Xanthogranulomatous Pyelonephritis 

Updated: Mar 15, 2021
Author: Samuel G Deem, DO; Chief Editor: Bradley Fields Schwartz, DO, FACS 

Overview

Practice Essentials

Xanthogranulomatous pyelonephritis (XGP), first described by Schlagenhaufer in 1916,[1] is a rare, serious, chronic inflammatory disorder of the kidney characterized by a destructive mass that invades the renal parenchyma.[2] XGP is most commonly associated with Proteus or Escherichia coli infection.[3, 4] Pseudomonas species have also been implicated. The kidney is usually nonfunctional. Most cases of XGP involve a diffuse process; however, up to 20% are focal. (See Etiology and Pathophysiology.)

Pathologically, XGP is characterized by lipid-laden foamy macrophages. XGP shares many characteristics with true renal neoplasms in terms of its radiographic appearance and its ability to involve adjacent structures or organs. CT findings include a staghorn calculus with contraction of the renal pelvis, multiple rounded hypoechoic foci in the kidney, enlargement of the kidney, and perinephric inflammation or abscesses. The arrangement of multiple rounded hypoechoic foci around the contracted renal pelvis has been described as the bear paw sign and is considered characteristic of XGP.[3, 4]

XGP is often associated with urinary tract obstruction, infection, nephrolithiasis, diabetes, and/or immunocompromise.[3] (See Workup.)

The treatment of XGP is almost universally extirpative and can pose a formidable challenge to the surgeon. Although open extirpative therapy has historically been the hallmark of management, an increasing number of reports have described successful laparoscopic intervention. (See Treatment.)

Most cases of XGP are unilateral, but bilateral disease has been reported. Bilateral nephrectomy and long-term dialysis is a treatment option in such cases. Although Perez et al described successful treatment with partial nephrectomies in 1 patient,[5] bilateral XGP is usually fatal. (See Treatment.)

Rare cases of coexisting  XGP and squamous cell carcinoma (SCC) have been reported.[6, 7] Surgery is rarely curative in those cases and the 5-year survival rate is less than 10%.[7]

The overall prognosis for XGP is good. Death from this entity is exceedingly rare, although morbidity is substantial.

Anatomy

The kidneys are paired organs in the retroperitoneum. They are covered in a thin, fibrous capsule that is in turn covered by Gerota’s fascia. On the right, the liver and adrenal gland abut the superior pole of the kidney. The second part of the duodenum is medial to the right kidney and may be reflected medially to gain exposure to the inferior vena cava (Kocher maneuver). On the left, the superior pole of the kidney is attached to the spleen superolaterally (splenorenal ligament) and is very near to or in direct contact with the tail of the pancreas medially.

The colon is anterior to the kidneys and is easily reflected anteriorly and medially when transabdominal exposure is required. The renal hilar structure, from anterior to posterior, includes the vein, the artery, and the collecting system. The left renal vein has 3 draining tributaries—namely, the adrenal, gonadal, and posterior lumbar veins.

Etiology and Pathophysiology

The exact etiology of xanthogranulomatous pyelonephritis (XGP) is unknown, but it is generally accepted that the disease process requires long-term renal obstruction and infection. As previously stated, XGP is most commonly associated with Proteus or Escherichia coli infection; Pseudomonas species have also been implicated.[8]

Stones (frequently of staghorn proportions) develop in 80% of patients with XGP but are not required to make the diagnosis. XGP is often observed in patients with diabetes, immunocompromise or both. Abnormal lipid metabolism has also been hypothesized as an etiologic factor in individuals with XGP.

XGP displays neoplasmlike properties capable of local tissue invasion and destruction and has been referred to as a pseudotumor. Adjacent organs, including the spleen, pancreas, or duodenum, may be involved. Malek and Elder have proposed the following stages of XGP involvement[9] :

  • Kidney
  • Perinephric fat
  • Adjacent retroperitoneal structures

The gross appearance of XGP is that of a mass of yellow tissue with regional necrosis and hemorrhage, superficially resembling renal cell carcinoma. The pathognomonic microscopic feature is the lipid-laden foamy macrophage accompanied by both chronic- and acute-phase inflammatory cells. Focal abscesses may be observed.

