Xanthogranulomatous pyelonephritis

INTRODUCTION — Xanthogranulomatous pyelonephritis (XPN) is an unusual variant of chronic pyelonephritis. Most cases occur in the setting of obstruction due to infected kidney stones [1-6]. Affected patients usually have massive destruction of the kidney due to granulomatous tissue containing lipid-laden macrophages.

Studies performed in the 1970s found XPN in 8.2 percent of kidneys surgically removed or biopsied for chronic pyelonephritis and in as many as 25 percent in patients with pyonephrosis [1,7].

CLINICAL PRESENTATION — The clinical picture of XPN is somewhat different in adults and children.

Adults — XPN most often occurs in middle-aged females with a history of recurrent urinary tract infections [2]. The typical presenting symptoms include flank pain, fever, malaise, anorexia and weight loss. A unilateral kidney mass can usually be palpated on physical examination. Blood tests reveal nonspecific abnormalities including anemia, an increased erythrocyte sedimentation rate, and liver function abnormalities reflecting mild biliary retention.

Examination of the urine confirms the presence of urinary tract infection. The urinalysis reveals pyuria and bacteriuria. Urine culture typically demonstrates Enterobacteriaceae. The most common organisms associated with XPN are Escherichia coli, Proteus mirabilis, Pseudomonas, Enterococcus faecalis, and Klebsiella [6]. The urine cultures are sterile in 25 to 40 percent of cases [4,8,9].

Patients often have kidney stones at the time of diagnosis. In a retrospective study of 40 cases from India from 2005 to 2017, 90 percent had kidney stones [8]. In another study from Spain reporting on 27 cases, 82 percent were female, the mean age was 60 years, and 78 percent had kidney stones [9].

Malignancies of the kidney also co-occur with XPN [8-10]. In the series from India, renal cell carcinoma was diagnosed at the time of XPN in 5 percent [8].

Children — There are two different presentations of XPN in children [4,11-14]. The most common form affects males and females equally and involves the entire kidney. The other form, which is more frequent in females, is localized and may mimic a tumor.

The presenting symptoms include flank and abdominal pain, fever, and growth and weight retardation. Approximately one-half of children have a palpable abdominal mass. Bacteriuria and pyuria are found in 50 to 70 percent of cases with Proteus (60 percent) and E. coli being the most common causative organisms.

Secondary amyloidosis — Some patients have a relatively prolonged course of chronic inflammation before the diagnosis of XPN is established. In this setting, secondary amyloidosis (amyloid AA) can occur, leading in some cases to the nephrotic syndrome [15,16]. (See "Causes and diagnosis of AA amyloidosis and relation to rheumatic diseases".)

Kidney transplant recipients — XPN rarely may complicate the course of kidney transplantation from the early weeks to up to 14 years after transplantation [16,17]. Immunosuppression, rejection and lymphatic blockade may be etiologic factors, and it may be difficult to distinguish XPN from rejection.

DIAGNOSIS — Although the urinalysis and urine culture typically indicate the presence of urinary tract infection, the diagnosis of XPN is confirmed by radiologic testing and pathology. Intravenous pyelography (IVP) is abnormal but generally not diagnostic. It usually reveals the shadow of a nonfunctioning, enlarged kidney containing several kidney stones or a staghorn calculus. In cases in which part of the kidney is still functioning, the IVP shows a space-occupying lesion resembling kidney cancer.

CT scan — Computed tomography (CT) scan has replaced renal angiography as the preferred diagnostic tool in the evaluation of XPN (image 1). The CT scan has several advantages [18]:

●It shows the characteristic replacement of the kidney tissue by several rounded, low-density (15 to 18 Hounsfield units) areas that are surrounded by an enhanced rim of contrast medium, resulting in a multiloculated appearance (image 2). These findings are similar in appearance to the paw print of a bear and are known as the "bear's paw sign" [19,20]. The imaging abnormalities correspond to dilated calyces lined with necrotic xanthomatous tissue extending into the kidney parenchyma.

●It can determine the extent of the lesion and any extension into the perirenal area. The extent of the lesion can be classified into three stages:

•Stage 1 – Localized disease confined to kidney parenchyma.

•Stage 2 – Extent of inflammation involves the perinephric fat.

•Stage 3 – Extent of inflammation involves the perinephric spaces and/or abdominal wall. In the most advanced forms, the mass of xanthogranulomatous tissue can involve the adjacent gastrointestinal tract, and fistulas may be created into the colon or duodenum [1].

●Kidney stones which, as noted above are a frequent cause of XPN, are clearly visible on CT scan films.

