Role of antiphospholipid antibodies in kidney disease: Risk factors, immunopathogenesis, and diagnosis

Table 1 Renal complications of antiphospholipid syndrome

Hypertension

Renal artery stenosis or thrombosis (unilateral or bilateral)

Renal vein thrombosis (unilateral or bilateral)

Ischemic nephropathy

APS nephropathy

Acute: Thrombotic microangiopathy

Chronic vaso-occlusive lesions: Cortical ischemia or infarction, interstitial fibrosis, tubular atrophy, specific intrarenal vasculopathy, arteriosclerosis, intimal hyperplasia, tubular thyroidization

Vascular access thrombosis in patients udergoing hemodialysis

Renal allograft

De novo or relapse of APSN of the allograft

Renal vein thrombosis

Renal artery thrombosis/stenosis

APS: Antiphospholipid syndrome; APSN: Antiphospholipid syndrome nephropathy.

Table 2 2006 Revised Sapporo criteria for antiphospholipid syndrome (also called the Sydney criteria)

Clinical criteria	Laboratory criteria
One or more of the following is present:	The presence of one or more of the following aPLs on two or more occasions at least 12 weeks apart
(1) Vascular thrombosis	IgG and/or IgM aCLs in moderate or high titer (> 40 GPL or MPL units, respectively, or a titer > 99th percentile for the testing laboratory), measured by a standardized enzyme-linked immunosorbent assay
One or more episodes of venous, arterial, or small vessel thrombosis in any tissue or organ
(2) Pregnancy morbidity	IgG and/or IgM anti-2 glycoprotein I > 40 GPL or MPL units, respectively, or a titer > 99th percentile for the testing laboratory, measured by a standardized ELISA according to recommended procedures
(a) One or more unexplained deaths of a morphologically normal fetus at ≥ 10 weeks gestation; (b) One or more premature births of a morphologically normal neonate before 34 weeks gestation because of eclampsia, preeclampsia, or placental insufficiency; and (c) Three or more consecutive spontaneous pregnancy losses at < 10 weeks gestation with maternal and paternal factors (anatomic normal and chromosomal abnormalities excluded)
	Lupus anticoagulant present in plasma, on 2 or more occasions at least 12 weeks apart

aCLs: Anticardiolipin antibodies; aPL: Antiphospholipid antibodies; ELISA: Enzyme-linked immunosorbent assay; GPL: IgG phospholipid units; IgG: Immunoglobulin G; IgM: Immunoglobulin M; MPL: IgM phospholipid units.

Table 3 EULAR 2023 classification criteria for antiphospholipid syndrome

(1) Entry criterion:

A patient must have at least one positive aPL test (LAC, aCL IgG/IgM, or anti-β2GPI IgG/IgM) on two occasions at least 12 weeks apart

The positive test must be from a solid-phase assay validated for clinical use, and at least one test must be high-titer or persistent

(2) Additive weighted scoring:

Once the entry criterion is met, clinical and laboratory features are assigned points

A score of ≥ 10 points is required to classify a patient as having APS

Clinical criteria

Venous thromboembolism 4 points

Arterial thrombosis 5 points

Pregnancy morbidity

≥ 3 consecutive unexplained early miscarriages 3 points

≥ 1 unexplained fetal death after 10 weeks 4 points

Preterm birth due to eclampsia/HELLP/severe 3 points preeclampsia

Laboratory criteria

LAC - 4 points

High-titer aCL IgG or anti-β2GPI IgG - 3 points

Double or triple antibody positivity - 3 points

C3/C4 (suggesting complement activation) - 2 points

Classification as APS requires a total score of ≥ 10 points, combining laboratory and clinical features

aCL: Anticardiolipin antibody; aPL: Antiphospholipid antibody; APS: Antiphospholipid syndrome; β2GPI: Β2 glycoprotein I; EULAR: European League Against Rheumatism; HELLP: Hemolysis, elevated liver enzymes, and low platelets; IgG: Immunoglobulin G; IgM: Immunoglobulin M; LAC: Lupus anticoagulant.