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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 4  |  Page : 860-864
Primary Anti-phospholipid Antibody Syndrome Presenting as Acute Nephritic Syndrome

Department of Nephrology, Lourdes Hospital, Kochi, Kerala, India

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Date of Submission25-Aug-2019
Date of Decision01-Nov-2019
Date of Acceptance04-Nov-2019
Date of Web Publication15-Aug-2020


Primary anti-phospholipid antibody (APLA) syndrome in males most commonly presents with clinical manifestations of venous thrombosis, thrombocytopenia, and pulmonary embolism. Although most present with acute symptoms following arterial thrombosis, diagnosis following evaluation for elevated renal function tests and hypertension is less common. We report here a case of a 22-year-old man who presented with acute nephritic syndrome following an acute febrile illness. He was detected to have altered renal function tests with serum creatinine of 1.6 mg/dL (141.4 μmol/L), microscopic hematuria, and proteinuria along with hypertension. His 24-h urine protein was 1700 g/day. He was planned for a kidney biopsy. Subsequent evaluations revealed an isolated elevation of activated partial thromboplastin time. Further evaluation revealed positive APLA syndrome. He underwent kidney biopsy later which showed mesangial hypercellularity with no involvement of the renal parenchymal vasculature. The reported case is an unusual presentation of primary APLA syndrome with acute nephritic syndrome.

How to cite this article:
Upendran B, Kumar VR, Thomas P. Primary Anti-phospholipid Antibody Syndrome Presenting as Acute Nephritic Syndrome. Saudi J Kidney Dis Transpl 2020;31:860-4

How to cite this URL:
Upendran B, Kumar VR, Thomas P. Primary Anti-phospholipid Antibody Syndrome Presenting as Acute Nephritic Syndrome. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2023 Jan 27];31:860-4. Available from: https://www.sjkdt.org/text.asp?2020/31/4/860/292322

   Introduction Top

The anti-phospholipid antibody (APLA) syndrome is a systemic autoimmune disease defined by thrombotic or obstetric events that occur in patients with persistent APLAs.[1] Patients with catastrophic APLA syndrome present with thrombosis involving multiple organs.[2]

The major nonthrombotic manifestations of APLA positivity includes valvular heart disease, livedo, thrombocytopenia, hemolytic anemia, and cognitive dysfunction. The APLA syndrome is often associated with other systemic autoimmune diseases such as systemic lupus erythematosus (SLE); however, it commonly occurs without other autoimmune manifestations (primary anti-phospholipid syndrome). Although criteria for the classification of the APLA syndrome have been proposed[3] the definition of clinically significant APLA positivity is not well established, and thrombosis is generally multifactorial.

Renal involvement as an initial presentation of APLA commonly affects the vascular component with microvascular thrombosis and thrombotic microangiopathy (TMA). It usually follows vascular thrombosis or pregnancy loss. Acute nephritic syndrome as the initial presentation is uncommon in primary APLA. Positivity for all three antibodies, anti- cardiolipin antibody, lupus anticoagulant, and anti beta 2 glycoprotein antibodies with primary renal involvement is rare.

We report here the case of a 22-year-old male who was initially diagnosed with enteric fever with subsequent elevated renal function tests and hypertension, which required multiple hospital admissions. Further work-up revealed a diagnosis of primary APLA syndrome.

   Case Report Top

Informed consent was obtained from the patient before publishing the case.

A 22-year-old man with a history of multiple joint pains presented with a one-week history of high-grade fever, loose stools and vomiting and was referred to this hospital for elevated renal function tests and accelerated hypertension. On presentation, the patient had severe left sided flank and abdominal pain. On examination, the temperature was 40°C, blood pressure was 180/100 mm Hg, pulse rate was 89/min, abdominal tenderness was present in the left iliac fossa and flank area; review of other systems was normal.

Laboratory investigations showed an elevated creatinine of 1.6 mg/dL (141.4 μmol/L). The patient continued to have elevated blood pressure despite starting clonidine 100 μg half, twice a day. At this time, as part of routine investigations, a Widal test was performed, and it was positive. Creatinine levels had risen to 2.6 mg/dL (229.84 μmol/L). Ultrasono- graphy of the abdomen was performed and showed borderline splenomegaly and minimal increased cortical echo-patterns of both kidneys.

Enteric fever was diagnosed, and after appropriate management with intravenous antibiotics and other supportive measures, patient was stabilized and sent home on clonidine 100 pg half to be taken twice daily and amlodipine 5 mg to be taken twice daily for his blood pressure control. He was asked to come in weekly for follow-up and plan future evaluation for elevated renal function tests.

After a month and weekly follow-ups, the patient’s creatinine levels remained at 1.9 mg/dL (167.96 μmol/L), and he was planned for a renal biopsy. Following admission and pre-procedure evaluations, the patient was found to have an isolated elevation of activated partial thromboplastin time (72 s), and renal biopsy was postponed to a later date.

