1. Severe vascular lesions and poor functional outcome
CASE 4
Severe vascular lesions and poor functional outcome
in a kidney transplant recipient
Marion Rabant1 MD, Canaud G2 MD, François A3 MD, Noël LH1 MD
Pathology Department, Necker Hospital, Paris, France
Transplantation Department, Necker Hospital, Paris, France
(3) Pathology Department, Rouen Hospital, Rouen, France 1

2. Membranous Nephropathy
CASE REPORT
50 year old caucasian woman
Medical history:
Single functioning kidney
Spontaneous abortion at the age of 25
Brutal nephrotic syndrom at the age of 28
« Idiopathic »
Membranous Nephropathy
type 2
Kidney biopsy
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3. CASE REPORT 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
Rapidly progressive chronic kidney disease
End stage renal disease at the age of 41 years
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First kidney transplantation one year later

4. Lupus anticoagulant antibodies +
Arterial allograft thrombosis at day 1
Transplantectomy
Lupus anticoagulant antibodies +
Anti-b2GP1 antibodies +
Antiphospholipid
syndrome
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Long term anticoagulation

5. CASE REPORT 8 years later at the age of 50
Second kidney transplantation
64-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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6. First renal biopsy (day 15) for slow functioning graft
trichrome
trichrome
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Acute tubular necrosis, intimal fibrosis CV1, IF/TA I

7. 3-months protocol biopsy Vacuoles cv2 Creatinine 120 umol/L
GFR 40 mL/min
Tubular necrosis
IF/TA
Grade II
Trichrome

8. One-year protocol biopsy Creatinine 120 umol/L GFR 40 mL/min
Glomerulitis (g3), no ptc, mm2
No IgG
Negative C4d
assymetrical cv2
Trichrome
PAS
Immunofluorescence: anti IgG
C4d
IF/TA grade III

9. Conclusion: sub-clinical acute humoral rejection
CASE REPORT
Conclusion: sub-clinical acute humoral rejection
Treatment with:
Steroids
Plasmapheresis (x5)
Rituximab
Intravenous immunoglobulin (x4)
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10. 2 years after transplantation for increased serum creatinine
Fourth renal biopsy
2 years after transplantation
for increased serum creatinine
and nephrotic range proteinuria (12g/d)
IF anti IgG
Trichrome

11. Trichrome
Trichrome
cv3
mesangiolysis
thrombosis
Jones
Thrombosis in a preglomerular arteriole
g2+ptc2

12. CASE REPORT Conclusion of the 4th biopsy
Persistent acute humoral rejection
Thrombotic microangiopathy
Severe fibrous intimal hyperplasia
No recurrence of membranous nephropathy
Recurrence of
APS nephropathy
Creatinine 230 μmol/L
Nephrotic range proteinuria
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13. Antiphospholipid 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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14. Antiphospholipid syndrom (APS) and kidney
29 biopsies with primary APS
20 biopsies with vascular APS nephropathy
9 cases of glomerulonephritis
3 Membranous Nephropathy
2 C3 mesangial deposits glomerulonephritis
3 MCD/FSGS
1 pauci-immune vasculitis
Several cases of MN
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Anticardiolipin antibody and renal disease: a report of 3 cases. D’Agati. JASN 1: , 1990
Primary antiphospholipid syndrome presenting as renal vein thrombosis and membranous nephropathy. Chaturvedi S. Pediatr Nephrol Jun;26(6):

15. APS and kidney transplantation
Canaud G, et al
To assess the long term clinical and histological significance of APA+ and APS
1359 transplantations (January 1, 2000 and Decembre 31, 2009)
AP antibodies (APA+)
n=37 (2,7%)
Lupus anticoagulant
n=37/37 (100%)
Anti β2GP1 (n=7/37)
Anti CL (n=11/37)
APS
n=12
APA+
n=25
Primary APS
n=3
Secondary APS
N=9
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Compared to 59 matched APA- transplant recipients

16. APS and kidney transplantationcv ah ci ct cv ah ci ct
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17. Vascular 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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18. CONCLUSION Antiphospholipid syndrome is a severe disease with
More thromboembolic events after transplantation
Poor graft outcome
Recurrence of APS nephropathy
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
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