In-Depth Review

Posttransplant Recurrence of Primary Glomerulonephritis

Claudio Ponticelli* and Richard J. Glassock†
*Division of Nephrology, Scientific Institute Humanitas, Milan, Italy; and †Department of Medicine, David Geffen
School of Medicine at the University of California–Los Angeles, Los Angeles, California

All forms of primary GN may recur after kidney transplantation and potentially jeopardize the survival of the graft. IgA
nephritis (IgAN) may recur in approximately one third of patients, more frequently in younger patients and in those with a
rapid progression of the original disease. However, with the exception of few patients with rapid progression, there is no
evidence that recurrence of IgAN has a deleterious effect on graft survival at least up to 10 years. Recurrence of focal segmental
glomerulosclerosis (FSGS) is often associated with nephrotic proteinuria and is more frequent in children, in patients with
rapid progression of the original disease, and in those who lost a previous transplant from recurrence. The natural course of
recurrent FSGS is usually unfavorable. Early and intensive plasmapheresis may obtain complete or partial response in several
patients. Good results have also been reported with rituximab. Idiopathic membranous nephropathy (IMN) may recur in 30%
to 40% of patients. The graft survival in patients with IMN is not different than that of patients with other renal diseases. Good
results with rituximab have been reported. Membranoproliferative GN (MPGN) may recur in 27% to 65% of patients. The
recurrence is more frequent and the prognosis is more severe in type II MPGN. Although recurrent GN is relatively frequent
and may worsen the outcome of renal allografts in some patients, its effect is diluted by several other risk-factors that may
have a greater effect than recurrent GN on the long-term graft survival.
Clin J Am Soc Nephrol 5: 2363–2372, 2010. doi: 10.2215/CJN.06720810

A
s for other patients with ESRD, renal transplantation
represents the treatment of choice for patients with
primary (idiopathic) GN and advanced, irreversible
renal failure. However, the possibility of recurrence of the
original disease after transplantation was described in a semi-
nal paper more than 40 years ago (1), and it is now clear that all
forms of GN may recur after kidney transplantation and po-
tentially jeopardize the long-term outlook for graft survival
(2,3), although the risk of recurrence is different for the various
categories of primary GN. Recent studies provided new clues
for better understanding the pathogenesis and thereby enhanc-
ing the possibility for improving the prevention or treatment of
some forms of recurrent GN. This review will focus on the four
more frequent forms of primary (idiopathic) GN that can recur
after renal transplantation in Western countries; namely, IgA
nephritis (IgAN), focal segmental glomerulosclerosis (FSGS),
membranous nephropathy (MN), and membranoproliferative
GN (MPGN). Recurrence of secondary forms of glomerular
diseases will not be discussed, nor will the uncommon event of
recurrent anti-neutrophil cytoplasmic antibody-positive small-
vessel vasculitis in renal allografts.
IgAN
IgAN is a primary GN characterized by the dominant or
co-dominant diffuse mesangial deposition of IgA, usually IgA1.
The deposits consist of an aberrant galactose-deficient form of
Published online ahead of print. Publication date available at www.cjasn.org.
Correspondence: Dr. Richard J. Glassock, 8 Bethany, Laguna Niguel, CA 92677.
Phone: (949) 388-8885; Fax: (949) 388-8882; E-mail: Glassock@cox.net
IgA1 and IgA or IgG autoantibodies to the aberrantly glycosy-
lated IgA1 (4,5). The disease usually runs an indolent course but
may lead to ESRD in 30% to 50% of patients after 25 years or
more of follow-up. IgAN is one of the most common recurrent
GN after transplantation (6).
A review of the literature reported that recurrences develop
in approximately 33% of patients with large differences, rang-
ing between 9% and 61%, among the different series (7). Several
reasons can account for these large discrepancies. The indica-
tions for undergoing a graft biopsy were variable in the differ-
ent studies and it is likely that several patients with asymptom-
atic hematuria and/or proteinuria never received biopsy. The
follow-ups were quite different and the risk of recurrence was
probably underestimated for patients followed for short times.
Longer follow-up times yield higher recurrence rates. There are
different racial and geographical distributions of IgAN. In some
cases, IgA deposits could be already present in the donated
kidneys. As an example, in a Japanese series, mesangial IgA
deposits were present in 16% of 510 donated kidneys (8), al-
though it is not clear if the deposited IgA were abnormally
glycosylated.
Recurrences of IgAN can be “immunopathologic” only; dis-
covered on a “protocol” renal biopsy in an asymptomatic pa-
tient; or “clinical,” which is delineated by abnormalities in the
urine and/or renal function leading to a renal biopsy. Clinical
recurrence of IgAN may occur immediately after transplanta-
tion, but on average the diagnosis is made approximately 3
years after transplantation (7,9) and is usually heralded by
hematuria and low-grade proteinuria. The results of renal
transplantation in patients with IgAN have been differently
estimated. Some investigators (10,11) reported a more favorable

Copyright © 2010 by the American Society of Nephrology ISSN: 1555-9041/512–2363

2364 Clinical Journal of the American Society of Nephrology
outcome of the renal allograft in patients with IgAN than in
other transplant recipients, but others found that graft survival
in an IgAN group was similar to that of non-IgAN renal trans-
plant recipients (12–14). An analysis of the Eurotransplant reg-
istry data reported the outcome of 1207 patients with IgAN and
7935 other renal transplant recipients. The 10-year death-cen-
sored graft survival was identical in the control group with and
without the HLA-B8, DR3 haplotype (71.1% versus 70.2%) but
significantly worse in IgAN patients carrying the HLA-B8, DR3
haplotype than in patients without it (52.5% versus 69.1%, P ⫽
0.009), suggesting that this HLA haplotype may represent a risk
factor for transplant recipients with IgAN (15). The limit of this
study rests on the large heterogeneity between patients with
IgAN and the control population. A case-control study com-
pared the long-term outcome of 106 patients transplanted be-
cause of IgAN with that of 212 non-IgAN patients transplanted
in the same period and in the same center (16). After censoring
the graft failures in the first 6 months, the 10-year graft survival
probability was not significantly different between the two
groups: 75% in patients with IgAN and 82% in controls. The
regression coefficient of the reciprocal of plasma creatinine was
also similar in the two groups. In a Cox proportional hazards
model analysis, IgAN recurrence was not associated with an
increased risk of graft failure. Other series reported that recur-
rence of IgA deposition has only a modest and inconsistent
effect on graft survival. In the Australia-New Zealand registry,
the long-term graft survival was not affected by the increased
risk of recurrence in zero-mismatched kidneys (17). In two
large Asian reports, the risk of graft loss due to recurrence
ranged around 3% to 4% (18,19). However, in the very long
term it is possible that recurrent IgAN may represent a sub-
stantial risk factor for graft failure. Rarely, a rapidly progressive
renal failure caused by an underlying crescentic GN may occur
(20,21).
Recurrence tends to occur more frequently in younger pa-
tients and in those with a rapid progression of the original
disease (16,22,23). It is unclear if recurrence is (24,25) or is not
(16,26) more frequent in transplants using related donors. A
review of the data collected by the Australia-New Zealand
registry reported that biopsy-proven IgAN recurrence was sig-
nificantly more frequent in zero HLA-mismatched living donor
grafts (17). However, these results should be interpreted with
caution because several details are lacking in retrospective re-
views of registry data. Most other pretransplant characteristics
are not consistently predictive for recurrence, although some
authors have suggested that latent IgA deposits in the donor
kidney (in “zero” time biopsies of the transplanted kidney) are
highly associated with a recurrence of disease (27), and under-
lying crescentic GN with rapid progression to ESRD may also
predict a higher risk for recurrence (28). There is now general
agreement that the type and intensity of posttransplant immu-
nosuppression does not influence the risk of IgAN recurrence.
