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Case 2
Erik Heyerdahl Strøm
Division of Pathology
Willy Aasebø
Department of Nephrology
Oslo University Hospital, Rikshospitalet Norway
Co-authorLars Ola Thorud
Innlandet Hospital, Lillehammer
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Case history -1
Male, born 1955
2002: Nephritis, creatinine >500, SR 120, C-ANCA: positive
Renal biopsy
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Initial biopsy native kidney 2002
Fibrocellular crescents
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Initial biopsy native kidney 2002
Fibrocellular crescents
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Initial biopsy native kidney 2002
Immunofluorescence: Negative
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Initial biopsy (EM) native kidney 2002
No electron dense immune deposits
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Diagnosis native kidney biopsy 2002
Focal segmental necrotizing glomerulonephritis with fibrocellular crescents without immune deposits.
Consistent with ANCA-related glomerulonephritis as in Wegener’s granulomatosis
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Case history -2
Hemodialysis from – August 2002
Kidney transplantation – January 2006
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Case history -3
November - December 2008: gradually increased dyspnoea + oedema, anaemia, and fever.
S-creatinine: 120 to 180 µmol/l
C-reactive protein: 15 to 70 mg/l
Protein/creatinine (urine): 60 to 400 mg/mmol
Urine microscopy: Nephritic sediment.
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Due to increase in s-creatinine and proteinuria
A graft biopsy was obtained
6 weeks after debut of symtoms
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What to consider in a transplant biopsyAcute rejection?
cellular rejection (T-cell mediated)
antibody-mediated rejection (C4d)
Chronic rejection?
Ischemia?
Drug toxicity?
•CNI (CyA, tacrolimus)?
•Antibiotics?
Infection?
•Virus (polyoma, CMV)
•Systemic infection?
De novo nephritis?
Recurrence of native disease?
Other? (Post transplant lymphoproliferative disease - PTLD)
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Minimal tubulitis No vasculitis
Biopsy of the transplant
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Double contour capillary wallMesangial cell interposition
Transplant glomerulopathy
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Necrosis? Thrombotic material?
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Cellular crescent
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Cellular crescent
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Diagnosis based on light microscopy
No acute rejection (C4d negative)
Transplant glomerulopathy
Focal necrotizing glomerulopathy with few cellular crescents (thrombi?)
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Immunfluorescence (paraffin block)
C1q C3
IgA, IgG and IgM were negative
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Electron microscopy
No glomeruli in the material submitted for EM
EM therefore performed on material retrieved from the paraffin block
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Electron microscopy (paraffin block)
Transplant glomerulopathy (doubling of basement membrane)
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Electron microscopy (paraffin block)
Mesangial deposits
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Subendothelial deposits
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Biopsy diagnosis of transplant
No definite acute rejection (i1 t1 v0, C4d negative)
Transplant glomerulopathy as in chronic rejection
Focal necrotizing glomerulonephritis with cellular crescents in 2 of 13 glomeruli (obs thrombi)
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Biopsy diagnosis of transplantConsider
Recurrence of Wegener’s granulomatosis
Systemic infection
Thrombotic microangiopathy
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Possible diagnosis -1
Thrombotic microangiopathy ?
TTP/HUS?
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Thrombotic Microangiopathy after Tx
As a complication to CNI`s: -- 4-6 %. Usually during the first weeks after Tx.
Other medicines
Acute rejection
Infection (viral, bacterial)
Carcinoma
Anti-cardiolipin antibodies
(Associated with OKT3)
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Case history -4
Hgb: 9,2. Thrombocytes: 220 109 . Lactate dehydrogenase: 356 U/l, Bilirubin: 15 µmol/l, (Haptoglobine: not analyzed)
No symptoms from CNS
Conclusion: no TTP-HUS!
! Few crescents are found in 5% of HUS!
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Possible diagnosis -2
Recurrence of Wegener’s granulomatosis?
