ImmunologyTier 1Medical Sciences concept

Antiphospholipid syndrome - renal pathology (thrombotic microangiopathy)

Core concept

The renal lesion of APS is a VASCULOPATHY, not a glomerulonephritis
- APS nephropathy = thrombotic microangiopathy of the intrarenal vessels
- Immune-complex deposition with proliferative glomerular change is lupus nephritis - a different problem, and the two coexist

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aPL bind beta-2-glycoprotein I on endothelium, platelets, monocytes

-> endothelial activation, inc tissue factor, complement activation
-> thrombosis at every calibre of renal vessel
- Large: renal artery stenosis/thrombosis, renal vein thrombosis, renal infarct
- Small/microvascular: acute TMA -> chronic changes

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Histology of APS nephropathy

Acute: glomerular and arteriolar fibrin thrombi, endothelial swelling, mesangiolysis, no immune deposits on IF
Chronic: fibrous intimal hyperplasia, arteriolar occlusion, focal cortical atrophy, organised thrombi with recanalisation
Distinguishing it from lupus nephritis matters because it changes the drug: anticoagulation, not more immunosuppression**

Clinical

Hypertension - often severe and disproportionate, the commonest finding
Slowly progressive renal impairment with mild proteinuria (usually <1-2 g/day, sub-nephrotic) and bland or mildly active sediment
Catastrophic APS (CAPS) - >=3 organs in <1 week with histological small-vessel thrombosis and aPL positivity; the kidney is involved in ~70% and is the commonest organ; mortality ~30-50%

Classification (2023 ACR/EULAR)

Entry criterion: at least one positive aPL test within 3 years of a clinical criterion, then domain-weighted scoring, >=3 points in both a clinical and a laboratory domain
Laboratory: lupus anticoagulant, anticardiolipin IgG/IgM, anti-beta-2-GPI IgG/IgM - positive on 2 occasions >=12 weeks apart at medium-high titre
- Triple positivity carries the highest thrombotic risk
- aPL nephropathy is included as a microvascular clinical domain in the 2023 criteria

Consider APS in any patient with unexplained TMA, refractory hypertension, or renal impairment out of proportion to the urinary findings - especially with SLE, prior thrombosis, or pregnancy morbidity
Anticoagulation is the treatment for thrombotic APS
- Warfarin, target INR 2-3 (2.5-3.5 or add aspirin after arterial or recurrent events)
- DOACs are inferior and are not recommended, particularly in triple-positive or arterial APS (TRAPS trial - excess arterial events)
- A lupus anticoagulant can spuriously raise the baseline INR - use chromogenic factor X or the DOAC-free equivalent to verify
CAPS: triple therapy - anticoagulation + high-dose corticosteroid + plasma exchange and/or IVIG, treat the trigger (infection, surgery, anticoagulant withdrawal); rituximab or eculizumab in refractory disease
Hydroxychloroquine in SLE-associated APS is antithrombotic as well as immunomodulatory
Renal transplant - high risk of early graft thrombosis; requires meticulous perioperative anticoagulation
Do not anticoagulate on the basis of a single positive result after an acute illness - repeat at 12 weeks

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