However, Berthoux et al. (29) recently reported that the 10-year
cumulative recurrence rate of IgAN was 9% (3 of 29) in patients
who received induction with anti-thymocyte globulins versus
41% (21 of 52) in patients who did not receive such induction
therapy. The authors hypothesized that the protective effect of
Clin J Am Soc Nephrol 5: 2363–2372, 2010
anti-thymocyte globulins could be related to an augmented
production of regulatory T cells.
The finding that some apparently normal donors (living or
deceased) may have “hidden” IgA deposits in the kidney (9)
may have important relevance for pathogenesis of the recurrent
disease. It may be presumed that the circulating autoantibody
to exposed N-acetylgalactosamine residues on galactose-defi-
cient IgA1 in some subjects with IgAN could react with the
“planted” IgA deposits (posited also to be deficient in galactose
residues thus exposing the neo-N-acetylgalactosamine epitopes)
in the allograft and thus promote an immunopathological recur-
rence (4,6,30,31). Whether this immunopathological recurrence
would rise to the level of clinical detection would depend on
the activation of accessory factors (e.g., complement and cyto-
kines [32]). Circulating immune complexes composed of IgG or
IgA autoantibodies to galactose-deficient IgA1 and the relevant
autoantigen might theoretically participate in recurrent disease,
especially if these immune complexes escape normal reticulo-
endothelial-dependent removal mechanisms (33).
No specific therapy for recurrent IgAN is currently available.
A review of the U.S. Renal Data System examined the effect of
immunosuppressive medication on allograft failure due to re-
current GN. After adjusting for important covariates, the use of
cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil,
sirolimus, or prednisone was not associated with graft failure
due to recurrent GN for any type of GN, including IgAN (34).
Angiotensin converting enzyme inhibitors (ACEIs) may be pre-
scribed because a study showed that their use could reduce
proteinuria and blood pressure in transplant recipients with
IgAN (35). However, in using these drugs one should take into
account that the use of ACEIs or angiotensin receptor blockers
(ARBs) in renal transplant recipients may be associated not
only with reduction in proteinuria but also with significant
decreases in GFR and hematocrit (36). Tonsillectomy has been
suggested to be of benefit by Japanese investigators. Sixteen of
28 transplant patients with biopsy-proven recurrence of IgAN
and persistent proteinuria underwent tonsillectomy alone,
whereas the remaining 12 patients did not receive tonsillec-
tomy. Proteinuria decreased significantly in all of the tonsillec-
tomized patients but in none of the other group. The reduction
in proteinuria after tonsillectomy was especially marked in
patients with mild mesangial changes on renal biopsy (37).
Long-term outcomes were not examined in this study. In the
rare cases of recurrent IgAN associated with a rapidly progres-
sive course and crescents at biopsy, a trial with high-dose
corticosteroids, cyclophosphamide, and plasmapheresis may be
attempted, although the results are usually poor.
FSGS
Idiopathic FSGS is often associated with a fully developed
nephrotic syndrome (NS) and may affect children and adults.
In the absence of a treatment-induced remission, FSGS com-
monly progresses to ESRD. Approximately 30% of patients
develop recurrence of FSGS in the first kidney allograft (38).
The risk of recurrence with a second graft in patients who lost
a first graft because of recurrence may approach 100% (39). Two
patterns of clinical presentations of recurrent FSGS after trans-
Clin J Am Soc Nephrol 5: 2363–2372, 2010
plantation are recognized: (1) an early recurrence (the most
frequent) characterized by a massive proteinuria within hours
to days after implantation of the new kidney, and (2) a late
recurrence that develops insidiously several months or years
after transplantation.
The graft survival in patients with FSGS is lower for children
than adults, particularly if the patient is white or Hispanic
(40,41), and is lower in children with FSGS than in those with
other renal diseases (42,43). The renal prognosis is strongly
influenced by recurrence because the relative risk of graft fail-
ure is 2.25 times higher in patients with recurrent FSGS as
compared with patients without recurrence (2). Graft loss
caused by recurrent FSGS is significantly higher in children
receiving living donor transplants compared with deceased
donor transplants in children (44). Only few single-center stud-
ies reported data on graft survival in adults with FSGS. Pardon
et al. (45) reported a graft survival rate of 73% at 5 years in 33
transplanted adults with FSGS, with a significant difference
between the patients with (57%) or without (82%) recurrence.
No comparison with a control group was made. Moroni et al.
(46) compared the long-term outcomes of 52 renal transplants
performed in adults with FSGS with those of 104 matched
controls. At 15 years, graft survival was not significantly dif-
ferent: 56% in FSGS and 64% in controls. Recurrence of FSGS
occurred in 12 patients (23%) and led to graft failure in 7 within
10 months (median). In the other five patients, proteinuria
remitted and grafts were functioning 106 months (median) after
transplantation. In the long term, patient and renal allograft
survivals of adults with FSGS were comparable to those of
controls.
Several clinical factors have been reported to be associated
with an increased risk of recurrence, including young age,
mesangial proliferation in the native kidneys, a rapid progres-
sion to ESRD, a pretransplant bilateral nephrectomy, white
ethnicity, and specific aspects of genetic background (47). The
histologic variant type of FSGS observed in the native kidneys
does not seem to reliably predict either recurrence or type of
FSGS seen on the allograft (48). There is a higher risk of recur-
rence in living donor transplant pediatric recipients (49); how-
ever, the reduced risk of rejection and a lower immunosuppres-
sion in living-related transplants may overcome the deleterious
effect of recurrent GN. A review of the U.S. Renal Data System
data reported that, after correction for other factors, living
donor transplants had no association with graft loss from re-
current FSGS; rather, a living donor transplant was associated
with superior overall graft survival (50). Cibrik and co-workers
(51) also found that the risk of death-censored graft loss was 1%
per year in adults with FSGS who received a zero HLA mis-
match kidney from living donors versus a 4.4% loss per year for
patients with FSGS who received a zero HLA mismatch kidney
from deceased donors. Another issue concerns the living-re-
lated kidney donation to a subject affected by familial FSGS.
Until recently the current opinion was that patients with famil-
ial FSGS caused by mutations of NPHS2, the gene encoding
podocin, did not run any risk of recurrence after transplanta-
tion. However, there is now evidence that the risk of recurrence
in patients with the NPHS2 mutation is low (but not zero) at
Recurrent Glomerulonephritis 2365
approximately 8% (52). Therefore, caution should be observed
in transplanting patients with NPHS2 mutations using the kid-
ney of their parents who are obligate carriers of the NPHS2
mutation (53). It is also possible to speculate that in patients
with genetic FSGS the transplant of a normal kidney may evoke
an alloimmune response to slit diaphragm proteins.
The frequent occurrence of a rapid relapse of proteinuria
after transplantation led to a postulate that a circulating factor,
perhaps secreted by an abnormal clone of T cells, may induce
redistribution and loss of nephrin and podocin, two critical
components of the glomerular slit-diaphragm of podocytes,
thereby reducing the efficiency of the glomerular barrier to
proteins. However, despite intensive research by different
groups of investigators (54 –58), the biochemical nature of the
posited circulating permeability factor(s) remains unknown,
and we still lack a reliable chemical or immunoassay for its
presence and quantitation.
The management of patients with recurrent FSGS and NS is
difficult, controversial, and none of the multiple approaches
currently available has been shown to be consistently benefi-
cial. Perhaps more targeted approaches will emerge based on
our improving knowledge of podocyte biology and function.
An amelioration of proteinuria has been reported in children
treated with intravenous cyclosporine at high doses (59 – 62).