Following repeated testing, the aPTT (60 s) was still elevated and the possibility of APLA syndrome was considered at this time. Shortly, patient was taken up for renal biopsy considering no history of easy bruising was present. The renal biopsy result showed mesangial proliferative glomerulopathy with nonspecific immunofluorescence and mild global glome- rulosclerosis with hypertensive vascular changes [Figure 1]. Hematology evaluation with a peripheral blood smear showed hypo- chromic anemia with anisopoikilocytosis.
Figure 1: Renal biopsy showing mesangioproliferative glomerulopathy with no full house pattern.

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The patient was re-admitted for left flank and abdominal pain after one month (not on regular follow-up due to financial issues). On examination, severe tenderness was elicited over left iliac fossa. Creatinine levels were at 1.6 mg/dL (141.4 μmol/L). The normal values range between 60 and 110 μmol/L. A computerized tomography (CT) of abdomen and pelvis was performed at this time, which showed an increase in the size of the left kidney with tiny inter-polar calculus, mild left hydronephrosis with dilatation of proximal and mid ureter. There was a long segment concentric thickening of the left ureteric wall. The pelvic ureter was not well visualized [Figure 2].
Figure 2: Computerized tomography of abdomen showing filling defect in the abdominal aorta.

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Urology evaluation with a CT urography showed the following: the right kidney showed a minimal smooth reduction in size with normal perfusion and contrast excretion. No dilatation of the pelvicalyceal system or ureter was seen. There was no renal or ureteric calculus. A single artery was noted on the right side with irregular thrombus involving the right lateral and anterior wall of aorta at the level involving renal ostium. The left kidney showed normal size, shape, and position with normal perfusion and contrast excretion. Mild dilatation of the pelvi-calyceal system was noted with thickening of the pelvic and upper ureteric wall. Aorta showed a normal caliber. Irregular thrombus involving the anterior and right lateral walls of abdo-minal aorta was noted from the level above the coeliac axis down to the level of the right renal artery. Thrombus involving the proximal segment of the superior mesenteric vein was noted with complete occlusion of the lumen. Right renal ostium was also involved. Multiple collaterals were noted in the mesentery between superior and inferior mesenteric arteries with dilated inferior mesenteric artery.

Following this, the patient was tested for lupus anti-coagulant and other auto-immune antibodies. IgM APA, IgM beta 2 glycoprotein antibody (32 RU/mL) and IgM anti-cardiolipin antibody (28.2 RU/mL) were positive. Homocysteine levels were also elevated in this patient. He was started on low dose aspirin and was counseled regarding the nature of the disease and the importance of adhering to medication.

   Discussion Top

The APLA syndrome is a pro-thrombotic disorder that can affect both the venous and arterial circulations. The deep veins of the lower limbs and the cerebral arterial circulation are the most common sites of venous and arterial thrombosis, respectively. However, any tissue or organ vascular bed can be affected. Catastrophic APLA syndrome, which is characterized by clots in multiple small vascular beds and leads to multi-organ failure with high mortality, develops in a small subgroup of patients. Given the low background risk of thrombosis in the general population, the absolute risk of a first thrombosis in antiphospholipid-antibody–positive patients who do not have other risk factors is probably <1% per year.[4],[5] As in the general population, arterial and venous thrombotic events in antiphospholipid-antibody–positive patients are often multicausal.[6],[7] A substantial proportion of patients with the antiphospho- lipid syndrome who present with thrombosis have one other thrombotic risk factor at the time of the event.[8]

Renal involvement occurs late in course of illness. In the vascular compartment, the renal parenchyma is the primary site of the renal involvement. Mesangial proliferation with C3 deposits is documented to occur in APLA nephropathy. The other kidney biopsy findings in patients with APLA nephropathy includes acute TMA lesions and chronic intra-renal vascular lesions such as inter-lobular fibrous intimal hyperplasia, arterial and arteriolar recanalizing thrombosis, fibrous arterial occlu- sion, and focal cortical atrophy. These findings were absent in our patient. Initial presentation as acute nephritic syndrome is rare without renal vascular involvement in primary APLA syndrome. The case is unique since acute nephritic syndrome was the initial syndrome and renal histology showed mesangial prolife- rative GN with minimal immune deposits. Vascular involvement occurred late in the course of illness in this patient. He had primary APLA with positivity for all the three antibodies of APLA syndrome.

