1. Recurrent And De Novo GN After Renal Transplantation

2. Introduction The 1 year kidney allograft survival rate has
improved dramatically during the last decade
with the introduction of newer IS agents
Development and progression of recurrent and
de novo disease does not seem to have been
influenced by the use of those agents

3. Introduction Clinically, recurrent GN manifests primarily as
an increase in proteinuria in the allograft, usually
associated with progressive loss of renal function
or chronic kidney disease (CKD).

4. Introduction 30- 50 % of KT recipients have GN as the
underlying cause of their ESRD
Those patients are at risk of the recurrence of
their original disease.

5. Introduction Among these patients, more than 40% develop
significant proteinuria, and around 15% develop
persistent nephrotic syndrome
The most common cause of post transplantation
proteinuria is chronic allograft nephropathy
(50%), followed by recurrent (15%) and de novo
(10%) glomerulonephritis

6. Introduction Persistent proteinurea is associated with a
significantly reduced rate of graft survival but
often can be controlled with non-disease
specific therapy including ACEI and ARB

7. Introduction In patients who develop recurrent and de novo
disease , there is a 190% increased risk of losing
the graft compared with those without recurrent
and de novo disease.
Glomerulonephritis in the allograft is also
associated with a reduction in long-term (5-year)
survival

9. Introduction Variables that have been found to be associated
with recurrence included younger age, male
gender, underlying GN as a cause of ESRD and
retransplants
Higher prevalence in young ages is probably
explained by the more frequent occurrence of GN
in this group.

10. Introduction No penalty paid in terms of increased recurrence
of GN for recipients who received their
transplants for GN and were maintained on
steroids-free IS regimen.

12. Focal glomerular sclerosis
FGS is the disease entity that carries the
highest incidence of clinically significant
recurrent disease with the greatest impact on
graft survival of any of the glomerular diseases

13. Focal glomerular sclerosis
The overall recurrence rate in FGS is about 30%
50% of these grafts are lost from recurrent
disease in 5 years .

14. Focal glomerular sclerosis
The mean time to recurrence of FGS is short, 10-
14 days, but recurrences have been reported
within hours and up to 6 months after
transplantation.

15. Focal glomerular sclerosis
Up to 50% of patients with recurrent FGS also
develop acute renal failure, 80% become
nephrotic, and hypertension and hematuria are
common

16. Focal glomerular sclerosis
Clearly, recurrence is more common in younger
patients. Patients under 5 years of age have a 50%
likelihood of recurrence versus only 10%-15% in
patients older than 30 years

17. Focal glomerular sclerosis
Caucasian recipients seem more likely to have
recurrences than African-Americans. Rapid
progression of the underlying disease from
initial diagnosis to development of ESRD,
particularly if it occurs within 3 years, also
predicts recurrence.

18. Focal glomerular sclerosis
Recurrence itself is a very bad prognostic sign
that predicts recurrence in second allograft.
Over 70% of such grafts have another recurrence
and most are lost. Thus, a history of graft
loss from recurrent FGS virtually precludes
subsequent successful transplantation in that
recipient.

19. Focal glomerular sclerosis
The pathogenesis of FGS is unclear, however a
circulating permeability factor that is removed by
plasmaphresis has been suspected to play a role
However recent data suggested the absence or
loss of an inhibitor factor could be the cause

20. Focal glomerular sclerosis
Further complicating the picture is the
recognition of the pivotal role of podocytes
proteins(podocin, nephrin, and actinin) in FSG

21. Focal glomerular sclerosis
Early institution of plasmaphresis is important as
the effectiveness of treatment decreases with
increased number of sclerosed glomeruli.
Relapses after cessation of plasmaphresis can be
prevented by chronic phresis or concurrent
cyclosporine or cyclophosphamide therapy

22. Focal glomerular sclerosis
The role of preemptive perioperative
plasmaphresis in high risk groups still awaits
further studies.
There is one recent case report of complete
remission of FSG with rituximab

23. Focal glomerular sclerosis
A number of case reports reported the
development of de novo FSG when cyclosporine
was switched to sirolimus with subsequent
improvement after switching back to cyclo.
Paradoxically sirolimus has achieved complete
remission in 12 out of 21 steroid resistant FSG in
another study

24. Membranous Nephropathy
Secondary causes of MN (infection,
malignancy… etc) should be screened
Idiopathic MN recurs in 10-30%
Recurrent disease should be differentiated from
de novo disease which is the most common de
novo GN in renal allograft

25. Membranous Nephropathy
The clinical presentation of recurrent MN is
characterized by nephrotic range proteinuria
with a mean onset time of (10-24) months post-
transplant as compared with the more insidious
and later onset of de novo MN (24-36) months

26. Membranous Nephropathy
Recent studies showed antibodies against
‘neutral endopeptidase’, a protein expressed on
the human podocyte cell membrane might be
playing a role in MG
Risk factors for recurrence include male sex,
rapid course of initial disease and LRD kidneys
Graft failure from recurrence is 10-15%