This anti-proteinuric effect of cyclosporine may be attributed to
suppression of T cells and inhibited production of their cyto-
kines and to the inhibition of calcineurin-mediated dephos-
phorylation of synaptopodin, a protein critical for stabilizing
the actin cytoskeleton in kidney podocytes (63). Cyclosporine
and other calcineurin inhibitors thus have systemic immuno-
regulatory and local podocyte modulatory actions: Either one
or both can be responsible for their anti-proteinuric effects in
recurrent FSGS. However, the long-term efficacy and tolerance
of such a therapy remains to be established. The most com-
monly used therapeutic approach is the use of plasma exchange
(PE) or immunoadsorption with protein A (59,64 – 66). A review
of the literature reported that 70% of children and 63% of adults
with recurrent FSGS who received PE entered complete or
partial remission of proteinuria (47). However, all studies were
retrospective, uncontrolled, and most of them had only short-
term follow-ups. In a pilot trial, 10 adults with FSGS recurrence
received concomitantly high-dose steroids, intravenous cyclo-
sporine for 14 days followed by oral cyclosporine therapy, and
an intensive and prolonged course of PE. Complete, rapid, and
sustained remission was obtained in 9 of 10 patients. At month
3 and month 12, proteinuria was 0.16 and 0.19 g/d, respec-
tively. PE was stopped at month 9 in all patients except for one
patient who remained PE dependent (64). A protective role of
prophylactic PE before transplantation has also been reported
(65,66). Several single-case reports pointed out the benefit of
rituximab when given alone or in combination with PE (67–72),
but failures were also reported (73–76). Currently, PE combined
with high-dose calcineurin inhibitors with or without rituximab
seems to be the most promising approach, but further con-
trolled trials are needed to define the optimal therapeutic reg-
imens to treat recurrence of FSGS (77).
Despite the risk of recurrence, patients with FSGS should not
2366 Clinical Journal of the American Society of Nephrology
be excluded from transplantation. In the case of living dona-
tion, the possibility of recurrence and its consequences should
be clearly explained to the donor and the recipient and pre-
emptive PE should be planned in advance of transplantation.
An early and aggressive treatment should be provided if pro-
teinuria develops.
IMN
IMN is characterized histologically by uniform thickening of
the glomerular capillary due to immune-complex deposits in
the outer or subepithelial aspect of the glomerular basement
membrane. IMN is a frequent cause of NS in adults and may
lead in 40% to 50% of patients to ESRD in the long term (78,79).
A recurrence of IMN after renal transplantation is probably
more frequent than generally estimated. Up to now, almost 300
cases of recurrent MN have been reported in renal transplant
patients (80 –108), most cases occurring in adults. However, the
true proportion of recurrence is difficult to assess because the
indications for graft biopsy are extremely variable among trans-
plant centers. Moreover a de novo form of secondary MN may
develop in transplanted kidneys showing a histologic pattern
indistinguishable from recurrent IMN. This de novo MN may
occur even more frequently than the recurrent MN. In a study
with protocol biopsies, 6 of 17 cases of MN were identified; of
them 6 (35%) were considered to be recurrent IMN and 11
(65%) de novo MN (108). With these difficulties in mind, the rate
of IMN recurrence has been estimated to range between 30%
and 44% (96,108).
Recurrence of IMN is usually diagnosed between the 2nd
and 3rd year after transplantation, but earlier and later cases
have been described. So far, no clinical or histologic factor
seems to reliably predict the risk of recurrence. In one series
(89) posttransplant recurrence occurred earlier in recipients of a
living-donor allograft (mean 9.3 months after transplantation)
than in deceased donor transplant recipients (18.2 months).
However, a study from Hong Kong reported that MN (includ-
ing recurrent IMN and de novo MN) occurred later, at a mean of
45 months after transplantation (98). The initial clinical mani-
festations of recurrent IMN may be mild or absent, and in
several patients recurrence could be detected only by protocol
renal biopsies (101). However, many patients show a progres-
sive increase in proteinuria over time and can eventually de-
velop a full-blown NS. Proteinuria may spontaneously improve
or even disappear only rarely (94,102).
The results of renal transplantation in patients with IMN are
not different than those observed in patients with other renal
diseases, including primary GN. The Australian registry re-
ported that the actuarial renal allograft survival at 10 years was
similar in patients transplanted because of IMN and in 1505
transplanted patients with other renal diseases (3). The out-
come of recurrent IMN may be as variable as in the original
native disease and its effect on graft survival has been differ-
ently estimated. Some studies have reported that 60% to 65% of
patients with recurrent IMN progressed to ESRD in a mean of
4 years after diagnosis (89,95). However, in many patients the
graft failure was caused by rejection rather than recurrence of
IMN. Other investigators reported that there was not any sig-
Clin J Am Soc Nephrol 5: 2363–2372, 2010
nificant difference in death, graft failures, or serum creatinine
between IMN with recurrent disease and those without recur-
rence after mean follow-ups of 73 and 57 months, respectively
(108).
The mechanisms leading to IMN recurrence are still far from
being elucidated. There is now evidence that MN is triggered
by autoantibodies directed against podocyte proteins. Debiec et
al. (109) identified in newborns from mothers deficient in these
podocyte proteins circulating specific antibodies (IgG4 and
IgG1) against neutral endopeptidase. This is an example of an
allo-immune reaction causing MN and may be more akin to the
pathogenesis of de novo MN. Recently, circulating autoantibod-
ies directed against other podocyte enzymes, such as M-type
phospholipase-2 receptors (110) and aldose reductase and man-
ganese superoxide dismutase (111), have been detected in
adults with IMN and are uniformly absent in secondary forms
of MN. The expression of these autoantigens in podocytes can
trigger the production of specific antibodies (mainly IgG4 and
IgG1) and in situ deposits of immune complexes on the epithe-
lial side of the glomerular basement membrane, with conse-
quent activation of complement, oxygen radicals, and other
components of the inflammatory response. As far as the patho-
genesis of recurrent IMN is concerned, it is possible to hypoth-
esize that recurrent disease is due to the reaction of autoanti-
bodies (anti-phospholipase A2 receptor) from the circulation
with conformational epitopes exposed or genetically deter-
mined in the donor kidney. This possibility has been recently
confirmed by clinical observations (112).
Symptomatic treatment with diuretics, ACEIs, ARBs, hypo-
lipemic drugs, and anticoagulants may help in reducing the
signs and symptoms related to the NS in recurrent IMN. No
convincing evidence exists that corticosteroids, cytotoxic drugs,
or other immunosuppressive agents are of benefit in recurrent
IMN. Rituximab has shown very promising effects in patients
with IMN in native kidneys (113,114) and has also been used
successfully in anecdotal cases of posttransplant IMN recur-
rence (100,103,104). In a recent study, eight patients with recur-
rent IMN and a mean proteinuria of 4.5 g/d were given two
separate doses of intravenous rituximab (1000 mg each) 2
weeks apart. Twelve months later, 35% of patients had a com-
plete remission and another 40% had a partial remission. After
24 months, one patient had relapsed. Post-treatment biopsies
showed reabsorption of electron-dense immune deposits in six
of seven patients (107). In another series, four patients with
recurrent IMN and severe proteinuria were given rituximab,
either at a weekly dose of 375 mg/m2 for 4 weeks, or at a dose
of 100 mg repeated 2 weeks later. Two patients responded to
the first course and the other two patients received a second
course of rituximab. Mean proteinuria decreased from 4.0 to
1.8 g per day, and serum creatinine remained stable at approx-
imately 1.5 mg/dl (108).
MPGN Types I and II (Dense Deposit
Disease)
MPGN is “pattern of injury” rather than a disease (115). It is
now known to have a very diverse array of underlying causes,
and the group designated as ‘idiopathic” MPGN has corre-
Clin J Am Soc Nephrol 5: 2363–2372, 2010
spondingly declined in size (115). Nevertheless. MPGN is com-
mon cause of recurrent GN in allografts. The reported rate of
recurrence of MPGN has been quite variable (27% to 65%) (116).
