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Retroperitoneal Fibrosis (RPF)

Retroperitoneal fibrosis (RPF) is a rare immune-mediated fibro-inflammatory disease characterized by tissue surrounding the abdominal aorta and iliac arteries that can encase the ureters, IVC, renal vessels, and adjacent retroperitoneal structures.[1][2] For the reconstructive urologist, RPF matters because 60–80% of patients develop ureteral obstruction and ~ 40% have renal function deterioration at diagnosis — making prompt drainage and coordinated medical + surgical management the central reconstructive priorities.[3][4]

The surgical pathway for RPF-related obstruction (stenting / nephrostomy → medical induction → ureterolysis for refractory disease) is covered in detail on the Ureterolysis technique page.

Epidemiology​

  • Estimated incidence 0.1 per 100,000 person-years; prevalence ~ 1.38 per 100,000.[3]
  • Men affected 2–3× more often than women; mean age at presentation 50–60 years.[3][5]
  • No clear ethnic predisposition or familial clustering.[3]

Classification and Etiology​

RPF is broadly divided into idiopathic (> two-thirds of cases) and secondary forms.[1][6]

Idiopathic RPF​

  • May be isolated or part of IgG4-related disease (IgG4-RD). IgG4-related RPF shows greater male predominance, higher serum IgG4 / IgE, elevated eosinophils, and multi-organ involvement vs non-IgG4 idiopathic RPF.[1][7]
  • Often associated with other autoimmune conditions (Hashimoto thyroiditis, psoriasis) and fibro-inflammatory disorders.[8]
  • Multifactorial: genetic susceptibility (notably HLA-DRB1*03), environmental exposures (asbestos, smoking), and immune dysregulation.[8][9]

Secondary RPF Causes​

CategoryExamples
DrugsErgot derivatives (methysergide, ergotamine), dopamine agonists (pergolide), β-blockers, hydralazine, analgesics
MalignanciesDesmoplastic reaction to metastases (prostate, breast, colon) or primary tumors (lymphoma, sarcoma, carcinoid)
InfectionsLocal spread from contiguous foci (tuberculosis)
RadiotherapyFibrosis limited to the radiation field
OtherPrior surgery, pancreatitis

Pathophysiology​

The immunopathogenesis involves complex B- and T-lymphocyte crosstalk, macrophage and fibrocyte chemotaxis, and eosinophil / mast cell recruitment.[1] Key mediators include chemokines (CXCL12, CCL11) and cytokines (IL-6, IL-12, IL-13) that simultaneously orchestrate inflammation and promote fibrosis.[8] The disease was historically thought to result from a local autoimmune reaction to antigens within atherosclerotic aortic plaques, but the systemic features and autoimmune associations suggest a broader immune-mediated process.[3]

Clinical Presentation​

  • Abdominal pain (65%) and low back pain (42%) are the most common symptoms.[5]
  • Systemic symptoms — fatigue, weight loss, malaise.[6]
  • Less common — constipation, testicular pain, lower-extremity claudication.[6]
  • Ureteral obstruction in 60–80%, often causing acute or chronic kidney injury.[6][8]
  • Other complications — caval occlusion, deep vein thrombosis, renal artery / vein stenosis, renal atrophy.[1][2]
  • Elevated acute-phase reactants (ESR, CRP) in ~ 75%.[5]
  • Renal function deterioration in ~ 40% at diagnosis.[5]

Diagnosis​

There are no standardized diagnostic criteria. Diagnosis combines clinical, laboratory, and imaging findings.[3]

Laboratory​

  • Elevated ESR and CRP (supportive but nonspecific).
  • Serum IgG4 levels (elevated in IgG4-related RPF).[7]
  • Renal function assessment (creatinine, eGFR).

Imaging​

  • CT — Most commonly used (~ 92%) and the imaging modality of choice along with MRI. RPF typically appears as a homogeneous soft-tissue plaque, isodense with muscle, surrounding the infrarenal aorta and iliac arteries, often enveloping the ureters and IVC. Contrast enhancement is variable depending on disease stage.[5][10][3]
  • MRI — Avoids nephrotoxic contrast and provides better soft-tissue definition, particularly with fat-saturation sequences.[3]
  • FDG-PET/CT — Increasingly used for disease staging, monitoring treatment response, and detecting relapse. Superior to CT alone in detecting disease progression; metabolic active volume (MAV) at baseline may predict progression.[11][12]
  • Key imaging distinction — Idiopathic RPF typically does not displace the aorta anteriorly and causes medial ureteral deviation, whereas malignant RPF tends to displace the aorta anteriorly and ureters laterally.[3][13]

