Transcript Document 7672875

Kidney transplant case
Niels Marcussen
Hans Dieperink
Odense University Hospital
Risc factors for the graft
Male_1961
• Nephrotic syndrome 2004
• MGUS
• Membranoproliferative glomerulonephritis, with
kappa-chains deposits
• Peritoneal dialysis 2006
• Renal transplant 16SEP2008
• Living donor, mismatch 4:1
• Immediately decreasing s-creatinine
• Simulect, Sandimmun, CellCept
Male_1961
• Suspected acute cellular rejection 19SEP2008,
s-creatinine rose to 623 µmol/l
• Methylprednisolon intravenously, Prograf
replaced Sandimmune
• Graft biopsy delayed to 25SEP2008 due to high
MAP. Biopsy 1…..
Graft 1
Male_1961
• 08OCT2008 s-creatinine 164 µmol/l
• 14OCT2008: s-creatinine 234 µmol/l; No
serum or urine M-komponent
• Graft biopsy 2….
• 24OCT2008: s-creatinine 293 µmol/l, graft
biopsy 3….
Graft 2
Graft 3
C4d, graft biopsy 3
C3, graft biopsy 3
Graft 3, CD68
Graft 3, CD3
Male_1961
• 24 OCT2008 Methylprednisolone
intravenously
• 17NOV2008: s-creatinine 564 µmol/l,
repeat X-match negative, no circulating
Class I or II antibodies. Graft biopsy 4…
Graft 4
CD68
graft biopsy 4
graft biopsy 4
Male_1961
•
•
•
•
Intravenous Immunoglobulin 24 gram *2
26NOV2008: peritoneal dialysis
01DEC2008: graft biopsy 5…
plasmapheresis * 10 (4 liters, substitution
with HA)
• 17DEC2008: CMV PCR positive
• 02JAN2009: graft biopsy 6…
• 10JAN2009: graftectomia
Graft 5
Graft 6
Graft 6, CD68
graft biopsy 6
Graftectomy
Graftectomy
Your diagnosis?
Glomerulitis in historic
perspective
• Richardson et al: Glomerulopathy
associated with cytomegalovirus viremia in
renal allografts. N Engl J Med 1981
• Olsen S et al. Endocapillary glomerulitis in
the renal allograft. Transplantation 1995.
13.5% of biopsies from the first 90 d
postTx.
Glomerulitis
• Characterized by
mononuclear cell
infiltration of the
glomerulus
• Both monocytes and
T cells may be
present
Banff Classification
• g0: No glomerulitis
• g1: Glomerulitis in less than 25% of
glomeruli
• g2: Segmental or global glomerulitis in
25% to 75% of glomeruli
• g3: Glomerulitis (mostly global) in more
than 75% of glomeruli
The Banff 97 working classification
Differential diagnosis:
Recurrent or denovo glomerulonephritis
Chronic transplant glomerulopathy
Glomerular inflammatory cells Monocytes vs. T cells:
Mean monocytes/glomerulus >1 independently
predicted poor renal functionat 2 years (Tinckam KJ et
al. Kidney Int 68:1866-1874, 2005)
Monocytes is present together with C4d
deposition, unlike T cells which are mainly
present i cases without C4d deposition (Magil AB, Am
J Kidney Dis 45:1084-1089, 2005)
Correlation to peritubular capillary C4d
deposition and to peritubular capillaritis
• Severe glomerulitis was present only in
cases with diffuse C4d deposition in the
study of 54 renal biopsies by Valente et al.
(Transpl Proceedings 39: 1827-1829, 2007)
• 82.8% of biopsies with glomerulitis had
peritubular capillaritis (Gibsin IW et al., Am J Transpl
8:819-825, 2008)
Conclusions
• Glomerulitis was found in 5% of protocol biopsies from
stable renal allografts (Gough, Rush et al, NDT 2002;17:10811084)
• Glomerulitis was seen in 30-60% of biopsies from
patients who had previous positive X-match or previous
or current class I or II panel reactive antibodies
(Anclicheau et al, Am J Transplant 2007;7:1185-1192).
• Glomerulitis was associated to poor graft outcome when
observed in patients with antibody-mediated rejection
(Lefaucheur et al, Am J Transplant 2007;7:832-841)
Conclusions
• Glomerulitis, however, did not significantly increase rate
of graft loss in patients without evidence of vascular
rejection, and was reported not to be an independent
predictor of graft survival (Messias et al, Transplantion
2001;72/4:655-660)
• Some degree of glomerulitis is present in most cases of
transplant glomerulopathy (i.e., glomerulitis and double
contours of GBM)
• Virus, including CMV, may cause glomerulitis (Cathro et
al, Am J Kidney Disease 2008;52/1:188-192.)
Conclusions
• Present case was a severe, progressive glomerulitis not
related to acute cellular or humoral rejection, to presence
of virus in the graft, or to transplant glomerulopathy
• The glomerulitis caused loss of graft function, in spite of
conventional anti-rejection therapy, plasmapheresis, and
IVIG
Native biopsy