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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2022  |  Volume : 33  |  Issue : 1  |  Page : 196-200
Pauci-immune Lupus Nephritis in Antiphospholipid Disease: A Diagnostic Challenge

1 Department of Nephrology, Department of Histopathology and Riyadh, Saudi Arabia
2 Department of Histopathology and Department of Rheumatology, Riyadh, Saudi Arabia
3 Department of Rheumatology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia

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Date of Web Publication16-Jan-2023


Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to immune complex deposition in different organs, especially the kidneys. Pauci-immune lupus nephritis (LN) is a very rare condition. About 40% of SLE cases have a positive antiphospholipid antibody (aPL). So, diagnosing primary antiphospholipid syndrome (APS) in SLE patients is challenging because most symptoms of primary APS can be similar to SLE as described in the American College of Rheumatology/Systemic Lupus Erythematosus International Collaborating Clinics classification criteria for SLE. APS might present as thrombotic microangiopathy (TMA) involving arterioles and glomerular capillaries. We need an adequate renal biopsy to differentiate between lupus and APS nephropathy. A 38-year-old man was diagnosed with biopsy-proven primary APS and LN. Hewas commenced on anticoagulants, pulse steroids, rituximab, and with mycophenolatemofetil as a maintenance therapy in collaboration with the rheumatologist. Here we discuss the occurrence and implications of primary APS and Pauci-immune LN in adults.

How to cite this article:
Alhemyadi SA, Al-Hamidi AA, Asiri S, Al-Swailem R. Pauci-immune Lupus Nephritis in Antiphospholipid Disease: A Diagnostic Challenge. Saudi J Kidney Dis Transpl 2022;33:196-200

How to cite this URL:
Alhemyadi SA, Al-Hamidi AA, Asiri S, Al-Swailem R. Pauci-immune Lupus Nephritis in Antiphospholipid Disease: A Diagnostic Challenge. Saudi J Kidney Dis Transpl [serial online] 2022 [cited 2023 Jan 29];33:196-200. Available from: https://www.sjkdt.org/text.asp?2022/33/1/196/367816

   Introduction Top

Antiphospholipid syndrome (APS) is an orphan and complex autoimmune disorder characterized by the presence of antiphospholipid antibodies in the body, which leads to recurrent thrombosis affecting both arteries and veins.1 In APS, renal involvement represents about 9% of patients.[1],[2]

In 1990, Ostuni et al reported for the first time the presentation of renal artery thrombosis and hypertension in a young patient with antiphospholipid antibodies.[3] Renal lesions could be acute or chronic, with thrombotic microangiopathy (TMA), a finding that may end with fibrosis, glomerular sclerosis, and cortical atrophy.[1]

APS nephropathy can also complicate patients with systemic lupus erythematosus (SLE). In the case of the SLE, the autoantibodies and immune complexes are deposited in glomeruli, and immunofluorescence shows positive staining for immunoglobulin (Ig) A, IgM, C3, and C1q,[1],[2],[4],[5]. Kant and Glueck reported higher glomerular capillary thrombotic lesions in SLE patients with positive antiphospholipid antibody (aPL) compared with patients who were negative.[6] Furthermore, SLE with positive aPL has a poor prognosis.[4],[7]

Pauci-immune glomerulonephritis (GN), also known as an antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, is mainly caused by ANCA, including granulosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. However, renal diseases such as pauciimmune GN may rarely be seen in SLE.[7],[8],[9]

We report this case as serologically active lupus nephritis (LN) but with negative immunofluorescence and with a feature of primary APS. It is an infrequent presentation that must be considered in the differential diagnosis because it carries a poor outcome.

   Case Report Top

A 38-year-old man was known to have hypertension for five years. Finally, he was diagnosed with a primary APS from recurrent episodes of deep venous thrombosis.

Initially, on the first admission, he developed thrombosis of the right leg. Three years later, on the second admission, he developed thrombosis of the left side and was treated accordingly. One year later, on his third admission, the diagnosis of SLE was established based on positive serology and anemia, and he was treated appropriately. However, after two years, his SLE was complicated by developing renal involvement (LN), and he was started on azathioprine, hydroxychloroquine, and prednisolone.

During that time, rivaroxaban was stopped because he had an attack of hemorrhagic stroke. After that, an inferior vena cava filter was inserted. Besides, he complained of bilateral flank pain radiating to the groins associated with frothy urine, shortness of breath, and chest pain confined to the retrosternal area and unrelated to respiration or any activity. It was localized and was associated with a minimal amount of hemoptysis. A fever, jaundice, skin rash or photosensitivity, and arthritis were not documented. There was no orthopnea or paroxysmal nocturnal dyspnea.

Clinical examination revealed that he had no arthritis or mucosal ulceration. His vital signs showed an elevation of blood pressure reading – 171/91 mm Hg, heart rate – 82 beats/min, and respiratory rate – 18 breaths/min, with oxygen saturation of 98% on room air.

