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Antiphospholipid antibodies (aPL) are considered to be non-pathogenic in patients with vasculitis. We present five patients with primary vasculitis who had aPL and renal artery stenosis (RAS); one of these patients had coexistent renal pathology due to primary vasculitis, and micro- and macropathology due to renal manifestations of the antiphospholipid syndrome.
A 44 year old white smoker presented with sinusitis, haemoptysis, and arthritis. She was normotensive. A chest x ray demonstrated cavitating lesions. She was cANCA positive and fulfilled the American College of Rheumatology criteria for Wegener’s granulomatosis (WG).1 aPL were detected, although she lacked a history of thromboses or pregnancy morbidity. Her serum C reactive protein level was raised at 100 mg/l. Clinical and serological remission was achieved with intravenous cyclophosphamide followed by maintenance methotrexate and corticosteroid treatment.
After discontinuing corticosteroids, she became hypertensive and her previously normal renal function deteriorated. Her serum creatinine rose to 154 μmol/l and she developed mild proteinuria (0.41 g/24 hours). Her cANCA titre rose to 40 with a rise in erythrocyte sedimentation rate to 28 mm/1st h. She remained aPL positive. Repeat echocardiography demonstrated mild mitral and tricuspid regurgitation, moderate aortic regurgitation with normal left ventricular function. Renal biopsy demonstrated crescentic focal and segmental proliferative glomerulonephritis with features of a thrombotic microangiopathy (figs 1A and B⇓). She received further intravenous cyclophosphamide and corticosteroid, with symptomatic resolution and improvement in serum creatinine (122 μmol/l), but the mild proteinuria persisted.
At follow up, she had persistent hypertension (220/100 mm Hg) despite treatment with three antihypertensive drugs, including an angiotensin converting enzyme inhibitor, proteinuria, and rising serum creatinine; oral cyclophosphamide was started. Her proteinuria increased to 2.14 g/24 hours and her serum creatinine rose to over 200 μmol/l within a few weeks. Magnetic resonance angiography of her renal arteries demonstrated tight ostial stenosis of the right renal artery with post-stenotic dilatation (fig 1C⇑) and a non-atheromatous aorta. After angioplasty (fig 1D⇑) the patient’s renal function improved, with a serum creatinine of 76 μmol/l and 24 hour urinary protein of 1.45 g/24 hours. She was formally anticoagulated with warfarin.
Table 1⇓ includes four other patients with primary vasculitis, aPL, persistent hypertension, and RAS.
Renal disease is not uncommon in WG, Churg-Strauss, and microscopic polyangiitis.2 Untreated it may lead to end stage renal failure. Hypertension seen in vasculitis may be secondary to corticosteroid treatment or renal disease.
Atherosclerosis is the major cause of RAS (>90%), with a minority of cases due to fibromuscular dysplasia.3 Hypertension is a recognised feature of antiphospholipid syndrome. Recently, a high prevalence of RAS (26%) was demonstrated in relatively young hypertensive patients with antiphospholipid syndrome.4 In our cohort, all the stenotic lesions were well defined and distal to the ostia, and the aortae showed no evidence of atherosclerosis.
We believe that RAS seen in our cohort may be associated with aPL. The relatively young age of our patients and the absence of atheromatous aortae on magnetic resonance angiography argues against the atherosclerotic type of RAS seen in elderly patients. A possible mechanism for the development RAS in our cohort is thrombosis, accelerated atherosclerosis, and/or smooth muscle hypertrophy.4
Earlier reports have suggested that the presence of aPL in primary vasculitis is not pathogenic.5,6 There are no reports to date of vasculitis associated with RAS and aPL. However, there have been case reports of aneurysmal dilatation of the renal arteries and RAS in polyarteritis nodosa and Takayasu’s arteritis; none of our cohort had either of these diseases.
In summary, the presence of systemic vasculitis and aPL may not be as benign as previously thought. When faced with patients with primary vasculitis, aPL, and uncontrolled hypertension, the possibility of RAS should be considered.
The authors have no competing interests.