J Artif Organs (2011) 14:922
DOI 10.1007/s10047-010-0529-5
REVIEW
Benefits and limitations of plasmapheresis in renal diseases:
an evidence-based approach
Sanjeev Baweja Kate Wiggins
Darren Lee Susan Blair Margaret Fraenkel
Lawrence P. McMahon
Received: 21 September 2010 / Accepted: 8 November 2010 / Published online: 10 December 2010
The Japanese Society for Artificial Organs 2010
Abstract In use for over 50 years, the rationale for
plasmapheresis remains based largely on case series and
retrospective studies. Recently, results from several ran-
domized controlled trials, meta-analyses, and prospective
studies have shown plasmapheresis may be of benefit in
various renal diseases, and have provided insights into
more rational use of this therapy. A multicenter trial by the
European Vasculitis Study Group has shown it is the
preferred additional form of therapy for patients with anti-
neutrophil cytoplasmic antibody-associated glomerulone-
phritis and severe renal failure. A recent study conducted at
Mayo Clinic also found it effective at reversing renal
failure from myeloma-related cast nephropathy if serum
free light chain levels were reduced by at least 50%.
In addition, a Cochrane review has analyzed the available
evidence for its use in thrombotic thrombocytopenic pur-
pura and hemolytic uremic syndrome. The objective of this
article is to review recent and past evidence and, thereby,
the current indications for treatment in renal disease.
Keywords Plasmapheresis  Renal failure 
Renal transplantation  Renal diseases
S. Baweja (&)  K. Wiggins  D. Lee  S. Blair  M. Fraenkel 
L. P. McMahon (&)
Eastern Health, 2nd floor, 5 Arnold Street, Box Hill,
Melbourne, VIC 3128, Australia
e-mail: sanjeev_b4us@yahoo.co.in
L. P. McMahon
e-mail: lawrence.mcmahon@easternhealth.org.au
Introduction
Plasmapheresis, or plasma exchange, is an extracorporeal
blood-purification process whereby plasma is removed
from the patient and artificially replaced. Abel [1] first
described the process in the dog in 1914 but the first
therapeutic plasmapheresis was performed by Schwab and
Fehay [2] in two patients with macroglobulinemia in 1960.
Since then, it has been widely used to remove either proven
or presumed large-molecular-weight pathogens from the
circulation. These include antibodies, immune complexes,
monoclonal proteins, endotoxins, drugs, and cholesterol-
containing lipoproteins [3]. It is essentially symptomatic
therapy, removing or replacing a product rather than
addressing any underlying pathology, although some the-
oretical immune-modulatory effects of plasmapheresis
have also been proposed [47].
Several plasmapheresis techniques are currently avail-
able. Centrifugation-based plasma separators are most
widely used, because the required blood flow can easily
be achieved by cannulating a large peripheral vein, thus
avoiding the need to access central veins. Other conventional
forms of plasmapheresis include membrane plasma separa-
tion, cryofiltration apheresis, immunoadsorption, and
chemical affinity column apheresis [8]. Compared with
centrifugal devices, membrane filtration has the advantages
of less platelet loss, less hemolysis, and minimum equipment
requirements. Membrane filtration can be performed by
using standard hemodialysis equipment, and patients with
kidney injury who require both hemodialysis and plasma-
pheresis can receive each sequentially. However, although
faster and more efficient, there seems little or no clinical
advantage compared with centrifugal devices [911].
The amount of plasma to be replaced during plasma-
pheresis must be determined in relation to the patients
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estimated plasma volume (EPV), which can be calculated
by use of the formula [12]:
EPV 0:065  weight kg  1  hematocrit): Disease
The decline in immunoglobulin levels after a single plas-
mapheresis is misleading, because extravascular immuno-
globulins enter the vascular space at the rate of 13% per
hour, yielding a post-treatment increase which begins to
plateau after 24 h, at which time there will be a further
opportunity for immunoglobulin removal. Usually, if pro-
duction rates are modest, at least daily exchanges for
3 days will be required to remove 70% of the patients
initial burden, and 5 separate treatments during a 7 to
10-day period will remove 90% of the patients initial total
body burden. If production rates are high, additional
treatments may be required [1214].
