Continuing Education Activity

Xanthogranulomatous pyelonephritis is a rare and aggressive variant of chronic pyelonephritis. It usually occurs due to chronic nephrolithiasis and infection. The diagnosis is often confused with renal cell carcinoma, and a computed tomography (CT) scan, as well as histology of the mass, helps to confirm the diagnosis. Since it can involve adjacent structures or organs, early diagnosis and treatment with nephrectomy have an excellent prognosis. This activity describes the evaluation and management of xanthogranulomatous pyelonephritis and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Identify the etiology of xanthogranulomatous pyelonephritis.
• Describe the imaging findings associated with xanthogranulomatous pyelonephritis.
• Outline the treatment options available for xanthogranulomatous pyelonephritis.
• Explain the importance of collaboration and communication amongst the interprofessional team to enhance the delivery of care for patients with xanthogranulomatous pyelonephritis.

Introduction

Xanthogranulomatous pyelonephritis (XGP) is a rare and aggressive variant of chronic pyelonephritis resulting in a non-functioning kidney. It is most often associated with chronic obstruction and stones with ongoing infection.[1] It is also referred to as a pseudotumor due to an enlarged kidney resembling a tumor and the ability of local invasion and destruction. The disease is characterized by the destruction and replacement of renal or peri-renal tissue with granulomatous tissue containing lipid-laden macrophages. The term "xantho" (Greek meaning yellow) is used in its name due to the infiltration of lipid-laden macrophages that appear yellow in the pathological section. XGP was first described by Schlagenhaufer in 1916 and was named xanthogranuloma by Osterlin in 1944.[2][3][4][5]

Xanthogranulomatous pyelonephritis is often confused with a true neoplasm, most commonly renal cell carcinoma due to its similarity in clinical and radiographic features, as well as the ability to involve the adjacent structures or organs. Therefore, early identification and treatment are required to decrease the morbidity and mortality associated with this condition. Although antibiotics can be given in acute infection, the treatment of choice for XGP is nephrectomy.[6]

Classification:

• Diffuse: Kidney involvement is diffuse.
• Segmental: Kidney involvement is segmental.
• Focal: Involvement within the cortex of the kidney.

Etiology

The etiology of XGP remains unknown. However, most of the cases result from chronic urinary obstruction and infection. The organisms most commonly associated with XGP are Escherichia coli, Proteus mirabilis, Pseudomonas, Enterococcus faecalis, and Klebsiella, etc. Urinary obstruction occurs as a result of calculus, most commonly, staghorn calculus (in almost 80% of patients), which serves as a nidus for infection resulting in the destruction of the renal parenchyma. However, in children, congenital ureteropelvic abnormalities may result in chronic urinary obstruction.[7][8]

Risk factors for XGP:

• Diabetes mellitus
• Hypertension
• Immunocompromised individuals
• Abnormal lipid metabolism
• Renal transplantation
• Brachydactyly mental retardation syndrome in children[9]

Epidemiology

The incidence of XGP varies from 0.6% to 1% of all cases of renal infections. The disease can occur in all age groups but is more common in women than in men, usually in their fifth and sixth decade of life. There is no specific race predilection. Although in most patients, a unilateral kidney is involved, bilateral involvement can rarely occur in a few cases. Both the kidneys are affected with equal frequency. 

XGP is extremely rare in children, but when it occurs, there are two different presentations. The most common form involves the entire kidney and equally affects males and females. The less common form includes a localized area of the kidney and mostly affects females.

