Struvite and Staghorn Calculi
- Author: Maxwell Meng, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS more...
Upper urinary tract stones that involve the renal pelvis and extend into at least 2 calyces are classified as staghorn calculi (see image below). Although all types of urinary stones can potentially form staghorn calculi, approximately 75% are composed of a struvite-carbonate-apatite matrix. Struvite is magnesium ammonium phosphate; a Swedish geologist named Ulex discovered the substance in bat droppings and named it after his friend and mentor, the 19th-century Russian diplomat and naturalist Baron von Struve.
Struvite stones are also known as triple-phosphate (3 cations associated with 1 anion), infection (or infection-induced), phosphatic, and urease stones. Other, less common staghorn calculi can be composed of mixtures of calcium oxalate and calcium phosphate.
History of the Procedure
The concept that urinary tract infections play a role in lithogenesis is not new. Hippocrates noted the relationship between renal calculi and loin abscesses. In 1817, Marcet recognized the association of phosphate calculi with infection, alkaline urine, and ammoniacal urine. Not until the early 20th century did Brown propose that urea-splitting bacteria were responsible for urinary ammonia, alkalinity, and stone formation. The isolation of urease, the first enzyme ever purified, earned Sumner the Nobel Prize for Chemistry in 1946. Urease-producing organisms are listed in Etiology.
Struvite stones are invariably associated with urinary tract infections. Specifically, the presence of urease-producing bacteria, including Ureaplasma urealyticum and Proteus species (most common), Staphylococcus species, Klebsiella species, Providencia species, and Pseudomonas species, leads to the hydrolysis of urea into ammonium and hydroxyl ions. Escherichia coli does not produce urease and is not associated with struvite stone formation. Other common bacteria that have not been shown to produce urea include Citrobacter freundii, enterococci, and streptococci.
The resulting increase in ammonium and phosphate concentrations combined with the alkalotic urine (pH >7.2) is necessary for struvite and carbonate apatite crystallization. Magnesium ammonium phosphate crystals (MgNH4 PO4 •6H2 O) are admixed with carbonate apatite (Ca10 (PO4) 6•CO3) in varying proportions along with matrix. The proportion of matrix, typically low molecular weight mucoproteins, is greater than in other types of calcium-based stones and is thought to protect the bacteria from antimicrobials.
Although calcium oxalate stones are most prevalent in the Western world, struvite calculi account for up to 30% of urinary tract stones worldwide. In the United States, 10-15% of all stones are composed of struvite. They are found more frequently in women and in persons older than 50 years, likely reflecting the population at increased risk of recurrent or persistent urinary tract infections. Accordingly, treatment of struvite stones must also address the source of these infections.
The natural history of struvite calculi mandates the complete removal of stones. First, infection stones generally grow rapidly, and any remaining stone material may serve as a nidus for future stone formation. Second, even after complete stone removal, struvite stones recur in approximately 10% of patients; if residual stones or fragments are left after treatment, recurrence rates approach 85%.
Third, struvite stones are a potential source of significant morbidity. Previously, it was believed that asymptomatic struvite stones could be managed expectantly; however, studies have demonstrated that 30% of patients treated conservatively (ie, no surgery to remove stones) died of renal failure or of pyelonephritis and sepsis.
In rare cases, chronic irritation, infection, and inflammation from staghorn calculi can cause squamous metaplasia, leading to squamous cell carcinoma of the renal collecting system. These malignancies carry a very poor prognosis, with a 5-year survival rate of less than 10%.
Priestley and Dunn reported a 41% 5-year survival rate in patients with untreated unilateral struvite stones. These data underscore the importance of approaches, primarily surgical, to completely remove the stone material.