The overall complication rate during plasmapheresis is
approximately 10% (reports vary from 1.4 to 20%) and
mostly occurs in patients receiving fresh frozen plasma
(FFP) as replacement fluid. The most frequent complica-
tions are symptoms of hypocalcemia, hypovolemia, and
anaphylactoid reactions [15] Serious adverse events occur in
\3% of patients and the procedure-related mortality rate is
very low (0.00.05%) [16, 17]. In particular, the infection
rate does not seem to be higher in immunocompromized
patients [18]. Some patients taking ACE inhibitors may
experience atypical symptoms such as flushing, hypoten-
sion, bradycardia, dyspnea, and abdominal cramping [19].
The latest guidelines for use of plasmapheresis were
published by the American Society for Apheresis in June
2007 [2023]. Current indications for renal diseases are
displayed in Table 1. Recently, results from several ran-
domized controlled trials (RCTs), meta-analyses, and pro-
spective studies have shown plasmapheresis may be of
benefit in various renal diseases, and have provided some
insight into more rational use of this therapy, although
many of the guidelines are still not based on results from
RCTs.
Anti-glomerular basement membrane (Anti-GBM)
disease
Anti-glomerular basement membrane disease, when
accompanied by pulmonary hemorrhage, is known as
Goodpastures disease [24]. It is caused by circulating
antibodies directed against the non-collagenous domain
of the a-3 chain of type IV collagen [25]. In 1975, before
the introduction of plasmapheresis [26], mortality was
8696% either from pulmonary hemorrhage or renal failure
[2729]. Since then, many uncontrolled trials or case
reports have demonstrated the clinical benefits of plasma-
pheresis [3036].
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J Artif Organs (2011) 14:922
Table 1 Indications for plasmapheresis in renal diseases (modified
from Ref. [20])
Rating
Anti-GBM disease 1
Rapidly progressive glomerulonephritis 2
Thrombotic thrombocytopenic purpura 1
Hemolytic uremic syndrome 34
Cryoglobulinemia 1
Multiple myeloma cast nephropathy 3
Hyperviscosity syndrome (Waldenstroms 1
macroglobulinemia)
Removal of cytotoxic antibodies in transplant candidate 2
Renal allograft rejection 2
Focal segmental glomerulosclerosis (recurrence after 2
transplantation)
Rheumatoid arthritis/rheumatoid vasculitis 2
Antiphospholipid antibody syndrome 2
Systemic lupus erythematosis 4
Scleroderma 4
Rating: 1, standard therapy, but not mandatory; 2, available evidence
tends to suggest efficacy, conventional therapy usually tried first; 3,
inadequately tested at this time; 4, no demonstrated value in con-
trolled trials
Only one randomized study has compared the effect of
immunosuppressive therapy alone (prednisone and cyclo-
phosphamide) with immunosuppression and plasmaphere-
sis [37]. Seventeen patients with anti-GBM disease were
studied. Only 2 of 8 patients who received plasmapheresis
became dialysis-dependent, in comparison with 6 of 9 in
the immunosuppression alone group. Patients treated with
plasmapheresis had a more rapid disappearance of anti-
GBM antibodies, with mean serum creatinine value half
that of the control group. Patients with\30% crescents and
well preserved renal functions did well with either treat-
ment, whereas patients with severe crescentic involvement
and impaired glomerular filtration rate uniformly did
poorly.
