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53. Asplin JR, Coe FL. Hyperoxaluria in kidney stone formers treated
with modern bariatric surgery. J Urol 2007; 177: 565–569
54. Patel BN, Passman CM, Fernandez A et al. Prevalence of hyperox-
aluria after bariatric surgery. J Urol 2009; 181: 161–166
55. Nasr SH, D’Agati VD, Said SM et al. Oxalate nephropathy compli-
cating Roux-en-Y gastric bypass: an underrecognized cause of irre-
versible renal failure. Clin J Am Soc Nephrol 2008; 3: 1676–1683
Nephrol Dial Transplant (2010) 25: 3147–3154
doi: 10.1093/ndt/gfq356
Advance Access publication 28 June 2010
What nephrologists need to know about antiphospholipid syndrome
Bassam Alchi1, Meryl Griffiths2 and David Jayne1
1
Renal Unit and 2Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK
Correspondence and offprint requests to: David Jayne; E-mail: dj106@cam.ac.uk
Abstract
Antiphospholipid syndrome (APS) is an autoimmune dis-
order characterized by recurrent arterial or venous throm-
bosis and/or pregnancy losses, in the presence of persistently
elevated levels of anticardiolipin antibodies (aCL) and/or
evidence of circulating lupus anticoagulant (LA). The kid-
ney is a major target organ in both primary and secondary
APS. With the expanding spectrum of renal diseases as-
sociated with APS, and the impact of APS in ESRD care,
this subject is of increasing relevance to nephrologists.
This review describes the various clinical manifestations
and histological features of this syndrome, with reference
to the kidney.
Keywords: anticardiolipin antibodies; antiphospholipid syndrome; lupus
anticoagulants; nephropathy
Introduction
The antiphospholipid syndrome (APS) was first described
by Hughes in the mid-1980s as a disorder of hypercoagul-
ability in association with antiphospholipid antibodies
(aPL), namely anticardiolipin antibodies (aCL) and/or cir-
culating lupus anticoagulants (LA) [1]. It was in systemic
lupus erythematosus (SLE) that this syndrome was first re-
ported [2]; however, APS may occur, though less frequent-
ly, in the absence of associated autoimmune disease, the
so-called primary APS [3]. In the past two decades, a var-
iety of immunologically mediated thrombotic events re-
lated to almost every organ system has been identified as
features of this syndrome. The diagnosis of definite APS is
made when the patient fulfils one clinical (vascular throm-
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: journals.permissions@oxfordjournals.org
3147
56. Wharton R, D’Agati V, Magun AM et al. Acute deterioration of renal
function associated with enteric hyperoxaluria. Clin Nephrol 1990;
34: 116–121
57. Harbottle L. Audit of nutritional and dietary outcomes of bariatric
surgery patients. Obes Rev 2010
Received for publication: 2.4.10; Accepted in revised form: 27.5.10
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bosis or pregnancy morbidity) and at least one laboratory
[LA, aCL and/or anti-β2-gylycoprotein-1 (anti-β2GP1)
antibodies] criterion [4]. As the kidney represents a major
target organ in both primary and secondary APS, some ne-
phrologists are now challenging to include the nephropathy
of APS in the classification criteria of definite APS [5–7].
Renal involvement in primary APS is typically caused by
thrombosis occurring at any location within the renal vascu-
lature, leading to diverse effects, depending on the size, type
and site of the vessel involved. The renal manifestations of
APS thus may include renal artery stenosis (RAS) and/or
renovascular hypertension, renal infarction, APS nephropa-
thy (APSN), renal vein thrombosis, and increased allograft
vascular thrombosis [8–12]. The spectrum of renal lesions
associated with primary APS has been more recently ex-
panded to involve non-thrombotic conditions, such as
glomerulonephritis [13]. It is unclear whether, in addition
to thrombosis, other mechanisms could also contribute to
the pathogenesis of APS-associated nephropathy. Further-
more, renal manifestations of APS may co-exist with
other pathologies, especially proliferative lupus nephritis.
The true incidence of renal involvement in primary APS
has not been well determined, in part because of the fre-
quent occurrence of thrombocytopaenia and systemic
hypertension, discouraging renal biopsy. It has also been
suggested that patients with APS may have a higher risk
of developing biopsy-related complications, which could
be challenging to manage.
Although the kidney represents a major target organ in
APS, renal involvement in this syndrome was poorly re-
cognized until recently. The objective of this review is to
present the best available information related to the renal
manifestations of APS. A summary of the treatment op-
tions will also be presented.
3148 Nephrol Dial Transplant (2010): Editorial Reviews
Table 1. The pro-coagulant/pro-inflammatory role of antiphospholipid antibodies