The primary mechanisms involved in XGP include nephrolithiasis, collecting system obstruction, and infection. No single factor can explain the process; rather, an inadequate host response to the acute inflammatory response occurs in the obstructed, necrotic kidney.[10]

Epidemiology

XGP occurs in approximately 1% of all renal infections. It is 4 times more common in women than in men and is usually noted in the fifth and sixth decades of life. XGP affects both kidneys with equal frequency.

Although XGP is rare in the pediatric population, it is found in approximately 16% of pediatric nephrectomy specimens. In children, XGP is more common in boys and usually affects those younger than 8 years.

 

Presentation

History and Physical Examination

Patients with xanthogranulomatous pyelonephritis (XGP) often appear chronically ill. Symptoms include anorexia, fever, chills, weight loss, and flank pain. The pain of XGP is not colicky in nature; it is usually dull and persistent.[11]

XGP is notorious for fistulization. Pyelocutaneous and ureterocutaneous fistulae have been well described. Other organs are occasionally involved in this process, including surrounding viscera (with resulting pyeloenteric fistulae).[12]

Obstruction associated with XGP in the pediatric population is more likely to be due to congenital factors than to obstructive calculi.

As an illustration of the varied presentation of XGP, a case report by Hitti et al describes XGP located in a renal allograft.[13] Another report describes a case of XGP associated with psoas abscess in a young pregnant woman in her third trimester.[14]

 

DDx

Diagnostic Considerations

Renal cell carcinoma may be indistinguishable from xanthogranulomatous pyelonephritis (XGP) radiographically and clinically.[15] A case of XGP involving thrombus of the renal vein has been reported.[16] XGP and renal cell carcinoma have even been observed in the same specimen.

Shah et al reported a mistaken diagnosis of renal XGP that was subsequently proved to be renal tuberculosis.[17] XGP must be diagnosed on the basis of histologic findings rather than solely on the basis of radiographic imaging studies.

 

Workup

Approach Considerations

A complete blood count (CBC) with differential may reveal leukocytosis and anemia. Expect these conditions to gradually resolve after nephrectomy. The erythrocyte sedimentation rate (ESR) is frequently elevated. Liver function findings are abnormal in up to 50% of patients with xanthogranulomatous pyelonephritis (XGP).

Serum chemistries are used to determine the presence of any baseline electrolyte abnormalities, although none is pathognomonic of XGP. Creatinine levels before nephrectomy may be abnormal, but removal of the nonfunctioning xanthogranulomatous kidney should not be expected to alter baseline renal function.[8]

Urine typically contains leukocytes and bacteria. Urinalysis often demonstrates proteinuria. The pH is often basic because Proteus mirabilis is a urease-producing organism. Urine cultures are important in determining the offending organism involved in the XGP process and in assisting in the appropriate selection of antibiotics.

Histologic findings

The pathognomonic microscopic feature of XGP (see the image below) is the lipid-laden foamy macrophage. These cells can be difficult to distinguish from clear cell carcinoma on frozen section.

Xanthogranulomatous pyelonephritis. Xanthogranulomatous pyelonephritis.

Imaging studies

Renal ultrasonography usually reveals an enlarged kidney with multiple hypoechoic masses; irregular, thinned parenchyma; and a dilated collecting system. These hypoechoic masses can range from 3 to 20 mm and represent abscesses, xanthogranulomas, or a combination of both. On ultrasound, the gallbladder wall usually appears diffusely thickened with prominent echogenic pericholecystic fat and increased vascularity representing inflammatory changes. In rare instances, focal or masslike thickening is apparent. Secondary findings may include intra- or extrahepatic ductal dilatation.[18]

Mercaptotriglycine (MAG-3) or technetium-99m dimercaptosuccinic acid (99m Tc-DMSA) renal scanning may be used to evaluate or confirm differential renal function.

