Kidney transplant case
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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

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Kidney transplant case

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Kidney transplant case

Kidney transplant case

Niels Marcussen

Hans Dieperink

Odense University Hospital


Risc factors for the graft

Risc factors for the graft


Male 1961

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 19611

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

Graft 1


Male 19612

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 2


Graft 3

Graft 3


Kidney transplant case

C4d, graft biopsy 3


Kidney transplant case

C3, graft biopsy 3


Graft 3 cd68

Graft 3, CD68


Graft 3 cd3

Graft 3, CD3


Male 19613

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

Graft 4

CD68


Kidney transplant case

graft biopsy 4


Kidney transplant case

graft biopsy 4


Male 19614

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 5


Graft 6

Graft 6


Graft 6 cd68

Graft 6, CD68


Kidney transplant case

graft biopsy 6


Graftectomy

Graftectomy


Graftectomy1

Graftectomy


Your diagnosis

Your diagnosis?


Glomerulitis in historic perspective

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

Glomerulitis

Characterized by mononuclear cell infiltration of the glomerulus

Both monocytes and T cells may be present


Banff classification

Banff Classification

The Banff 97 working 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


Kidney transplant case

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

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

Conclusions

  • Glomerulitis was found in 5% of protocol biopsies from stable renal allografts (Gough, Rush et al, NDT 2002;17:1081-1084)

  • 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)


Conclusions1

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.)


Conclusions2

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

Native biopsy


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