Thrombotic pathway Underlying mechanism/evidence References

Persistent activation of coagulation Increase markers of thrombin generation [70]

Enhance endothelial release of tissue factor [71]
Interfere with endogenous anticoagulant systems (β2GP1 and annexin A2) [72,73]
Cause activated protein C resistance [74]
Reduce fibrinolytic activity [75]

Platelet activation Bind phospholipid epitopes on platelets [76]

Vessel wall abnormalities
Endothelial injury
Inflammation
Accelerated atherosclerosis
Increase the ratio of thromboxane to prostacyclin biosynthesis [77]
Increase markers of platelet activation (CD62P and platelet microparticles) [78,79]
Induce apoptosis in human umbilical vein endothelial cells [80]
Increase expression of vascular cell adhesion molecules ICAM-1, VCAM-1 and E-selectin [81,82]
Activate the complement pathway [83,84]
Promote the binding of oxidized LDL/B2GP1 complexes to macrophages [29]

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Increase carotid intima media thickness in patients with thrombotic primary APS [85]

The role of aPL antibodies
APS is considered an autoimmune disorder with multifac-
torial aetiology that includes cellular, molecular, genetic
and pathogenic mechanisms, as reported in detail else-
where [11,14,15]. Antiphospholipid antibodies are a het-
erogeneous group of antibodies observed in a range of
pathological conditions as well as in healthy populations
[16]. They play a crucial role in the pathogenesis of APS
(Table 1); however, not all patients with these antibodies
develop clinical features of APS, suggesting that additional
factors are also involved. Antibodies to cardiolipin and
β2GP1 of IgG and IgM isotype are routinely measured in
serum by solid-phase ELISA, or similar, assays. Lupus
anticoagulant is suggested by a prolonged activated partial
thromboplastin time (APTT) and confirmed by prolonga-
tion of the diluted Russell viper venom test (DRVVT)
indicating the presence of a transferable inhibitor of co-
agulation. Lupus anticoagulant cannot be readily mea-
sured in patients receiving anticoagulants.
It is unclear which patients with aPL will develop
thrombosis. In general, LA are more specific for APS,
whereas aCL are more sensitive. The association between
aPL and thrombosis is stronger with LA than with aCL. In
a recent meta-analysis of 25 studies involving >7000 pa-
tients, the odds ratio for thrombosis was 11.0 for LA and
1.6 for aCL [17]. Moreover, LA for which the prolongation
of clotting times is dependent on the presence of β2GP1
show a much stronger association with thrombosis (odds
ratio, 42.3) than do LA that are independent of β2GP1
(odds ratio, 1.6) [18]. Again, which particular subset of
aPL is associated with renal involvement is yet to be de-
fined. Antiphospholipid antibodies can be detected in
lupus nephritis patients without evidence of APS-related
renal disease. Both antiplatelet agents and warfarin have
been considered in this context, but there is no clear evi-
dence that they are beneficial.
Systemic hypertension
Hypertension is one of the first major features described
in association with livedo reticularis and aPL [19]. It is
exceedingly common in both primary and secondary
APS, and is considered to be a sensitive marker of ne-
phropathy in this syndrome. In the series of primary
APS reported by Nochy et al., hypertension was present
in 93% of their 16 patients and was sometimes the only
clinical sign suggestive of nephropathy [20]. Consequently,
it was recommended to investigate patients with APS
complicated by hypertension for an underlying renal le-
sion. Imaging the renal arteries should be considered as
RAS/thrombosis has been shown to respond well to an-
ticoagulation with or without percutaneous balloon
angioplasty, leading to recovery of renal function and
return to normal blood pressure [21,22]. Hypertension
in APS may often be severe, with some patients present-
ing with hypertensive emergencies [23,24]. Malignant
hypertension in APS without overt lupus nephritis or
stenosis/thrombosis of the main renal arteries was docu-
mented by Cacoub and colleagues in five patients. Inter-
estingly, they used high-dose steroids and anticoagulation
to treat the biopsy-proven microangiopathy, resulting in
rapid resolution of the hypertensive crisis in three of their
patients [23].
Renal artery lesions
APS has been well documented as a unique, non-traditional
cause of RAS with important clinical consequences. It may
manifest in multiple ways ranging from renal infarction to
ischaemic acute renal failure to slowly progressive ischae-
mic chronic renal failure to renovascular disease. Using
magnetic resonance angiography, 26% of aPL-positive pa-
tients with poorly controlled hypertension were found to
have RAS, significantly higher compared with 8% of rela-
tively young (≤50 years) hypertensive controls and 3% of
healthy potential kidney donors [25]. Two patterns of sten-
otic lesions have been described in APS. The more common
pattern is characterized by smooth, well-delineated and
often non-critical stenoses in the mid-portion of the renal
artery, quite distinct from either fibromascular dysplasia or
atherosclerosis (Figure 1). The less common pattern is
similar to atherosclerotic lesions situated proximally and
occasionally involving the aorta [25].
Nephrol Dial Transplant (2010): Editorial Reviews 3149