The largest published series of long-term outcomes of
anti-GBM disease is from the Hammersmith Hospital,
London [38]. All 71 patients received a standard regimen
of plasmapheresis, oral prednisolone, and oral cyclophos-
phamide. Plasmapheresis (50 mL/kg to a maximum of 4 L)
was performed daily for at least 14 days or until anti-GBM
titers were undetectable. One-year patient and renal sur-
vival were 100 and 95%, respectively, when creatinine was
\500 lmol/L (5.7 mg/dL), 83 and 82% when creatinine
was C500 lmol/L but not dialysis-dependent, and 65 and
8% when patients were dialysis-dependent at onset. Five-
year patient and renal survival were 94 and 94%, 80 and
50%, and 44 and 13%, respectively. All patients who
required immediate dialysis and had 100% crescents on
J Artif Organs (2011) 14:922
renal biopsy remained dialysis-dependent. Pulmonary hem-
orrhage remained the most common cause of death in this
series, but resolved in 90% of patients after plasmapheresis.
These data suggest that all patients with anti-GBM
disease and renal failure not requiring immediate dialysis
should be immunosuppressed and immediately receive
intensive plasmapheresis. Because pulmonary hemorrhage
is associated with high mortality, plasmapheresis should be
initiated in all patients who have pulmonary hemorrhage,
irrespective of the severity of the renal failure, although
avoidance of both cigarette consumption and fluid overload
remain important preventative clinical measures.
Anti-neutrophil cytoplasmic antibody
(ANCA)-associated glomerulonephritis
Approximately 4045% of patients with rapidly progres-
sive glomerulonephritis (RPGN) have crescentic glomeru-
lonephritis characterized by few or absent immune deposits
(pauci-immune RPGN) [39, 40]. Most of these patients
have Wegeners granulomatosis, microscopic polyarteritis,
or renal-limited pauci-immune glomerulonephritis. Eighty
to ninety percent of these patients have circulating anti-
neutrophil cytoplasmic antibodies which are directed
against myeloperoxidase (MPO) or proteinase 3 (PR-3)
present within the azurophil granules of neutrophils and
monocytes [4143]. There is evidence suggesting that the
antibodies themselves may contribute to the pathophysi-
ology of the RPGN [4448].
If not treated promptly, rapid deterioration of renal
function and death are common with severe ANCA-asso-
ciated vasculitis [49]. Although cyclophosphamide and
corticosteroids lead to remission in over 90% of cases [50,
51], and recent studies showed similar outcome with the
rituximab-based regime [52, 53], patients with advanced
renal failure have poorer outcomes with only 50% sur-
viving with independent renal function at 1 year [54, 55].
Additional benefits of plasmapheresis, particularly when
patients are dialysis-dependent, were first reported in 1977
and since confirmed in numerous RCTs [5660].
Recently, a large multicenter randomized study conducted
by the European Vasculitis Study Group has compared
Table 2 Randomized
Outcome
controlled trial of
methylprednisolone versus
plasmapheresis for severe renal Renal recovery at 3 months
vasculitis
Survival at 12 months
ESKD at 12 months
ESKD end stage kidney disease, Overall
CI confidence interval, NS not Survivors
significant
11
intravenous methylprednisolone (IVMP) with plasmaphere-
sis as adjuvant therapy for severe ANCA-associated glo-
merulonephritis (serum creatinine [500 lmol/L, [ mg/dL)
[61, 62]. All 137 patients followed a standard treatment
regimen and, for adjunctive therapy, were randomly assigned
to receive either IVMP (1000 mg/day for 3 consecutive days)
or plasmapheresis (7 plasma exchanges of 60 mL/kg during
the first 14 days after diagnosis). Although patient survival
was similar in both groups (results are summarised in
Table 2), plasmapheresis increased the rate of renal recovery
without improving the risk of adverse events. Compared with
IVMP, plasmapheresis was associated with a reduced risk for
progression to end-stage kidney disease (ESKD) at both
3 months (22%) and 12 months (24%). The hazard ratio for
ESKD over 12 months was also lower in the plasmapheresis
group (0.47). By multivariate analysis renal recovery was
significantly associated with plasmapheresis (P = 0.04) but
not with stratification (nonoliguric or dialysis requiring), age,
diagnosis, or ANCA subtype.
