Retroperitoneal Fibrosis with Ureteric Obstruction

Retroperitoneal fibrosis is a fibro inflammatory process that forms a mass around the abdominal aorta and iliac arteries and encases the ureters, causing obstruction. It is also called chronic periaortitis.

The incidence is about 0.1 to 1.3 for every 100 000 people each year, with a peak at 40 to 60 years and a male to female ratio of about 2 to 3 to 1.

Without treatment it progresses to bilateral obstruction and renal failure.

Pathophysiology. About two thirds of cases are idiopathic, and many of these belong to IgG4-related disease. Secondary causes:

• Drugs: methysergide, ergot derived dopamine agonists (cabergoline, pergolide, bromocriptine), and rarely beta blockers, hydralazine and methyldopa.
• Malignancy (lymphoma, sarcoma, carcinoid, metastases), radiotherapy and retroperitoneal surgery.
• Infection (tuberculosis), asbestos exposure and inflammatory aortic aneurysm.

The plaque typically lies in front of the lower lumbar spine, medially pulling the ureters, with relative sparing of the posterior aorta. Ureteric obstruction is functional and structural, and peristalsis is lost without a true intrinsic stricture.

Dull, poorly localised back, flank or abdominal pain, often worse at night and relieved by NSAIDs. Weight loss, malaise and low grade fever. Hypertension, lower limb oedema, deep vein thrombosis, scrotal pain, varicocele or hydrocele from vascular compression. Renal impairment, oliguria or anuria with bilateral obstruction, and obstructive uropathy with infection are urgent presentations.

• ESR and C-reactive protein (often markedly raised), creatinine and eGFR, urinalysis, full blood count.
• Serum IgG and IgG4, antinuclear antibodies, and ANCA. Lactate dehydrogenase and serum markers when lymphoma is suspected.
• Ultrasound for hydronephrosis. CT or MRI of the abdomen and pelvis shows a periaortic soft tissue plaque that encases the vessels, medial deviation of the ureters, and hydronephrosis. Contrast enhancement indicates active inflammation.
• Fluorodeoxyglucose PET-CT for disease activity and to find other sites of IgG4-related disease.
• Biopsy (image directed or laparoscopic) for atypical features: age under 40, a mass extending laterally or reaching the renal hilum or higher, displacement of the aorta from the spine, adenopathy, or poor response to treatment.
• Tuberculosis testing before immunosuppression, and hepatitis B screening. In endemic regions, treat or test for Strongyloides before high dose steroids.

Differential diagnosis.

• Lymphoma and other retroperitoneal malignancy
• Metastatic retroperitoneal disease
• Tuberculosis
• Inflammatory abdominal aortic aneurysm
• IgG4-related disease at other sites
• Erdheim-Chester disease
• Radiation fibrosis

• Relieve obstruction first: double-J ureteric stent or percutaneous nephrostomy. Stents may fail to pass because of extrinsic compression, and nephrostomy is then needed. Change stents every 3 to 6 months while treatment begins.
• Stop the causative drug. Treat tuberculosis before steroids.
• Glucocorticoid induction: prednisolone 0.5 to 1 mg/kg orally once daily (usual 40 to 60 mg) for 4 to 6 weeks. Then reduce by 5 to 10 mg every 2 to 4 weeks to about 10 mg daily, and then reduce slowly to 5 mg daily, continuing for 12 to 24 months in total. Most patients show clinical and radiological response within weeks.
• Steroid cautions: check blood glucose, blood pressure and bone health. Give calcium and vitamin D, a proton pump inhibitor when there is added risk, and bone protection (a bisphosphonate) for courses over 3 months. Give co-trimoxazole 480 mg orally once daily as prophylaxis against Pneumocystis jirovecii when combined with a second immunosuppressant.
• Steroid sparing agents for relapse, intolerance or severe disease:
  • Methotrexate 15 to 25 mg orally once weekly with folic acid 5 mg once weekly (avoid in eGFR under 30).
  • Azathioprine 2 mg/kg orally once daily after testing thiopurine methyltransferase activity.
  • Mycophenolate mofetil 1 g orally twice daily.
  • Rituximab 1 g intravenously on days 1 and 15, used mainly for IgG4-related disease.
  • Tamoxifen 20 mg orally twice daily is used in some centres, with limited evidence.
• Ureterolysis (laparoscopic or open), with intraperitoneal transposition and omental wrapping of the ureters, for refractory disease or failure of medical therapy. Nephrectomy for a non-functioning kidney.
• Malignant causes: treat the underlying cancer.
• Relapse occurs in roughly 20 to 30%, usually during steroid taper or after stopping.

Monitoring. ESR, C-reactive protein, creatinine and blood pressure every 4 weeks initially, then every 3 months. Imaging (CT, MRI or PET-CT) at 3 to 6 months, then yearly. Stent changes as scheduled. Long term follow up for relapse.

Referral and escalation. Refer to urology, and to rheumatology or nephrology for medical treatment. Urgent referral for anuria, acute kidney injury, infected obstruction, or atypical features suggesting malignancy.