Fig. 1. Right renal artery stenosis associated with hypertension in

antiphospholipid syndrome. The aorta is smooth, suggesting that the

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stenosis is not related to atherosclerosis. Reprinted from reference [9]
with permission. Fig. 2. Glomerulus showing reduplication of the capillary basement
membrane (arrows) (hexamine silver stain ×400).

Although the nature of the RAS in APS remains unclear,

the response to anticoagulation does suggest a thrombotic
process. Previous reports have shown that anticoagulation
treatment with international normalized ratio (INR) >3 may
reverse RAS and achieve subsequent clinical improvement
[26,27]. Remondino et al. [28] reported a case of bilateral
RAS associated with APS in which complete recanalization
of both renal arteries was observed on a repeat renal spiral
CT scan after 5 months of treatment with anticoagulation.
Besides thrombosis, other potential aetiologic factors for
RAS in APS include accelerated atherosclerosis [29] as
well as increased endothelin levels resulting in vasocon-
striction [29,30].
Renal infarction
Renal infarction results from occlusive lesions in smaller
diameter intraparenchymal vessels, which are caused by ei-
ther in situ thrombosis or emboli from a pre-existing up-
stream arterial lesion or a cardiac valvular lesion [20].
Clinically, patients with renal infarction, which could be
the first manifestation of APS, may present with flank
pain, severe hypertension and/or renal dysfunction. Some
of these patients may have multiple, often serious, throm-
botic episodes, and many have multiple infarctions in the
renal cortex [31]. Histologically, glomerular ischaemia,
tubular atrophy and interstitial fibrosis may be seen in pa-
tients with renal infarction due to primary APS. Interestingly,
in five out of eight such patients in whom biopsies were
performed, no histological evidence of associated throm-
botic microangiopathy (TMA) was found, as summarized
in the report by Poux et al. [32]. Although renal infarc-
tion is a rare complication of APS, this diagnosis should
be considered in any young subject who presents with
renal infarction.
the so-called TMA, and/or chronic, such as arteriosclerosis,
fibrous intimal hyperplasia, tubular thyroidization and
focal cortical atrophy [7,20]. APSN has been described in
patients with primary APS, SLE-related APS and SLE/
non-APS patients with aPL. The same histologic lesions,
especially TMA, are also observed in patients with cata-
strophic APS [33]. Generally, APSN manifests with
hypertension, acute and/or chronic renal failure, and often
a low-grade proteinuria. Multiple cortical infarctions can
result in a ‘moth-eaten’ appearance on renal imaging.
TMA is the best known and most characteristic lesion of
APSN, with distinctive microscopic and ultrastructural
changes [7,20,34]. The pathological changes of TMA,
however, are not exclusive for APS, as they can occur
in many other conditions caused by coagulation distur-
bances or endothelial cell injury, such as thrombotic
thrombocytopaenic purpura, haemolytic uraemic syndrome,
scleroderma renal crisis, malignant hypertension, pre-
eclampsia, cyclosporine toxicity, chemotherapy and renal
transplant rejection [6]. The pathological features of TMA
are characterized by fibrin thrombi in glomeruli and in the

