Anemia can be defined as HB <12 g/dL in females & <13 g/dL in males, is commonly observed before and after KTx.
Anemia in KTR
Abbreviations (read
twice please and put your comments):
o
+ve:
Positive
o
AB: antibodies
o
ACEi:
angiotensin-converting enzyme inhibitors
o
ALERT:
Assessment of Lescol in Renal Transplantation study
o
APR: acute-phase reactant
o
ARBs:
angiotensin receptor blockers
o
Aza: Azathioprine
o
BM:
Bone marrow
o
BTx:
blood (RBCs) transfusions
o
CAPRIT: Correction of Anemia and Progression of Renal
Insufficiency in Transplant Patients
o
CHOIR:
Correction of HB and Outcomes in Renal
Insufficiency
o
CKD:
Chronic kidney disease
o
CMV: cytomegalovirus
o
CNI: calcineurin inhibitors
o CPGAABB: Clinical Practice Guidelines of the
American Association of Blood Banks
o
CREATE: Cardiovascular Reduction Early Anemia Treatment
Epoetin beta
o
CVD:
Cardiovascular disease
o
CVS:
Cardiovascular system
o
CyA: Cyclosporine
o
DCGS: death-censored graft
survival
o
DGF: delayed graft function
o
Dgx: diagnosis
o
DX: Dialysis
o
EBV:
Epstein-Barr virus
o
EC-MPS: enteric-coated mycophenolate sodium
o
eCrCl: Estimated creatinine
clearance
o
eGFR:
estimated glomerular filtration rate
o
EPO:
erythropoietin
o
ESA:
erythropoiesis-stimulating agent
o
ESKD:
end-stage kidney disease
o
GI: gastrointestinal
o
HB: hemoglobin
o
HDX: hemodialysis
o
HF: heart failure
o
HUS: Hemolytic uremic
syndrome
o
IF/TA: Interstitial
fibrosis and tubular atrophy
o
IL-6: Interleukin-6
o
im/m: immunosuppressive/immunosuppression
o
IVIG: Intravenous
immune globulin
o
KDIGO:
Kidney Disease:
Improving Global
Outcomes
o
KTR: kidney transplant recipients
o
KTx:
kidney transplantation
o
LDH: lactate dehydrogenase
o
LVH:
Left ventricular hypertrophy
o
MAHA:
microangiopathic hemolytic anemia.
o
MMF: Mycophenolate mofetil
o
MR: mortality
o
mTORi:
mammalian (mechanistic)
target of
rapamycin inhibitors
o
NAAT:
nucleic acid amplification testing
o
NICE:
United Kingdom National Institute for Health and Care Excellence
o
NKF KDOQI: National Kidney Foundation Kidney Disease Outcomes
Quality Initiative
o
NOA: new-onset anemia
o
PLS: Passenger leukocyte
syndrome
o
Pph:
plasmapheresis
o
Prox: prophylaxis/prophylactic
o
PVD: peripheral vascular
disease
o
RBCs: Red blood cell
o
RCT: randomized controlled trial
o
RES: reticuloendothelial
system
o
RETIC: Reticulocyte count
o
Rj: rejection
o
Sms: symptoms
o
Sns: signs
o
Snz: sensitization
o
SOT: Solid organ transplant
o
SRL: Sirolimus
o
Tac: Tacrolimus
o
TIBC: Total iron-binding
capacity
o
TMA:
thrombotic microangiopathy.
o
TMP-SMX: Trimethoprim-sulfamethoxazole.
o
TR:
transplant recipients
o
TREAT:
Trial to Reduce Cardiovascular Events with Aranesp Therapy
o
TSAT:
transferrin saturation
o
ttt: treatment
o
Tx: transplant
o
Tx: transplant/Transplantation
o
-ve: Negative
Anemia
can be defined as HB <12 g/dL in females &
<13 g/dL in males, is commonly observed before and
after KTx. It’s mostly related to iron deficiency, graft Rj or dysfunction,
EPO deficiency, viral infection, im/m,
and infection
Prox agents. We will discuss the epidemiology, pathogenesis, evaluation,
and ttt of anemia in KTR. TR
mostly have an average eGFR <60 mL/min/1.73 m2, a
level that’s consistent with the current definition of CKD.