Gram-positive bacteria that cause struvite stones are as follows:
Corynebacterium species (ie, C ulcerans, C renale, C ovis, C hofmannii, C murium, C equi)
Mycobacterium rhodochrous group
Gram-negative bacteria that cause struvite stones are as follows:
Proteus species (ie, P mirabilis, P morganii, P rettgeri)
Klebsiella species ( K pneumoniae, K oxytoca)
Yeasts that cause struvite stones are as follows:
Two conditions must coexist for the formation of struvite calculi. These are (1) alkaline urine (pH >7.2) and (2) the presence of ammonia in the urine. This leads to magnesium ammonium phosphate and carbonate apatite crystallization. The conversions of urea to ammonia, ammonia to ammonium, and acidification from carbon dioxide are as follows:
H2 NCONH2 + H2 O → 2NH3 + CO2 2NH3 + H2 O → 2NH4+ + 2OH- (increase pH >7.2)CO2 + H2 O → H+ + HCO3 → 2H+ + CO32-
The clinical presentation of patients with struvite stones can be variable. Consider struvite stones in patients with risk factors for developing urinary tract infections (eg, prior urinary diversion or urologic surgery, presence of indwelling catheters, neurogenic bladder, vesicoureteral reflux, other anatomic abnormalities).
Infections may result in pyelonephritis, pyonephrosis, or perinephric abscess. Symptoms may include flank pain classic for renal colic, fever, urinary symptoms (eg, frequency, dysuria), and hematuria (either gross or microscopic). However, struvite stones rarely manifest as a solitary ureteral stone with acute renal colic in the absence of prior intervention. Concomitant urinary obstruction and hydronephrosis may be present and can result in nausea or vomiting.
In institutionalized patients susceptible to infection stones, the ability to elicit symptoms may be limited; sepsis may be the only evidence of an underlying struvite staghorn calculus. Note that patients with struvite calculi can be asymptomatic, even when calculi occupy the entire renal collecting system. Even with progression to xanthogranulomatous pyelonephritis, 25% of patients may remain completely free of symptoms. Systemic manifestations of large struvite stones and associated chronic infection include generalized fatigue, malaise, and weight loss.
Staghorn calculi represent a less-common nephrolithiasis subgroup so named because the significant stone burden that fills the renal pelvis and calyces forms a shape on radiographs that resembles a deer's horns. Most staghorn stones in Western society are composed of struvite and can cause significant morbidity and mortality if left untreated; therefore, large struvite stones must typically be removed.
Interestingly, an article investigating the structural analysis of renal calculi in northern India reported that over 90% of staghorn stones were composed of oxalates. In a study from southern Thailand, the most common component of staghorn calculi was uric acid; struvite was found in only 11.6% of cases. A US study, published in 2011, reported that slightly over half of complete staghorn calculi were metabolic in origin, consisting of calcium phosphate (55%), uric acid (21%), calcium oxalate (14%), or cystine (10%).
Unlike other urinary stones that commonly produce symptoms (eg, renal colic) that necessitate intervention, treatment of struvite stones often occurs in patients without classic signs of nephrolithiasis; this is because large staghorn calculi may not cause acute renal or ureteral dilatation and resultant pain.
A comprehensive discussion of renal anatomy is beyond the scope of this article; however, several points relevant to endourologic techniques are discussed.
First, the kidneys are retroperitoneal organs enclosed within several layers, including the adjacent adherent renal capsule and the renal Gerota fascia surrounding the perinephric fat. Severe renal infections associated with struvite stones may lead to abscess formation, both within the kidney and within the Gerota fascia (ie, perinephric abscess).
Second, the kidneys are intimately associated with many nearby organs. On the right side, the liver may be posterolateral to the kidney at the level of the superior pole; on the left side, the spleen resides in an analogous position. These organs may be injured during percutaneous renal access. On both sides, the colon has retroperitoneal portions that can be located posterior to the kidneys. Studies have demonstrated that retrorenal colon positions are present in up to 10% of patients.
A single kidney contains 5-14 calyces, each of which drains a renal papilla. These minor calyces may coalesce to form major calyces, all of which subsequently drain into an infundibulum.