APSN

APSN refers to the kidney damage caused by vascular le- Fig. 3. Glomerulus showing extensive mesangiolysis (arrowhead) and
sions in the glomeruli, arterioles and/or interlobular arteries intracapillary fibrin thrombi (arrows) (haematoxylin and eosin stain
in patients with aPL. APSN vascular lesions may be acute, ×400).
3150
whole intrarenal vascular tree, without inflammatory cells
or vascular immune deposits. During the acute phase, fi-
brin thrombi containing fragmented blood cells, along with
oedema of endothelial cells, narrow or occlude the vascular
lumen. Thrombi eventually organize into fibrocellular and
fibrous vascular occlusions, which can be recannulated by
endothelialized channels resulting in onion-skin arrange-
ment of intimal fibrosis [20]. Similarly, as a consequence
of repeated thrombosis/recanalization, splitting and multi-
layering of the glomerular basement membrane (GBM) de-
velop [34]. On light microscopy, the silver stains show a
combination of GBM wrinkling and duplication (Figure 2).
Other light microscopic features include fibrin microthrom-
bi in the glomerular capillary lumen and mesangiolysis
(Figure 3). Neither necrotizing vasculitis nor fibrinoid ne-
crosis are seen in primary APS. By immunofluorescence
study, fibrin is the sole element of the thrombi, with immu-
noglobulins being absent. Electron microscopy (Figure 4)
shows widening of the GBM, with areas of mesangial inter-
position accounting in part for the double contours on light
microscopy. No electron-dense deposits are seen [34].
Among the chronic pathological aspects, arteriosclerosis
is typically seen associated with fibrous intimal hyperplasia,
intimal thickening of the arteries and arterioles primarily
by myofibroblastic cellular proliferation, with consequent
lumen restriction and ischaemia (Figure 5). Focal cortical
atrophy involves the superficial cortex under the renal
capsule, as foci or triangles with sharp borders with the
rest of the normal cortex, accompanied by depression of
the contour of the renal capsule. In these atrophic areas,
all elements of the renal parenchyma were altered in a pat-
tern considered to be very typical of APSN. The glomeruli
Fig. 4. Electron micrograph. A capillary loop shows pronounced wrinkling
of the basement membrane (arrow). Where mesangial interposition occurs
(star), there is an apparently ‘new’ subendothelial basement membrane
(arrowhead) forming a double contour. There is a widespread flattening
of the epithelial foot processes. No immune deposits are seen (original
magnification ×6200).
Nephrol Dial Transplant (2010): Editorial Reviews
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Fig. 5. Interlobular artery showing striking fibroelastic intimal thickening
with almost complete obliteration of its lumen (haematoxylin and eosin
stain ×400).
appear either small and sclerotic or voluminous, but almost
devoid of glomerular tuft ‘glomerular ballooning’. The tu-
bules are atrophic packed with eosinophilic casts, resem-
bling thyroid tissue ‘tubular thyroidization’. The arterioles
are occluded by fibrin microthrombi or often by fibrous
tissue [20].
Renal vein thrombosis
Thrombosis of the renal veins classically presents with
nephrotic-range proteinuria and has been described in
aPL-positive patients with lupus nephritis, as well as in pri-
mary APS, and it can be the first clinical manifestation of
APS [35,36]. Nephrotic syndrome, a common finding in
APS associated with SLE, is unusual in patients with pri-
mary APS. Thus, careful Doppler studies of the renal vas-
culature should be considered in any patient with
persistently positive aPL who develops sudden heavy pro-
teinuria or acute deterioration of renal function to rule out
renal vein thrombosis. Alternatively, contrast-enhanced
computed tomography and magnetic resonance angiog-
raphy can be used to provide the diagnosis.
The significance of aPL and glomerular
microthrombosis in lupus-associated nephritis
There is sound evidence that APS contributes to the renal
morbidity in patients with lupus nephritis [5,37,38]. Moroni
and co-workers [39] prospectively followed up 111 patients
with lupus nephritis (LN) for a mean of 173 ± 100 months.