EPIDEMIOLOGY
The
prevalence of anemia after KTx varies
according to the given definition of anemia, the post-Tx timing, im/m protocol, and frequency of ttt. While anemia is found in almost 90 % of ptns within
the 1st mo post-Tx, this
prevalence declines to 34-45 % among ptns > one y.
post-Tx. At the timing of Tx, most adult ptns can be termed anemic
as target levels for HB among US DX ptns are mostly 10-11 g/dL. Mean HB
levels rise to > 11
g/dL by 3 mo post-Tx and to > 12 g/dL at 6-12 mo post-Tx. The evolution
of acute/chronic graft dysfunction is mostly associated with worsened anemia, e.g.:
o
At 6
mo post-Tx, about one-½ of ptns have
an HB level below normal (defined as
<14 g/dL
in men & <12
g/dL in women).
o
At one y., 10-40 % are anemic despite showing normal graft
function.
o
During the 1st 5-y post-Tx period,
about one-1/3rd of ptns have HB <12 g/dL. More severe anemia, (HB <11 g/dL),
seen in 12-15 % of ptns.
o
Registry study: 20 European centers, 3699 ped ptns Tx,
49.8 & 7.8
% of TR were anemic, according
to the NKF KDOQI (defining anemia in
children as HB < 5th percentile for age & sex) & NICE guidelines (defining anemia as HB <9.5 g/dL
in ptns <2 ys old & <10 g/dL for ptns ≥2 ys old), resp. HB were strongly linked to allograft
function. Low HB were correlated with higher
risk of allograft failure or combined graft failure
& death but not with death only.
PATHOGENESIS &
RISK FACTORS
Pathogenesis
of anemia after Tx varies by the timing after
Tx. Common risk factors linked to anemia development
may include female sex, age, graft dysfunction, ACEi/ARBs use,
and im/m agents. Administration of ESA or iron therapy may be paradoxically associated
with anemia owing to ttt via indication
bias.
Early post-Tx: Immediate anemia after Tx is almost entirely due to lower-than-normal HB targets in the CKD
& ESKD cohorts, surgical
blood losses, and frequent phlebotomies. Dilutional anemia also
occurs due to aggressive peri-operative volume
expansion. Recovery to normal adult HB
can be impeded by graft dysfunction and other comorbidities, higher donor age,
and iron deficiency.
[1]
Inadequate EPO: Improving erythropoiesis after
KTx is due to the provided EPO from
the graft and lack of the uremic milieu. Generally, EPO levels starts to rise on post-Tx day 2, reaching 4-folds at 2-3 weeks, after that time restored -ve feedback
control ensue. Early EPO production can
be inefficient in anemia correction as EPO
seems still inefficient with the persisting uremic
setting. Relative deficient EPO
in the setting of graft dysfunction is mostly simulating that encountered with
anemia in non-Tx-associated CKD. However, graft endocrine function may
not be correlating with excretory function, mostly due to peri-tubular interstitial cells producing EPO, are selectively disabled or showed
defective functional regulations. Anemia may be also corrected in some TR despite the relative lowered EPO levels.
[2]
Iron deficiency: has a crucial role in persisting anemia in the immediate post-Tx period. Despite recognizing iron requirements
for successful ESA therapy, iron deficiency still commonly
encountered among ptns candidate for KTx.
Iron stores may be seriously depleted after-Tx due to surgical blood losses, recurrent
phlebotomy, and the utilized stores for triggered erythropoiesis. Return of normal
menses with iron losses may be also contributing to iron
deficiency in women.
