Transcript Document

Case 2
Erik Heyerdahl Strøm
Willy Aasebø
Division of Pathology
Department of Nephrology
Oslo University Hospital, Rikshospitalet
Norway
Co-author
Lars Ola Thorud
Innlandet Hospital, Lillehammer
Case history -1
Male, born 1955
2002: Nephritis, creatinine >500, SR 120,
C-ANCA: positive
Renal biopsy
Initial biopsy native kidney 2002
Fibrocellular crescents
Initial biopsy native kidney 2002
Fibrocellular crescents
Initial biopsy native kidney 2002
Immunofluorescence: Negative
Initial biopsy (EM) native kidney 2002
No electron dense immune deposits
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
Case history
-2
Hemodialysis from – August 2002
Kidney transplantation – January 2006
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.
Due to increase in s-creatinine
and proteinuria
A graft biopsy was obtained
6 weeks after debut of symtoms
What to consider in a transplant biopsy
Acute 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)
Biopsy of the transplant
Minimal tubulitis
No vasculitis
Transplant glomerulopathy
Mesangial cell interposition
Double contour capillary wall
Necrosis? Thrombotic material?
Cellular crescent
Cellular crescent
Diagnosis based on light microscopy
No acute rejection (C4d negative)
Transplant glomerulopathy
Focal necrotizing glomerulopathy with few cellular crescents (thrombi?)
Immunfluorescence (paraffin block)
C1q
C3
IgA, IgG and IgM were negative
Electron microscopy
No glomeruli in the material submitted for EM
EM therefore performed on material retrieved
from the paraffin block
Electron microscopy (paraffin block)
Transplant glomerulopathy (doubling of basement membrane)
Electron microscopy (paraffin block)
Mesangial deposits
Subendothelial deposits
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)
Biopsy diagnosis of transplant
Consider
Recurrence of Wegener’s granulomatosis
Systemic infection
Thrombotic microangiopathy
Possible diagnosis -1
Thrombotic microangiopathy ?
TTP/HUS?
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)
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!
Possible diagnosis
-2
Recurrence of Wegener’s granulomatosis?
ANCA positive vasculitis after Tx
N=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
Patient and Graft survival after renal transplantation in
Wegener, PKD, IgA-nephropathy and diabetes
Schmitt W, Curr Opin Rheumatol, 2003
Case history
-5
ANCA: 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
Possible diagnosis -3
Systemic infection?
Case history
Bacterial growth in blood cultures:
- Streptococcus sanguis
-7
Ultrasound of the heart
Dr. S. Urheim, Dept. of Cardiology, Rikshospitalet
Ultrasound of the heart
Dr. S. Urheim, Dept. of Cardiology, Rikshospitalet
Case history
-8
Ecco-cardiography: aortic valve with vegetations on
all three cusps.
Endocarditis!!!
Possible diagnosis
-3b
Renal affection related to endocarditis
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
Renal pathological findings in
infective endocarditis
354 Patients with endocarditis
62: Renal tissue for examination (20+42)
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
Majumdar A, NDT 2000
Postinfectious glomerulonephritis
in general
Previously associated with streptococcus.
Now: associated with several infectious syndromes
and a wide variety of bacteria, fungi, viruses and
parasites.
Postinfectious glomerulonephritis
clinical manifestations
Acute 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”
Postinfectious glomerulonephritis
histological findings
In 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
Final diagnosis :
Postinfectious glomerulonephritis related to acute
endocarditis
Transplant glomerulopathy
Case history
Treatment: 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
-9
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
Thank you for your attention