His chest examination revealed moderate bilateral crackles but no rhonchi or bronchial breathing. His cardiac analysis also revealed a loud first heart sound, an opening snap with a mid-diastolic rumbling murmur. In addition, he had moderate lower-limb pitting edema with an unremarkable central nervous system and abdominal examination.

Dipstick urine testing revealed 4+ red blood cells and 3+ proteins. The 24-h urine collection revealed that the protein excretion was 3.80 g/day and a urine output of 2.130 mL/24 h. Further investigations showed a hemoglobin level of 9 g/dL, platelet count of 183000/mm3, white blood cell count of 6000/mm3, the international normalizing ratio of 1.2, partial thromboplastin of 98/mm3, sodium level of 136 mmol/L, potassium level of 3.8 mmol/L, with significant impairment of renal function as evidenced by a serum creatinine of 177 umol/L, and urea of 30 mmol/L. The liver function tests were normal.

Immunological investigations revealed moderately positive dsDNA of 534, positive dilute Russell’s viper venom time, high inflammatory markers with an erythrocyte sedimentation rate of 127 mm/h and a Creactive protein level of 123 mg/L. Additionally, antinuclear antibody homogenous titer was of 1/320, hemolytic complements (CH50), anti-extractable nuclear antigen (ENA), c-ANCA and p-ANCA were negative, and complement (C3 and C4) were standard. Immunoglobulins and anti-basement membrane antibodies were normal. Screening for hepatitis B and C were negative. Lupus anticoagulant was negative with a high-titer of anticardiolipin at 50 units (normal 12 units).

Doppler abdominal ultrasound eliminated the possibility of portal thrombosis apart from mild hepatic steatosis. A computed tomography (CT) of the abdomen and pelvis with contrast showed no evidence of bowel ischemia or dilatation. The chest X-ray showed bilateral air space infiltrates, possibly indicating pulmonary edema or alveolar hemorrhage.

Echocardiography (echo) showed an ejection fraction of 60% with severe mitral stenosis. Electrocardiography (ECG) showed sinus rhythm.

Renal biopsy [Figure 1] showed nine glomeruli, three of which showed fibrinoid necrosis, and three showed TMA. There was no evidence of immune complex-mediated GN.
Figure 1: (a) Arrow: Thrombotic microangiopathy involving afferent artery (PAS stain), (b) arrows: Fibrinoid necrosis involving glomerular tuft (H and E), (c) arrow: Thrombotic microangiopathy involving glomerular tuft (trichrome stain), and (d) EM ultrastructural examination shows a lucent expansion of the subendothelial zone (arrows). No electron-dense deposit.

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The patient was diagnosed as a case of active pauci-immune LN with the primary antiphospholipid syndrome based on the clinical findings of malaise, flank pain, proteinuria, hematuria, and recurrent thrombosis with positive aPL and biopsy findings of negative immunofluorescence.

The patient was counseled about the treatment plan and was willing to proceed with it. After that, he was started on pulse steroid therapy with methylprednisolone, 1 g infusion per day for three days, followed by prednisolone, 60 mg oral daily with a plan to be taper down gradually. Additionally, rituximab, 1 g was also given along with mycophenolate mofetil, 1 g orally twice daily as maintenance therapy. In addition, aspirin, 81 mg daily, was added along with heparin infusion ands ubsequently switched to warfarin alone after removing the inferior vena cava filter.

The patient was discharged in stable condition without requiring renal replacement therapy with a serum creatinine level of 215 umol/L. He will be followed upregularly in rheumatology, nephrology, and cardiology clinics with a plan for mitral valve replacement surgery in the future.

The authors obtained all appropriate consent forms from the patient to publish this case report.

   Discussion Top

SLE is a chronic autoimmune disease with multisystem involvement characterized by the deposition of the immune complex in many organs in the body.[1] Renal involvement in SLE can be present in various forms, mostly with immune complex-mediated glomerular disease.[1],[2],[7],[8]

Pauci-immune LN is a rare condition but can be present in ANCA-positive GN.[1],[3],[7],[9],[10]

Diagnosis of APS in SLE is a dilemma because they share many manifestations, such as hemolytic anemia and proteinuria, which overlap in two conditions.

In this case, the patient was diagnosed with primary APS and SLE more than five years back, based on his clinical and serological criteria. He presented with bilateral flank pain, hypertension, significant nephrotic range proteinuria, and microscopic hematuria with an active lupus serology. Hence, a kidney biopsy was done to differentiate between the two diseases, which elicited TMA, fibrinoid necrosis of three glomeruli with no evidence of immune complex GN or crescent formation [Figure 1].