MPGN has previously been divided into subtypes (types I, II,
III, etc.) on the basis of ultrastructural features. Type I MPGN
characteristically has subendothelial electron-dense deposits
containing IgG and C3, which presumably represent immune
complexes. Type II MPGN (also known as dense deposit dis-
ease [DDD]) shows an electron-dense transformation of the
glomerular basement membrane and deposition of C3 (and
other complement components without IgG deposition). In
previous series, types I and II MPGN (DDD) were considered
together, whereas the current trend is to separate DDD as a
unique clinicopathologic entity having a higher risk of recur-
rence than typical type I MPGN (117). Differences in recurrence
rates between type I MPGN and DDD may relate more to the
superimposition of crescents than to the underlying ultrastruc-
tural features (118). Risk of recurrence may be marginally
higher in living related donors. The most important aspect of
recurrent MPGN or DDD is the identification of the processes
responsible for the original native disease. Recurrent MPGN
due to lupus nephritis, monoclonal gammopathies, thrombotic
microangiopathies, and more frequently HCV infection (119)
do occur, but they are beyond the scope of this review.
Recurrent MPGN type I can have significant deleterious ef-
fects on graft survival, especially when superimposed extensive
crescentic disease is present (118), and thus should be pre-
vented in so far as is possible by careful pretransplant evalua-
tion.
Intensification of immunosuppressive therapy in recurrent
MPGN can be hazardous because it may lead to overimmuno-
suppression and has little documented effect on the outcome of
the recurrence, except perhaps when extensive crescentic dis-
ease is present. Occasional anecdotes and small series have
suggested that improvement may be seen in recurrent MPGN
type I with cyclophosphamide (120) or high-dose mycopheno-
late mofetil (121), but no controlled trial has yet confirmed the
efficacy or safety of these approaches. Treatment of truly “id-
iopathic” recurrent MPGN is generally very disappointing and
graft loss due to recurrence is common (116).
DDD
This disease has a very high risk of recurrence (approaching
100%). Most patients have low serum C3 levels, and 70% to 80%
also have a circulating autoantibody to C3Bb known as C3
nephritic factor (C3Nef). Some patients with DDD may also
have an abnormality in complement cascade regulation such as
deficiencies of factor H) (122). Thus, hypocomplementemia
and/or isolated C3 deposits suggesting DDD in a native kidney
biopsy showing a pattern of MPGN is a feature highly associ-
ated with risk for recurrence (115,116), When ultrastructural
analysis of the native kidney biopsy reveals DDD an evaluation
for complement dysregulation (factor H, I, or membrane cofac-
tor protein levels) seems appropriate. Serum C3 nephritic factor
levels do not reliably predict the risk of recurrence of DDD in
the renal allograft. Subtle monoclonal Ig deposition diseases
such as light-chain deposition disease can also mimic idiopathic
Recurrent Glomerulonephritis 2367
MPGN and contribute to recurrent disease (115,116), frequently
appearing within a few months after transplantation (116).
Finally, a newly described entity, known as “GN C3,” may also
have clinical features similar to DDD and type I MPGN, but it
lacks the ultrastructural features of typical DDD and fails to
show any immune complex deposits characteristically found in
type I MPGN. Only C3 without IgG deposits are observed.
Deficiencies of complement factor H, I, or membrane cofactor
protein are frequently noted. The risk of recurrence of GN C3 in
the allograft is not well known but would be presumed to be
elevated if abnormalities in complement dysregulation are
found.
The successful treatment of an established recurrence of
DDD is problematical, so prevention and anticipatory manage-
ment based on precise assessment of the underlying mecha-
nism responsible for the MPGN is very important. Patients with
complement dysregulation (e.g., factor H deficiency) should
receive replacement infusions (fresh frozen plasma) before and
after grafting (123), although no controlled trials of the efficacy
of this approach have yet been conducted. Plasma therapy has
shown very promising results in atypical hemolytic uremic
syndrome associated with genetic mutations in factor H
(124,125). PE (with fresh frozen plasma replacement) and/or
rituximab might also be helpful in patients with a neutralizing
autoantibody to factor H. Eculizumab (a monoclonal antibody
to C5a) may also be beneficial, but this has not been yet been
shown in a randomized trial (123). Patients with genetic causes
for factor H or I deficiency may require combined liver and
kidney transplantation to avoid recurrences (125), but this is
mainly derived from experience with hereditary forms of atyp-
ical hemolytic uremic syndrome also associated with factor H
deficiency (126). Patients with documented underlying mono-
clonal gammopathies should receive appropriate aggressive
chemotherapy and/or autologous stem cell transplantation be-
fore kidney grafting so as to minimize the risk of recurrence.
Conclusions
Although recurrent GN is relatively frequent and may
worsen the outcome of renal allograft in some patients, its effect
on the fate of a renal allograft is diluted by several other risk
factors, including death with functioning graft, the quality of
the donated kidney, rejection, drug nephrotoxicity, infections,
and other renal and extrarenal complications such as hyperten-
sion, diabetes, coronary artery disease, liver disease, and can-
cer. These factors may have a greater effect than recurrent GN
on long-term graft survival, as demonstrated by large series
showing that overall long-term graft survival is similar in re-
cipients with many forms of primary GN and in those with
other renal diseases (2,127).
Disclosures
None.