The placement of percutaneous tubes into the kidney should be guided by the following three principles:
- Access should not be placed through an infundibulum, because of greater risks of vascular injury
- In all areas of the kidney (both superior and inferior), access should be gained near the fornix of the calyx
- Entry into a posterior calyx allows the greatest ability to examine and remove stones in the renal pelvis and in additional infundibula and calyces
The presence of an active, untreated urinary tract infection is a contraindication to stone removal. Patients with struvite stones have chronic bacteriuria, and their urine is never sterilized by antibiotics alone; however, appropriate antibiotics should be administered prior to surgical intervention in an attempt to minimize the potential for sepsis during treatment. Similarly, if concomitant urinary obstruction and purulent infection exist (ie, pyonephrosis), percutaneous drainage and antibiotics are necessary before further manipulation of the stone and urinary tract.
If pyonephrosis is seen at the time of percutaneous renal access, percutaneous drainage should be left in place to maximally drain the infected collecting system, and nephrolithotomy should be deferred. The patient should be left on antibiotics and admitted for monitoring for urosepsis. Stone removal should be deferred to a later time to minimize infectious complications.
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|Generic name||Citric Acid, glucono-delta-lactone, and magnesium carbonate|
|Description||Action on susceptible apatite calculi results from exchange of magnesium from irrigating solution for insoluble calcium contained in stone matrix or calcification. Magnesium salts thereby formed are soluble in gluconocitrate irrigating solution, resulting in dissolution of calculus. Struvite calculi are composed mainly of magnesium ammonium phosphates, which are solubilized by hemiacidrin due to acidic pH. Essential that patients be free from urinary tract infections prior to initiating chemolytic therapy. Used for local irrigation dissolution of renal calculi composed of apatite (a calcium carbonate-phosphate compound) or struvite (magnesium ammonium phosphates) in patients who are not candidates for surgical removal of calculi. Also used as adjunctive therapy to dissolve residual apatite or struvite calculi and fragments after surgery or to achieve partial dissolution of renal calculi to facilitate surgical removal.|
|Adult Dose||Renal calculi:
Place nephrostomy tube at surgery or percutaneously to permit lavage of calculi; single catheter may be sufficient if calculus not obstructing ureter or ureteropelvic junction; in patients with obstructed ureter, a retrograde catheter can be placed through ureter to renal pelvis via a cystoscope (used to irrigate calculus while percutaneous nephrostomy tube used for drainage)
Pressure measurements are made under fluoroscopic guidance to ensure 2-3 mL/min can be infused without causing pain, pyelovenous or pyelotubular backflow, or manometric evidence of elevated pressure within collecting system
Irrigation should not be started before fourth or fifth postoperative day; irrigation of renal pelvis is begun with sterile saline only after sterile urine demonstrated
Saline is infused at rate of 60 mL/h initially, and rate is increased until pain or an elevated pressure (25 cm water) appears or until maximum flow rate of 120 mL/h achieved; inspect site of insertion for leakage; if leakage occurs, irrigation is discontinued temporarily to allow for complete healing around nephrostomy tube; if no leakage or flank pain occurs, start irrigation with flow rate equal to maximum rate achieved with saline solution
Place clamp on inflow tube and instruct patients and nursing personnel to stop irrigating solution whenever pain develops; nursing personnel responsible for performing irrigation must be instructed concerning location of nephrostomy tube(s) and direction of flow of irrigating solution to ensure against misconnection of inflow and egress tubes
Perform nephrotomography periodically to assure proper placement of catheter tip and to assess efficacy; if stones fail to change size after several days of adequate irrigation, discontinue procedure; upon demonstration of complete dissolution of calculus, inflow tube is clamped and left in place for few days to ensure that no obstruction exists, after which time nephrostomy tube should be removed
