Sensitization of recipients is an increasing problem in children. Some case
series in children exist comparing the diverse desensitizing protocols. These
protocols include intravenous immunoglobulin, cytomegalovirus immune globulin,
plasmapheresis, and some adjunctive therapies such as rituximab. Desensitizing
protocols have advantages and disadvantages.
Clinical trials are required to determine suitable protocols for sensitized
pediatric recipients. We performed a systematic review of these protocols in
children. A massive search was done in PubMed, Embase, and the Cochrane library
system. The results of these studies are compared.
Key words: Renal transplant, Highly sensitized recipients, Children
All candidates for renal transplant should be screened for anti-HLA antibodies
before transplant. The presence of these antibodies for anti-donor HLA
antibodies may lead to hyperacute or acute humeral rejections and ultimately, to
chronic graft dysfunction and loss. In these cases, antibody-mediated rejection
can be subclinical with long-term chronic graft microvascular damage,
interstitial fibrosis, and tubular atrophy. Thus, presence of donor-specific
antibodies (DSA) is an contraindication to transplant. Sensitization usually
occurs after transfusion and previous transplant.1 Sensitized patients have a
Sensitization is an increasing problem in children. Approximately 3% of children
who are candidates for transplant have sensitization and panel reactive
antibodies (PRA) more than 80%.2 Desensitizing protocols with aim of antibody
lowering and preventing more antibody production may result in a successful
transplant. In this review, we discuss treatment methods of sensitized pediatric
Sensitization of patients
The presence of anti-donor antibodies causes recipients to be sensitized. We
consider recipients as highly sensitized when their PRA is at least 30% to 50%.
Unsensitized recipients are considered when their PRA is 0% to 10%. However, it
seems that the presence of specific anti-donor antibodies is the real definition
of sensitization. These antibodies are produced when a nonimmunosuppressed
recipient is exposed to foreign antigens and include antibodies against ABO
antigens, HLA class I and II, and perhaps endothelial monocyte antigens. The
reasons for long-term persistence of these antibodies are the persistence of
donor proteins in the recipient follicular dendritic cells and chimerism or
microchimerism (presence of donor stem cells in the recipient).3
The main anti-donor antibodies are anti-HLA antibodies. These antibodies can be
detected by PRA or crossmatch. The limitations of PRA are the detection of anti-HLA
I not anti-HLA II and the lack of the specificity of anti-HLA antibodies.4 All
patients with positive PRA are not at risk of graft rejection and/or lost.
Antibodies against HLA without reactions with donor HLA antigens cannot damage a
graft. In addition, PRA cannot truly indicate the anti-HLA antibodies level.
Anti-HLA antibodies also can be detected by other laboratory methods. The
standard complement dependent cytotoxicity (CDC crossmatch = CDCXM) is the basic
method for anti-HLA antibody detection. The negative CDCXM usually eliminates
the hyperacute rejection after transplant. The sensitivity of this method is
enhanced by antihuman globulin (AHG) antibody (enhanced or modified CDC). Flow
cytometry cell-based assay or crossmatch is a more-sensitive test that detects
low titer and noncytotoxic antibodies.4 This assay is sensitive but not specific.
Recently, flow PRA and flow single antigen beads are suggested to increase the
specificity of flow cytometry crossmatch. The single-antigen bead method is a
sensitive and specific assay. However, controversies remain regarding the
association between the results of this test and the outcome of transplant.5 It
is thought that CDC-AHG is sufficient for predicting hyperacute rejection.
Patients with low titer anti-HLA antibodies with negative CDC and positive flow
cytometry may be involved by acute cellular and/or humeral rejection but not
involved by hyperacute rejection.
Recent studies show that the antibodies against non-HLA antigens also are
associated with antibody-mediated rejection after solid-organ transplant. The
association between non-HLA antibodies and immunologic damage of graft can be
better explained by observations that immunologic damage occurred despite
identical HLA renal transplant. These non-HLA antigens include polymorphic
antigens of endothelial cells, major histocompatibility complex class I-related
chain A (MICA). Major histocompatibility complex (MHC) class I-related chain A
antigens are endothelial cell surface antigens. Anti-MHC class I-related chain A
antibodies are found in sensitized recipients.
