Antiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis

doi:10.1053/j.ajkd.2003.09.011

American Journal of Kidney Diseases

Volume 43, Issue 1, January 2004, Pages 28-36

https://doi.org/10.1053/j.ajkd.2003.09.011 Get rights and content

Abstract

Background: Previous studies have documented the high frequency of thrombosis and fetal loss in patients with lupus nephritis and antiphospholipid (aPL) antibodies, but there is little information on the impact of aPL antibodies on the outcome of lupus nephritis. The aims of this study are to evaluate the prevalence of aPL antibodies in patients with lupus nephritis and assess their prognostic value for thrombosis and pregnancy morbidity and impact on long-term renal outcome. Methods: One hundred eleven patients with lupus nephritis followed up for a mean of 173 ± 100 months were tested regularly for immunoglobulin G (IgG) and IgM anticardiolipin antibodies and lupus anticoagulant. Results: The overall prevalence of aPL antibodies was 26%. In follow-up, 79% of aPL antibody-positive patients experienced thrombotic events and/or fetal losses, and aPL antibodies were associated significantly with arterial or venous thrombosis (P = 0.00001), pregnancy morbidity (P = 0.045), thrombocytopenia (P = 0.0015), and persistent arterial hypertension (P = 0.028). aPL antibodies were significantly more frequent in patients with biopsy-proven membranous lupus nephritis (P = 0.01). A strong association between aPL antibodies and the development of chronic renal insufficiency in the long-term outcome also was found (P = 0.01). With multivariate analysis, aPL antibody positivity (P = 0.02), high plasma creatinine level at presentation (P = 0.01), and chronicity index (P = 0.00004) were independent predictors of chronic renal function deterioration. Conclusion: Detection of aPL antibodies in patients with lupus nephritis is useful not only to identify patients at risk for vascular and obstetric manifestations, but also for their potential deleterious impact on renal outcome.

Section snippets

Patients

Between January 1990 and June 2002, we performed a prospective study on aPL antibodies in consecutive patients with lupus nephritis seen in our renal unit. At the beginning of the study, 64 patients had already been tested for aPL antibodies and followed up for a median of 73.5 months. An additional 47 patients were enrolled during the study period. In all patients, basal measurement of aPL antibodies (time 0) was made by month 6 after the diagnosis of lupus nephritis. LA titer was determined

Patient clinical and biochemical characteristics at diagnosis of lupus nephritis

Of 111 patients, 101 patients were women and 10 were men, mean age was 28.5 ± 10.4 years (median, 27 years; range, 15 to 63 years), and 39 patients had renal insufficiency (mean plasma creatinine, 2.6 ± 1.6 mg/dL [229.8 ± 141.4 μmol/L]), with a creatinine clearance lower than 20 mL/min (0.33 mL/s) in 9 patients. Renal insufficiency was associated with nephrotic syndrome in 24 of 39 patients. The other 72 patients had normal plasma creatinine levels (mean, 0.87 ± 0.24 mg/dL [76.9 ± 21.2

Discussion

We confirmed that aPL antibodies in patients with SLE with renal involvement represent a strong risk factor for thrombotic events and fetal loss, and for the first time, we found an association with worse renal outcome in long-term follow-up.

Although similar to that reported in many other studies of patients with SLE,25 our aPL antibody prevalence apparently is lower than that observed in renal SLE by others.7, 9, 12 Such a discrepancy probably is caused by the enrollment of persistently aPL