The regulatory steps of iron absorption/mobilization
from its stores to assist erythropoiesis is also disabled in the early post-Tx period and during Rj episodes. Hepcidin is the regulator of intestinal iron absorption & release of iron from RES stores.
It is an APR, and its levels are increased in most DX ptns with poorly absorbed & mobilized iron for erythropoiesis. Hepcidin levels have also been found to be still
elevated in many KTR, and the increased
levels are correlated with poor Tx function,
increased ferritin, and other inflammatory markers. IL-6,
a crucial regulator of hepcidin production, has been shown to be increased
immediately after Tx and within acute Rj episode.
The
precise evaluation of iron stores after Tx is
difficult as ferritin is a +ve APR while TSAT is varying inversely with APR. A higher ferritin level
could be reflecting adequate iron storing, inflammation,
or both, while low TSAT may be related to lowered iron stores, inflammation, or both. The combined [higher ferritin & low TSAT] is characterizing anemia of chronic disease and reflecting
the impact of IL-6, hepcidin,
and other inflammatory signals. Acute/chronic Rj,
progressive drop in graft function, and inflammation or infectious episodes may
induce ferritin rise. On the other
hand, ferritin levels decline with iron consumption but also rising with enhanced
GI iron
absorption after Tx. So, ferritin levels are
inconsistently reflecting iron stores among KTR and do not always reflecting anemia
setting.
[3]
Donor kidney criteria: Cold/warm ischemic timing are not
correlated with EPO levels. However, ptns with DGF have a slower
production of EPO levels, which increases with improved allograft
function. IF/TA in the
donor kidney at timing of Tx have been shown
to be associated with anemia at 12 mo after Tx.
Later (>3 mo) post-Tx
[1] im/m agents: The antimetabolites MMF, EC-MPS,
& Aza can induce BM
suppression, leading to anemia. However, the mean
relative decline in HB level by these agents
may only be 0.2-0.3 g/dL,
resp. Generally, CNI do not induce BM suppression directly and do not
typically induce anemia development. SRL also can also cause BM suppression and anemia, especially early
after starting, but the effect could be lessened by time. Of note, SRL & the CNI (Tac & CyA) can also induce TMA-associated hemolytic anemia.
[2] Other
agents:
Using ACEi/ARBs has been linked to anemia in a
dose-related manner in KTR. According to this
action, these agents have been also successfully used to control post-Tx erythrocytosis. Other agents commonly used in KTR causing
anemia may include ganciclovir, valganciclovir, & TMP-SMX.
[3] Allograft
dysfunction &
Rj: In KTR, SCr levels
>2 mg/dL (177 micromol/L) are tightly correlated with
anemia. Moreover, episodic acute Rj
also have been correlated with a medium decline of
0.5 g/dL in HB level that may be attributed to declined
EPO production. Ptns returned
to HDX after failed KTx are suffering from a chronic inflammatory
status that’s complicated by resistance to ESAs action.
Removal of the failed Tx in symptomatizing ptns
can induce alleviation of the chronic inflammatory markers with
recovered sensitivity to ESAs
effects.
[4] Donor
&
recipient criteria: Donor of age >50-60 y. has been associated with a decline in EPO levels
with increasing incidence of anemia. Women are more prone to develop
post-Tx HB <12 g/dL at 6
& 12 mo. This may be due to
the higher iron losses with menses as well as androgen level decline to men.
[5] Infections: Infections due to
parvovirus B19, EBV, CMV,
BK polyomavirus, varicella-zoster virus, TB,
herpesviruses, & staph sp., have also been complicated with a greater risk
of anemia.
[6] Other
causes:
in the later post-Tx period may include
certain comorbidities (new Dgx of HF,
gastritis, PVD, & cerebrovascular events), secondary hyperparathyroidism, and folate/vit. B12 deficiency.
The PLS is a very rare syndrome for hemolytic anemia in
SOT recipients
that observed with ABO-compatible or Rh-compatible, but non-identical, donor and TR mismatching. PLS is most commonly reported after Tx of an organ from a donor with ABO-O blood type into a TR
with ABO-A or -B blood type or from an Rh--ve
donor into an Rh-+ve TR.