Some studies have shown that anti-MICA antibodies may play some roles in
immunologic damage of vascularized grafts. Because MICA is not expressed on the
lymphocytes, recent crossmatch assays cannot detect anti-MICA antibodies, and we
cannot recognize sensitized recipients with these antibodies by current
laboratory methods.6 There is also cellular sensitization (donor reactive T-cell
sensitization) in addition to humeral sensitization. The importance of this
sensitization is unclear.
Prevention of sensitization in children who are candidates for renal transplant
is important. Avoiding transfusions, particularly multiple transfusions, is
suggested. Some authors have suggested transfusions be performed under
cyclosporine cover if necessary.7 This idea is not for widespread use because
most candidates have severe renal failure with high serum potassium levels which
limit cyclosporine use. Although many centers suggest using leukocyte poor blood
in transplant candidates when necessary, the effect of leukoreduction procedures
on transfused blood and on sensitization rates is unknown. Many physicians also
advise their sensitized patients that their PRA may decrease spontaneously with
time; thus, they can wait for a deceased-donor transplant. Meanwhile, we can use
desensitizing protocols if sensitized patients have living donors or persistent
high PRA with time.
Successful renal transplant is the main goal in sensitized patients. This is
achieved by HLA-matched donor selection and the use of desensitizing protocols.
The aim of desensitizing protocols is to reduce DSA levels to those associated
less with the immunologic damage, and to maintain this reduced level of
antibodies for the first several months after transplant. Accommodation can be
due to some protective genes that protect the graft from antibody-mediated graft
injury after several months of transplant.
Some protocols exist to achieve these therapeutic aims. These desensitizing
high-dose intravenous immunoglobulin (IVIG),8-11 plasmapheresis alone,
plasmapheresis/low-dose IVIG,12-14 plasmapheresis/rituximab, plasmapheresis/
immunosuppressive agents,15 immunoadsorption, immunosuppressive medicines such
as alkylating agents, and infusion of rituximab.13,14,16 Each desensitizing
protocol has some strengths and weaknesses. Infections and rebound of anti-donor
antibodies (after cessation of desensitizing treatment) are major problems of
these protocols. The endpoint of desensitizing treatments is elimination of DSAs.
At this point, transplant can be performed. If the transplant cannot be
performed at this time, the sensitization protocol should be continued until the
Studies on the effects and complications of desensitizing protocols are rare in
children. This can be due to the lower numbers of sensitized recipients in the
pediatric age group and higher complications of some desensitizing methods such
as splenectomy and plasmapheresis in them.
Intravenous immunoglobulin is prepared by isolating polyclonal IgG from healthy
donors. It can lower PRA and/or convert the positive crossmatch to the negative
form. The main mechanism of IVIG is blocking the anti-HLA antibodies effects.
Other mechanisms of IVIG are down-regulating B cell differentiation, B cell
apoptosis, and ultimately reducing antibody production, inhibiting T cell
proliferation, and activating and inhibiting ¡-IFN,
complement system inhibition, suppression of dendritic cells, and anticytokine
activity.17,18 Intravenous immunoglobulin also can inhibit memory cells. The
suppressive effect of IVIG on antibody production persists long term.
Pradhan and associates showed that IVIG was not effective in reducing panel
reactive antibodies. They used high-dose IVIG (2 g/kg) every 4 weeks (3 doses
each week) but it was not effective.15 In contrast,
Al-Uzri and associates have shown that long-term high-dose IVIG use can change
the PRA to zero.19 They used 500 mg/kg IVIG weekly for 3 consecutive weeks every
12 weeks. The PRA activity fell to zero after almost 40 months.19
Tyan and associates used IVIG to reduce panel reactive antibodies in vitro and
in vivo in a 13-year-old recipient awaiting retransplant and showed a reduction
of PRA from 95% to 15% and a successful retransplant.8 The results of IVIG
therapy alone in sensitized adults are inconsistent. Sometimes sensitized
patients had only a partial response or none at all. After achieving
inconsistent results from adult studies focusing IVIG use in sensitized
recipients they used the combination of IVIG and other medicines to increase the
The major complications of IVIG are infusion-related reactions, renal tubular
toxicity, and thrombotic events. To prevent acute renal failure, we must use
types with lower sucrose concentrations. The use of higher sucrose IVIG products
result in acute renal tubular damage, whereas the lower sucrose concentration
may lead to volume overload. Administration of 5% IVIG solution (with lower
osmolality) instead of 10% form also helps reduce thrombotic events and graft
loss after transplant.11, 20, 21
Some centers have used Cytomegalovirus-Ig (CMVIg) in place of IVIG.16
Cytomegalovirus-Ig has an additional anti-CMV effect. There are no well-controlled
trials comparing the efficacy of these products, and the idea that
administration of CMVIg has additional immunomodulatory effects.
Plasmapheresis can be used in sensitized patients alone or with other treatments
such as rituximab and CMVIg. Plasmapheresis is performed until negative PRA and
DSAs are achieved. It is important for all patients to continue the
plasmapheresis treatments until after transplant. The numbers of these
treatments before and after transplant depends on the DSA titer at initiation.
Patients with higher starting DSA levels have a higher risk of antibody-mediated
rejection and consequently need more desensitizing treatments before and after
transplant. Montgomery and associates determined the numbers of plasmapheresis/CMVIg
treatments before and after transplant based on starting DSA titer
(Table 1).16 Plasmapheresis has a transient effect on the DSA titer, and a
rebound of antibodies occurs after its discontinuation. Thus, plasmapheresis is
not suggested for desensitization of recipients with deceased-donor transplant.
Concurrent use of IVIG or rituximab maintains the antibody lowering effects of
plasmapheresis and the combination of plasmapheresis and these modalities can be
used in deceased-donor transplant. Plasmapheresis has problems. It needs a
vascular access. Thus, its administration is difficult in patients with
peritoneal dialysis. Plasmapheresis can lead to complications including
infection, reduction in platelets, hemoglobin and coagulation factors, and
consequently bleeding tendencies. We avoid the plasmapheresis on the day of
transplant or hemodialysis. We also must perform coagulation tests before
transplant and administer fresh frozen plasma if needed.
Protein A immunoadsorption
This modality as plasmapheresis can rapidly reduce the serum level of
alloantibodies. This modality also can be used in combination with other
modalities. There is no report regarding the use of this modality in sensitized
Rituximab is monoclonal antibodies against CD20 “a pan B cell marker.” This
marker is present on the surface of premature and mature B cells but not on the
surface of plasma cells. Thus, rituximab inhibits proliferation and
differentiation of B cells but not plasma cells. For this reason, this
medication cannot reduce the serum anti-HLA antibody level, but it can prevent
clonal B cell expansion and consequently DSA production. In this regard,
rituximab should be administered in combination with other modalities such as
plasmapheresis/CMVIg and splenectomy as adjunctive therapy. In these states,
rituximab maintains low levels of antibodies achieved by other modalities such
It appears that rituximab therapy does not result in severe infections in
sensitized patients22 and is well tolerated. The effects of rituximab can be up
to 6 months. Montgomery and associates suggested a desensitizing protocol
including rituximab and plasmapheresis/CMVIg (Figure 1).16 The use of rituximab
in this protocol can reduce the risk of immunologic complications during
transplant and the number of treatments before or at the time of transplant.16
Mycophenolate mofetil (MMF) inhibits proliferation of T and B cells, and
consequently antibody production. Mycophenolate mofetil has been shown to
decrease PRA in solid-organ transplant by some studies.23-25 Wong and associates
have suggested that MMF starting early after exposure is a good prophylaxis for
anti-HLA antibodies suppression in a 4-year-old sensitized recipient. The
recommended dosage of MMF is 390 to 500 mg/m2/d divided twice daily.26
Splenectomy may remove many B cells and consequently reduce antibody production.
The most important problem with this is its permanent effect on the immune
system and increase in the risk of sepsis with encapsulated microorganisms
especially in children. Splenectomy is sometimes suggested in ABO incompatible
renal transplant and/or high-risk sensitized patients.