Instill 30 mL through urinary catheter into bladder; clamp catheter for 30-60 min and release clamp to drain; repeat 4-6 times/d; continuous drip through 3-way Foley catheter is alternative means of dissolving bladder stones; in presence of bladder spasm and associated high pressure reflux, all precautions required for irrigation of renal pelvis must be observed
|Pediatric Dose||Not established|
|Contraindications||Urinary tract infections; presence of demonstrable urinary tract extravasation; ureteral catheters, nephrostomy or pyelostomy tubes, or renal lavage for dissolving calculi|
|Interactions||May increase toxicity of magnesium-containing medications|
|Pregnancy||C - Safety for use during pregnancy has not been established.|
|Precautions||Fever, urinary tract infection, signs and symptoms consistent with urinary tract infection, persistent flank pain, or if hypermagnesemia or elevated serum creatinine level develops (urea-splitting bacteria reside within struvite and apatite stones and serve as source of infection); dissolution therapy in presence of infected urinary tract may lead to sepsis and death; severe hypermagnesemia has occurred
Caution when irrigating renal pelvis of patients with impaired renal function; severe hypermagnesemia may result in hyporeflexia, dyspnea, apnea, coma, cardiac arrest, and subsequent death; treatment should include discontinuation of therapy followed by treatment with IV calcium gluconate, fluids, and diuresis in severe cases
|Generic name||Suby solution G|
|Brand names||Suby solution G|
|Description||Used to dissolve phosphatic calculi or incrustations in the bladder and urethra.|
|Adult Dose||1-3 L qd by intermittent irrigation or by tidal instillation and drainage to allow continuous irrigation of bladder for periods of several hours; intermittent irrigation of bladder (after manner of intermittent peritoneal dialysis) may be preferred to promote longer contact of irrigant with bladder stones; tidal (continuous inflow and outflow) irrigation may be less efficient and require larger amounts of irrigation fluid|
|Pediatric Dose||Administer as in adults|
|Contraindications||Bladder infections, bleeding, ulcerations, or other open wounds; IV/IM/SC injections|
|Pregnancy||C - Safety for use during pregnancy has not been established.|
|Precautions||For use only in irrigation of lower urinary tract; not for dissolving phosphate calculi in renal pelvis (may cause back pressure that could reactivate existing pyelonephritis); repeated or continuous use may cause bleeding (irritating to urethra; after each treatment, irrigate with sterile saline or water); 4 cases of sudden death reported during lavage therapy with similarly acting solution; not to be used in place of other indicated measures, including correction of underlying metabolic disorders, surgical intervention, and treatment of infection|
|Generic name||Acetohydroxamic acid|
|Description||Reversibly inhibits bacterial enzyme urease, thereby inhibiting hydrolysis of urea and production of ammonia in urine infected with urea-splitting organisms. Reduced ammonia levels and decreased pH enhance effectiveness of antimicrobial agents and increase cure rate of these infections. Does not acidify urine directly, nor does it have direct antibacterial effect. In patients with urea-splitting urinary infections (often accompanied by struvite stone disease) that are recalcitrant to other management, reduces pathologically elevated urinary ammonia and pH levels.|
|Adult Dose||12 mg/kg/d PO tid/qid on empty stomach recommended initially; not to exceed 1.5 g/d|
|Pediatric Dose||10 mg/kg/d PO initially; monitor clinical condition and hematologic status; dosage titration may be required|
|Contraindications||Patients whose physical state and disease are amenable to surgery or antimicrobial agents, urine is infected by non–urease-producing organisms, or renal function is poor (eg, serum creatinine >2.5 mg/dL or CrCl < 20 mL/min) and females without satisfactory method of contraception whose urinary infections can be controlled by culture-specific oral antimicrobial agents|
|Interactions||Absorption of iron and AHA may be reduced from intestinal lumen when both drugs taken concomitantly (give iron IV when indicated)|
|Pregnancy||X - Contraindicated in pregnancy|
|Precautions||Bone marrow depression (ie, leukopenia, anemia, thrombocytopenia) has occurred in animals receiving large doses (never reported in humans); hemolysis with decrease in circulating red blood cells, hemoglobin levels, and hematocrit values also noted; in renal impairment, closely monitor patients and reduce daily dose to avoid excessive drug accumulation|