Renal biopsy is one of the gold standards to arrive at a diagnosis, and the risk of post- biopsy complications in APLA should be well understood. Major bleeding complications were significantly more common in those with co-existing APLAS and/or anti-phospholipid antibodies (aPL). LAC, presence of TMA on renal biopsy, older age at the time of the biopsy (age > 40 years), and elevated serum creatinine (>400 μmol/L) were independent risk factors for increased risk of bleeding. TMA and severe fibrous intimal hyperplasia on renal biopsy were significantly more prevalent in those who developed severe bleeding complications.[9]

Nephropathy associated with aPL is defined as histologically proven TMA and/or other small vessel vasculopathies in the kidney in the presence of aPL which should be distinguished from lupus nephritis. Although the precise prevalence of aPL associated nephro- pathy in patients with APS or aPL carriers remains to be determined, a retrospective study using kidney biopsy specimens from 151 patients with SLE revealed a frequent and exclusive occurrence of renal microangiopathy in patients with aPL compared with those without aPL (39.5% vs. 4.3%). Of note, aPL associated nephropathy is related not only to a poor renal outcome but also to an increased risk of thrombosis particularly in the non-APS aPL carriers, with a clinical evolution to APS in 35% of patients with renal microangiopathy during a mean follow-up period of seven years, compared with that in only 9% of patients without renal microangiopathy. Complement activation may play a role in the formation of aPL associated nephropathy, supported by a strong relationship between glomerular microthrombosis and C4d deposition in SLE patients, particularly in those with aPL.[10]

This case study has relevance in the fact that this young man had a presentation of acute nephritic syndrome, which was diagnosed incidentally during an attack of enteric fever and further evaluation suggested a diagnosis of primary APLA. This case prompts us to think about the diagnosis of APLA as a possibility in young patients with acute nephritic syndrome and warrants an early evaluation if possible and prevent catastrophic events.

Treatment approaches in patients with APS nephropathy lesions may include the use of heparin based on its role on complement activation pathway inhibition or the use of intravenous immunoglobulin and/or plasma exchange. Targeted therapies may also be considered based on potential APS nephro- pathy including pathogenetic mechanisms such as B-cell directed therapies, complement inhibition, tissue factor inhibition, mTOR pathway inhibition, or anti-interferon antibodies, but prospective multi-center studies are needed to address their role.[10]

   Conclusion Top

The anti-phospholipid syndrome has a broad spectrum of thrombotic and nonthrombotic clinical manifestations. The diagnosis requires positive APLA tests; however, not every positive test has diagnostic importance. Thus, both misdiagnosis due to under-recognition of signs or symptoms and over-diagnosis due to over interpretation of APLA tests are common. In addition, renal manifestations such as acute nephritic syndrome warrants a detailed evaluation for early diagnosis of primary APLA. Although antithrombotic medications are still the cornerstone of treatment, advances in our understanding of the mechanisms by which APLAs cause disease have revealed additional targets that may lead to immunomodulatory treatment options.

Conflict of interest: None declared.

   References Top

Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite anti- phospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306.  Back to cited text no. 1
Asherson RA, Cervera R, de Groot PG, et al. Catastrophic antiphospholipid syndrome: International consensus statement on classification criteria and treatment guidelines. Lupus 2003;12:530-4.  Back to cited text no. 2
Zuily S, Barbhaiya M, Costenbader K, Erkan D. 15th International congress on antiphospho- lipid antibodies task force on antiphospholipid syndrome classification report. In: Erkan D, Lockshin MD, editors. Antiphospholipid Syndrome: Current Research High-lights and Clinical Insights. New York: Springer; 2017. p. 279-90.  Back to cited text no. 3
Otomo K, Atsumi T, Amengual O, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum 2012;64:504-12.  Back to cited text no. 4
Sciascia S, Cuadrado MJ, Sanna G, et al. Thrombotic risk assessment in systemic lupus erythematosus: Validation of the global anti- phospholipid syndrome score in a prospective cohort. Arthritis Care Res (Hoboken) 2014;66: 1915-20.  Back to cited text no. 5
Rosendaal FR. Thrombosis in the young: Epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost 1997; 78:1-6.  Back to cited text no. 6
Vaarala O, Mānttāri M, Manninen V, et al. Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation 1995;91:23-7.  Back to cited text no. 7
Erkan D, Yazici Y, Peterson MG, Sammaritano L, Lockshin MD. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphos-pholipid syndrome. Rheumatology (Oxford) 2002;41:924-9.  Back to cited text no. 8
Jordan N, Chaib A, Sangle S, et al. Association of thrombotic microangiopathy and intimal hyperplasia with bleeding post-renal biopsy in antiphospholipid antibody-positive patients. Arthritis Care Res (Hoboken) 2014;66:725-31.  Back to cited text no. 9
Tektonidou MG. Antiphospholipid Syndrome Nephropathy: From Pathogenesis to Treatment. Front Immunol 2018;9:1181.  Back to cited text no. 10

Correspondence Address:
Varadha Retna Kumar
Department of Nephrology, Lourdes Hospital, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.292322

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