Magnetic resonance imaging (MRI) is being studied selectively, but reports have not shown MRI to provide any diagnostic benefit beyond that which is achievable with traditional computed tomography (CT) scanning. However, MRI is frequently used in patients with renal insufficiency in whom contrasted images are required, in order to avoid the nephrotoxic intravenous (IV) contrast used for CT imaging.[19]

For full discussion, see Xanthogranulomatous Pyelonephritis Imaging.

Computed Tomography

CT scanning is the most useful radiographic technique in evaluating xanthogranulomatous pyelonephritis (XGP), although XGP cannot be diagnosed solely on the basis of radiographic findings. A CT scan demonstrates a heterogenous, nonenhancing mass on a hydronephrotic, nonfunctioning kidney with a central stone.[20] The arrangement of multiple rounded hypoechoic foci around the contracted renal pelvis has been described as the bear paw sign and is considered characteristic of XGP.[3, 4] In higher-stage disease, the mass may appear to involve adjacent organs. CT scans may also reveal a large staghorn calculus within the collecting system. (See the images below.)[21]

The following combination of findings strongly supports the diagnosis of XGP[19] :

  • Enlarged non-functioning kidney
  • Obstructing stone within a contracted renal pelvis
  • Enlarged calyces
  • Perinephric fat stranding
Xanthogranulomatous pyelonephritis appearing as no Xanthogranulomatous pyelonephritis appearing as nonenhancing, low-attenuation areas of the dilated collecting system surrounded by enhancing, high-attenuation parenchyma (known as the "bear paw" sign).
Xanthogranulomatous pyelonephritis with obstructio Xanthogranulomatous pyelonephritis with obstruction and staghorn calculus.

 

 

Treatment

Approach Considerations

Xanthogranulomatous pyelonephritis (XGP) is a surgically managed disease that is treated with either nephrectomy or, in rare circumstances, partial nephrectomy. Antibiotics are used in all cases, but medical care rarely suffices for treatment.

Extirpation is necessary because the disease occurs or results in an infected, nonfunctioning kidney. Nephron-sparing surgery will continue to be explored, provided that viable renal parenchyma is demonstrated. Now that laparoscopic nephrectomy is the criterion standard in many regions, this approach can be entertained depending on the individual surgeon’s skill level.

Contraindications to surgical therapy of XGP are those consistent with all major operations and intolerance to anesthesia, uncorrected coagulopathy, and severe connective-tissue disorders.

Annual imaging of the contralateral urinary tract is important. Aggressively treat all urinary tract infections. If possible, eliminate or control the agent or illness that is predisposing the patient to XGP. Evaluation of lower urinary tract pathology and voiding dysfunction may be important in these patients.

Antibiotic Therapy

Medical therapy has proven sufficient for treatment of XGP in only a handful of cases. Antibiotics may be appropriate as a temporizing measure in patients who require a medical workup before nephrectomy. Similarly, appropriate prophylactic antibiotics should be administered before operative intervention.

The choice of antibiotic should be geared toward the identity and sensitivity of the organism. Proteus organisms and E coli are usually sensitive to various antibiotics, including first-generation cephalosporins and trimethoprim-sulfamethoxazole. Pseudomonas species have a narrower spectrum to which they are sensitive, however, and may require the use of aminoglycosides, third-generation cephalosporins, or fluoroquinolones.

In patients who are not in a septic state and who have been evaluated on an outpatient basis, the author’s preference is to use an oral antibiotic until surgery, at which point IV antibiotics may be administered. Guidelines have not been established regarding the duration of antibiotic therapy after nephrectomy, but the author usually continues an active oral agent for 1 week.

