Marion Rabant 1 MD, Canaud G 2 MD, François A 3 MD, Noël LH 1 MD (1)Pathology Department, Necker Hospital, Paris, France (2)Transplantation Department,

Marion Rabant1 MD, Canaud G2 MD, François A3 MD, Noël LH1 MD

(1) Pathology Department, Necker Hospital, Paris, France(2) Transplantation Department, Necker Hospital, Paris, France(3) Pathology Department, Rouen Hospital, Rouen, France

Severe vascular lesions and poor functional outcome in a kidney transplant recipient

CASE 4

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50 year old caucasian woman

Medical history: Single functioning kidneySpontaneous abortion at the age of 25Brutal nephrotic syndrom at the age of 28

Kidney biopsy

CASE REPORTCASE REPORT

« Idiopathic » Membranous Nephropathy

type 2

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CASE REPORTCASE REPORT

Rapidly progressive chronic kidney diseaseEnd stage renal disease at the age of 41 years

First kidney transplantation one year later

50 year old caucasian woman

Medical history: Single functioning kidney Spontaneous abortion at the age of 25 Brutal nephrotic syndrome at the age of 28

Kidney biopsy

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Arterial allograft thrombosis at day 1

Transplantectomy

Long term anticoagulation

Lupus anticoagulant antibodies +Anti-b2GP1 antibodies +

Antiphospholipid

syndrome

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CASE REPORTCASE REPORT

8 years later at the age of 50Second kidney transplantation64-year-old deceased donor (ECD)

Immunosuppressive regimen: Thymoglobulin induction, Plasmapheresis and IVIG (x4) for anti HLA class I DSA Steroids, MMF, Tacrolimus

No day-0 biopsy

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First renal biopsy (day 15)First renal biopsy (day 15)for slow functioning graftfor slow functioning graft

Acute tubular necrosis, intimal fibrosis CV1, IF/TA I

trichrome trichrome

Vacuoles

cv2

IF/TAGrade II

Tubular necrosis

Trichrome

Creatinine 120 umol/LGFR 40 mL/min

3-months protocol biopsy

Glomerulitis (g3), no ptc, mm2

No IgG

Negative C4d assymetrical cv2

Trichrome

PAS

Immunofluorescence: anti IgG

C4d

IF/TA grade III

One-yearprotocol biopsy

Creatinine 120 umol/LGFR 40 mL/min

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CASE REPORTCASE REPORT

Conclusion: sub-clinical acute humoral rejection

Treatment with:•Steroids•Plasmapheresis (x5)•Rituximab•Intravenous immunoglobulin (x4)

Trichrome

Fourth renal biopsy 2 years after transplantation

for increased serum creatinine

and nephrotic range proteinuria (12g/d)

IF anti IgG

cv3 mesangiolysis thrombosis

g2+ptc2Thrombosis in a preglomerular arteriole

Trichrome Trichrome

Jones

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CASE REPORTCASE REPORT

Conclusion of the 4th biopsy

Persistent acute humoral rejection

Thrombotic microangiopathy

Severe fibrous intimal hyperplasia

No recurrence of membranous nephropathy

Recurrence ofAPS nephropathy

Creatinine 230 μmol/LNephrotic range proteinuria

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Antiphospholipid syndrom (APS) and kidneyAntiphospholipid syndrom (APS) and kidney

Definition (Sydney criteria, 2006): 1 clinical and 1 biological criteria

Clinical:•1 episode of arterial, venous, or small vessel thrombosis•1 or more unexplained deaths of a normal fetus <10th week and/or•3 or more unexplained consecutive spontaneous abortions <10th•1 or more premature birth of a morphologically normal neonate <34th week of gestation due to eclampsia or severe pre-eclampsia

Biological (on 2 or more occasions)•Anti-cardiolipin IgG and/or IgM•Anti-β2 glycoprotein I IgG and/or IgM•Lupus anticoagulant

Primary or secondary (autoimmune disease such as SLE)

Classic histological signs: vascular nephropathy

Fibrous intimal hyperplasia Focal cortical atrophy Thrombotic microangiopathy

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Antiphospholipid syndrom (APS) and kidneyAntiphospholipid syndrom (APS) and kidney

Primary antiphospholipid syndrome presenting as renal vein thrombosis and membranous nephropathy. Chaturvedi S. Pediatr Nephrol. 2011 Jun;26(6):

Several cases of MN

Anticardiolipin antibody and renal disease: a report of 3 cases. D’Agati. JASN 1:777-784, 1990

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APS and kidney transplantationAPS and kidney transplantation

1359 transplantations (January 1, 2000 and Decembre 31, 2009)

AP antibodies (APA+)n=37 (2,7%)

APS n=12

Primary APSn=3

Secondary APSN=9

APA+n=25

• Lupus anticoagulantn=37/37 (100%)• Anti β2GP1 (n=7/37)• Anti CL (n=11/37)

Compared to 59 matched APA- transplant recipients

Canaud G, et al

To assess the long term clinical and histological significance of APA+ and APS

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cv ah

ci ct

cv ah

ci ct

APS and kidney transplantationAPS and kidney transplantation

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Vascular lesions and humoral rejectionVascular lesions and humoral rejection

Between M3 and M12

Mean Banff cv score

DSA+ (n=40) : 0.65 ±0.11 to 1.12± 0.10, P=0.014

DSA - (n=59): 0.65 ± 0.11 to 0.81±0.10, P=ns

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CONCLUSIONCONCLUSION

Antiphospholipid syndrome is a severe disease with o More thromboembolic events after transplantationo Poor graft outcomeo Recurrence of APS nephropathy o Progression of IF/TA

Importance of screening APA in case of thromboembolic events

High risk renal transplantation in APS patients

DSA and humoral rejection may have contributed to accelerate vascular lesions