The overall prevalence of aPL in their cohort was 26%.
Interestingly, they reported not only an increased risk of
vascular and obstetric complications in lupus patients with
aPL but also a strong association between aPL antibodies
and prognosis in LN. With multivariate analysis, aPL anti-
body positivity, high plasma creatinine level at presenta-
tion and chronicity index were independent predictors of
chronic renal function deterioration [39]. Tektonidou and
colleagues [6] examined the prevalence and long-term
Nephrol Dial Transplant (2010): Editorial Reviews
outcome of APSN in 151 SLE patients with or without
aPL as well as the histologic evolution of APSN lesions
on serial kidney biopsies. APSN was documented, in
addition to and independently from lupus nephritis, in al-
most 40% of patients with aPL compared with only 3 out
of 70 patients without aPL, suggesting a critical role of
aPL in the pathogenesis of APSN. Compared with patients
without APSN, those with APSN had a higher frequency
of hypertension and raised serum creatinine levels at the
time of kidney biopsy, and developed progression of histo-
logic lesions, all of which are associated with a poor renal
outcome [6].
Glomerular microthrombosis (GMT) is seen in ∼20–30%
of patients with lupus nephritis, especially in those with
severe diffuse proliferative glomerulonephritis, and has
been shown to be a strong predictor of glomerular scler-
osis and poor renal outcome [40,41]. The mechanism
underlying the formation of GMT is largely unknown. Al-
though several studies have reported the association of
aPL with GMT [6,41,42], the relation between GMT and
aPL remains controversial. Zheng et al. [41] compared the
clinical and serological profile of 124 LN patients with
and without GMT. The authors showed higher rates of
LA and antibodies against β2GP1 and thrombin in lupus
patients with GMT, who also had a lower serum C3 level
and more intense glomerular C3 and C1q staining than
those without GMT [41]. Their findings imply that com-
plement activation, induced by or coordinated with aPL,
may play a pathogenic role in the development of renal
tissue injury leading to thrombosis. However, not all pa-
tients with SLE and aPL develop GMT. According to Harris
and Pierangeli [43], a ‘second hit’, e.g. infection or trauma,
is necessary to trigger thrombosis at the vessel site where
aPL have deposited. On the other hand, Cohen et al. [44]
demonstrated a strong relationship between the intensity
of glomerular C4d staining and the presence of GMT, irre-
spective of the type of circulating antibodies present. Taking
into account the impact of GMT on the prognosis of LN,
whether those patients with renal biopsy-proven GMT
should be treated with anticoagulants in the absence of other
thrombotic processes remains unclear and warrants further
study.
It is also worth mentioning that patients with primary
APS and SLE share some common clinical and sero-
logical manifestations [45,46]. Primary APS may evolve
into full-blown SLE suggesting that these apparently
different diseases are related [45,47]. It is not known to
what extent these two conditions share a common genetic
background.
Catastrophic antiphospholipid syndrome (CAPS)
CAPS (also known as Asherson’s syndrome) is an accel-
erated variant of APS resulting in multi-organ failure
[48]. A definitive diagnosis of CAPS requires (i) clinical
evidence of involvement of three or more organ systems
in a period of less than a week, (ii) histopathological evi-
dence of small vessel occlusion in at least one organ sys-
tem, and (iii) laboratory confirmation of the presence of
aPL, usually in high titre [49]. Approximately 60% of the
3151
catastrophic episodes are preceded by a precipitating
event, mainly infections.
The kidney is the organ most commonly affected by
CAPS. According to the CAPS registry data [50], no fewer
than 71% of patients had renal involvement, usually re-
sulting in acute renal failure, severe hypertension and la-
boratory evidence of glomerular damage (proteinuria and
haematuria). Renal biopsy, in the vast majority of cases,
revealed the typical frank microangiopathy. Immune com-
plex nephritis was seldom encountered. Renal infarctions