Pathophysiology

The exact pathophysiology of XGP is unclear. The mechanism involved in the pathogenesis of XGP is nephrolithiasis leading to chronic obstruction and infection. It is an inflammatory disorder that may occur due to a defect in the degradation of bacteria by a macrophage. The disease is characterized by the destruction and replacement of renal or peri-renal tissue with granulomatous tissue containing lipid-laden macrophages. However, the accumulation of lipids and cholesterol in the lesion is not well understood. It starts from the renal pelvis and calyces spreading to the renal parenchyma and finally to the adjacent organs if left untreated. Adjacent organs such as the liver, spleen, duodenum, pancreas, and great vessels can be involved in a severe form of XGP.[10]

Histopathology

The microscopic examination of a xanthogranulomatous pyelonephritis lesion shows three distinct zones centered by a calyx with the following findings in each zone:

• Inner zone: Consists of leukocytes, lymphocytes, plasma cells, histiocytes or macrophages, and necrosis.
• Middle zone: Consists of granulation tissues surrounded by hemorrhage. The pathognomonic feature is the presence of lipid-laden foamy macrophages (xanthoma cells) that gives a yellow color to the tissue.
• Outer zone: Consists of giant cells, cholesterol clefts, and fibrous tissues.

The gross pathology of the mass may show yellow tissue with necrosis and hemorrhage.

History and Physical

The typical history of a patient with XGP is a middle-aged female presenting with recurrent urinary tract infections most commonly due to Escherichia coli and Proteus mirabilis. In children, the presenting complaint may be fever, flank or abdominal pain, and growth retardation.

The presentation is similar to renal tuberculosis. Hence, the history of travel to the endemic region should be evaluated.

The adult patient with XGP may present with the following symptoms:

• Unilateral flank pain and fever, which are the most common presenting complaints in a patient with XGP. Flank pain is usually unilateral, and the nature of the pain is dull and persistent.
• Urinary symptoms like dysuria, hematuria, and increased urinary frequency
• Anorexia, chills, and weight loss in a few cases[11]                                                        

Physical findings:

• High temperature
• Conjunctival pallor due to anemia
• Unilateral or bilateral renal mass on palpation
• Costovertebral angle tenderness on palpation
• Cutaneous draining of fistula due to nephrocutaneous fistula formation
• Hepatomegaly in a few cases when there is an invasion of the liver

Evaluation

Evaluation of a patient with XGP requires an appropriate history, physical examination, and comprehensive lab work. The detailed laboratory and radiographic findings are explained below:

• Blood examination: Includes a complete blood count (CBC) with a differential that may show anemia and leukocytosis in a patient with XGP. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are often elevated. Renal function tests may show elevated blood urea nitrogen and creatinine levels. The liver function test is often abnormal due to mild biliary retention.
• Urine examination: Urinalysis may show signs of a urinary tract infection (UTI) that includes pyuria, bacteriuria, and hematuria. Urine culture shows the growth of organisms like Escherichia coli, Proteus mirabilis, Pseudomonas, Enterococcus faecalis, Klebsiella, etc.
• Radiographic imaging: Plain X-ray of the abdomen may show calculi, especially staghorn calculi. Renal ultrasonography may reveal hydronephrosis and loss of normal renal architecture. Computed tomography (CT) scan findings are most useful for diagnosing a case of XGP. CT scan with contrast may show replacement of the normal renal tissue by multiple, hypoechoic areas of the dilated collecting system that is surrounded by an enhanced rim of contrast medium that results in a multiloculated appearance (known as the "bear paw" sign).[12][13] It can also identify renal stones within the collecting system. CT scan can also determine the extent and local invasion of the lesion and can be used to stage the disease. Magnetic resonance imaging (MRI) can be done in patients who are allergic to contrast. Intravenous urography and DTPA (diethylenetriamine pentaacetic acid) renal scan may show a poorly functioning kidney.
• Biopsy: The pathognomonic finding is the lipid-laden foamy macrophages, which can be challenging to differentiate from clear cell carcinoma of the kidney.
• Immunohistochemical staining: In cases where differentiation between XGP and renal cell carcinoma is difficult, it has been found that patients with XGP stained positive for PAS (periodic acid Schiff) stain.[14][15]

The preoperative diagnosis of XGP can be difficult due to the similar findings associated with renal cell carcinoma. CT scan helps differentiate these two conditions as well as knowing the extension of the disease. However, confirmatory diagnosis of XGP is made by pathological examination.