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Renal and vascular outcomes in patients with isolated antiphospholipid syndrome nephropathy
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Citation Excerpt :
Most of the information available on the functional outcomes of APSN come from studies of lupus nephritis. The presence of antiphospholipid antibodies in patients with lupus nephritis is associated with worsening renal function during follow-up [20]. Two studies found evidence of APSN in respectively 32% and 39.5% of SLE patients but did not find an association between APSN and renal outcomes [8,9].
Antiphospholipid syndrome (APS) nephropathy (APSN) is a rare pattern with specific features resulting from microvascular lesions. The prognosis of APSN, outside of lupus nephritis, is unknown. The aim of this study was to describe the renal, vascular and overall outcomes of patients with APSN.
Retrospective multicenter study of patients with antiphospholipid antibodies (aPL) associated with histological APSN lesions and no other nephropathy, identified through a national call for medical records. End-stage renal disease (ESRD)-free survival, thrombosis recurrence-free survival and overall survival were assessed.
Thirty patients were included (19 women) with a median age of 40 years (34–52 years). Fifteen patients had APS, 26/28 had lupus anticoagulant, and 15/26 had triple positivity for aPL. Median eGFR was 50 (31–60) mL/min/1.73 m². Glomerular thrombotic microangiopathy was found in 12/24 cases, fibrous intimal hyperplasia in 12/22 cases and focal cortical atrophy in 17/29 cases. Nineteen patients had moderate to severe interstitial fibrosis (>25%). Six patients developed ESRD at a median follow-up of 6.2 (1.8–9.1) years. The ESRD-free survival rates at 5 and 10 years were 80.0% (95% CI 57.6%–91.4%) and 72.7% (95% CI, 46.9%–87.4%) respectively. None of the histological factors considered was significantly associated with a decrease in eGFR at 12 months. Thrombosis recurrence-free survival was 77.8% (95% CI 48.2%–91.6%) at 10 years. Overall survival was 94% at 10 years (95% CI 65.0%–99.2%).
The renal prognosis of isolated APSN is poor. The severe fibrotic lesions observed are suggestive of late diagnosis.
Increased risk of acute and chronic microvascular renal lesions associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: A systematic review and meta-analysis
2022, Autoimmunity Reviews
Citation Excerpt :
All studies were in the English language. The designs of the studies were categorized into cohort (n = 10) [13,25,26,28–30,32,38,42,43], cross-sectional (n = 18) [9–12,17–19,21–24,31,34–37,39,40] and case-control (n = 7) [14–16,20,27,33,41]. Total number of SLE participants was 3505, taking into account the studies that reported sex of participants, the total number of female participants was 3170 (90.4%).
Microvascular renal lesions have been described in patients with antiphospholipid antibodies (aPL), however their association with aPL is inconsistent among studies. Therefore, our objective was to investigate associations between microvascular renal lesions and aPL among systemic lupus erythematosus (SLE) patients.
Studies were selected if they included SLE patients with and without aPL positivity with a description of kidney biopsy identifying acute and/or chronic microvascular renal lesions as well as lupus nephritis. Data sources were Pubmed, Embase, Cochrane Library, hand search, congress abstracts, and reference lists of studies, without language restrictions. Risk estimates were independently extracted by 2 investigators. Pooled effect estimates were obtained by using the Mantel-Haenszel method (random effects).
Of 1860 identified records obtained between 1991 and 2021, 35 published studies (10 cohorts, 7 case-control, 18 cross-sectional) met inclusion criteria, including 3035 SLE patients according to American College of Rheumatology criteria and 454 cases of microvascular renal lesions. Frequency of microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 31.3% vs. 10.4%, respectively. The overall pooled odds ratios (OR) for microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 3.03 (95% confidence interval [CI], 2.25–4.09). The risk of microvascular renal lesions was the highest for lupus anticoagulant (OR = 4.84 [95% CI, 2.93 to 8.02]) and IgG anticardiolipin antibodies (OR = 3.12 [95% CI,1.08–9.02]) while the association with anti-β₂-glycoprotein I antibodies (OR = 1.88 [95% CI, 0.25–14.14]) did not reach statistical significance. Furthermore, aPL were not associated with any classes of lupus nephritis.
In SLE patients, aPL-positivity is associated with a significant 3- to 5-fold increased risk for specific microvascular renal lesions. This risk is mainly driven by lupus anticoagulant and IgG anticardiolipin antibodies. Our results support the inclusion of microvascular renal lesions as new criteria for definite antiphospholipid syndrome.
Antiphospholipid Syndrome Nephropathy and Other Thrombotic Microangiopathies Among Patients With Systemic Lupus Erythematosus
2019, Advances in Chronic Kidney Disease
Antiphospholipid syndrome (APS) and other causes of thrombotic microangiopathy (TMA) negatively impact the renal outcomes of patients with systemic lupus erythematosus (SLE) and lupus nephritis. Here we review the diagnosis and management of occlusive renal vascular lesions due to APS and other TMAs, with a focus on patients with SLE and lupus nephritis. The presence of a thrombotic event, unexplained hypertension, thrombocytopenia, or hemolytic anemia should prompt consideration for TMA syndromes. The differential diagnosis of a TMA in a patient with SLE includes APS, thrombocytopenic purpura, complement-mediated or infection-associated hemolytic uremic syndrome, drug-mediated TMA (particularly due to calcineurin inhibitor toxicity), and malignant hypertension. Treatment of APS with a documented thrombotic event focuses on anticoagulation to reduce the risk for further thrombotic events. Treatment of classic presentations of thrombocytopenic purpura and hemolytic uremic syndrome in the SLE population is the same as in patients without SLE. Treatment of APS nephropathy or TMA when it is diagnosed by biopsy with concomitant lupus nephritis presents a challenge to clinicians because there is no clear standard of care. Small and retrospective studies suggest potential benefit of complement inhibition, mammalian target of rapamycin (mTOR) inhibition, B cell depleting therapy, and plasma exchange therapy for patients with lupus nephritis and TMA, and prospective investigation of these therapies should be a research priority.

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: Supported in part by Ricerca Finalizzata and Corrente IRCCS Istituto Auxologico Italiano (2000 to 2002) of the Italian Ministry of Health (P.L.M.) and the grant Project Glomerulonephritis in memory of Pippo Neglia (C.P.).

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Original investigation: pathogenesis and treatment of kidney disease and hypertensionAntiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis

Abstract

Section snippets

Patients

Patient clinical and biochemical characteristics at diagnosis of lupus nephritis

Discussion

Semin Arthritis Rheum

Kidney Int

Am J Kidney Dis

Am J Med

Blood

Thromb Res

Am J Med

Am J Med

Am J Kidney Dis

J Autoimmun

Kidney Int

Kidney Int

Am J Kidney Dis

The antiphospholipid syndrome

N Engl J Med

The anticardiolipin syndrome

J Rheumatol

International consensus statement on preliminary classification criteria for definite antiphospholipid syndromeReport of an international workshop

Arthritis Rheum

Renal manifestations in the antiphospholipid syndrome

The intrarenal vascular lesions associated with primary antiphospholipid syndrome

J Am Soc Nephrol

Antiphospholipid syndrome nephropathy in systemic lupus erythematosus

J Am Soc Nephrol

Association of anticardiolipin antibodies with intraglomerular thrombi and renal dysfunction in lupus nephritis

QJM

Catastrophic antiphospholipid syndromes in systemic lupus erythematosus

Ren Fail

Anticardiolipin antibodies in systemic lupus erythematosusClinical correlates, HLA associations, and impact on survival

J Rheumatol

Systemic lupus erythematosus: Clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus

Medicine

Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus

Arthritis Rheum

Criteria for the diagnosis of lupus anticoagulants: An update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH

Thromb Haemost

A sensitive test demonstrating lupus anticoagulant and its behavioural patterns

Br J Haematol

Original investigation: pathogenesis and treatment of kidney disease and hypertension
Antiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis