therapy following surgery, which usually consists of short- or long-term antibiotic therapy and, in selected patients, treatment with a urease inhibitor (acetohydroxamic acid [AHA]), may help prevent stone recurrence and growth of residual stone fragments. Medical therapy alone is not preferred and should be reserved for patients who are too ill to tolerate, or who refuse, stone removal surgery. (See 'Surgical therapy for most patients' below and 'Adjunctive medical therapy' below.)
Surgical therapy for most patients — Patients who present with obstructing stones and urinary tract infection (UTI) or acute kidney injury require emergency intervention for urgent decompression of the collecting system. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Indications and contraindications'.)
For most patients with struvite stones who do not require emergency intervention, we suggest surgical stone removal followed by medical therapy, rather than medical therapy alone. Given that the majority of these complex stones contain bacteria, the only way to subsequently sterilize the patient's urine is to completely remove all stone material. Patients who are too ill to tolerate, or who refuse, stone removal surgery may be managed conservatively with medical therapy alone (ie, antibiotic therapy and urease inhibition). However, medical therapy alone is rarely successful. (See 'Adjunctive medical therapy' below.)
There are no randomized trials comparing surgical with medical therapy for the treatment of struvite stones. However, several observational studies have suggested that conservative therapy of struvite stones, compared with surgical therapy, is associated with higher mortality and progressive deterioration of kidney function [11-15]:
●In one series of 185 patients with a staghorn calculus, the 10-year mortality rate was 28 percent among those receiving conservative therapy, compared with 7.2 percent among those receiving surgical therapy .
●A retrospective analysis of 177 consecutive patients with a staghorn calculus found that death from kidney-related causes occurred in 67, 3, and 0 percent of patients who refused treatment, were treated without complete clearance of stone fragments, or had complete clearance of fragments, respectively .
●In an observational study of 167 patients with a staghorn calculus followed for an average of 7.8 years, chronic kidney disease (CKD) developed in 36 percent of those who received conservative therapy, compared with 16 percent of those who received surgical therapy .
Complete surgical stone removal is associated with a lower rate of recurrent stones compared with the presence of residual stone fragments. As an example, in a series of 43 patients with struvite stones, there were no recurrences among those with complete stone removal, compared with 40 percent among those with residual stone fragments . Independent predictors of stone recurrence included the presence of residual stones >4 mm, preoperative large stone burden (>10 cm), and the presence of medical comorbidities.
Choice of surgical approach — The major surgical options for struvite stones include percutaneous nephrolithotomy (PNL), ureteroscopy (URS), shock wave lithotripsy (SWL), or open surgery. Ultimately, surgical therapy should result in complete stone removal. A more detailed discussion of these techniques is presented elsewhere. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Surgical options'.)
Our approach to the choice of surgical procedure, which is consistent with the guidelines of the American Urological Association [17-19], is as follows:
●For most patients with struvite stones, we suggest PNL as first-line therapy rather than SWL, URS, or other surgical options. For patients who have a smaller stone volume (<500 mm2) and normal collecting system anatomy (eg, no hydroureteronephrosis), SWL, with placement of adequate drainage of the kidney prior to the procedure (usually a ureteral stent), is an alternative option; however, PNL is still preferred for these patients. If PNL is not available or contraindicated, staged URS (ie, performed in separate, planned sessions) can be performed as an alternative option.
●Open surgery (most commonly anatrophic nephrolithotomy) should not be offered as first-line surgical therapy. However, open surgery can be considered in very selected circumstances:
•Patients with a large stone burden, especially if the collecting system anatomy is very distorted, in whom a reasonable number of less-invasive procedures would not be expected to successfully remove the stone
•Individuals with severe obesity in whom endoscopic and fluoroscopic techniques are difficult
●For patients with a struvite stone in a nonfunctioning or poorly functioning kidney, especially if it is chronically infected, nephrectomy is a reasonable treatment option.
Complete stone removal of infected struvite stones is imperative since the only way to clear the patient's infection is to remove the stone in its entirety. Thus, PNL is the preferred surgical approach for most patients with struvite stones because of its significantly higher stone-free rate (SFR) compared with SWL or URS and its lower morbidity compared with open surgery [17,20-23]. The following studies illustrate the range of findings:
●In a trial that randomly assigned 50 patients with complete staghorn stones to SWL monotherapy or combined therapy with PNL followed by SWL, the SFR was 74 percent with combined PNL and SWL and 22 percent with SWL . The rate of septic complications (defined as fever >38.5°C for longer than three days) was higher with SWL monotherapy (15 versus 2 complications).