Biopsy​

Retroperitoneal biopsy is reserved for atypical cases — atypical location (pelvic, peripancreatic), suspicion of malignancy, or when clinical / laboratory findings are inconclusive.[3][14] Laparoscopic or open biopsy is preferred over needle biopsy for diagnostic accuracy.[15] Histology shows abundant fibrosis with mononuclear inflammatory infiltrate (lymphocytes, plasma cells, macrophages).[6]

Treatment​

Treatment aims to relieve ureteral obstruction and induce disease regression. Medical therapy is the cornerstone; surgical drainage / ureterolysis address mechanical obstruction.[1][14]

Surgical Drainage and Ureterolysis​

Surgical pathway covered in full on the Ureterolysis technique page. Briefly:

  • Ureteral stenting or PCN is the first priority for hydronephrosis — relieve obstruction and preserve renal function.[15][16]
  • Surgical ureterolysis (open / laparoscopic / robotic, with omental wrapping) for refractory cases.[15][14]
  • Medical management with temporary stenting alone achieves resolution in ~ 69% of patients (median stent duration 16 months); ~ 15% ultimately require ureterolysis.[17][18]

Medical Therapy​

  • Glucocorticoids remain first-line — induce rapid symptom remission, reduction in acute-phase reactants, and often mass shrinkage. Typical induction: prednisone 0.5–1 mg/kg/day with gradual taper over 6–9 months.[6][8][12]
  • Prednisone vs tamoxifen — The only RCT in RPF (Vaglio 2011) showed prednisone was effective; tamoxifen (previously used for antifibrotic properties) was less effective as monotherapy.[6]
  • Combination therapy (glucocorticoids + immunosuppressants) may offer advantages over monotherapy — meta-analysis showed higher response rate (98.9% vs 85.1%) and lower long-term relapse.[19] Commonly used agents:
    • Mycophenolate mofetil — favorable efficacy and safety; 89% had ≥ 25% mass reduction; only 7% relapsed in one series.[6]
    • Methotrexate and azathioprine — steroid-sparing agents.[8]
    • Cyclophosphamide — generally avoided due to toxicity.[6]
  • Rituximab (anti-CD20 B-cell depletion) — increasingly used for refractory or relapsing disease. In a retrospective series (n = 26), all 19 with pain improved symptomatically, and 88% had radiologic improvement; 73% received rituximab without additional glucocorticoids. Severe infections in 12%.[20]

Secondary RPF​

  • Drug-induced — withdrawal of the offending agent often leads to resolution; steroids may still be needed.[3]
  • Infection-related — antimicrobial therapy; steroids generally contraindicated.[3]
  • Malignancy-related — chemotherapy / radiotherapy directed at the underlying neoplasm.[3]

Monitoring and Follow-Up​

Serial assessment of symptoms, ESR/CRP, renal function, and imaging.[3] CT and MRI track mass size; FDG-PET is superior for assessing metabolic activity and predicting progression — residual masses with absent FDG uptake likely represent inactive sclerotic tissue not requiring further treatment.[11][3] Positive FDG-PET at end of treatment independently predicts relapse (HR 3.47).[12]

Prognosis and Relapse​

With appropriate treatment the overall prognosis is good, with patient survival 95% at 5 years, 84% at 10 years, 68% at 15 years.[21] However, relapse is a major challenge:

  • Up to 38–50% of patients experience at least one relapse.[8][21]
  • Cumulative relapse incidence: 21% at 5 years, 41% at 10 years, 48% at 15 years.[21]

Predictors of relapse: male sex, antinuclear-antibody positivity, higher baseline ESR, shorter glucocorticoid courses, smoking, atypical localization, thoracic vessel involvement, and persistent FDG-PET activity after treatment.[21][12][22]

Prompt relief of hydronephrosis is critical to prevent irreversible renal atrophy — the reconstructive surgeon's central responsibility in the multidisciplinary RPF team.[22]

See Also​

References​

1. Vaglio A, Peyronel F, Bajema IM, Pegoraro F. "Retroperitoneal Fibrosis." Lancet. 2026. doi:10.1016/S0140-6736(26)00037-1

2. Vaglio A, Maritati F. "Idiopathic Retroperitoneal Fibrosis." Journal of the American Society of Nephrology. 2016;27(7):1880–1889. doi:10.1681/ASN.2015101110

3. Vaglio A, Salvarani C, Buzio C. "Retroperitoneal Fibrosis." Lancet. 2006;367(9506):241–251. doi:10.1016/S0140-6736(06)68035-5

4. Raglianti V, Rossi GM, Vaglio A. "Idiopathic Retroperitoneal Fibrosis: An Update for Nephrologists." Nephrology, Dialysis, Transplantation. 2021;36(10):1773–1781. doi:10.1093/ndt/gfaa083

5. Loricera J, Secada-Gómez C, Martín-Gutiérrez A, Blanco R, González-Vela C. "Clinical Features, Diagnosis, and Management of Retroperitoneal Fibrosis in a University Referral Hospital and Literature Review." Internal and Emergency Medicine. 2026. doi:10.1007/s11739-026-04298-x