27. Membranous Nephropathy
Cyclosporine and MMF which have been used in
the treatment of primary MN do not prevent or
change the course of recurrent disease
No reports to suggest superiority of tacrolimus or
cyclophosphamide over cyclosporine

28. MPGN Secondary causes of MPGN should be treated to
reduce the risk of recurrence.
Type I and II primary MPGN have high rate of
recurrence after transplantation, 20-50% and 80-
100 %respectively

29. MPGN Risk of recurrence increases in those with HLA-
B8DR3, LRD and previous graft loss due to
MPGN
Recurrent disease is more common in type II and
presents with non-nephrotic range proteinurea
Complement level has nothing to do with the risk
of recurrence

30. MPGN Type II usually has more aggressive golmerular
changes and a poorer prognosis
No effective therapy is available

31. Pauci-Immune Crescentic GN
Pretransplantation course, cANCA, pANCA titer,
disease subtype(WG, MPAN or CGN) in the
absence of clinically active disease, duration of
follow up or donor type, do not predict
recurrence.
Recurrence rate is around 20%

32. Pauci-Immune Crescentic GN
It is advisable to defer transplant until the disease
is inactive
Patients with renal relapses showed good
response to cyclophopsphamide.

33. Pauci-Immune Crescentic GN
For patients with cellular crescent and high
ANCA titer, favorable outcome has been
reported with combined cyclophosphamide,
plasmaphresis with or without intravenous
immunoglobulin

34. SLE Histological recurrence has been reported in 30%
Clinically significant recurrence occurs in 2-9%
Most center postpone re-transplant until the
disease is quiescent for 6-9 months

35. SLE The duration of dialysis before transplantation
and the serological markers in the absence of
clinically active disease do not predict recurrence
MMF has been shown to be very efficient.
Graft loss due to recurrent lupus is uncommon,
2-4%

36. SLE Long term patients and graft survival are similar
to kidney allograft recipients with other
underlying disease.

37. Anti-GBM Histological recurrence has been reported in 50%
if transplantation is performed while circulating
anti-GBM antibodies are still present
Defer transplantation until the disease become
quiescent and the anti-GBM antibodies become
undetectable for 12 months

38. Anti-GBM Good response has been reported in one patient
with steroids, plasmaphresis and
cyclophosphamide, another patient responded
well to immune adsorption and
cyclophosphamide

39. Immunoglobulin A Nephropathy
IgAN is the commonest GN worldwide and
accounts for 20 % of renal failure of all renal
transplant cases.
Great variation in the incidence of recurrence has
been reported by many centers as most centers
perform biopsies only when patients are
symptomatic, underestimating the real number

40. Immunoglobulin A Nephropathy
For centers where routine biopsies were being
carried out, histological recurrence had been
reported in %
Recurrence rate for patients with renal biopsies
done for clinical symptoms ranges from 13-50%

41. Immunoglobulin A Nephropathy
Recurrent disease is not as benign as had been
reported previously
Graft loss from the severest form ranges from
1.3 to 16 %
No single parameter including age, gender, race,
HLA or biochemical characteristic can predict
recurrence

42. Immunoglobulin A Nephropathy
The relationship between recurrence and donor
type remains controversial except in the familial
form of IgAN where recurrence is high in LRD
cases
Renal allograft survival in the first 10 years after
transplantation is better when compared to other
primary disease

43. Immunoglobulin A Nephropathy
The situation is different for patients with prior
graft loss due to IgAN where the recurrence risk
in the second transplant is %, and patients
should be excluded from LRD list
There is no effective therapy to prevent recurrent
IgAN

44. Immunoglobulin A Nephropathy
Despite initial enthusiasm about MMF, recent
data are not substantiated
Data on sirolimus is limited
Steroids-free or rapid steroid withdrawal
regimen does not seem to affect recurrence risk

45. Immunoglobulin A Nephropathy
ACE-I and ARB are used in proteinuric patients.
HSP recurrence rate after transplantation is
similar to IgAN

46. Conclusion With improving long-term renal allograft
survival, recurrent disease has increased
prominence as a significant contributor
to late graft loss.
Knowledge of the risk factors for
recurrence, onset time and impact on graft
function is prerequisite to informed decisions

47. Conclusion Apart from plasmaphresis for patients
with recurrent FSGS, there is no consensus on
Strategies to prevent or treat recurrent
glomerular disease in the kidney allograft.

48. Conclusion Also, in spite of the controversy over the risk of
recurrence with certain types of
glomerulonephritis when the source of allograft
is from living donors, the graft survival is largely
comparable to patients with other causes of end-
stage renal failure. Thus, living related kidney
Donation can still be encouraged

49. Conclusion Caution should be exercised in patients
with previous rapid graft loss due to
recurrent disease in view of the
markedly increased risk with subsequent
transplants.