The donor graft containing B
cells & plasma cells (so-called passenger leukocytes) producing anti-isoagglutinin
or anti-Rh AB leading to the syndrome development. PLS typically presented as a mild hemolytic anemia with an acute onset within
the 1st few wks after Tx. Dgx can be
made by the direct antiglobulin (Coombs)
test. However, ttt is commonly supportive, despite Pph & cytolytic agents can be used. Clinical behavior is
typically self-limiting, despite AB may
be persisting at detectable values for 12-851 d.s after Tx.
SCREENING: KTR should be currently
screened for anemia after Tx via regular CBC. Most Tx centers
obtain a CBC at least weekly for
the 1st 3 mo and then
every 2-4 weeks for a year and
then monthly
to every 3 monthly after that.
Most TR are anemic at the timing of Tx and within the early post-Tx period, but HB
levels are expected to gradually elevated along the 1st 3 mo post-Tx
if the ptn has a well-functioned graft. So, the suggested approach to anemic
ptns on routine screening:
o
Assessment of iron stores (S. iron, TIBC, % TSAT, S. ferritin).
o
TR <
3 mo post-Tx, no further testing
unless ptns showed worsened anemia (i.e., HB
decline to a level less than that at the timing of Tx).
o
Failed HB
levels to be normalized by 3rd
mo
post-Tx > diagnostic assessment.
o
TR with
HB levels normalized by 3 mo post-Tx,
> diagnostic assessment for anemia if the ptn
has developed NOA.
DIAGNOSTIC ASSESSMENT:
KTR having persistent (i.e., HB fail to be normalized at 3 mo post-Tx)
or NOA should proceed to diagnostic
evaluation to recognize the etiology
of anemia. This assessment should evaluate the cause(s) of anemia shared with
non-Tx ptns, and other specific causes confined
to KTR, via evaluating:
1)
History of blood losses
2)
Detailed dietary habits.
3)
RBCs indices & RETIC
4)
Testing for folate &
vit. B12 deficiency
5)
Sms/Sns of infection (e.g., fever, malaise)
6)
Iron studies (S. iron, TIBC, % TSAT,
S. ferritin)
7)
Graft function (SCr, spot urine protein-to-Cr ratio)
8)
Testing for presence of hemolysis (e.g.,
indirect bilirubin, LDH, haptoglobin)
9)
History for potential drug-induced anemia
(e.g., MMF, EC-MPS, Aza, mTORi, ACEi, ARBs, ganciclovir, TMP-SMX
Routine
evaluation of all anemic TR for
infection with parvovirus B19 or other viruses is not performed.
However, if the initial diagnostic assessment may not show a clear etiology for
anemia, testing for parvovirus B19 can be proceeded via NAAT. Distinct evaluation of iron stores in KTR could be challenging. As lowered
ferritin & TSAT means true
deficiency, inflammation may suppress TSAT & elevate ferritin,
masking the diagnostic value of these tests. Moreover, as no trials defining specified
ferritin &
TSAT levels
for TR, criteria from the 2012 KDIGO Guideline for Anemia in CKD can be applied to determine iron deficiency. The concomitant finding of leukopenia, thrombocytopenia,
and/or acute graft dysfunction are suggesting the following potential etiology
for anemia:
o
Global myelosuppression, commonly
induced by im/m, nutritional deficits, & Prox agents
but can also be observed with viral infections.
o
HUS Dgx should
be expected if anemia is seen with graft dysfunction, thrombocytopenia, and the finding of MAHA.
On contrary,
parvovirus B19 infection
or anti-EPO AB,
expected with
1)
Lone anemia, (no leukopenia or
thrombocytopenia)
2)
Lowered RETIC &
3)
No nutritional deficits.