were also present in some patients.
Although patients with CAPS represent <1% of all pa-
tients with APS, the condition is life threatening, with a
50% mortality rate. The presence of SLE is the only
identified poor prognostic factor for a higher mortality
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rate in patients with CAPS. Causes of death include
major organ involvement (other than the kidney) as well
as infection [51].
The significance of aPL in haemodialysis patients
A few studies have reported an unexpectedly high preva-
lence of aPL in ESRD patients undergoing haemodialysis
[52,53]. These antibodies were independent of age, length
of time on dialysis, sex, type of dialysis membrane, drugs,
and chronic B and C hepatitis [53]. Although the precise
mechanisms involved in the genesis of aPL in ESRD are un-
known, they appear to be mostly β2GP1-independent [54].
Possible causes include dialysis membranes, trauma to
blood passing through the haemodialysis circuit, and induc-
tion by microbial agents or their products, such as endotox-
ins present in the dialysate. The precise risk associated with
the presence of aPL in ESRD is also uncertain. While some
studies suggest that these antibodies are not pathogenic
[55,56], others have reported that aPL are associated with
haemodialysis vascular access thrombosis [57,58].
The significance of aPL in renal transplantation
There is considerable evidence that aPL-positive patients
undergoing renal transplantation are at significantly in-
creased risk of renal vascular thrombosis with consequent
graft loss. In a striking study, within a group of 78 patients
who received renal transplant, six had APS. Each of these
patients thrombosed their renal allografts within a week of
transplantation. In contrast, the remaining 72 patients were
all doing well 1 year after transplantation [59]. Wagenknecht
and co-workers [60] reported significantly more aPL in pa-
tients with early renal allograft failure than in patients with
functioning grafts. In that study, 57% of final crossmatched
sera from patients with early allograft non-function were
positive for IgG, IgM and IgA aPL. Biopsies of these failed
allograft kidneys from aPL-positive patients showed thrombi
in nine patients and infarction in five. In addition, aPL-
positive patients who had no history of haemodialysis were
at the greatest risk. Thus, it was suggested that aPL that
develops during dialysis may be less pathogenic. Another
possibility is a possible protective effect of residual heparin
received at haemodialysis [60].
3152
It has been reported that renal allograft recipients, even
those without SLE, have an increased incidence of aPL.
Among 178 non-SLE renal allograft recipients, 50 (28.1%)
had positive aPL; a minority (15.7%) acquired these anti-
bodies post-transplant [61]. How aPL may be acquired
after transplantation is curious, but is as yet unexplained.
It has been suggested that these aPL may be related to
post-transplant infection or autoimmune reactions to infec-
tions. Patients with and without aPL did not differ for age,
gender, underlying disease, immunosuppressive regimen,
serum creatinine concentration and platelet count. Both
pre-transplant and post-transplant aPL were associated
with thrombosis; however, the risk was greater in the latter
group [61]. Patients with SLE, who generally have similar
cadaveric and living-related allograft survival to the general
population undergoing renal transplantation when adjusted
for multiple confounding variables, appear to be at consid-
erable risk of graft thrombosis if they are positive for aPL,
particularly when no anticoagulation is administered [62].
Although hepatitis C virus (HCV)-positive patients may
have aPL, they do not usually manifest the APS. Prelimin-
ary data suggest that this may not be the case in post-renal
transplantation, as these patients may be at increased risk for
thrombotic complications after renal transplantation [63].
Given these risks, there are some who question whether
aPL-positive patients should undergo transplantation at all,
because even when full anticoagulation is administered fol-