These studies suggest use of plasmapheresis as the
preferred additional form of therapy for patients who have
ANCA-associated glomerulonephritis and severe renal
failure. There is also evidence to suggest that it should be
initiated in any patient with diffuse pulmonary alveolar
hemorrhage [52, 6366].
Thrombotic thrombocytopenic purpura (TTP)/
hemolytic uremic syndrome (HUS)
Thrombotic thrombocytopenic purpura is an occlusive
microangiopathy characterized by platelet aggregation,
hemolysis, thrombocytopenia, and organ ischemia [67]. If
severe renal failure is the predominant feature, the disorder
is often considered to be HUS, divided into D? (preceded
by diarrhea) or D- (atypical HUS, not preceded by diar-
rhea) [68, 69]. However, the clinical distinction between
TTP and HUS is not always clear-cut [70, 71]. Postulated
pathogenic mechanisms in HUS/TTP include a deficiency
of anti-thrombotic or fibrinolytic activity, bacteria-derived
toxins, anti-endothelial antibodies, immune complexes,
abnormal von Willebrand multimers, and various toxic
agents [72]. In TTP, unusually large von Willebrand
IV methylprednisolone Plasmapheresis P value
(n = 67, %) (n = 70, %)
33 (49) 48 (68) P = 0.02 (95% CI 1835%)
51 (76) 51 (73) NS
29 (43) 41 (59) P = 0.008 (95% CI 440%)
29 (57) 41 (80)
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multimers accumulate because of absolute or functional
deficiency of the cleaving protease ADAMTS13, resulting
in platelet microthrombus formation, endothelial cell
damage, and complement activation [7375]. In some
patients with idiopathic TTP, inhibitory autoantibodies to
the ADAMTS13 metalloproteinase distinguish the condi-
tion from HUS [7678]. By removing autoantibodies to
ADAMTS13, and using plasma containing ADAMTS13
activity (usually FFP), plasmapheresis can reverse the
damage caused by ADAMTS13 deficiency [79]. Before the
discovery of the role of plasma infusion or plasmapheresis
in TTP/HUS, the disease was almost uniformly fatal (93%
mortality); however mortality is currently estimated to be
between 9 and 46% [8083].
Various uncontrolled studies have shown the benefits
of plasmapheresis with FFP in adults with the TTP/HUS
but most of the studies were conducted before the iden-
tification of ADAMTS13 [8487]. A recent Cochrane
review has analyzed the available evidence of treatment
options for HUS or TTP [88]. Six RCTs (331 partici-
pants) evaluating different interventions (antiplatelet
therapy plus plasmapheresis with FFP, FFP infusion and
plasmapheresis with cryosupernatant plasma) in TTP
were included [8994]. In all studies, plasmapheresis with
FFP was used as the control and was found to be the most
effective treatment. Two studies which compared FFP
infusion alone with plasmapheresis with FFP demon-
strated the advantage of the latter treatment. FFP infusion
alone was less likely to achieve remission at 2 weeks (RR
1.48, 95% CI 1.121.96) and had higher all-cause mor-
tality (RR 1.91, 95% CI 1.093.33) in the FFP infusion
alone group. There was no difference in outcome after
use of cryoprecipitate or cryosupernatant plasma as
replacement fluid. There is some evidence that early
treatment with vincristine and plasmapheresis may be
more effective than plasmapheresis alone in TTP [95].
Splenectomy has also been used, with variable success, in
refractory and relapsing TTP, but its role has never been
studied in a controlled fashion. Plasma infusions are
effective in the treatment and prevention of relapses in
rare congenital forms of TTP [96].
Plasmapheresis is usually performed daily until the
platelet count has risen to 100150 9 109/L, and evidence
of hemolysis has resolved. If needed, it can be performed
twice daily, exchanging 1.5 L of plasma each time [97].
Plasmapheresis should be gradually tapered by increasing
the interval between treatments.