Nephrectomy

Nephrectomy is the criterion standard of treatment for XGP. Cases of XGP are often challenging, particularly in patients with local organ involvement. The goal is to remove all involved granulomatous tissue. If this is not accomplished, the remaining infected tissue may lead to cutaneous fistulae. Some authors have advocated a role for partial nephrectomy if the disease is limited and therefore amenable to this operation.[22]

Laparoscopic nephrectomy is feasible for certain cases of XGP. Small pediatric series of XGP have reported success with this technique. However, Bercowsky et al reported that the technical difficulty and associated complications of the procedure negated any benefits over open nephrectomy.[23] The increased use of hand-assisted laparoscopic nephrectomy may allow a reasonable compromise between technical feasibility and acceptable patient morbidity.[24]

Shah and colleagues, in a retrospective analysis of 37 patients with XGP treated with either with either open (n=20) or laparoscopic nephrectomy (n=17), found that laparoscopic surgery was associated with lower mean blood loss, a shorter mean hospital stay, and a lower complication rate. Conversion to open surgery was necessary in one laparoscopic nephrectomy patient.[25]

When use of the laparoscopic approach is being entertained, the patient and his or her family should be informed that a conversion rate of nearly 50% can be expected.

Perioperative considerations

Appropriate preoperative imaging studies are essential. This is best accomplished with CT scanning. Administer bowel preparation and preoperative antibiotics. Ensure that surgical consent includes provisions for the possibility of operation on adjacent organs. If the patient is diabetic, establish control of hyperglycemia preoperatively. Correct any preexisting coagulopathy.

Intraoperatively, a flank approach through the appropriate intercostal/subcostal space (often the 11th rib) is desirable to avoid contamination of the peritoneum. Transabdominal subcostal exposure may be unavoidable if adjacent organs are involved with the mass.

The basic principles of nephrectomy apply to the extirpation of renal XGP. If possible, a radical nephrectomy (including Gerota’s fascia) should be performed, since the mass may still represent a neoplasm. All involved tissue must be removed. Liberal irrigation with antibiotic fluid is performed, and a suction drain is left in place.

Immediate postoperative care for patients with XGP is consistent with that for patients who have undergone standard nephrectomy. Watch for signs of sepsis. Institute aggressive pulmonary toilet. Encourage early ambulation.

Complications

The urologic surgeon should maintain a low threshold for involving a general surgeon in the management of XGP patients. Bleeding should be aggressively controlled. On the left side, splenic injury may result; if possible, preservation of the spleen should be attempted. Any pancreatic injuries must be identified, repaired, and appropriately drained.

On the right side, injuries may occur to the duodenum and liver. Liver lacerations during nephrectomy are frequently limited to capsular tears, which may be easily controlled with argon-beam coagulation and pressure. Duodenal injuries necessitate repair and nasogastric and cutaneous drainage. The colon is vulnerable to injury on either side. In a patient who has received adequate bowel preparation, these colonic injuries typically can be repaired primarily.

Vascular injury, especially on the right side, that involves the inferior vena cava can be humbling. The right-side processes are often highly inflamed and may involve the adrenal and gonadal veins in such a way as to render them vulnerable to avulsion and injury. Great care must be taken in dissecting out the right renal hilum. An alternative is to cross-clamp the hilum, transect it, and oversew the entire bundle. This approach can be planned or used in an emergency.

Postoperative abscess and cutaneous fistulization may occur, often after the drain has been removed and the patient has been discharged from the hospital. Patients typically present with drainage from the wound and fevers. CT scanning and percutaneous drainage should be performed, along with administration of IV antibiotics.

 

Medication

Medication Summary

Perioperative antibiotic recommendations are based on the classification of the procedure being performed. Radical nephrectomy for xanthogranulomatous pyelonephritis (XGP) would be considered a clean-contaminated case and would require prophylaxis. The American Urological Association best practice policy recommends either first- or second-generation cephalosporins or an aminoglycoside with metronidazole or clindamycin for 24 hours as first-line prophylaxis. Alternative regimens would include an ampicillin/sulbactam combination or a fluoroquinolone.[26]

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Clindamycin (Cleocin, Cleocin Pediatric)

Clindamycin is a lincosamide semisynthetic antibiotic produced by 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent compound lincomycin. This agent inhibits bacterial growth, possibly by blocking the dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. Clindamycin widely distributes in the body, without penetration of the central nervous system (CNS). It is protein bound and excreted by the liver and kidneys.

