Xanthogranulomatous Pyelonephritis

Xanthogranulomatous pyelonephritis (XGP) is a chronic, destructive granulomatous renal infection. Renal parenchyma is replaced by lipid laden macrophages (foamy xanthoma cells), with chronic inflammation, giant cells and fibrosis. Its main clinical significance is its resemblance to renal cell carcinoma and its need for surgical treatment.

It is usually secondary to long standing obstruction by a stone (staghorn calculus in 50 to 80 percent) with chronic infection. The most common organisms are Proteus mirabilis and Escherichia coli (also Klebsiella, Pseudomonas, Enterococcus and Staphylococcus aureus). The result is a defective macrophage response and failure to clear bacteria.

It mostly affects middle aged women (4th to 6th decade, female-to-male ratio of 3 to 4:1), diabetics and those with recurrent urinary infection or urinary tract anomalies. It typically involves one kidney (bilateral in under 5 percent).

Forms:

• Diffuse (over 80 percent): the whole kidney is enlarged and destroyed, with a non-functioning kidney.
• Focal or segmental (5 to 15 percent): a mass mimicking a tumour.
• Paediatric (rare).

The kidney is enlarged and yellow nodular, with calyceal dilation filled with pus and debris. Extension into the perinephric fat, psoas muscle, colon and skin (nephrocutaneous fistula) may occur.

• Persistent flank pain, fever, and recurrent urinary tract infections that respond poorly to antibiotics.
• Weight loss, malaise, anorexia and anaemia (chronic disease).
• Palpable flank mass (about 50 to 60 percent), and haematuria or pyuria.
• Abnormal liver tests (cholestasis, in some, which normalise after nephrectomy).
• A history of urolithiasis or obstructive uropathy, diabetes or immunosuppression.
• Rare: perinephric abscess, sepsis, fistula to the skin or bowel, and psoas abscess.

• Urine: pyuria, bacteriuria, alkaline urine in Proteus infection; urine culture positive in about 70 to 80 percent.
• Blood tests show anaemia, leucocytosis, raised C-reactive protein and erythrocyte sedimentation rate, and abnormal liver enzymes.
• CT is the best investigation. It shows an enlarged, non-functioning kidney with a central staghorn calculus, and dilated calyces with low density (negative 10 to 30 Hounsfield units, lipid rich) rounded masses ("bear paw" sign).
• CT also shows thin rim enhancing parenchyma, perinephric inflammation, and extension to adjacent structures. The focal form appears as a hypodense mass, which may mimic a tumour.
• Ultrasound: a hydronephrotic kidney with stones and echogenic debris; plain film shows a staghorn stone.
• Renal scintigraphy (DMSA, MAG3): non-functioning kidney.
• Percutaneous biopsy or surgical specimen histology: foamy macrophages (CD68 positive, PAS positive), neutrophils, plasma cells, lymphocytes and multinucleated giant cells.
• Frozen section excludes renal cell carcinoma (xanthogranulomatous change can coexist with carcinoma, and clear cell carcinoma and squamous cell carcinoma may be associated).
• Differential diagnosis: renal cell carcinoma, tuberculosis (acid fast bacilli, PCR), renal abscess, and urothelial carcinoma.

• Antibiotic therapy before surgery, directed by the culture: for 1 to 2 weeks or longer (for example ciprofloxacin 500 mg twice daily, amoxicillin clavulanate 625 mg three times daily or trimethoprim-sulfamethoxazole 160/800 mg twice daily; intravenous ceftriaxone 2 g daily or piperacillin tazobactam 4.5 g every 6 to 8 hours if septic). This reduces perioperative infectious complications.
• Correct anaemia, optimise diabetes control and renal function.
• Decompression with percutaneous nephrostomy or ureteral stent if infected obstruction or sepsis, as a bridge to surgery.
• Definitive management of diffuse disease is nephrectomy (simple, usually open or laparoscopic) with removal of all inflamed tissue, including perinephric fat and adhesions, and removal of any fistula tract.
• The surgery is difficult because of dense adhesions to the peritoneum, great vessels, duodenum, colon or spleen, so complications such as bowel or vascular injury are possible.
• Laparoscopic nephrectomy is feasible in experienced hands, but conversion rates are higher (up to 20 to 30 percent). Drain the retroperitoneum.
• Focal or segmental disease: partial nephrectomy or antibiotics with follow up when the diagnosis is confirmed by biopsy, as segmental disease may resolve with antibiotics and stone removal.
• Bilateral or solitary kidney disease: medical therapy, drainage, stone removal and surgery to preserve renal tissue, with careful follow up.
• Management of the cause: remove stones, treat obstruction and underlying risk factors, and control diabetes.
• Tuberculosis exclusion before surgery; if present, antituberculous therapy for 6 months (isoniazid, rifampicin, pyrazinamide, ethambutol for 2 months, then isoniazid and rifampicin for 4 months).
• Follow up: contralateral kidney function, urine culture, renal function and imaging at 3 and 12 months; recurrence in the remaining kidney is rare.
• Prognosis is excellent after complete surgical removal.