There is no convincing evidence for recommending
plasmapheresis for HUS. In a meta-analysis of seven RCTs
in children with HUS (predominantly post-diarrheal) sup-
portive therapy was compared with a range of interven-
tions, including anticoagulation, FFP infusion, steroids, and
a shiga toxin binding agent [98104]. None of the tested
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J Artif Organs (2011) 14:922
interventions was superior to supportive therapy. There are
no RCTs evaluating the effectiveness of plasmapheresis in
atypical HUS.
From the available data, it would seem that when no
clear differentiation between TTP and HUS can be made, it
is better to initiate plasmapheresis promptly in all cases,
particularly in severely affected patients [105]. If plasma-
pheresis is not available, patients should be treated with
plasma infusion (at least 25 mL/kg/day), which seems to be
superior to no plasma therapy at all [106].
Cryoglobulinemia
Cryoglobulinemia is associated with diseases including
lymphoproliferative disorders, autoimmune diseases, and
viral infections (particularly hepatitis C) [107]. Renal
disease occurs at presentation in \25% of patients, but
develops in up to 50%. The characteristic glomerular
lesion is membranoproliferative exudative glomerulone-
phritis with subendothelial deposits [108, 109]. Although
plasmapheresis has been used for treatment of cryo-
globulinemia for over 35 years, to rapidly reduce the
circulating cryocrit (immunoglobulin concentration in
cryoprecipitate), there are no RCTs, and recommenda-
tions are based on uncontrolled studies or case series
[20, 110]. It is claimed to be most effective in acute
systemic vasculitic exacerbations, acute renal failure,
hyperviscosity syndrome, acute neuropathy, and skin
ulcers [111114]. Overall, plasmapheresis has been
associated with improved renal function in 5587% of
patients [115119].
Plasmapheresis is used in both short and long term
management, and for the first 2 weeks is performed thrice
weekly, removing 11.5 times the plasma volume, with
albumin replacement. There is a poor correlation between
the cryocrit concentration and disease activity, so benefits
of therapy should be judged according to the clinical and
biochemical response [20, 113]. Double-cascade filtration,
immunoadsorption, and cryofiltration have also been used
to treat cryoglobulinemia [120122]. Most studies have
used plasmapheresis in combination with immunosup-
pressive or immunomodulatory therapy, and antiviral
therapy in patients with viral infections. There are also
reports of successful outcome with rituximab alone in
hepatitis C-associated cryoglobulinemia [123].
Multiple myeloma
Multiple myeloma accounts for 10% of all hematological
malignancies [124] and has a high incidence of renal fail-
ure (1656%) [125127]. Renal impairment can be caused
J Artif Organs (2011) 14:922
Table 3 RCTs evaluating the role of plasmapheresis in multiple myeloma-associated renal failure
Reference Number
Total Plasmapheresis Control
Zucchelli et al. [137] 29 15 14
Johnson et al. [138] 21 11 10
Clark et al. [139] 97 58 39
a
Statistically significant difference
b
No significant difference
by a variety of factors, including hypercalcemia, hyper-
uricemia, amyloidosis, hyperviscosity, infections, and
chemotherapeutic agents [128, 129]. However, the most
common pathology is light chain cast nephropathy, which
is found in 3060% of cases [130132]. Renal failure is
also the most common cause of death, second only to
infection [131]. Dialysis-dependent patients with myeloma
have an adjusted relative risk of death 2.5-fold that of other
dialysis patients [133]. Serum levels of myeloma protein,
and the type and severity of renal lesions, are the major
factors that predict recovery of renal function [134].
Plasmapheresis combined with chemotherapy has been
advocated as the best means of rapidly reducing the
plasma concentration of myeloma proteins, to reduce the
filtered load and thus the nephrotoxicity of these proteins
[135, 136], but the results of available RCTs have been
mixed, with each of the three main studies reported to be
flawed (Table 3). Zucchellis [137] study used hemodi-
alysis for the plasmapheresis group and peritoneal dial-
ysis for the control group. The study by Johnson was
underpowered, and used more patients with severe renal
disease in the plasmapheresis group (although renal
function in dialysis patients recovered only in those
receiving plasmapheresis) [138]. A larger randomized
study of 97 patients with newly diagnosed myeloma and
acute renal failure failed to show any significant benefit
of plasma exchange [139]. Of likely significance in these
studies, histopathologic confirmation of cast nephropathy
was rarely available.