lowing renal transplantation, the risks of graft loss and sys-
temic thrombosis are not completely eliminated [64].
Identifying high-risk patients through pre-transplant screen-
ing for pro-thrombotic risk, including aPL, will reduce the
morbidity and risk of failed transplantation.
Treatment
Treatment of APS remains centred on anticoagulation;
however, it has also included the use of corticosteroids
and other immunosuppressive therapy.
The current recommendations in a patient with arterial
or venous thrombosis are treatment with heparin followed
by long-term warfarin as long as the abnormal antibody
persists. In general, intermediate-intensity treatment with
warfarin (INR 2.0–3.0) is sufficiently effective in most pa-
tients with a first episode of venous thrombosis who do not
have a major risk of bleeding. In patients with arterial
events or with recurrent thrombotic events, however, a
higher high-intensity treatment (INR 3.0–4.0) or an add-
itional antiplatelet agent may be required [65].
In pregnancy, a prophylactic therapy with unfractionated
heparin or low-molecular-weight heparin plus aspirin should
be considered, particularly in the presence of prior preg-
nancy loss [66]. Women with previous renal disease from
APS and renal impairment are at high risk of complications
during pregnancy and in the puerperium. To improve the
outcomes of pregnancies in such women, a closer obstetric
surveillance and multidisciplinary clinics, including ne-
phrologists, are essential. The prophylactic role of anticoa-
gulation in non-pregnant patients who are aPL positive but
have had no manifestations of APS remains unclear [65].
Nephrol Dial Transplant (2010): Editorial Reviews
While corticosteroids and other immunosuppressive
agents may alter the presence or the titre of aPL, they do
not reduce the risk of thrombosis. A few reports have
shown, however, beneficial effects of immunosuppression
in primary APSN [67,68]. It has been suggested that cor-
ticosteroids and/or immunosuppressive agents may prevent
target organs from further damage by decreasing inflam-
matory response likely to develop due to aPL.
Patients with catastrophic APS usually receive a com-
bination of anticoagulants and corticosteroids plus intra-
venous immunoglobulin and/or plasma exchange, as the
first-line therapy. Additionally, cyclophosphamide should
be considered in SLE-associated CAPS patients but not
in primary CAPS patients [51].
Other potential approaches for the management of persist-
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ently aPL-positive patients include hydroxychloroquine, sta-
tins, rituximab, anti-C5 antibodies and other targeted
therapies that have been effective in experimental APS mod-
els [69]. A better understanding of the intracellular mechan-
isms of aPL-mediated thrombosis will help us design more
targeted anti-inflammatory or immunomodulatory therapies.
Conclusions
APS is being increasingly recognized as an important cause
of renal injury due to thrombosis at any location within the
renal vasculature. Accordingly, the renal manifestations of
APS may include systemic hypertension in association with
livedo reticularis, RAS, renal infarction, APSN, renal vein
thrombosis and increased allograft vascular thrombosis.
Testing for aPL must therefore be considered in patients
with any of these manifestations. Nephrologists are ex-
pected to be involved more frequently in managing patients
with APS, whether it is primary, secondary or, most certain-
ly, with CAPS. Renal pathologists should carefully exam-
ine renal biopsies obtained from SLE patients with positive
aPL for the presence of APSN, as this may have significant
implications on therapeutic decisions. Anticoagulation re-
mains the mainstay treatment of patients with renal involve-
ment due to APS. In addition, patients with catastrophic
features often require immunosuppressive therapy. Future
studies may help to identify more targeted therapeutic
agents.
Acknowledgements. This work was supported by the Cambridge Bio-
medical Research Centre.
Conflict of interest statement. None declared.
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Received for publication: 29.5.10; Accepted in revised form: 1.6.10