New treatments include complement blockers and proteasome inhibitor-mediated
plasma cell depletion (bortezomib). Alloantibodies bind to endothelial cells of
the graft and stimulate the complement pathway. The complement system activation
is the key event in this antibody-mediated graft damage. The blockade of
complement system such as soluble CD35+ or eculizumab (an inhibitor of the
terminal complement protein C5) can be an important medicine for both prevention
and treatment of antibody-mediated rejection.27,28 Wahrmann performed a pilot
study and administered bortezomib alone to 2 sensitized patients. The results of
this study demonstrated no effect or little effect of bortezomib on the
sensitization status of recipients.28 However, it appears that the combination
of bortezomib and plasmapheresis is a better desensitizing treatment than IVIG-based
desensitization protocols. This idea needs to be confirmed by more studies.29
Clinical trials of desensitizing protocols
To our knowledge, there are no clinical trials in children focusing on
desensitizing protocols in sensitized recipients. Adult studies are also low in
numbers. The IGO2 study is a double-blind controlled clinical trial regarding
the comparison the 2 groups of sensitized adult patients who are treated with
IVIG or placebo.
The results of this study showed the superiority of IVIG when compared with
placebo to reduce the anti-HLA antibodies titer.10 Recently, a clinical trial
showed promising results about the use of
high-dose IVIG and rituximab combination in sensitized adults.30 Now, the first
clinical trial comparing high-dose IVIG alone and combined rituximab and IVIG is
being done in pediatric sensitized patients at Stanford University, but its
results are not available.
Recently Montgomery and associates31 performed a clinical trial by comparing a
group of sensitized patients treated with plasmapheresis and low-dose IVIG with
a control group. Incompatible HLA transplant was performed in patients under
desensitizing treatment after reaching negative crossmatch. Compatible
transplant or dialysis was performed for control. The patients showed better
survival rate compared with controls during 11-year study.31 In another
randomized clinical trial, thymoglobulin and daclizumab were compared as
induction therapy in sensitized patients. The results of this study showed the
superiority of thymoglobulin compared with daclizumab for preventing
biopsy-proven acute rejection. However, graft and patient survival at 1-year
posttransplant were similar in both groups.32
Which sensitized recipients are more susceptible to immunologic complications
We must recognize sensitized recipients who are more susceptible to
antibody-mediated rejection and graft loss after transplant. This immunologic
risk determination should be performed in all recipients with a positive
crossmatch. First, we must rule out false-positive crossmatches (autoantibodies
in donor or recipients and non-HLA specific antibodies).
Then, for immunologic risk assessment, we should evaluate the titer of these
antibodies. Patients with higher starting titers have a higher risk of
immunologic reactions after transplant. Other factors also increase the risk of
immunologic damage. The presence of multiple risk factors causes early
antibody-mediated rejection even in the presence of low titer of DSA. In these
patients, although the low numbers of desensitization protocols convert positive
crossmatch to a negative form, they remain at high risk of antibody-mediated
rejection after transplant. Thus, we must know these risk
factors, including previous early graft loss, multiple donor reactive
antibodies, rising DSA titer at the time of desensitization starting, rebound
DSA titer between treatments, multiple sensitizing events,
and high-risk transplants (eg, husband to wife
and child to mother transplants).16 The presence of
DSA reactive to DRW52 and DRW53 HLA
antigens causes the resistance to desensitizing protocols.8, 33 Additionally,
comorbid conditions in other organs such as heart and liver should be
recognized, because these conditions can result in complications during
desensitization protocols such as plasmapheresis.
Who needs desensitization treatment?
It seems that every patient with highly positive panel reactive antibody should
be assessed for DSA. We must determine if the positive PRA is due to DSA or not.
It appears that the patients with anti-HLA DSA need desensitizing treatments
(preconditioning). We do not know what to do regarding the desensitizing
treatment of patients with non-HLA antibodies. There also are controversies
treating patients with high anti-HLA antibodies titers. Some transplant centers
do not perform desensitization for patients with AHA-CDC > 1/16.15,34,35
There are also some problems in treating patients with positive crossmatch
reported by different assays (complement-dependent cytotoxicity assay vs flow
cytometry). Should we start desensitization treatment in patients with positive
flow-cytometric crossmatching as patients with positive complement-dependent
cytotoxicity assay? Are the treatment protocols similar in patients with
positive flow cytometry or positive CDCXM? Should we continue treatment until
achieving negative flow cystometry results, or several treatments are enough?