In a recent study of 40 patients with myeloma con-
ducted at the Mayo Clinic, plasmapheresis was found to
be effective in reversing renal failure if due to cast
nephropathy and if serum free light chain (sFLC) levels
could be reduced by at least 50%. When both criteria
were met, renal function improved in 78% of the patients.
Median survival was 31.8 months for responders versus
11.0 months for non-responders. Renal function did not
improve in any cast nephropathy patient whose sFLC
13
Dialysis-dependent Outcome
at entry
Recovery from dialysis Mortality
24 Plasmapheresis 85%a Plasmapheresis 34%a
Control 18% Control 72%
12 Plasmapheresis 43%b Plasmapheresis 25%b
Control 0 Control 25%
29 Plasmapheresis 42%b Plasmapheresis 33%b
Control 37% Control 33%
could not be reduced by [50% [140]. This finding may
explain the differences in outcomes reported by the three
previous randomized trials, where neither biopsy diag-
nosis nor markers of therapy was used. However, it seems
likely that a combination of chemotherapy and plasma-
pheresis is required to achieve a positive outcome in cast
nephropathy.
Recently, daily extended hemodialysis with a high cut-
off (HCO) dialyzer (Gambro HCO 1100) has been shown
to remove large quantities of free light chains [141]. In an
open label study, 19 patients with biopsy-proven cast
nephropathy and dialysis-dependent acute renal failure
were treated with combined chemotherapy and HCO
dialysis. There was sustained early reduction of sFLC
concentrations in 13 patients who became dialysis-inde-
pendent. In 6 patients chemotherapy was interrupted
because of early infection. These patients did not achieve
sustained early sFLC reduction and 5 of these did not
recover renal function [142]. Patients who recovered
renal function had significantly improved survival
(P \ 0.012). A large study (EuLITE trial) is being
attempted to investigate these promising initial results
further [143].
Waldenstroms macroglobulinemia
Waldenstroms macroglobulinemia (WM) is a small B-cell
lymphoproliferative disorder resulting in an abnormal
secretion of monoclonal IgM protein [144]. Plasmapheresis
should be considered for symptomatic hyperviscosity and
for prophylaxis in patients in whom rituximab therapy is
contemplated, because rituximab therapy can cause an IgM
flare [145]. For patients requiring immediate disease con-
trol (including symptomatic hyperviscosity with serum
viscosity [4 centipoises, cryoglobulinemia or moderate to
severe cytopenia), rapid paraprotein reduction should be
achieved by plasmapheresis [146]. One plasma exchange
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daily, using albumin as replacement fluid, is performed
until resolution of symptoms is achieved [147].
ABO-incompatible renal transplantation
Traditionally, ABO blood group incompatibility has been
regarded as an absolute contraindication to renal trans-
plantation because preformed anti-A or anti-B antibodies
usually result in hyperacute or acute antibody-mediated
rejection. Desensitization to remove these pre-existing
antibodies is necessary pre-transplantation. Plasmaphere-
sis, double filtration plasmapheresis, or immunoadsorption
procedures are used to remove antibodies before trans-
plantation when the titer of IgG and IgM ABO antibodies is
more than 1:8. A2 is thought to be less immunogenic than
the A1 and B blood groups, and A2 kidneys are less likely
to undergo antibody-mediated rejection [148150]. How-
ever, recent studies have revealed equally good graft sur-
vival with A2B and non-A2 kidneys, although there may be
a greater early graft loss [151153].