●A randomized trial that compared open surgery and PNL in 79 patients with complete staghorn stones found comparable SFRs between the two procedures (49 versus 66 percent at hospital discharge and 74 versus 82 percent at follow-up for PNL and open surgery, respectively), but patients undergoing PNL had fewer intraoperative (16 versus 38 percent) and postoperative (19 versus 31 percent) complications, shorter hospital stay (6.4 versus 10 days), and earlier return to work (2.5 versus 4.1 weeks) .
●In a retrospective analysis of 380 cases of staghorn stones, 298 of which were treated with PNL with or without SWL and 82 of which were treated with SWL monotherapy, overall SFRs were higher with PNL compared with SWL (84 versus 51 percent) . While SFR with SWL monotherapy was as high as 63 percent for stones <500 m2, the SFR decreased to 46 percent for stones 501 to 1000 mm2 and to only 22 percent for stones >1000 mm2.
Although URS is generally not performed as monotherapy for struvite stones, it is sometimes performed as an adjunctive procedure in patients undergoing PNL. With this technique, the ureteroscopic component provides the ability to remove peripheral stones, avoiding the need for multiple nephrostomy tracts [24,25].
Other surgical considerations — Specific surgical considerations for patients with struvite stones are discussed below. General surgical considerations for patients with kidney and ureteral stones are discussed elsewhere:
Preoperative imaging — Preoperative imaging for patients undergoing surgical stone removal for struvite stones is similar to that for patients undergoing surgery to remove other stone types. We obtain a noncontrast computed tomography (CT) of the abdomen and pelvis to define the anatomy and guide the surgical approach. In addition, if there is concern for a nonfunctioning or poorly functioning kidney, we obtain a nuclear renal scan to evaluate kidney function in the affected kidney. If poor function (<15 percent on nuclear renal scan) is confirmed and the contralateral kidney has relatively normal kidney function, nephrectomy of the affected kidney is a reasonable option. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Preoperative imaging' and "Radiologic assessment of kidney disease", section on 'Renal scans'.)
Role of intraoperative cultures — Identification of the urease-producing organism causing upper UTI and struvite stone formation is important in guiding postoperative antimicrobial therapy. However, there is no high-quality evidence or consensus agreement regarding the optimal site to obtain a culture. While many clinicians base their antibiotic decisions upon the results of urine cultures obtained from the bladder, others prefer urine cultures sampled from the renal pelvis during percutaneous puncture of the pelvicaliceal system or cultures of extracted stones. We obtain preoperative urine cultures but also obtain a stone culture during the time of stone removal in case the patient develops postoperative sepsis.
The results of a stone culture obtained at the time of surgery may help guide antibiotic therapy if the patient develops a postoperative infection or urosepsis. In one study of 328 patients who underwent PNL or URS for kidney or ureteral stones, of whom 11 developed postoperative sepsis, the urine culture upon hospital readmission correlated with stone culture in 64 percent of cases and with preoperative urine culture in only 9 percent .
Postoperative monitoring — In patients with struvite stones who have undergone surgical stone removal, we monitor as follows:
●We obtain postoperative imaging at two to three months after surgery to assess for the presence of residual fragments and for possible urinary tract obstruction. Periodic monitoring with imaging should then be obtained every 6 to 12 months since new stone formation can occur, occasionally affecting the contralateral kidney. We prefer digital pelvic tomosynthesis (DT) paired with kidney ultrasound to assess for residual stone fragments and obstruction, respectively. If DT is not available, an alternative approach is to obtain abdominopelvic radiograph paired with kidney ultrasound or a low-dose, noncontrast CT of the abdomen and pelvis. A discussion of the imaging modalities used for diagnosing and monitoring kidney stones is presented separately. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Postoperative imaging' and "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Diagnostic imaging'.)
●We perform a urinalysis every 6 to 12 months to monitor for recurrent UTI since patients with struvite stones may continue to be at risk for persistent or recurrent UTI after surgical stone removal. In patients with signs of infection (eg, presence of leukocyte esterase and nitrite in the urine), we obtain a urine culture and, if positive, treat with culture-specific antibiotics.
Residual stone fragments — Patients with struvite stones may require repeat procedures (with the same or a different modality) to completely remove residual stone fragments if the patient develops recurrent UTI or experiences stone growth. In general, endoscopic procedures (PNL or URS) are preferred for the management of residual struvite stone fragments since these techniques enable direct extraction of infected stone material. However, there are no data comparing the use of different surgical procedures for residual struvite stone fragments.