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ANCA positive vasculitis after TxN=35 with ANCA-associated vasculitis
20: microscopic polyangitis
15: Wegener
Median time from diagnosis to Tx: 25 months
15: ANCA positive at Tx
Overall graft survival 5 years: 94%
Death censored graft survival: 100%
Relapse: Microscopic polyangitis: 1/20, Wegener: 2/15
All relapses: Non-renal Gera M. Kidney int. 2007
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Patient and Graft survival after renal transplantation in Wegener, PKD, IgA-nephropathy and diabetes
Schmitt W, Curr Opin Rheumatol, 2003
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Case history -5ANCA: negative
PR3 and MPO: <9 (negative)
ANA: negative
Anti GBM: neg
C3 : 1.44 g/l (0.80 – 2.00) (normal)
C4: 0.28 g/l (0.10-0.50) (normal)
Conclusion: No recurrence of Wegener
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Possible diagnosis -3
Systemic infection?
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Case history -7
Bacterial growth in blood cultures:
- Streptococcus sanguis
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Dr. S. Urheim, Dept. of Cardiology, Rikshospitalet
Ultrasound of the heart
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Ultrasound of the heart
Dr. S. Urheim, Dept. of Cardiology, Rikshospitalet
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Case history -8
Ecco-cardiography: aortic valve with vegetations on all three cusps.
Endocarditis!!!
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Possible diagnosis -3b
Renal affection related to endocarditis
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Renal disease in infective endocarditis
Embolic disease --
Microbiological emboli Drug-induced disease --Acute interstitial nephritis - antibiotics --Acute tubular necrosis - Aminoglycosides
Postinfectious immune complex-mediated glomerulonephritis
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Renal pathological findings in infective endocarditis354 Patients with endocarditis
62: Renal tissue for examination (20+42)
Majumdar A, NDT 2000
Findings in the Kidney Renal biopsy (n=20) Autopsi (n=42) Total (n=62)
Localized infarction 0 19 19
Acute glomerulonephritis 9 7 16
Acute tubular damage 4 8 12
Cortical necrosis 0 6 6
Acute Interstitial nephritis 5 1 6
Pre-existing glom disorder or Hydronephrosis
4 1+1 5+1
Normal Kidney 0 3 3
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Postinfectious glomerulonephritisin general
Previously associated with streptococcus.
Now: associated with several infectious syndromes and a wide variety of bacteria, fungi, viruses and parasites.
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Postinfectious glomerulonephritisclinical manifestationsAcute Nephritic Syndrome.
--Hematuria, proteinuria, edema, often hypertension, and a mild degree of kidney injury
Rapidly progressive nephritic syndrome
--Rare (4,6% of biopsies). Rapidly increase in s-creatinine. Crescent formation (often limited)
Subclinical or asymptomatic glomerulonephritis
--Low grade proteinuria, microscopic hematuria. 4-19 times as common as “classic acute nephritic syndrome”
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Postinfectious glomerulonephritis histological findingsIn light microscopy:
-diffuse exudative proliferation without crescents
-diffuse endocapillary proliferation with crescents
-mild segmental, mesangial proliferation
-membranoproliferative glomerulonephritis
Immunofluorescence:
-most commonly: deposition of C3 often IgG,
-occasionally: IgM, rarely: IgA (except in patients with diabetes-particularly Staphylococcal infections)
- “Full house”: IgG. IgA, IgM, C3, C4 and C1q is frequently reported
Electron microscopy:
-mesangial, subendothelial and ”humps”
Kanjanabuch T, Nature Reviews Nephrology, 2009
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Final diagnosis :
Postinfectious glomerulonephritis related to acute endocarditis
Transplant glomerulopathy
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Case history -9Treatment: Penicillin + Gentamycin for 6 weeks
13.1-2009: removal of the affected aortic valve: Implant: biological aortic valve
8 months after surgery: S-creatinine: 128 µmol/l Urea: 11.5 mmol/l
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Take home message
1: Focal glomerulonephritis with crescents
-----Don’t forget infection !
2: ANCA-associated vasculitis vs. postinfectious glomerulonephritis:
-----Correct diagnosis is pertinent; treatment and outcome different
3: Histological findings must always be considered in concert with clinical findings
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Thank you for your attention