Most of the previous studies have used pre-transplant
conditioning procedures including splenectomy [154
156], a practice which is slowly being abandoned [157,
158]. In Japan, among 1012 ABO-incompatible renal
transplantations performed during the period 19892006,
1, 3, 5, and 10-year patient survival were 95, 93, 91 and
87%, respectively, and corresponding graft survival was
90, 86, 80, and 63%, respectively [159]. These results are
comparable with those for ABO-compatible renal trans-
plantation. Typically, recipients underwent 24 sessions
of plasmapheresis before surgery, then splenectomy or
rituximab and intravenous immunoglobulins (IVIG)
infusion in addition to regular immunosuppression. Sig-
nificantly, in 2001, a new treatment incorporating blood
group antigen-specific immunoadsorption and rituximab
was introduced [160]. Immunoadsorption has the advan-
tage of removing only anti-A or anti-B antibodies rather
than whole plasma, and is thus devoid of many adverse
events associated with plasmapheresis. More than 400
transplants have now been performed, with overall results
comparable with ABO-compatible kidney transplantation
[161164].
After transplantation, the risk for early humoral allograft
rejection after ABO-incompatible transplantation is highest
within the first 2 weeks and the antibody titers are kept low
by additional intermittent plasmapheresis or immunoad-
sorption. Although anti-ABO antibodies tend to recur
subsequently, graft function is usually not affected,
because of a process known as accommodation; hence
regular plasmapheresis does not seem necessary to prevent
antibody-mediated rejection [165].
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J Artif Organs (2011) 14:922
Renal transplantation with a positive cross match
The presence of donor-specific anti-HLA antibodies is
associated with a high risk of graft loss and has therefore
been regarded as a contraindication for transplantation
[166]. Various desensitization protocols incorporating a
combination of plasmapheresis, immunoadsorption, IVIG,
and rituximab have been used to downregulate the anti-
body-mediated immune responses [167172]. Although
high doses of IVIG alone have been used successfully,
plasmapheresis based treatments result in more reliable
desensitization and lower rejection rates [172174]. Plas-
mapheresis is generally performed thrice weekly, using
albumin as replacement fluid, until a negative cross-match
is achieved [20]. Similarly, immunoadsorption has been
used in highly sensitized patients to achieve a negative
cross-match [175177]. Recently, protocols using high-
dose IVIG and rituximab without plasmapheresis have
been found to be as effective in sensitized live and
deceased transplants, achieving 2-year patient and graft
survival of 95 and 84%, respectively [178]. All patients
who undergo desensitization for transplantation are at high
risk of antibody-mediated rejection. In the first week post
transplant, plasmapheresis is performed several times to
remove any rebound antibodies. Treatment of rejection is
essentially the same as the desensitization.
Antibody-mediated renal allograft (AMR) rejection
The true incidence of AMR is variable, ranging from 5.6 to
23% in unselected transplant populations, and up to 60% in
ABO-incompatible transplantation or in sensitized hosts
[179]. Diagnosis of AMR depends on a triad of donor-
specific alloantibodies, characteristic histology of tissue
injury, and positive C4d staining in the peritubular capil-
laries [180, 181]. The management of AMR is based on
alloantibody removal and effective control of their pro-
duction. In the absence of data from RCTs, treatment relies
on the combination of plasmapheresis or immunoadsorp-
tion and IVIG, along with intense immunosuppression
(tacrolimus and mycophenolate mofetil) with or without
T-cell-depleting antibodies, rituximab, and a proteasome
inhibitor. Most studies have incorporated plasmapheresis
for removal of antibodies and demonstrated its effective-
ness, which seems superior to that of IVIG alone [180,
182189]. The number of plasmapheresis sessions is based
on the clinical response to therapy as measured by urine
output and serum creatinine [190]. In combination with
IVIG, rituximab, and tacrolimus/mycophenolate, plasma-
pheresis has achieved 5-year graft survival of over 75%
[185, 190193].