TREATMENT
General
concepts: The general lines of anemia therapy
in ptns with CKD or ESKD can be also applied to the ttt of anemia in KTR.
These include ttt of the underlying cause(s)
(if identified), ttt of iron deficiency, and the administration of ESA to decrease the need for RBCs
transfusion. As applied in non-Tx ptns with CKD or ESKD, options of individual therapy relied mainly
upon the severity of anemia and the finding of iron
deficiency. Anemic ptns with iron deficits should be ttt with iron before commencing
ESAs
therapy.
Special
considerations in ttt of anemia in KTR may include:
o
Target HB: Optimal target HB levels for KTR is not well determined and may vary according
to allograft function.
o
Management of im/m & others: im/m agents, (EC-MPS, Aza,
SRL) and other agents (e.g.,
ACEi/ARBs, ganciclovir, TMP-SMX) are current causes of
post-Tx anemia. Dose decline/discontinuation
of these agents may be indicated according to the timing from Tx and current status of the graft.
o
Use of iron: It’s unknown whether IV or oral iron provides better ttt among KTR.
With iron deficiency, we provide IV iron therapy
rather than oral iron therapy. Several IV iron formulas
are available, including ferric gluconate, iron sucrose, ferumoxytol, ferric carboxymaltose,
& iron dextran. All of these formulas
are equally effective, and selection may
vary by team preference.
NB: oral iron has been inadequate
to replace/maintain adequate iron stores and could bind with im/m members,
e.g., MMF/MPS. Using PO4 binder
ferric citrate that has been approved
for ttt of iron deficits in CKD, has not been studied in KTR. Like standard oral iron agents, it can
bind to im/m.
Post-Tx erythrocytosis may develop in ptns on
oral iron supplements. However, HB usually decline 4 weeks after iron withdrawal.
o
ESAs: Use of ESAs in
KTR varies according to
the timing from Tx, e.g., we do NOT
provide ESAs immediately after Tx. With CKD
anemia seen > 3
mo post-Tx in the iron-repleted ptn,
we may provide an ESA. Ptns on ESA should be learned about the risk of stroke, thrombotic events, and possibly higher risk of recurrent cancer before commencing ESA therapy.
o
Using BTx: We should avoid using BTx if possible, to limit the risk of allo-Snz &
Rj. However, if BTx is mandated in KTR, CMV-seronegative
and/or filtered blood
products are preferred to leukocyte-reduced products as CMV and
other viruses can be transmitted in plasma.
Blood products irradiation is not advised.
Approach
based on timing from Tx: suggested approach to the ttt
anemia in KTR varies mainly
with the timing from Tx and the defined
etiology of anemia.
Ptns on
waiting list: Anemia in ptns on waiting
list should be ttt with the same
approach applied in treat anemia in the CKD or ESKD cohort. Using RBC transfusion
should be prohibited, if possible, to limit the risk of immunological Snz, that any delay or limit the option of
future KTx. This’s consistent with
the 2012 KDIGO guidelines for anemia ttt in ptns candidate for SOT.
Ptns perioperative/early
post-Tx: Suggested
approach is as follows:
o
Perioperative targeted HB of >10 g/dL that seems safe & limiting CVS events in the early post-Tx timing. The pre-Tx use of ESAs & iron in DX and pre-DX
ptns should maintain HB between 10-11.5 g/dL, hence
limiting peri-Tx RBC requirements. We limit RBC Tx
to ptns with HB <7 g/dL or <8 g/dL in those with preexisting CVD that’s consistent with the 2016 CPGAABB.
o
With HB
<10 g/dL and iron deficiency (i.e., TSAT
≤20 % and S. ferritin ≤200 ng/mL) at the timing of Tx, we provide 1 g of IV iron (typically iron sucrose) with anticipated iron
loss with phlebotomy during the early post-Tx timing. This’s based on a clinical experience and not based on high-quality evidence.
o
TR with
previous ESA therapy, we often hold ESA at
the timing of Tx as hypo-responsiveness
to ESAs in the early post-Tx period, thrombotic & CVS risks of these agents, and the expected
effect of endogenous EPO will ensue post-Tx. We do not provide ESAs to
ptns with DGF, as using ESA agents
in this population is debated and response to ESAs may be currently poor.