What about B-cell crossmatch? Are treatments needed in patients with positive
Most centers believe that they should check DSA in recipients with positive flow
cytometry crossmatch to increase the specificity of this test by other assays
such as single antigen beads. Maryland University recommends the desensitizing
treatment in patients with negative AHG and positive flow cytometry which
anti–DSA are positive. Plasmapheresis, IVIG, and immunosuppressive medications
have been suggested in these patients. The degree of positivity of the flow
crossmatch is also an important factor in determining the type of treatment.
Meanwhile, they do not insist on converting positive flow cytometry to negative
Additionally there is no consensus regarding the association between the
positive single antigen beads and graft outcome. Some small studies have been
performed in children and the results are inconsistent.5,35,36
Which protocol is better?
As mentioned before, each protocol has some advantages and some disadvantages.
There are no clinical trials comparing methods of desensitization in children.
We do not have any therapeutic approach in sensitized pediatric recipients.
Another problem is to decide which protocol is suitable for which patients.
Ultimately, selection of each protocol depends on the transplant center, cost of
treatment, living compared with deceased transplant, and the degree of
sensitization of patients. Figure 1 shows the desensitization protocol of John
Some treatment protocols are considered the main desensitizing treatment such as
plasmapheresis and/or IVIG/CMVIg and other protocols are adjunctive or enhancer
treatments such as rituximab and splenectomy.
Regarding the comparison between high-dose IVIG and plasmapheresis,
plasmapheresis removes anti-HLA antibodies more potently and more rapidly than
does high-dose IVIG, and DSA monitoring is more easily performed in patients on
the plasmapheresis than those on the IVIG treatment. Thus, plasmapheresis is
considered a suitable method for antibody removal in patients with high titer
DSA preparing for living transplant. Plasmapheresis also is expensive and the
rebound of DSA when plasmapheresis is discontinued. Thus, this modality must
continue until transplant and can be used in a living-donor transplant, not a
deceased transplant, where waiting is unpredictable. In some articles,
continuation of immunosuppression is suggested after plasmapheresis
discontinuation to prevent rebound antibodies.
In contrast to plasmapheresis, IVIG is less expensive and is easier to perform.
This desensitizing protocol can be used in both living and deceased transplants.
Intravenous immunoglobulin also has some disadvantages. The DSA monitoring is
difficult and the antibody removal is slow in patients receiving IVIG. Table 2
shows the sensitizing protocols that have been reported in children.
How does one treat and monitor patients after transplant?
Lymphocyte depleting antibodies are suggested as induction therapy in sensitized
patients to prevent re-formation of alloantibodies and cellular rejection. In
some studies, daclizumab is suggested as an induction therapy.16 The superiority
of thymoglobulin was shown in a recent clinical trial in adults. In most
studies, triple immunosuppressive therapy is used in sensitized patients
including MMF, steroids, and tacrolimus. It appears that the patients should be
treated with several additional plasmapheresis, IVIG, and/or CMVIg after
transplant. The type and number of treatments before and after transplant
depends on the DSA titer at initiation and the risk of AMR after transplant
shows the number of PP/CMVIg treatments after transplant based on starting DSA
titer as explained in the John Hopkins protocol.16
It is necessary to follow the DSA titer and graft function closely after
transplant, especially in patients undergoing plasmapheresis because of rapid
rebound of antibodies. The John Hopkins University has a protocol for monitoring
of sensitized recipients after transplant. This protocol includes protocol
biopsies at 1, 3, and 12 months posttransplant, antibody titer measurement and
crossmatch before and after each posttransplant plasmapheresis, 72 hours after
the last plasmapheresis, and at 2, 3, 6, and 12 months after transplant.