References
1. Glassock RJ, Feldman D, Reynolds ES, Dammin GJ, Merrill
2368 Clinical Journal of the American Society of Nephrology
JP: Human renal isografts: A clinical and pathologic anal-
ysis. Medicine (Baltimore) 47: 411– 454, 1968
2. Hariharan S, Adams MB, Brennan DC, Davis CL, First RM,
Johnson CP, Ouseph R, Peddi VR, Pelz CJ, Roza AM,
Vincenti F: Recurrent and de novo glomerular disease after
renal transplantation. A report from the Renal Allograft
Disease Registry (RADR). Transplantation 68: 635– 641, 1999
3. Briganti EM, Russ GR, McNeil JJ, Atkins RC, Chadbans J:
Risk of renal allograft loss from recurrent glomerulone-
phritis. N Engl J Med 347: 103–109, 2002
4. Novak J, Julian B, Tomana M, Mestecky J: IgA glycosyla-
tion and IgA immune complexes in the pathogenesis of
IgA nephropathy. Semin Nephrol 28: 78 – 87, 2008
5. Barratt J, Eitner F, Feehally J, Floege J: Immune complex
formation in IgA nephropathy: A case of the “right” anti-
bodies in the “wrong” place at the “wrong” time? Nephrol
Dial Transplant 24: 3620 –3623, 2009
6. Furness PN, Roberts ISD, Briggs JD: Recurrent glomerular
disease in transplants. Transplant Proc 34: 242, 2002
7. Ponticelli C, Traversi L, Banfi G: Renal transplantation in
patients with IgA mesangial glomerulonephritis. Pediatr
Transplant 8: 334 –338, 2004
8. Suzuki K, Honda K, Tanabe K, Toma H, Nihei H, Yamagu-
chi Y: Incidence of latent mesangial IgA deposition in renal
allograft donors in Japan. Kidney Int 63: 2286 –2294, 2003
9. Hariharan S, Savin VJ: Recurrent and de novo disease after
renal transplantation: A report from the Renal Allograft
Disease Registry. Pediatr Transplant 8: 349 –350, 2004
10. Lim EC, Chia D, Terasaki PI: Studies of sera from IgA
nephropathy patients to explain high kidney graft sur-
vival. Hum Immunol 32: 81– 86, 1991
11. Jeong HJ, Park SK, Cho YM, Kim MS, Kim YS, Choi J, Kim
SI, Lim BJ: Progression of renal allograft histology after
renal transplantation in recurrent and nonrecurrent immu-
noglobulin A nephropathy. Hum Pathol 39: 1511–1518, 2008
12. Bumgardner GL, Amend WC, Ascher NL, Vincenti FG:
Single-center long-term results of renal transplantation for
IgA nephropathy. Transplantation 65: 1053–1060, 1998
13. Soler MJ, Mir M, Rodriguez E, Orfila A, Munne A, Vázquez
S, Lloveras J, Puig JM: Recurrence of IgA nephropathy and
Henoch–Schoenlein purpura after kidney transplantation:
Risk factors and graft survival. Transplant Proc 37: 3705–
3709, 2005
14. Chacko B, George JT, Neelakantan N, Korula A, Chakko
JK: Outcomes of renal transplantation in patients with
immunoglobulin A nephropathy in India. J Postgrad Med
53: 92–95, 2007
15. Andresdottir MB, Haasnoot GW, Persijn GG, Claas FH:
HLA-B8, DR3: A new risk factor for graft failure after renal
transplantation in patients with underlying immunoglob-
ulin A nephropathy. Clin Transplant 23: 660 – 665, 2009
16. Ponticelli C, Traversi L, Feliciani A, Cesana BM, Banfi G,
Tarantino A: Kidney transplantation in patients with IgA
mesangial glomerulonephritis. Kidney Int 60: 1948 –1954,
2001
17. McDonald SP, Russ GR: Recurrence of IgA nephropathy
among renal allograft recipients from living donors is
greater among those with zero HLA mismatches. Trans-
plantation 27, 759 –762, 2006
18. Choy BY, Chan TM, Lo SK, Lo WK, Lai KN: Renal trans-
plantation in patients with primary immunoglobulin A
nephropathy. Nephrol Dial Transplant 18: 2399 –2404, 2003
Clin J Am Soc Nephrol 5: 2363–2372, 2010
19. Ng YS, Vathsala A, Chew ST, Chiang GS, Woo KT: Long-
term outcome of renal allografts in patients with immuno-
globulin A nephropathy. Med J Malaysia 62: 109 –113, 2007
20. Benabdallah L, Rerolle JP, Peraldi MN, Noël LH, Bruneel
MF, Carron PL, Morelon E, Kreis H: An unusual recur-
rence of crescentic nephritis after renal transplantation for
IgA nephropathy. Am J Kidney Dis 40: E20, 2002
21. Kowalewska J, Yuan S, Sustento-Reodica N, Nicosia RF,
Smith KD, Davis CL, Alpers CE: IgA nephropathy with
crescents in kidney transplant recipients. Am J Kidney Dis
45: 167–175, 2005
22. Chailimpamontree W, Dmitrienko S, Li G, Balshaw R,
Magil A, Shapiro RJ, Landsberg D, Gill J, Keown PA;
Genome Canada Biomarkers in Transplantation Groupe:
Probability, predictors, and prognosis of posttransplanta-
tion glomerulonephritis. J Am Soc Nephrol 20: 843– 851, 2009
23. Floege J: Recurrent IgA nephropathy after renal transplan-
tation. Semin Nephrol 24: 287–291, 2004
24. Andresdottir MB, Haasnot GW, Doxiadis II, Persjin GG,
Claas FH: Exclusive characteristics of graft survival and
risk factors in recipients of immunoglobulin A nephropa-
thy: A retrospective analysis of registry data. Transplanta-
tion 80: 1012–1018, 2005
25. Wang AYM, Lai FM, Yu AWY Lam PK, Chow KM, Choi
PC, Lui SF, Li PK: Recurrent IgA nephropathy in renal
transplant allografts. Am J Kidney Dis 38: 588 –596, 2001
26. Kim YS, Moon JI, Jeong HJ, Kim MS, Kim SI, Choi KH, Lee
HY, Han DS, Park K: Live donor renal allograft in end-
stage renal failure patients from immunoglobulin A ne-
phropathy. Transplantation 71: 233–238, 2001
27. Moriyama T, Nitta K, Suzuki K, Honda K, Horita S, Uchida
K, Yumura W, Tanabe K, Toma H, Nihei H, Yamaguchi Y:
Latent IgA deposition from donor kidney is the major risk
factor for recurrent IgA nephropathy in renal transplanta-
tion. Clin Transplant 19[Suppl 14]: 41– 48, 2005
28. Tang Z, Ji SM, Chen DR Wen JQ, Liu ZH, Li LS: Recurrent
or de novo IgA nephropathy with crescent formation after
renal transplantation. Ren Fail 30: 611– 616, 2008
29. Berthoux F, El Deeb S, Mariat C, Diconne E, Laurent B,
Thibaudin L: Anti-thymocyte globulin (ATG) induction
therapy and disease recurrence in renal transplant recipi-
ents with primary IgA nephropathy. Transplantation 85:
1505–1507, 2008
30. Suzuki H, Fan R, Zhang Z, Brown R, Hall S, Julian BA,
Chatham WW, Suzuki Y, Wyatt RJ, Moldoveanu Z, Lee JY,
Robinson J, Tomana M, Tomino Y, Mestecky J, Novak J:
Aberrantly glycosylated IgA1 in IgA nephropathy patients
is recognized by IgG antibodies with restricted heteroge-
neity. J Clin Invest 119: 1666 –1677, 2009
31. Glassock RJ: Analyzing antibody activity in IgA nephrop-
athy. J Clin Invest 119: 1450 –1452, 2009
32. Coppo R, Feehally J, Glassock RJ: IgA nephropathy at two
score and one. Kidney Int 77: 181–186, 2010
33. Mestecky J, Suzuki H, Yanagihara T, Moldoveneanu Z,
Tomana M, Matousovic C, Julian BA, Novak J: IgA ne-
phropathy: Current views of immune complex formation.
Contrib Nephrol 157: 58 – 63, 2007
34. Mulay AV, van Walraven C, Knoll GA: Impact of immu-
nosuppressive medication on the risk of renal allograft
failure due to recurrent glomerulonephritis. Am J Trans-
plant 9: 804 – 811, 2009
35. Oka K, Imai E, Moriyama T, Akagi Y, Ando A, Hori M,
Clin J Am Soc Nephrol 5: 2363–2372, 2010
Okuyama A, Toki K, Kyo M, Kokado Y, Takahara S: A
clinicopathological study of IgA nephropathy in renal
transplant recipients: Beneficial effect of angiotensin-con-
verting enzyme inhibitor. Nephrol Dial Transplant 15: 689 –
695, 2000
36. Hiremath S, Fergusson D, Doucette S, Mulay AV, Knoll
GA: Renin angiotensin system blockade in kidney trans-
plantation: A systematic review of the evidence. Am J
Transplant 7: 2350 –2360, 2007
37. Kennoki T, Ishida H, Yamaguchi Y, Tanabe K: Proteinuria-
reducing effects of tonsillectomy alone in IgA nephropathy
recurring after kidney transplantation. Transplantation 88:
935–941, 2009
38. Couser W: Recurrent glomerulonephritis in the renal allo-
graft: An update of selected areas. Exp Clin Transplant 3:
