study of sirolimus in idiopathic retroperitoneal fibrosis

Conditions: Retroperitoneal Fibrosis

Summary: retroperitoneal fibrosis refers to a group of diseases characterized by hyperplasia of the fibrosclerotic tissues in the retroperitoneal space, which can compress the surrounding ureters and inferior vena cava and cause serious complications such as aortic aneurysm, renal failure, and even death. the lesion is diffuse and difficult to resect. corticosteroid is the first-line medication, but the recurrence rate of the disease is high, especially after dose reduction of corticosteroid. therefore, the combined use of immunosuppressants is very important in preventing disease recurrence and reducing the toxic and side effects of long-term corticosteroid. sirolimus plays dual roles in inhibiting lymphocyte activation and fibroblast proliferation. it is inferred from its mechanism that sirolimus is a good potential treatment option for idiopathic retroperitoneal fibrosis. therefore, we conducted this rct on patients with idiopathic retroperitoneal fibrosis to determine the efficacy and safety of sirolimus.

retroperitoneal fibrosis refers to a group of diseases characterized by hyperplasia of the fibrosclerotic tissues in the retroperitoneal space, which mostly involve the abdominal aorta and iliac artery distal to the kidneys. the hyperplastic tissues can compress the surrounding ureters and inferior vena cava and cause serious complications such as aortic aneurysm, renal failure, and even death. there is no clear boundary between the lesion and its surrounding tissues. the lesion is diffuse and difficult to resect. corticosteroid is the first-line medication, but the recurrence rate of the disease is high, especially after dose reduction of corticosteroid. therefore, the combined use of immunosuppressants is very important in preventing disease recurrence and reducing the toxic and side effects of long-term high- and medium-dose corticosteroid. in recent years, as the immunological characteristics of retroperitoneal fibrosis have gradually been recognized, some rheumatologists and immunologists have attempted to use immunosuppressants commonly used for autoimmune diseases in this population, including biologics. however, high-level evidences of evidence-based medicine such as randomized controlled trials (rcts) were still lacking. sirolimus plays dual roles in inhibiting t lymphocyte activation and fibroblast proliferation. it is inferred from its mechanism that sirolimus is a good potential treatment option for idiopathic retroperitoneal fibrosis. therefore, we conducted this rct on patients with idiopathic retroperitoneal fibrosis to determine the efficacy and safety of sirolimus.

Eligibility criteria:
inclusion criteria: 1. idiopathic retroperitoneal fibrosis diagnosed on ct or mri. for patients with suspected secondary retroperitoneal fibrosis or atypical idiopathic retroperitoneal fibrosis suggested by imaging, idiopathic retroperitoneal fibrosis should be confirmed by puncture biopsy 2. increased esr and crp levels caused by this disease and/or active lesions suggested on imaging exclusion criteria: 1. secondary retroperitoneal fibrosis 2. having used corticosteroid (equivalent to \>10 mg per day of prednisone), immunosuppressant, or biologic within 3 months prior to enrollment 3. having any contraindication of prednisone or sirolimus, or allergy to sirolimus, or having experienced serious adverse reactions from the previous use of any of the above drugs 4. massive proteinuria (24-hour urine protein quantitation ≥3 g), moderate-to-severe anemia (hemoglobin \<90 g/l), agranulocytosis (white blood cell count \<1.5×10\^9/l or neutrophil count \<0.5×10\^9/l), platelet count \<50×10\^9/l, interstitial pneumonia 5. uncontrollable diabetes, hypertension, hyperlipidemia, infection, or heart failure, or other serious complications 6. malignancy 7. pregnancy or need for pregnancy in the near future 8. unable to adhere to follow-up or refuses to provide consent

Keywords: mtor inhibitor sirolimus retroperitoneal fibrosis