The biopsy findings favor the diagnosis of primary antiphospholipid over LN. They are suggestive that the pathogenesis of pauciimmune LN may be due to factors other than antigen-antibody reaction, which causes the glomerular injury. Furthermore, in this case, the failure of immunofluorescence to reveal full-house glomerular deposits seen in SLE directed us to the diagnosis of APS. The presence of aPL in SLE nephropathy is associated with a worse prognosis because of the possibility of recurrence of TMA even after renal transplant.[1],[2],[6]

This reported case has a unique feature of negative immunofluorescence in LN in a patient diagnosed with primary antiphospholipid disease and negative ANCA titer. There were two reported cases from Saudi Arabia of pauci-immune necrotizing GN; those cases were classified as class III and IV LN with no deposit of immune complex, which might suggest an alternative mechanism of the glomerular injury that is not based on antigen-antibody reaction.[5] In addition, those cases reported pauci-immune lupus necrotizing GN but without APS.

During his last admission, he has an episode of tachycardia with retrosternal chest pain and a mild episode of hemoptysis, together with an X-ray finding raising the suspicion of either alveolar hemorrhage or lupus myocarditis. The anticoagulant was held after the inferior vena cava filter was inserted. The average oxygen saturation, normal cardiac enzymes, ECG, and echo findings of severe mitral stenosis make this suspicion less likely. Moreover, his result was most likely due to acute pulmonary edema since he responded to diuretic therapy. Metoprolol was added to control the heart rate, and he was booked for elective surgery later.

Two weeks after the treatment, the patient’s condition improved. In addition, the inferior vena cava filter was removed, and anticoagulant therapy was resumed with heparin infusion bridged with warfarin. Finally, he was discharged home on warfarin alone with stable renal function (serum creatinine level of 215 umol/L).

We want to draw the attention of the nephrologists about the possibility of the development of pauci-immune LN with the primary APS. Early diagnosis will help the treating physicians start the immunosuppressants and/or plasmapheresis. Hence, it will help recovery and prevent further renal injury and can influence the course of the disease. However, this scenario presents actual diagnostic challenges as the clinical features of SLE and APS are almost similar in these two diseases.

In conclusion, pauci-immune GN with SLE can coexist in a primary APS. Thus the diagnosis is challenging. However, a clear understanding of the pathophysiology of these diseases, timely diagnosis, and early initiation of appropriate therapy are crucial to reducing the morbidity and mortality of the disease.


We want to express our gratitude toward our patient for this kind cooperation and encouragement, which helped us complete this project. Furthermore, we would like to thank Dr. Ebadul Rahman and Dr. Mamoun Elawad, consultant nephrologist, for their supervision and support.

Conflict of interest: None declared.

   References Top

Sinico RA, Cavazzana I, Nuzzo M, et al. Renal involvement in primary antiphospholipid syndrome: Retrospective analysis of 160 patients. Clin J Am SocNephrol 2010;5:1211-7.  Back to cited text no. 1
Schreiber K, Sciascia S, de Groot PG, et al. Antiphospholipid syndrome. Nat Rev Dis Primers 2018;4:17103.  Back to cited text no. 2
Ostuni PA, Lazzarin P, Pengo V, Ruffatti A, Schiavon F, Gambari P. Renal artery thrombosis and hypertension in a 13-year-old girl with antiphospholipid syndrome. Ann Rheum Dis 1990;49:184-7.  Back to cited text no. 3
Bhandari S, Harnden P, Brownjohn AM, Turney JH. Association of anticardiolipin antibodies with intraglomerular thrombi and renal dysfunction in lupus nephritis. QJM 1998;91:401-9.  Back to cited text no. 4
Akhtar M, al-Dalaan A, el-Ramahi KM. Pauciimmune necrotizing lupus nephritis: Report of two cases. Am J Kidney Dis 1994;23:320-5.  Back to cited text no. 5
Glueck HI, Kant KS, Weiss MA, Pollak VE, Miller MA, Coots M. Thrombosis in systemic lupus erythematosus. Relation to the presence of circulating anticoagulants. Arch Intern Med 1985;145:1389-95.  Back to cited text no. 6
Cansu DÜ, Temiz G, Açikalin MF, Korkmaz C. Pauci-immune lupus nephritis: Possibility or co-incidence? Eur J Rheumatol 2017;4:73-5.  Back to cited text no. 7
Anders HJ, Weening JJ. Kidney disease in lupus is not always ‘lupus nephritis’. Arthritis Res Ther 2013;15:108.  Back to cited text no. 8
Meehan SM, Chang A, Khurana A, Baliga R, Kadambi PV, Javaid B. Pauci-immune and immune glomerular lesions in kidney transplants for systemic lupus erythematosus. Clin J Am Soc Nephrol 2008;3:1469-78.  Back to cited text no. 9
Chen M, Kallenberg CG, Zhao MH. ANCAnegative pauci-immune crescentic glomerulonephritis. Nat Rev Nephrol 2009;5:313-8.  Back to cited text no. 10

Correspondence Address:
Salwa A Alhemyadi
Department of Nephrology, Prince Sultan Military Medical City, P. O. Box 7897, Postal code 11159, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.367816

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