Clindamycin is available in parenteral (ie, clindamycin phosphate) and oral forms (ie, clindamycin hydrochloride). Oral clindamycin is absorbed rapidly and almost completely and is not appreciably altered by the presence of food in the stomach. Appropriate serum levels are reached and sustained for at least 6 hours following the oral dose. No significant levels are attained in the cerebrospinal fluid (CSF). Clindamycin is also effective against aerobic and anaerobic streptococci (except enterococci).

Metronidazole hydrochloride (Flagyl)

Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).

Cefazolin

Cefazolin is a first-generation semisynthetic cephalosporin, which, by binding to 1 or more penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial replication. It has a poor capacity to cross the blood-brain barrier. It is primarily active against skin flora, including Staphylococcus aureus. Regimens for IV and intramuscular (IM) dosing are similar. Cefazolin is typically used alone for skin and skin-structure coverage. It may be administered at 0.5-1.5g IM/IV every 6-8 hours.

Cefotetan

Cefotetan is a second-generation cephalosporin with activity against some gram-positive cocci, gram-negative rod infections, and anaerobic bacteria. It inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins; it inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death.

Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefotetan. Antibiotics have proved effective in decreasing the rate of postoperative wound infection and improving outcome in patients with intraperitoneal infection and septicemia. It may be administered at 1-2g IM/IV every 12 hours.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone that inhibits bacterial deoxyribonucleic acid (DNA) synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerase, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity against anaerobes. Continue treatment for at least 2 days (7-14 days typical) after signs and symptoms have disappeared. It may be administered at 200-400mg IV every 12 hours.

Ampicillin and sulbactam (Unasyn)

This drug is a combination of beta-lactamase inhibitor with ampicillin that is used as an alternative to amoxicillin when the patient is unable to take oral medication. The combination of ampicillin and sulbactam covers skin flora, enteric flora, and anaerobes, but it is not ideal for nosocomial pathogens. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It may be administered at 1.5-3g IM/IV every 6 hours.

Gentamicin

Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. This drug is used in combination with both an agent against gram-positive organisms and one that covers anaerobes.

Note that gentamicin is not the drug of choice. Consider using this drug if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms. The dosing regimens are numerous. Adjust the dose based on creatinine clearance (CrCl) and changes in volume of distribution. Gentamicin may be administered IV/IM.

Aztreonam (Azactam)

Aztreonam is a monobactam, not a beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. This agent has activity against gram-negative bacilli but very limited gram-positive activity, and it is not useful for anaerobes. Aztreonam lacks cross-sensitivity with beta-lactam antibiotics; it may be used in patients allergic to penicillins or cephalosporins.

The duration of aztreonam therapy depends on the severity of the infection and is continued for at least 48 hours after the patient is asymptomatic or evidence of bacterial eradication is obtained. Doses smaller than indicated should not be used.

Transient or persistent renal insufficiency may prolong serum levels. After an initial loading dose of 1 or 2g, reduce the dose by half for an estimated CrCl rate of 10-30 mL/min/1.73 m2. When only serum creatinine concentration is available, the following formula based on sex, weight, and age can approximate CrCl (serum creatinine should represent a steady state of renal function):

In patients with severe renal failure (CrCl < 10 mL/min/1.73 m2) and those supported by hemodialysis, a usual dose of 500mg, 1g, or 2g, is given initially.

The maintenance dose is one fourth of the usual initial dose given at a usual fixed interval of 6, 8, or 12 hours.

For serious or life-threatening infections, supplement the maintenance doses with one eighth of the initial dose after each hemodialysis session.

Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by the kidneys, obtain estimates of the CrCl, and make appropriate dosage modifications.

Data are insufficient regarding IM administration to pediatric patients or dosing in pediatric patients with renal impairment. Aztreonam is administered IV only to pediatric patients with normal renal function. It may be administered at 1-2 g IV every 8-12 hours.