Additionally, close monitoring of antibody-mediated rejection should be done. It
is important to know that the risk of antibody-mediated rejection is highest in
the first days of transplant whereas its occurrence is rare after 1 month
posttransplant. In patients involved with acute mediated rejection, the endpoint
of AMR treatment is achieving negative cytotoxicity and/or flow cytometry
Sensitization is a problem with increasing incidence in children, but our
information about definition, approach, and treatment in sensitized children is
lacking. We also do not know what amount DSA increases the risk of acute and
subclinical antibody-mediated rejection. We do not know how to assess and
monitor non-HLA antibodies and their exact roles in immunologic damage after
There are some case series in sensitized pediatric patients to suggest some
treatment protocols for crossmatch conversion from positive to negative.
However, the results of these studies are controversial. Desensitizing
procedures are expensive and invasive. To clarify and determine the best
desensitizing methods in this age group, we must have clinical trials with
larger numbers of pediatric patients and longer follow-ups.
- Sanfilippo F, Vaughn WK, Bollinger RR, Spees EK. Comparative effects of
pregnancy, transfusion, and prior graft rejection on sensitization and renal
transplant results. Transplantation. 1982;34(6):360-366.
- Shapiro R, Sarwal MM. Pediatric kidney transplantation. Pediatr Clin North
- Nogueria JM, Schweitzer EJ. Approach to the highly sensitized patient. In:
Wier MR, eds. Medical Management of Kidney Transplantation. Philadelphia, PA:
Lippincott Williams Wilkins; 2005:53-63.
- Grafals M, Akalin E. The Highly Sensitized Renal Transplant Recipient.
Nephrology Rounds Web site. www.nephrologyrounds.org. Accessed August 7, 2012.
- Roberti I, Vyas S, Pancoska C. Donor-specific antibodies by flow single
antigen beads in pediatric living donor kidney transplants: single center
experience. Pediatr Transplant. 2007;11(8):901-905.
- Narayan S, Tsai EW, Zhang Q, Wallace WD, Reed EF, Ettenger RB. Acute
rejection associated with donor-specific anti-MICA antibody in a highly
sensitized pediatric renal transplant recipient. Pediatr Transplant.
2011;15(1):E1-E7. doi: 10.1111/j.1399-3046.2010.01407.x.
- Niaudet P, Dudley J, Charbit M, Gagnadoux MF, Macleay K, Broyer M.
Pretransplant blood transfusions with cyclosporine in pediatric renal
transplantation. Pediatr Nephrol. 2000;14(6):451-456.
- Tyan DB, Li VA, Czer L, Trento A, Jordan SC. Intravenous immunoglobulin
suppression of HLA alloantibody in highly sensitized transplant candidates and
transplantation with a histoincompatible organ. Transplantation.
- Jordan SC, Vo A, Bunnapradist S, et al. Intravenous immune globulin treatment
inhibits crossmatch positivity and allows for successful transplantation of
incompatible organs in living-donor and cadaveric recipients. Transplantation.
- Jordan SC, Tyan D, Stablein D, et al. Evaluation of intravenous
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disease: Report of the NIH IGO2 trial. J Am Soc Nephrol. 2004:15(12):3256-3262.
- Glotz D, Antoine C, Julia P, et al. Desensitization and subsequent kidney
transplantation of patients using intravenous immunoglobulins (IVIg). Am J
- Montgomery RA, Zachary AA, Racusen LC, et al. Plasmapheresis and intravenous
immune globulin provides effective rescue therapy for refractory humoral
rejection and allows kidneys to be successfully transplanted into
cross-match-positive recipients. Transplantation. 2000:70(6):887-895.
- Gloor JM, DeGoey SR, Pineda AA, et al. Overcoming a positive crossmatch in
living-donor kidney transplantation. Am J Transplant. 2003:3(8):1017-1023.
- Schweitzer EJ, Wilson JS, Fernandez-Vina M, et al. A high panel-reactive
antibody rescue protocol for cross-match-positive live donor kidney transplants.
- Pradhan M, Raffaelli RM, Lind C, et al. Successful deceased donor renal
transplant in a sensitized pediatric recipient with the use of plasmapheresis.
Pediatr Transplant. 2008;12(6):711-716.
- Montgomery RA, Zachary AA. Transplanting patients with a positive
donor-specific crossmatch: A single center’s perspective. Pediatr Transplant.
- Toyoda M, Pao A, Petrosian A, Jordan SC. Pooled human gammaglobulin
modulates surface molecule expression and induces apoptosis in human B cells. Am
J Transplant. 2003;3(2):156-166.
