Advancements in Medical and Surgical Treatments of Takayasu Arteritis-Induced Renal Arteritis: A Systematic Review

Takayasu arteritis (TA) is a rare, chronic, granulomatous, large-vessel vasculitis that predominantly affects young females, particularly those under 40 years of age. It is more prevalent in Asian countries, with an incidence of 1 to 2 cases per million per year and an estimated prevalence of 12.9 to 40 cases per million. TA primarily involves the aorta and its major branches, leading to stenosis, occlusion, or aneurysm formation. Among the complications of TA, Takayasu arteritis-induced renal arteritis (TARA) is a significant contributor to poor prognosis and early mortality. TARA can progress to Takayasu arteritis-induced renal artery stenosis (TARAS), which may result in severe complications such as malignant hypertension, cardiac-cerebral vascular disease, and ischemic nephropathy. This systematic review aims to provide a comprehensive overview of the advancements in medical and surgical treatments for TARA, based on a thorough analysis of the available literature.

Introduction

TA is characterized by inflammation of the large vessels, particularly the aorta and its major branches. The disease is classified into five types based on the anatomical involvement of the vessels, with types III–V involving the renal arteries. TARA, which affects 38.0% to 76.2% of TA patients in China, is an inflammatory process mediated by immune dysfunction, leading to structural lesions in the renal artery wall and hemodynamic dysfunction. This dysfunction activates the renin-angiotensin-aldosterone system (RAAS), causing hypertension and renal ischemia. Persistent inflammation in TARA can progress to TARAS, characterized by significant luminal stenosis or occlusion, further exacerbating renal dysfunction and systemic complications.

The management of TARA is complex and requires a multidisciplinary approach involving rheumatologists, vascular surgeons, nephrologists, and other specialists. This review systematically examines the medical and surgical treatments for TARA, highlighting the advancements in therapeutic strategies and their clinical outcomes.

Medical Treatments for TARA

Medical treatment for TARA aims to induce and maintain disease remission, control inflammation, and prevent complications. The cornerstone of medical therapy includes glucocorticoids (GC), conventional synthetic disease-modifying anti-rheumatic drugs (cDMARDs), and biological disease-modifying anti-rheumatic drugs (bDMARDs).

Glucocorticoids (GC)

GCs are the first-line treatment for inducing remission in TA and TARA. Prednisone is commonly used at an initial dose of 0.5 to 1.0 mg/kg per day for 4 to 8 weeks, followed by a gradual taper to a maintenance dose of 5 to 10 mg per day. However, only 20% of TA patients achieve remission with GC monotherapy, and 80% experience disease progression or recurrence, necessitating the addition of immunosuppressive agents. Long-term GC use is associated with adverse effects, including osteoporosis, diabetes, and increased infection risk.

Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (cDMARDs)

cDMARDs are used in combination with GC to enhance remission rates and reduce GC dependency. Methotrexate (MTX) is a commonly used cDMARD, with clinical remission rates of 75% to 81% and sustained remission rates of 50%. However, MTX is associated with a recurrence rate of 54% and radiological progression in 38% of patients. Leflunomide (LEF) and mycophenolate mofetil (MMF) are alternative cDMARDs, with remission rates of 80% and 75% to 90%, respectively. Cyclophosphamide (CTX) is reserved for severe cases, with remission rates of 82.1% to 100%, but it carries risks of serious adverse effects, including infection and hemorrhagic cystitis.

Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs)

bDMARDs are recommended for refractory TARA patients who fail to respond to GC and cDMARDs. Tocilizumab (TCZ), an interleukin-6 receptor inhibitor, has shown remission rates of 64% to 100% in refractory TA patients, with significant GC tapering. Tumor necrosis factor-alpha inhibitors (TNFi), such as infliximab, have remission rates of 74% to 93%, but with a high relapse rate of 33% to 62%. Rituximab, a B-cell depleting agent, has shown efficacy in small case series, while abatacept, a CTLA-4 inhibitor, did not demonstrate significant benefits in a randomized trial.

Surgical Treatments for TARA

Surgical interventions are indicated for TARA patients with severe vascular lesions, such as significant stenosis or occlusion, that do not respond to medical therapy. The primary surgical options include endovascular interventions, such as percutaneous transluminal angioplasty (PTA) and stenting, and open surgical procedures, such as aortic-renal artery bypass and kidney transplantation.

Endovascular Interventions

PTA is the first-choice surgical procedure for TARAS, with a technical success rate of 91.6%. PTA has shown a hypertension cure rate of 49%, an improvement rate of 43%, a restenosis rate of 17%, and a 5-year patency rate of 91%. Stenting is considered for ostial and long lesions, with a hypertension improvement rate of 41%, a restenosis rate of 48%, a 1-year patency rate of 73%, and a 5-year patency rate of 35%. However, stenting is associated with a higher risk of restenosis compared to PTA.

Open Surgery

Open surgical procedures, such as aortic-renal artery bypass, have shown a hypertension improvement rate of 57%, a restenosis rate of 27.6%, a 1-year patency rate of 92.7%, and a 5-year patency rate of 81.5%. Open surgery is associated with a 10-year cumulative survival rate of 73.5%, but it carries risks of peri-operative complications, including infection, hemorrhage, and acute thrombosis. Long-term complications include renal artery restenosis, chronic thrombosis, and stroke.

Discussion

The management of TARA requires a comprehensive and sequential approach, combining medical and surgical treatments. Medical therapy aims to control inflammation and induce remission, while surgical interventions address severe vascular lesions and complications. A multidisciplinary team (MDT) approach is essential for optimizing patient outcomes, particularly in cases with multiple organ involvement or severe complications.

Medical Treatment Strategies

For active TARA, medical therapy is the first-line treatment. GC combined with cDMARDs is the standard induction therapy, with MTX, LEF, or MMF preferred for patients without severe complications. CTX is reserved for severe cases, while bDMARDs, such as TCZ and TNFi, are used for refractory patients. Maintenance therapy involves gradual tapering of GC and cDMARDs to prevent disease relapse.

Surgical Treatment Strategies

Surgical interventions are indicated for TARA patients with significant stenosis or occlusion that do not respond to medical therapy. PTA is the preferred endovascular intervention, while stenting is considered for specific lesion types. Open surgery, such as aortic-renal artery bypass, is reserved for complex cases with favorable long-term outcomes. It is crucial to ensure disease activity is controlled before surgical intervention to reduce the risk of complications.

Limitations and Future Directions

The current evidence on TARA treatment is limited by the rarity of the disease, the lack of randomized controlled trials, and the heterogeneity of treatment protocols. Future research should focus on developing standardized guidelines for TARA management, evaluating the long-term efficacy and safety of medical and surgical treatments, and identifying biomarkers for disease activity and treatment response.

Conclusions

TARA is a severe complication of TA that requires a comprehensive and multidisciplinary approach to management. Medical therapy, including GC, cDMARDs, and bDMARDs, is essential for inducing and maintaining disease remission. Surgical interventions, such as PTA and open surgery, are effective for addressing severe vascular lesions and improving long-term outcomes. The integration of medical and surgical treatments, along with a collaborative MDT approach, is crucial for optimizing patient care and improving prognosis in TARA.

doi.org/10.1097/CM9.0000000000000704

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