283–288, 2005
39. Newstead CG: Recurrent disease in renal transplants.
Nephrol Dial Transplant 18[Suppl 6]: 68 –74, 2003
40. Tejani A, Stablein DH: Recurrence of focal segmental glo-
merulosclerosis posttransplantation: A special report of the
North American Pediatric Renal Transplant Cooperative
Study. J Am Soc Nephrol 2[Suppl]: S258 –S263, 1992
41. Fine RN: Recurrence of nephrotic syndrome/focal segmen-
tal glomerulosclerosis following renal transplantation in
children. Pediatr Nephrol 22: 496 –502, 2007
42. Carraro M, Caridi G, Bruschi M, Artero M, Bertelli R,
Zennaro C, Musante L, Candiano G, Perfumo F, Ghiggeri
GM: Serum glomerular permeability activity in patients
with podocin mutation (NPHS2) and steroid resistant ne-
phrotic syndrome. J Am Soc Nephrol 13: 1946 –1952, 2002
43. Fuentes GM, Meseguer CG, Carrion AP, Hijosa MM, Gar-
cia-Pose A, Melgar AA, Torres MN: Long-term outcome of
focal segmental glomerulosclerosis after pediatric renal
transplantation. Pediatr Nephrol 25: 529 –534, 2010
44. Baum MA: Outcomes after renal transplantation for FSGS
in children. Pediatr Transplant 8: 329 –333, 2004
45. Pardon A, Audard V, Caillard S, Moulin B, Desvaux D,
Bentaarit B, Remy P, Sahali D, Roudot-Thoraval F, Lang P,
Grimbert P: Risk factors and outcome of focal and segmen-
tal glomerulosclerosis recurrence in adult renal transplant
recipients. Nephrol Dial Transplant 21: 1053–1059, 2006
46. Moroni G, Gallelli B, Quaglini S, Banfi G, Montagnino G,
Messa P: Long-term outcome of renal transplantation in
adults with focal segmental glomerulosclerosis. Transpl Int
23: 208 –216, 2010
47. Ponticelli C: Recurrence of focal segmental glomeruloscle-
rosis (FSGS) after renal transplantation. Nephrol Dial Trans-
plant 25: 25–31, 2010
48. Canaud G, Dion D, Zuber J, Gubler MC, Sberro R, Thervet
E, Snanoudj R, Charbit M, Salomon R, Martinez F, Leg-
endre C, Noel LH, Niaudet P: Recurrence of nephrotic
syndrome after transplantation in a mixed population of
children and adults: Course of glomerular lesions and
value of the Columbia classification of histological variants
of focal and segmental glomerulosclerosis (FSGS). Nephrol
Dial Transplant 25: 1321–1328, 2010
49. Baum MA, Stablein DM, Panzarino VM Tejani A, Harmon
WE, Alexander SR: Loss of living donor renal allograft
advantage in children with focal segmental glomeruloscle-
rosis. Kidney Int 59: 328 –333, 2001
50. Abbott KC, Sawyers ES, Oliver JD III, Ko CW, Kirk AD,
Welch PG, Peters TG, Agodoa LY: Graft loss due to recur-
Recurrent Glomerulonephritis 2369
rent focal segmental glomerulosclerosis in renal transplant
recipients in the United States. Am J Kidney Dis 237: 366 –
373, 2001
51. Cibrik DM, Kaplan B, Campbell DA, Meier-Kriesche HU:
Renal allograft survival in transplant recipients with focal
segmental glomerulosclerosis. Am J Transplant 3: 64 – 67,
2003
52. Weber S, Gribouval O, Esquivel EL, Morinière V, Tête MJ,
Legendre C, Niaudet P, Antignac C: NPHS2 mutation anal-
ysis shows genetic heterogeneity of steroid-resistant ne-
phrotic syndrome and low post-transplant recurrence. Kid-
ney Int 66: 571–579, 2004
53. Vincenti F, Ghiggeri GM: New insights into the pathogen-
esis and the therapy of recurrent focal glomerulosclerosis.
Am J Transplant 5: 1179 –1185, 2005
54. Savin VJ, Sharma R, Sharma M, McCarthy ET, Swan SK,
Ellis E, Lovell H, Warady B, Gunwar S, Chonko AM,
Artero M, Vincenti F: Circulating factor associated with
increased glomerular permeability to albumin in recurrent
focal segmental glomerulosclerosis. N Engl J Med 334: 878 –
883, 1996
55. Dantal J, Godfrin Y, Koll R, Perretto S, Naulet J, Bouhours
JF, Soulillou JP: Antihuman immunoglobulin affinity im-
munoadsorption strongly decreases proteinuria in patients
with relapsing nephrotic syndrome. J Am Soc Nephrol 9:
1709 –1715, 1998
56. Rea R, Smith C, Sandhu K, Kwan J, Tomson C: Successful
transplant of a kidney with focal segmental glomeruloscle-
rosis. Nephrol Dial Transplant 16: 416 – 417, 2001
57. Savin VJ, McCarthy ET, Sharma M: Permeability factors in
focal segmental glomerulosclerosis. Semin Nephrol 23: 147–
160, 2003
58. Trachtman H, Greenbaum LA, McCarthy ET, Sharma M,
Gauthier BG, Frank R, Warady B, Savin VJ: Glomerular
permeability activity: Prevalence and prognostic value in
pediatric patients with idiopathic nephrotic syndrome.
Am J Kidney Dis 44: 604 – 610, 2004
59. Canaud G, Martinez F, Noel LH, Mamzer MF, Niaudet P,
Legendre C: Therapeutic approach to focal and segmental
glomerulosclerosis recurrence in kidney transplant recipi-
ents. Transplant Rev (Orlando) 24: 121–128, 2010
60. Ingulli E, Tejani A: Incidence, treatment and outcome of
recurrent focal segmental glomerulosclerosis posttrans-
plantation in 42 allografts in children: A single center ex-
perience. Transplantation 51: 401– 405, 1991
61. Salomon R, Gagnadoux MF, Niaudet P: Intravenous cyclo-
sporine therapy in recurrent nephrotic syndrome after
transplantation in children. Transplantation 75: 810 – 814,
2003
62. Raafat RH, Kalia A, Travis LB, Diven SC: High-dose cyclo-
sporine therapy for recurrent focal segmental glomerulo-
sclerosis in children. Am J Kidney Dis 44: 50 –56, 2004
63. Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz
S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K,
Reiser J, Mundel P: The actin cytoskeleton of kidney podo-
cytes is a direct target of the antiproteinuric effect of cy-
closporine A. Nat Med 14: 931–938, 2008
64. Canaud G, Zuber J, Sberro R, Royale V, Anglicheau D,
Snanoudj R, Gaha K, Thervet E, Lefrère F, Cavazzana-
Calvo M, Noël LH, Méjean A, Legendre C, Martinez F:
Intensive and prolonged treatment of focal and segmental
2370 Clinical Journal of the American Society of Nephrology
glomerulosclerosis recurrence in adult kidney transplant
recipients: A pilot study. Am J Transplant 9: 1081–1086, 2009
65. Ohta T, Kawaguchi H, Hattori M, Komatsu Y, Akioka Y,
Nagata M, Shiraga H, Ito K, Takahashi K, Ishikawa N,
Tanabe K, Yamaguchi Y, Ota K: Effect of pre-and postop-
erative plasmapheresis on posttransplant recurrence of fo-
cal segmental glomerulosclerosis in children. Transplanta-
tion 71:628 – 633, 2001
66. Gohh RY, Yango AF, Morrissey PE, Monaco AP, Gautam
A, Sharma M, McCarthy ET, Savin VJ: Preemptive plasma-
pheresis and recurrence of FSGS in high-risk renal trans-
plant recipients. Am J Transplant 5: 2907–2912, 2005
67. Apeland T, Hartmann A: Rituximab therapy in early re-
current focal segmental sclerosis after renal transplanta-
tion. Nephrol Dial Transplant 23: 2091–2094, 2008
68. Meyer TN, Thaiss F, Stahl RA: Immunoadsorbtion and
rituximab therapy in a second living-related kidney trans-
plant patient with recurrent focal segmental glomerulo-
sclerosis. Transpl Int 20:1066 –1071, 2008
69. Westphal S, Hansson S, Mjörnstedt L, Mölne J, Swerkers-
son S, Friman S: Early recurrence of nephrotic syndrome
(immunoglobulin m nephropathy) after renal transplanta-
tion successfully treated with combinations of plasma ex-
changes, immunoglobulin, and rituximab. Transplant Proc
38: 2659 –2660, 2006
70. Hristea D, Hadaya K, Marangon N, Buhler L, Villard J,
Morel P, Martin PY: Successful treatment of recurrent focal
segmental glomerulosclerosis after kidney transplantation
by plasmapheresis and rituximab. Transpl Int 20: 102–105,
2007
71. Dello Strologo L, Guzzo I, Laurenzi C, Vivarelli M, Parodi
A, Barbano G, Camilla R, Scozzola F, Amore A, Ginevri F,
Murer L: Use of Rituximab in focal glomerulosclerosis
relapses after renal transplantation. Transplantation 88:
417– 420, 2009
72. Sakai K, Takasu J, Nihei H, Yonekura T, Aoki Y,
Kawamura T, Mizuiri S, Aikawa A: Protocol biopsies for
focal segmental glomerulosclerosis treated with plasma
exchange and rituximab in a renal transplant patient. Clin
Transplant 24[Suppl 22]: 60 – 65, 2010
73. Kamar N, Faguer S, Esposito L, Guitard J, Nogier MB,
Durand D, Rostaing L: Treatment of focal segmental glo-
merular sclerosis with rituximab: 2 case reports. Clin Neph-
rol 67: 250 –254, 2007
74. El-Firjani A, Hoar S, Karpinski J, Bell R, Deschenes MJ,
Knoll GA: Post-transplant focal segmental glomeruloscle-
rosis refractory to plasmapheresis and rituximab therapy.