●The imaging appearance may be confused with kidney malignancy; however, kidney malignancy can coexist with XPN [8-10], and CT scan can identify a concomitant kidney mass. In such patients, malignancy may be a precipitating factor for XPN, particularly if they do not have kidney stones, probably through urinary tract obstruction.

Pathology — XPN is almost always unilateral. On macroscopic examination, the kidney is enlarged and usually destroyed by the inflammatory process. Necrotic yellow material surrounded by layers of orange-colored tissue is typically seen (picture 1). Kidney stones, including staghorn calculi, are usually present within the mass. The inflammatory tumor is adherent to the surrounding structures if there has been perirenal extension. Extension to the duodenum, the spleen, the lung and the skin is uncommon, but may lead to fistula formation and require extensive surgical intervention [14,17].

On microscopic examination, the lesion comprises three layers centered by a calyx [21]. The inner zone consists of necrosis, leukocytes, lymphocytes, plasma cells and macrophages. The middle zone contains vascularized granulation tissue interspersed with hemorrhage. The inflammatory cells are largely lipid-laden macrophages, which account for the yellow color (picture 2). The outermost part of the lesion is characterized by giant cells and cholesterol clefts [18].

PATHOPHYSIOLOGY — XPN is due to inflammation which may occur as a result of a defect in macrophage processing of bacteria. In the case of XPN complicating kidney transplantation, kidney ischemia, lymphatic blockade and immunosuppression may also be important factors [14]. The factors responsible for the accumulation of lipids and cholesterol in the lesion are not well understood.

DIFFERENTIAL DIAGNOSIS — XPN is most frequently confused with renal carcinoma in its clinical presentation and radiographic appearance. There is also report of pulmonary septic emboli masquerading as metastatic malignancy [22]. Evidence of chronic urinary tract infection and CT scan findings usually facilitates differentiation of these disorders, although rarely the two can occur together. XPN must also be distinguished histologically from two other inflammatory conditions, renal parenchymal malakoplakia and megalocytic interstitial nephritis [23]. The clinical differential diagnosis is similar to that of kidney abscess, although the imaging findings are distinct. (See "Renal and perinephric abscess", section on 'Differential diagnosis'.)

TREATMENT — XPN is almost always unilateral and is associated with virtually complete destruction of the kidney. Treatment is therefore surgical (after an initial course of antimicrobials to control the local infection) and consists of en-bloc nephrectomy, in which all the involved tissue is removed and any fistulas closed. Patients with a localized form (usually children) or with bilateral disease can be treated with partial nephrectomy [24]. Laparoscopic nephrectomy is a potential approach, depending on the extent of the lesions and the urologist's expertise [25].

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: Urinary tract infections in adults".)

SUMMARY AND RECOMMENDATIONS

●Definition – Xanthogranulomatous pyelonephritis (XPN) is an unusual variant of chronic pyelonephritis in which there is massive destruction of the kidney by granulomatous tissue containing lipid-laden macrophages. It is thought to be due to aberrant inflammation as a result of a macrophage defect in microbial processing. (See 'Introduction' above.)

●Clinical presentation – In adults, XPN most commonly occurs in middle-aged females with a history of recurrent urinary tract infections, particularly with Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis, and Klebsiella species. In children, XPN can involve the entire kidney or may be localized, mimicking a tumor, and is most commonly associated with Proteus and E. coli. XPN is a rare complication of kidney transplantation. (See 'Clinical presentation' above.)

Presenting symptoms include flank or abdominal pain, fever, malaise, and weight loss or growth retardation. A unilateral kidney mass can usually be palpated, and blood tests can reveal evidence of nonspecific systemic inflammation. In some cases, chronic inflammation can lead to secondary amyloidosis and the nephrotic syndrome. (See 'Clinical presentation' above.)

●Diagnosis – The diagnosis is confirmed by characteristic findings on computed tomography (CT) scan and pathology. (See 'Diagnosis' above.)

•On CT, kidney tissue appears replaced by several rounded low-density areas that are surrounded by an enhanced rim of contrast medium and correspond to dilated calyces lined with necrotic xanthomatous tissue (image 2). (See 'CT scan' above.)

•On gross examination, the kidney is enlarged with necrotic yellow material surrounded by layers of orange-colored tissue. Microscopically, the lesion consists of three layers of inflammatory cells surrounding the calyx. (See 'Pathology' above.)

●Differential diagnosis – XPN is almost always unilateral and is most frequently confused clinically and radiographically with renal cell carcinoma. Histology is typically necessary to distinguish the two. (See 'Differential diagnosis' above.).

●Management – XPN is treated with partial or full nephrectomy following an initial course of antibiotics to control the local infection. (See 'Treatment' above.)