ESA agents immediately after-Tx
may shorten the timing to correct HB but
has not been proved to improve the clinical
outcome. In RCT:104 ptns examining the effect of high-dosing EPO B
before Tx and during the 1st 2 weeks after Tx,
there was no difference in the rate of DGF
between TR receiving and not receiving EPO. Also, a retrospective study: no
difference in 3-mo HB values or DGF
between TR receiving and not receiving EPO during
the 1st 6 mo post-Tx.
2 studies: assessed the impact of high-dose EPO on DGF.
One study: 72 ptns were assigned to get an intra-arterial EPO (40,000 units) or placebo at the timing of
reperfusion of the graft. No difference seen between g.s in the need for DX within the 1st week or in the % of “slow graft function”
(= ≤40 % decline
in SCr by the 3rd day postoperatively).
The 2nd trial: assigned 92 TR to
IV EPO (33,000 units)/d./3
doses, starting 3-4
hs before Tx. EPO ttt had NO impact on the rate/duration of DGF but did
augment the
risk of thrombotic events at one mo. to one y.
Ptns
later (>3
mo) post-Tx: Anemia in immediately post-Tx
typically improved within 2-3 mo with endogenous EPO production from the graft. However,
several factors, including im/m medications,
others (e.g., ACEi/ARBs), graft dysfunction, and infection, may be
contributing to persisting or NOA after the early post-Tx
timing. Such potentially correctable factors should be recognized and ttt properly before starting ESA therapy.
Moreover, the inlet to ttt of anemia in TR >3
mo post-Tx relied primarily upon the functional status of
the renal allograft.
Ptns
with stable allograft function: with
stable allograft function (eGFR ≥45 mL/min/1.73 m2), suggested
approach may include:
o
Finding of folate and/or
vit B12 deficits> correct
the deficits.
o
Finding of iron deficiency, > ttt with IV iron.
o
With lack of definite cause of anemia &
taking ACEi/ARBs, we balance the possible risks/benefits
of keeping these agents. If the ptn has no urgent need to
ACEi/ARBs to manage other comorbidities (e.g., HF), it’s reasonable to hold ACEi/ARBs.
If anemia improved, ACEi/ARBs can be re-used later on (e.g., after one
y), if indicated, with observing any worsened HB levels.
o
In ptns on high dosing of an
antimetabolite (e.g., MMF 1000 mg twice/d. or EC-MPS
720 mg twice/d.) as maintenance im/m, we decrease the dosing, typically by 50 %, if anemia is severe and
dose decrease is amenable, e.g., if the ptn is on EC-MPS
720 mg twice/d., we reduce to 360 mg twice/d. Also, if ptn is on MMF 1000 mg
twice/d, we reduce the dose to 500 mg twice/d.
o
In ptns on ganciclovir and/or TMP-SMX, we assure that their proper dosing for
the level of graft function. We do not reduce/hold these drugs to ttt
anemia.
o
If anemia persists despite these
regulations, we start an ESA with HB
<9
g/dL & target HB of 10-11.5 g/dL that’re
similarly advised for non-DX & DX CKD
ptns. During routine monitoring, ptns may exceed 11 g/dL,
the dose of ESA should be temporarily hold/reduced by 25 % monthly until reaching the target.
Optimum
target HB level for TR with stable allograft
function is not certain. Studies
in KTR have suggested that MR may be triggered with HB >12.5 g/dL.