J Artif Organs (2011) 14:922
Recurrent focal segmental glomerulosclerosis (FSGS)
after renal transplantation
The incidence of post transplant recurrence of primary
FSGS is between 20 and 30%. If the first graft is lost
because of recurrent disease the risk of recurrence in sub-
sequent grafts is 80% [194197]. Without treatment,
5080% of patients lose their graft in the first year [198].
There is emerging evidence that the pathogenesis may
involve a low-molecular weight anionic circulating per-
meability factor, which is the rationale for using plasma-
pheresis and immunoadsorption in cases of recurrence
[199, 200]. Plasmapheresis seems of substantial benefit for
treatment of recurrent primary FSGS after transplantation.
Studies have shown marked improvement and complete
remission in some cases [201205]. Long-term graft sur-
vival is also better with plasmapheresis (85% in the plas-
mapheresis group vs. 30% in the untreated group) [206].
The American Society for Apheresis recommends daily
or alternate-day plasmapheresis, replacing 11.5 times
the total plasma volume with albumin [20]. Mixed results
have been obtained after combining plasmapheresis with
cyclophosphamide, high-dose cyclosporine, and myco-
phenolate mofetil [198, 207209]. There are also several
recent reports of a successful outcome with rituximab in
patients with recurrent FSGS resistant to plasmapheresis
[210, 211].
Systemic lupus erythematosis (SLE), catastrophic
antiphospholipid antibody syndrome (CAPS),
pre-eclampsia, systemic sclerosis (SSc)
Disappointing results from RCTs have led to a reduction in
the use of plasmapheresis to treat SLE patients. In an RCT
by Lewis, addition of plasmapheresis to a regimen of
corticosteroid and oral cyclophosphamide did not improve
clinical outcome for 84 patients with severe lupus nephritis
after a mean follow-up of 136 weeks [212]. Despite early
reports of success [213], RCTs also showed that a syn-
chronized plasmapheresis regimen with high-dose cyclo-
phosphamide was not beneficial in long-term treatment of
lupus nephritis [214, 215]. However, data from the various
international registries show that 0.53.1% of SLE patients
are treated with plasmapheresis every year. Such anecdotal
data also suggest that plasmapheresis might be useful as an
adjunctive therapy in selected cases where manifestations
of SLE include conditions shown to benefit to some extent
from plasmapheresis, for example refractory renal disease,
alveolar hemorrhage, some neuropsychiatric manifesta-
tions, thrombotic thrombocytopenic purpura, CAPS, the
hyperviscosity syndrome, or symptomatic cryoglobuline-
mia [216].
15
In 2005, Uthman [217] examined the role of plasma-
pheresis in CAPS and demonstrated improved patient
survival. Recently, the data from European CAPS registry
has also showed the best recovery using a combination of
anticoagulants, corticosteroids, and plasmapheresis and/or
IVIG. The main reasons for the improved recovery were
considered to be the use of plasmapheresis and/or IVIG
[218]. Most CAPS patients received FFP as the replace-
ment fluid. No comparative studies with use of albumin or
other replacement fluid are available [219].
Few studies have assessed the benefit of plasmapheresis
in preeclampsia. In one case series of 18 patients with
persistent postpartum, hemolytic anaemia, elevated liver
enzymes, and low platelets (HELLP syndrome), the use of
plasmapheresis was associated with improved maternal and
perinatal outcome. However, a uniformly positive response
to this therapy could not be achieved for patients with
additional organ injury [220]. Another prospective study of
29 patients reported better survival with plasmapheresis
(maternal mortality rate 0% in plasmapheresis group vs.
23% in historical control group) [221]. However, there
were no differences in dialysis requirements or the devel-
opment of renal failure. Most other reports are case pre-
sentations [222226].
A few small case series and isolated case reports have
suggested some additional benefit of plasmapheresis in
retarding the progression and reversing the symptoms of
SSc [227, 228]; however, recently published guidelines
from the European League Against Rheumatism (EULAR)
Scleroderma Trials and Research group (EUSTAR) do not
currently advocate use of plasmapheresis in SSc [229].
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