In patients with residual struvite stone fragments that cannot be accessed endoscopically, we treat with a urease inhibitor (eg, AHA) to help slow struvite stone growth and inhibit recurrent infection. (See 'Urease inhibition in select patients' below.)
The presence of residual struvite stone fragments after surgical stone removal increases the risk for recurrent stone disease. As an example, the persistence of fragments >5 mm in size at three months is associated with a high incidence of progressive stone growth (seven of nine patients [78 percent] in one series) . By comparison, the stone-free and infection-free rates at three years are approximately 90 percent if all fragments are removed during the initial therapy. Thus, all attempts to render a patient completely stone free should be made. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Residual stone fragments and additional surgery'.)
Adjunctive medical therapy — Following surgical stone removal, adjunctive pharmacologic measures to prevent stone recurrence and growth of residual stone fragments include antibiotic therapy and, in select patients, a urease inhibitor. Such therapies can also be used in patients who are unable to tolerate, or refuse, surgical therapy.
For patients on medical therapy alone, routine surveillance with kidney ultrasound should be performed every four to six months to monitor stone growth if the patient is medically eligible for a stone removal procedure.
In general, the medical treatment of struvite stones is rarely successful (see 'Surgical therapy for most patients' above). Bacteria live within interstices of the stone where antimicrobial agents may not penetrate and create a persistently alkaline local environment, promoting stone growth. Nevertheless, if a bacterium has been identified in culture, chronic administration of a culture-specific antimicrobial agent can sometimes prevent further stone growth and should be initiated. One retrospective study of 29 patients who were managed conservatively found that two-thirds of the patients maintained stable kidney function and there was only one admission for pyelonephritis over a mean of two years .
Antibiotic therapy — Antibiotic therapy is an important component for the medical management of struvite stones. Sterilization of the urine with antibiotic therapy may help decrease the rate of stone recurrence; however, there is no high-quality evidence to support this approach. In addition, there is no high-quality evidence to guide the optimal choice of agent or timing or duration of therapy, and clinical practice varies [17,29,30].
In patients undergoing surgical stone removal for struvite stones, our approach to antibiotic therapy is as follows:
●Prior to surgery, we obtain a urine culture and treat as appropriate with culture-specific antimicrobial therapy. Although patients should ideally have a sterile urine prior to stone removal, bacteriuria within those with struvite stones may not be cleared until the patient is stone free. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Preoperative evaluation'.)
●Perioperatively, we administer a single dose of oral or intravenous broad-spectrum antibiotic prophylaxis (such as ampicillin plus gentamycin) within one hour of the procedure, as discussed elsewhere. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Antibiotic prophylaxis'.)
●Postoperatively, we administer continuous prophylactic antibiotics to all patients with documented struvite stones for three to six months. We typically give nitrofurantoin monohydrate/macrocrystals (100 mg once daily) or trimethoprim-sulfamethoxazole (TMP-SMX; one-half of a single-strength tablet once daily). If the patient's urine remains uninfected after three to six months of prophylaxis, we discontinue antibiotic therapy. If the patient continues to have positive urine cultures in spite of prophylactic antibiotics, we switch to an alternative regimen of prophylactic antibiotics. An alternative approach is to periodically monitor a urine culture after surgery (eg, monthly for three months) and treat as appropriate with culture-specific antibiotics. However, there are no data supporting one of these antibiotic approaches over the other. (See 'Postoperative monitoring' above.)
In patients who are unable to tolerate, or refuse, stone removal surgery, we treat with low-dose, culture-specific suppressive antibiotics indefinitely.
Urease inhibition in select patients — Urease inhibitors, such as AHA, can cause complete, noncompetitive inhibition of urease production, thereby slowing struvite stone growth. However, these agents are associated with significant side effects that frequently limit their use. Thus, we reserve the use of AHA for patients who have residual stone fragments following surgical stone removal, with recurrent struvite stones, or who are unable to tolerate, or refuse, surgical stone removal.
If treatment with AHA is initiated, we administer 250 mg twice daily for as long as it can be tolerated without significant side effects. A complete blood count with reticulocytes should be obtained after two weeks of treatment and at three-month intervals during the treatment to monitor for bone marrow suppression, hemolytic anemia, and reticulocytosis. In addition, close monitoring of hepatic function is also advised.