However, one study has showed that allograft survival could be better
among ptns with high HB level. The 2-y, open-label trial CAPRIT: 125 KTR
with eCrCl
<50
mL/min/1.73 m2
assigned ptns to get EPO targeting 13-15 g/dL (full correction
g.) or 10.5-11.5 g/dL (partially corrected). Compared with the partially
corrected g., complete correction g. had a little decline in eCrCl (5.9 vs 2.4 mL/min/1.73 m2),
lowered rate of ESKD (21 vs 4.8 %),
& higher DCGS (80 vs 95 %). This trial is limited by shortened duration, open-label
design, and smaller size.
These findings are highly different from
that reported by the much larger CHOIR
& TREAT trials that randomly
assigned non-Tx CKD ptns. The CHOIR & TREAT
trials found a higher risk of CVS events and non-delay in
progressive renal failure via normalizing HB by ESA
agents. The CREATE trial applied anemia
management like CAPRIT and showed that
randomization to a higher HB level induced significant
rise in chronic DX. It’s difficult to conclude
the mechanism by which higher HB
and/or more ESA may protect TR but not native one.
Much larger trials comparing ESA
with placebo are currently required to determine the risk/benefit ratio of
anemia control among TR. Providing darbepoetin alfa is also often efficacious in KTR. Retrosp., 12-wk study: 36 ptns, 81 % achieving target HB of >12
g/dL (average 4.4 wks). A longer duration of ttt was needed with established anemia
and/or exposing to concurrent ACEi agents.
Ptns with
a failed allograft: TR in stage 4/5 CKD usually became anemic, and ESA agents may be urgently provided to ameliorate
Sms and
limit the risk of BTx. Control of
anemia in this population is simulating that in CKD/ESKD cohort,
except that higher dosing of ESAs usually required to overcome the impact of chronic inflammation. Ptns with stable allograft function, any potential
reversible cause should be addressed (e.g., nutritional
deficits, iron deficiency,
im/m, etc.). We start ESA therapy if HB
between 9-10 g/dL and
the iron stores seems adequate. We also evaluate the risks related
to ESA agents
that’re usually greater in ptn with CVD,
previous thrombotic events, stroke, or prior cancer.
With higher risks of ESA agents, we may
avoid ESAs
until the extent of anemia is more intense (i.e., HB <9 g/dL). KTR returning
to DX have lowered HB levels if compared with non-Tx CKD ptns (HB
of 8.9 vs 10.2 g/dL, resp.) that correlated
with higher hospitalization and increased
MR. Using ESAs
may decrease the frequency/intensity of anemia in ptns with failed Tx but have not been reported to decrease MR. Ptns returned to DX
with ESAs
resistance may benefit from graft nephrectomy.
Special populations: Ptns with parvovirus B19 infection: Anemia
can be corrected by IVIG + decreasing im/m burden to enhance viral clearance.
PROGNOSIS: debated findings have been reported regarding
the prognosis of KTR with anemia. For
better definition of this relation, the correlation between anemia (= <12 g/dL in females %
<13 g/dL
in males) and ptn allograft outcome was assessed in a prospective
study: 938 KTR, at 4 ys, multivariate
analysis showed that anemia was complicated with higher risk of MR &
allograft failure. Similar findings were seen if anemia was
defined = <11
g/dL. However, analyzing 825 KTR over 8.2 ys showed no relationship of anemia to MR.
In the
ALERT study: 2102 KTR, 29 %
of females & 30 % of males were anemic, HB were not complicated with any
effect on CVS morbidity & MR or all-cause death after advanced adjustment
for clinical & demographic factors. HB
value, however, were passively associated with allograft loss. LVH,
a crucial risk factor for CVS MR among CKD
ptns, may be partially showing an impact of un-ttt anemia.
As CVD is the leading cause of
death in diabetic KTR, the adverse impacts
of anemia may be clearer in diabetic KTR
in the US, if compared with other countries, as the US
Tx population has a relative increase in CVS
risk, with a higher % in diabetics. Unfortunately, the current trials have not proved
that robust ttt of anemia regresses /retards
LVH progression, and any benefit of ESA use may
be outweighed by their associated risks.
COMMENTS