Nephrol Dial Transplant 23: 425, 2008
75. Yabu JM, Ho B, Scandling JD, Vincenti F: Rituximab failed
to improve nephrotic syndrome in renal transplant pa-
tients with recurrent focal segmental glomerulosclerosis.
Am J Transplant. 8: 222–227, 2008
76. Rodríguez-Ferrero M, Ampuero J, Anaya F: Rituximab and
chronic plasmapheresis therapy of nephrotic syndrome in
renal transplantation patients with recurrent focal segmen-
tal glomerulosclerosis. Transplant Proc 41: 2406 –2408, 2009
77. Vinai M, Waber P, Seikaly MG: Recurrence of focal seg-
mental glomerulosclerosis in renal allograft: An in-depth
review. Pediatr Transplant 14: 314 –325, 2010
78. Hogan SL, Muller KE, Jennette JC, Falk RJ: A review of
therapeutic studies of idiopathic membranous glomeru-
lopathy. Am J Kidney Dis 25: 862– 875, 1995
Clin J Am Soc Nephrol 5: 2363–2372, 2010
79. Ponticelli C, Passerini P: Can prognostic factors assist ther-
apeutic decisions in idiopathic membranous nephropathy?
J Nephrol 23: 156 –163, 2010
80. Crosson JT, Wathen RL, Raij L, Andersen RC, Andersen
WR: Recurrence of membranous nephropathy after renal
transplantation. Arch Int Med 135: 1101–1106, 1975
81. Petersen VP Olsen TS, Kissmeyer-Nielsen F, Bohman SO,
Hansen ES, Skov PE, Solling K: Late failure of human renal
transplant. An analysis of transplant disease and graft
failure among 125 recipients surviving for one to eight
years. Medicine 54: 45– 69, 1975
82. Morzycka M, Croker BP, Seigler HF, Tisher CC: Evaluation
of recurrent glomerulonephritis in kidney allografts. Am J
Med 72: 588 –598, 1982
83. Berger BE, Vincenti F, Biava C, Amend WJ Jr, Feduska N,
Salvatierra O Jr: De novo and recurrent membranous glo-
merulopathy following kidney transplantation. Transplan-
tation 35: 315–319, 1983
84. Obermiller LE, Hoy WE, Eversole M, Sterling WA: Recur-
rent membranous glomerulonephritis in two renal trans-
plants. Transplantation 40: 100 –102, 1985
85. Bansal VK, Kozeny GA, Fresco R, Vertuno LL, Hano JE: De
novo membranous nephropathy following renal transplan-
tation between conjoint twins. Transplantation 41: 404 – 406,
1986
86. Montagnino G, Colturi C, Banfi G, Aroldi A, Tarantino A,
Ponticelli C: Membranous nephropathy in cyclosporine-
treated renal transplant recipients.Transplantation 47: 725–
727, 1989.
87. Truong L, Gelfand J, D’Agati V, Tomaszewski J, Appel G,
Hardy M, Pirani CL: De novo membranous nephropathy in
renal allograft. A report of ten cases and review of the
literature. Am J Kidney Dis 14: 131–141, 1989
88. Monga G, Mazzucco G, Basolo B, Quaranta S, Motta M,
Segoloni G, Amoroso A: Membranous glomerulonephri-
tis (MGN) in transplanted kidneys: Morphologic inves-
tigation on 256 renal allografts. Mod Pathol 6: 249 –258,
1993
89. Josephson MA, Spargo B, Hollandsworth DO, Thistlewait
MD: The recurrence of membranous glomerulopathy in a
renal transplant recipient: Case report and literature re-
view. Am J Kidney Dis 24: 873– 878, 1994
90. Innes A, Woodrow G, Boyd SM, Beckingham IJ, Morgan
AG: Recurrent membranous nephropathy in successive
renal transplants. Nephrol Dial Transplant 9: 323–325,
1994
91. Heidet L, Gagnadoux ME, Beziau A, Niaudet P, Broyer
M, Habib R: Recurrence of de novo membranous glomer-
ulonephritis on renal grafts. Clin Nephrol 41: 314 –318,
1994
92. Couchoud C, Pouteil-Noble C, Colon S, Touraine JL:
Recurrence of membranous nephropathy after renal
transplantation. Transplantation 59: 1275–1279, 1995
93. Odorico JS, Knechtle SJ, Rayhill SC, Pirsch JD,
D’Alessandro AM, Belzer FO, Sollinger HW: The influ-
ence of native nephrectomy on the incidence of recurrent
disease following renal transplantation for primary glo-
merulonephritis. Transplantation 61: 228 –234, 1996
94. Marcen R, Mampaso F, Teruel JL, Rivera ME, Orofino L,
Navarro-Antolin J, Ortuño J: Membranous nephropathy:
Recurrence after kidney transplantation. Nephrol Dial
Transplant 11: 1129 –1133, 1996
Clin J Am Soc Nephrol 5: 2363–2372, 2010
95. Cosyns JP, Couchoud C, Pouteil-Noble C, Squifflet JP,
Pirson Y: Recurrence of membranous nephropathy after
renal transplantation: Probability, outcome and risk fac-
tors. Clin Nephrol 50: 144 –153, 1998
96. Lazowski P, Sablay LB, Glicklich D: Recurrent crescentic
membranous nephropathy in two successive renal trans-
plants: Association with choroidal effusions and retinal
detachment. Am J Nephrol 18: 146 –150, 1998
97. Poduval RD, Josephson MA, Javaid B: Treatment of de novo
and recurrent membranous nephropathy in renal trans-
plant patients. Semin Nephrol 23: 392–399, 2003
98. Chan KW, Chan GS, Tang S: Glomerular pathology of
allograft kidneys in Hong Kong. Transplant Proc 37: 4293–
4296, 2005
99. Carneiro-Roza F, Medina-Pestana JO, Moscoso-Solorzano
G, Franco M, Ozaki K, Mastroianni-Kirsztajn G: Initial
response to immunosuppressive and renoprotective treat-
ment in posttransplant glomerulonephritis. Transplant Proc
38: 3491–3497, 2006
100. Gallon L, Chhabra D: Anti-CD20 monoclonal antibody
(rituximab) for the treatment of recurrent idiopathic mem-
branous nephropathy in a renal transplant patient. Am J
Transplant 6: 3017–3021, 2006
101. Dabade TS, Grande JP, Norby SM, Fervenza FC, Cosio FG:
Recurrent idiopathic membranous nephropathy after kid-
ney transplantation: A surveillance biopsy study. Am J
Transplant 8: 1318 –1322, 2008
102. Liebl R, Krämer BK: Recurrence and spontaneous remis-
sion of membranous nephropathy after renal transplanta-
tion. Clin Nephrol 70: 419 – 421, 2008
103. Weclawiak H, Ribes D, Guilbeau-Frugier C, Touchard G,
Kamar N, Mehrenberger M, Modesto A, Rostaing L: Re-
lapse of membranous glomerulopathy after kidney trans-
plantation: Sustained remittance induced by rituximab.