Evidence in support of the use of AHA comes from three randomized trials that collectively show that struvite stone growth can be arrested in approximately 80 percent of AHA-treated patients compared with only 40 percent of placebo-treated patients [31-33]. However, treatment with AHA has not been shown to reduce existing stone burden. In addition, 20 to 60 percent of patients receiving AHA experience significant side effects such as palpitations, edema, nausea, vomiting, diarrhea, headache, loss of taste, hallucinations, rash, abdominal discomfort, anemia, and reticulocytosis (all reversible).
Infrequently used therapies
●Dissolution therapy – Irrigation (chemolysis) of the collecting system, with solutions such as a citric acid mixture (Renacidin), to dissolve remaining fragments of infected stones, particularly after PNL, has been advocated by some clinicians. Chemolysis is rarely used today since its use prolongs hospitalization and requires in-hospital monitoring .
●Urine acidification – Urinary acidification with drugs such as ascorbic acid and L-methionine has been proposed to treat residual stone fragments and prevent recurrent stone formation after stone removal surgery [35,36]. However, we do not use these agents, as their efficacy has not been clearly demonstrated and there are potential important side effects (eg, systemic metabolic acidosis).
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney stones".)
SUMMARY AND RECOMMENDATIONS
●General principles – Struvite stones are composed of magnesium ammonium phosphate (struvite) and calcium carbonate-apatite. Such stones are often referred to as "infection stones" since they only form in the setting of urinary tract infections (UTIs) with urea-splitting organisms (such as Proteus mirabilis). (See 'Introduction' above and 'Epidemiology' above and 'Pathogenesis' above.)
●Clinical manifestations – Symptoms directly attributable to struvite stones are uncommon. Most frequently, patients will present with symptoms of a UTI, mild flank pain, or hematuria. Severe pain is uncommon unless significant obstruction is present. The stone may grow rapidly over a period of weeks to months and, if not adequately treated, can develop into a staghorn or branched calculus filling the entire renal pelvis and calyces. (See 'Clinical manifestations' above.)
●Diagnosis and evaluation – Confirmation of the diagnosis of struvite stones requires a stone composition analysis demonstrating the presence of struvite. In patients without a prior history of struvite stones, the diagnosis should be suspected if the patient has a history of recurrent or persistent UTIs, persistently alkaline urine pH (>8), magnesium ammonium phosphate crystals present in the urine sediment (picture 1), or a staghorn calculus identified by abdominal imaging (image 1 and image 2). Struvite stone formers should undergo a metabolic evaluation, similar to the evaluation performed in patients who form other types of kidney stones. (See 'Diagnosis and evaluation' above.)
•Surgical therapy – Patients who present with obstructing stones and UTI or acute kidney injury require emergency intervention for urgent decompression of the collecting system. For most patients with struvite stones who do not require emergency intervention, we suggest complete surgical stone removal, rather than medical therapy alone (Grade 2C). Patients who are too ill to tolerate, or who refuse, stone removal surgery may be managed conservatively with medical therapy alone. However, medical therapy alone is rarely successful. (See 'Surgical therapy for most patients' above.)
-For most patients with struvite stones who are undergoing surgical stone removal, we suggest percutaneous nephrolithotomy (PNL) as first-line surgical therapy, rather than shock wave lithotripsy (SWL) or other surgical options (Grade 2C). However, for patients who have a smaller stone volume (<500 mm2) and normal collecting system anatomy, SWL is an alternative option. If SWL monotherapy is used, a stent should be placed to ensure adequate drainage of the kidney. (See 'Choice of surgical approach' above.)
-Open surgery should not be offered as first-line surgical therapy. However, open surgery can be considered for patients with a large stone burden or in individuals with severe obesity in whom endoscopic and fluoroscopic techniques are difficult. (See 'Choice of surgical approach' above.)
•Medical therapy – Medical therapy should ideally be used in conjunction with surgical therapy. Medical therapy alone is not considered the preferred option for patients with struvite stones except in those who are too ill to tolerate, or who refuse, stone removal. (See 'Adjunctive medical therapy' above.)
-For patients who have undergone surgical stone removal, we suggest prophylactic antibiotics (Grade 2C); therapy is usually continued for three to six months after complete stone removal. There is no high-quality evidence to guide the optimal choice of agent or timing or duration of therapy. (See 'Antibiotic therapy' above.)
-For patients with residual stone fragments after surgical stone removal, with recurrent struvite stones, or who are unable to tolerate, or refuse, surgical stone removal, we offer treatment with acetohydroxamic acid (AHA). However, these agents may be associated with significant side effects that frequently limit their use. (See 'Urease inhibition in select patients' above.)
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