6. Vaglio A, Palmisano A, Alberici F, et al. "Prednisone Versus Tamoxifen in Patients With Idiopathic Retroperitoneal Fibrosis: An Open-Label Randomised Controlled Trial." Lancet. 2011;378(9788):338–346. doi:10.1016/S0140-6736(11)60934-3

7. Wang K, Wang Z, Zeng Q, et al. "Clinical Characteristics of IgG4-related Retroperitoneal Fibrosis Versus Idiopathic Retroperitoneal Fibrosis." PLoS One. 2021;16(2):e0245601. doi:10.1371/journal.pone.0245601

8. Raglianti V, Rossi GM, Vaglio A. "Idiopathic Retroperitoneal Fibrosis: An Update for Nephrologists." Nephrology, Dialysis, Transplantation. 2021;36(10):1773–1781. doi:10.1093/ndt/gfaa083

9. Uibu T, Oksa P, Auvinen A, et al. "Asbestos Exposure as a Risk Factor for Retroperitoneal Fibrosis." Lancet. 2004;363(9419):1422–1426. doi:10.1016/S0140-6736(04)16100-X

10. Caiafa RO, Vinuesa AS, Izquierdo RS, et al. "Retroperitoneal Fibrosis: Role of Imaging in Diagnosis and Follow-Up." RadioGraphics. 2013;33(2):535–552. doi:10.1148/rg.332125085

11. Bayerl C, Kaufmann J, Metzger G, et al. "[18F]FDG PET/CT for Treatment Monitoring and Prediction of Progression in Retroperitoneal Fibrosis." European Journal of Nuclear Medicine and Molecular Imaging. 2025. doi:10.1007/s00259-025-07479-6

12. Bond M, Bettiol A, Buttini EA, et al. "Predictors of Remission and Relapse in Retroperitoneal Fibrosis." Journal of Internal Medicine. 2025. doi:10.1111/joim.70017

13. Cohan RH, Shampain KL, Francis IR, et al. "Imaging Appearance of Fibrosing Diseases of the Retroperitoneum: Can a Definitive Diagnosis Be Made?" Abdominal Radiology. 2018;43(5):1204–1214. doi:10.1007/s00261-017-1282-5

14. Fenaroli P, Maritati F, Vaglio A. "Into Clinical Practice: Diagnosis and Therapy of Retroperitoneal Fibrosis." Current Rheumatology Reports. 2021;23(3):18. doi:10.1007/s11926-020-00966-9

15. Tanaka T, Masumori N. "Current Approach to Diagnosis and Management of Retroperitoneal Fibrosis." International Journal of Urology. 2020;27(5):387–394. doi:10.1111/iju.14218

16. Zhang W, Stone JH. "Management of IgG4-related Disease." The Lancet Rheumatology. 2019;1(1):e55–e65. doi:10.1016/S2665-9913(19)30017-7

17. Santiago J, Swartz R, Marder W, et al. "Including Medical Management in the Urologic Approach to Idiopathic Retroperitoneal Fibrosis." Urology. 2021;152:167–172. doi:10.1016/j.urology.2021.03.002

18. Mertens S, Zeegers AG, Wertheimer PA, Hendriksz TR, van Bommel EF. "Efficacy and Complications of Urinary Drainage Procedures in Idiopathic Retroperitoneal Fibrosis Complicated by Extrinsic Ureteral Obstruction." International Journal of Urology. 2014;21(3):283–288. doi:10.1111/iju.12234

19. Zheng T, Wu Z, Ding Y, et al. "Glucocorticoid Monotherapy vs. Immunosuppressant-Combined Therapy in Retroperitoneal Fibrosis: Clinical Evidence and Mechanistic Insights From Bioinformatics." European Journal of Medical Research. 2026. doi:10.1186/s40001-026-03856-5

20. Wallwork R, Wallace Z, Perugino C, Sharma A, Stone JH. "Rituximab for Idiopathic and IgG4-related Retroperitoneal Fibrosis." Medicine. 2018;97(42):e12631. doi:10.1097/MD.0000000000012631

21. Raffiotta F, da Silva Escoli R, Quaglini S, et al. "Idiopathic Retroperitoneal Fibrosis: Long-Term Risk and Predictors of Relapse." American Journal of Kidney Diseases. 2019;74(6):742–750. doi:10.1053/j.ajkd.2019.04.020

22. Zhao J, Li J, Zhang Z. "Long-Term Outcomes and Predictors of a Large Cohort of Idiopathic Retroperitoneal Fibrosis Patients: A Retrospective Study." Scandinavian Journal of Rheumatology. 2019;48(3):239–245. doi:10.1080/03009742.2018.1497700