Treatment / Management

Individuals with a clinical presentation and pre-operative diagnosis of focal or segmental XGP can be treated with antibiotics and percutaneous drainage. With no improvement, partial nephrectomy or total nephrectomy can be done.

In patients with a diagnosis of diffuse or advanced stage XGP, the treatment of choice is nephrectomy. The use of antibiotics before and after surgery controls the local infection and avoids septic complications. The aim of surgery is to remove all granulomatous tissue so that there is no fistula formation in the future. Sinuses or fistulas should be repaired if found.[5]

Rare cases of bilateral XGP should be treated with bilateral nephrectomy and long-term dialysis.

There has been debate regarding open versus laparoscopic nephrectomy. Because of the inflammatory nature of the disease, laparoscopic nephrectomy is often challenging, and the conversion rate from laparoscopic to open nephrectomy is 50%. Laparoscopic nephrectomy can be done in selected patients by a surgeon with advanced laparoscopic experience and skills. Laparoscopic nephrectomy is associated with less blood loss and reduced hospital stay in patients with XGP.[16]

Differential Diagnosis

The differential diagnosis for xanthogranulomatous pyelonephritis includes:

• Clear cell renal cell carcinoma
• Papillary renal cell carcinoma
• Sarcomatoid renal cell carcinoma[17]
• Renal parenchymal malakoplakia
• Renal tuberculosis[18]
• Renal abscess
• Megalocytic interstitial nephritis[19]
• Angiomyolipoma of the kidney

The clinical presentation and radiographic appearance of XPG and renal cell carcinoma are similar. However, fever and raised inflammatory markers (CRP and ESR) are most commonly associated with XPG. If present, the "bear paw" sign is a pathognomonic feature of XPG. However, histology gives the confirmatory diagnosis for XGP.

Staging

Xanthogranulomatous pyelonephritis is classified as focal, segmental, and diffuse. The diffuse form is more common, which is further staged by Malek and Elder into three different stages according to the extent of involvement in the nearby tissues.

• Stage 1 (Nephric): Disease limited to the kidney.
• Stage 2 (Perinephric): Disease involving the renal pelvis or the peri-renal fat within Gerota fascia.
• Stage 3 (Paranephric): Disease involving the wider area, including the adjacent organs or retroperitoneum.[20]

Prognosis

The overall prognosis of XGP is excellent. Unilateral cases have a better prognosis, while bilateral cases are usually fatal. Nephrectomy is the treatment of choice without any incidence of recurrence.

Complications

The complications of xanthogranulomatous pyelonephritis are due to the involvement of adjacent organs and are as follows:

• Psoas abscess
• Perinephric abscess
• Nephrocutaneous fistula
• Nephrocolonic fistula/pyelo-duodenal fistula[21]
• Secondary amyloidosis and nephrotic syndrome
• Sepsis[5]

Consultations

• Nephrologist
• Infectious disease specialist
• Oncologist
• Urologist and urological surgeon
• Radiologist

Deterrence and Patient Education

• The contralateral kidney should be evaluated annually with imaging modalities.
• In patients with recurrent urinary tract infections, further evaluation and removal of any obstructions are important. These patients should be aggressively treated with antibiotics.
• Antibiotics should be continued for one week after surgery.

Enhancing Healthcare Team Outcomes

Xanthogranulomatous pyelonephritis is a rare and aggressive form of chronic pyelonephritis that is best managed with an interprofessional team approach. It is often confused with renal cell carcinoma and renal tuberculosis due to similar signs and symptoms. The diagnosis of XGP is based on the CT scan finding of the "bear paw" sign and histology showing lipid-laden foamy macrophage. It has the ability to involve the adjacent structures or organs if left untreated. Hence, early diagnosis and treatment can prevent the complications of this disease. Treatment with nephrectomy has an excellent prognosis. As the disease can involve multiple organs when left untreated, a team consisting of an infectious disease specialist, oncologist, radiologist, urologist, and a urological surgeon should carefully evaluate the disease and look for any complications.