Clin Nephrol 69: 373–376, 2008
104. Sirimongkolrat T, Premasathian N, Vongwiwatana A, Lim-
srichamrern S, Cheunsuchon B, Vasuvattakul S: Anti-CD20
monoclonal antibody (rituximab) for the treatment of
membranous nephropathy after living-unrelated kidney
transplantation: A case report. Transplant Proc 40: 2440 –
2441, 2008
105. El Kossi M, Harmer A, Goodwin J, Wagner B, Shortland J,
Angel C, McKane W: De novo membranous nephropathy
associated with donor-specific alloantibody. Clin Trans-
plant 22: 124 –127, 2008
106. Aline-Fardin A, Rifle G, Martin L, Justrabo E, Bour JB,
D’Athis P, Tanter Y, Mousson C: Recurrent and de novo
membranous glomerulopathy after kidney transplanta-
tion. Transplant Proc 41: 669 – 671, 2009
107. El-Zoghby ZM, Grande JP, Fraile MG, Norby SM, Fervenza
FC, Cosio FG: Recurrent idiopathic membranous nephrop-
athy: Early diagnosis by protocol biopsies and treatment
with anti-CD20 monoclonal antibodies. Am J Transplant 9:
2800 –2807, 2009
108. Sprangers B, Lefkowitz GI, Cohen SD, Stokes MB, Valeri A,
Appel GB, Kunis CL: Beneficial effect of rituximab in the
treatment of recurrent idiopathic membranous nephropa-
thy after kidney transplantation. Clin J Am Soc Nephrol 5:
790 –797, 2010
109. Debiec H, Guigonis V, Mougenot B, Decobert F, Hay-
mann JP, Bensman A, Deschênes G, Ronco PM: Antena-
tal membranous glomerulonephritis due to anti-neutral
Recurrent Glomerulonephritis 2371
endopeptidase antibodies. N Engl J Med 346: 2053–2060,
2002
110. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell
DW, Cummins TD, Klein JB, Salant DJ: M-type phospho-
lipase A2 receptor as target antigen in idiopathic mem-
branous nephropathy. N Engl J Med 361: 11–21, 2009
111. Prunotto M, Carnevali ML, Candiano G, Murtas C, Bruschi
M, Corradini E, Trivelli A, Magnasco A, Petretto A, San-
tucci L, Mattei S, Gatti R, Scolari F, Kador P, Allegri L,
Ghiggeri GM: Autoimmunity in Membranous Nephropa-
thy Targets Aldose Reductase and SOD2. J Am Soc Nephrol
21: 507–519, 2010
112. Stahl R, Hoxha E, Fechner K: PLA2R autoantibodies and
recurrent membranous nephropathy after transplantation.
N Engl J Med 363: 496 – 498, 2010
113. Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bon-
tempelli M, Ruggenenti P: Rituximab for idiopathic
membranous nephropathy. Lancet 360: 923–924, 2002
114. Fervenza FC, Cosio FG, Erickson SB, Specks U, Herzenberg
AM, Dillon JJ, Leung N, Cohen IM, Wochos DN, Bergstralh
E, Hladunewich M, Cattran DC: Rituximab treatment of
idiopathic membranous nephropathy. Kidney Int 73: 117–
125, 2008
115. Glassock RJ: Membranoproliferative glomerulonephritis.
In: Evidence-Based Nephrology, edited by Molony DA, Craid
JC. London, Wiley-Blackwell, 2009:183–196
116. Lorenz EC, Sethi S, Leung N, Dispenzieri A, Fervenza F,
Cosio FG: Recurrent membranoproliferative glomerulone-
phritis after kidney transplantation. Kidney Int 77: 721–728,
2010
117. Braun MC, Stablein DM, Hamiwka LA, Bell L, Bartosh SM,
Strife CF: Recurrence of membranoproliferative glomeru-
lonephritis type II in renal allografts: the North American
Pediatric Renal Transplant Cooperative Study Experience.
J Am Soc Nephrol 16: 2225–2233, 2005
118. Little MA, Dupont P, Campbell E, Dorman A, Walshe JJ:
Severity of primary MPGN, rather than MPGN type deter-
mines renal survival and post-transplant recurrence risk.
Kidney Int 69: 504 –511, 2006
119. Morales JM: Hepatitis C virus infection and renal disease
after renal transplantation. Transplant Proc 36: 760 –762,
2004
120. Lien YH, Scott K: Long term cyclophosphamide treatment
for recurrent type I membranoproliferative glomerulone-
phritis after transplantation. Am J Kidney Dis 35: 539 –543,
2000
121. Wu J, Jaar BG, Briggs WA, Choi MJ, Kraus ES, Racusen LC,
Atta MG, Samaniego MD: High-dose mycophenolate
mofetil in the treatment of post-transplant glomerular dis-
ease in the allograft: A case series. Nephron Clin Pract 98:
c61– 66, 2004
122. Pickering MC, Cook HT: Translational mini-review se-
ries on complement factor H: Renal diseases associated
with complement factor H: Novel insights form humans
and animal. Clin Exp Immunol 151: 210 –230, 2008
123. Smith RJ, Alexander J, Barlow PN, Botto M, Cassavant TL,
Cook HT, de Córdoba SR, Hageman GS, Jokiranta TS,
Kimberling WJ, Lambris JD, Lanning LD, Levidiotis V,
Licht C, Lutz HU, Meri S, Pickering MC, Quigg RJ, Rops
AL, Salant DJ, Sethi S, Thurman JM, Tully HF, Tully SP,
van der Vlag J, Walker PD, Würzner R, Zipfel PF; Dense
Deposit Disease Focus Group: New approaches to the
2372 Clinical Journal of the American Society of Nephrology
treatment of dense deposit disease. J Am Soc Nephrol 18:
2447–2456, 2007
124. Andresdottir MB: Recommendations for the diagnosis and
treatment of dense deposit disease. Nat Clin Pract Nephrol 4:
68 – 69, 2008
125. Licht C, Weyersberg A, Heinen S, Stapenhorst L, Devenge
J, Beck B, Waldherr R, Kirschfink M, Zipfel PF, Hoppe B:
Successful plasma therapy for atypical hemolytic uremic
syndrome caused by factor H deficiency owing to a novel
Clin J Am Soc Nephrol 5: 2363–2372, 2010
mutation in the complement cofactor domain 15. Am J
Kidney Dis 45: 415– 421, 2005
126. Saland JM, Ruggenenti P, Remuzzi G and the Consensus
Study Group: Liver-kidney transplantation to cure atypical
hemolytic uremic syndrome. J Am Soc Nephrol 20: 940 –949,
2009
127. Ponticelli C, Villa M, Cesana B, Montagnino G, Tarantino
A: Risk factors for late kidney allograft failure. Kidney Int
62: 1848 –1854, 2002