- Lutz HU, Stammler P, Bianchi V, et al. Intravenously applied IgG stimulates
complement attenuation in a complement-dependent autoimmune disease at the
amplifying C3 convertase level. Blood. 2004;103(2):465-472.
- Al-Uzri AY, Seltz B, Yorgin PD, Spier CM, Andreoni K. Successful renal
transplant outcome after intravenous gamma-globulin treatment of a highly
sensitized pediatric recipient. Pediatr Transplant. 2002;6(2):161-165.
- Dalakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk
of precipitating thromboembolic events. Neurology. 1994:44(2):223-226.
- Gottlieb S. Intravenous immunoglobulin increases risk of thrombotic events.
- Scemla A, Loupy A, Candon S, et al. Incidence of infectious complications in
highly sensitized renal transplant recipients treated by rituximab: a
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- Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of
mycophenolate mofetil (MMF). Clin Transplant. 1996;10(1 Pt 2):77-84.
- Schmid C, Garritsen HS, Kelsch R, et al. Suppression of panel-reactive
antibodies by treatment with mycophenolate mofetil. Thorac Cardiovasc Surg.
- Shaddy RE, Fuller TC, Anderson JB, et al. Mycophenolic mofetil reduces the
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- Wong H, Laberge R, Harvey E, Filler G. Preventing sensitization with
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- Tydén G, Kumlien G, Berg UB. ABO-incompatible kidney transplantation in
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- Wahrmann M, Haidinger M, Drach J, et al. Proteasome inhibition for recipient
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subjected to bortezomib treatment. Clin Transpl. 2009:415-420.
- Everly MJ, Everly JJ, Terasaki PI. Role of proteasome inhibition in
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- Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune
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- Montgomery RA, Lonze BE, King KE, et al. Desensitization in HLA-incompatible
kidney recipients and survival. N Engl J Med. 2011;365(4):318-326.
- Noël C, Abramowicz D, Durand D, et al. Daclizumab versus antithymocyte
globulin in high-immunological-risk renal transplant recipients. J Am Soc
- Zachary AA, Montgomery RA, Ratner LE, et al. Specific and durable
elimination of antibody to donor HLA antigens in renal-transplant patients.
- Stastny P, Salvador IM, Lavingia B. Evaluation of the highly sensitized
transplant recipient. Pediatr Nephrol. 2011;26(11):1927-1935.
- Verghese PS, Smith JM, McDonald RA, Schwartz SM, Nelson KA, Warner PR.
Impaired graft survival in pediatric renal transplant recipients with
donor-specific antibodies detected by solid-phase assays. Pediatr Transplant.
- Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of
plasmapheresis versus high-dose IVIG desensitization in renal allograft
recipients with high levels of donor specific alloantibody. Am J Transplant.
- Valentini RP, Nehlsen-Cannarella SL, Gruber SA, et al. Intravenous
immunoglobulin, HLA allele typing and HLAMatchmaker facilitate successful
transplantation in highly sensitized pediatric renal allograft recipients.
Pediatr Transplant. 2007;11(1):77-81. Erratum in: Pediatr Transplant.
- Shapiro R, Ellis D, Tan HP, et al. Alemtuzumab pre-conditioning with
tacrolimus monotherapy in pediatric renal transplantation. Am J Transplant.
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ABO-incompatible kidney transplantation and rituximab. Transplant Proc.
Volume : 10
Issue : 6
Pages : 523-530
From the 1Pediatric Transplantation Dialysis Research Center, Tehran University
of Medical Science; 2Labafi Nejad Hospital; and the 3Pediatric Transplantation
Dialysis Research Center, Tehran University of Medical Science, Tehran, Iran
Acknowledgements: This study was sponsored by Tehran University of Medical
Corresponding author: Rozita Hoseini: Labafi Nejad Hospital Pasdaran Avenue,
Phone: +98 21 222 261 Fax: +98 212 222 0063 E-mail:
Table 1. Number of PP/CMVIg Treatments Based on Starting DSA Titer16
Figure 1. Desensitization Protocol in John Hopkins University22
Table 2. Studies on Desensitization Protocols in Children