Ptns receiving a KTx have greatly declined MR as compared to ptns maintained on DX. Preetx that can be defined as an elective Tx before DX need
PERI-TRANSPLANT
DX
Abbreviations (read
twice please):
o
AAKHI: Advancing
American Kidney Health initiative.
o
AB: antibody
o
Ac Rj: acute
rejection
o
AKI: acute
kidney injury.
o
Bic: biocompatible
membrane.
o
Binc: bioincompatible
o
C: Complement
o
CKD: chronic
kidney disease
o
CRRT: Continuous
renal replacement therapy
o
CST: Canadian
Society of Transplantation
o
DCGF: death-censored
graft failure
o
DCGL: death-censored
graft loss
o
DCGS: death-censored
graft survival
o
DDKT: Deceased-donor
kidney transplant.
o
DGF: delayed
graft function
o
DNOTR: Dutch National
Organ Transplant Registry
o
DX: dialysis
o
eGFR: estimated
glomerular filtration rate
o
ESKD: end-stage
kidney disease.
o
H/C: hypercoagulable
o
HDX: hemodialysis
o
Hpt: hypotension
o
Kru: residual kidney
function
o
Kt/V: urea
kinetic modelling.
o
KTx: Kidney
transplantation
o
LDKT: Live-donor
kidney transplants
o
MDRD:
Modification of Diet in Renal Disease
o
MR: mortality
o
Nc: Nephrectomy
o
NKF/KDOQI: National
Kidney Foundation/Kidney Disease Outcomes Quality Initiative.
o
NS: nephrotic
syndrome
o
PD: peritoneal
dialysis
o
Preetx:
Preemptive transplantation
o
RR: relative
risk
o
RRT: renal
replacement therapy
o
Sms: symptoms
o
Sns: signs
o
TR: transplant
recipients
o
ttt: treatment.
o
Tx: transplantation
o
UF: ultrafiltration
o
UNOS: United
Network for Organ Sharing
o
USRDS: United
States Renal Data Systems
o
W/L: waiting
list
o
Wt: weight
Ptns
receiving a KTx have greatly
declined MR as compared
to ptns maintained on DX. Preetx that can be defined as an elective Tx before
the need for maintenance on chronic DX, may allow the TR to avoid DX entirely.
Preetx can improve
ptn outcome compared to Tx after commencing DX. However,
DX is often needed
by ptns whilst awaiting Tx or receiving a Tx that has
no immediate function. This article will discuss the proper timing of KTx and the suggested
optimal DX modality to
be prescribed for ptns requiring DX either prior to or after Tx.
Preemptive
transplantation (Preetx):
Preetx can be defined
as elective Tx before the start of
chronic DX. A better ptns & graft
survival associating Preetx may
be attributed to the lowered rates of DGF and biopsy-proven Ac
Rj for both DDKT & LDKT.
Moreover, a relative lowered clearance given by DX,
as compared to a Tx graft, may induce accumulated materials related
to:
1)
Malnutrition
states,
2)
Atherosclerotic
alterations &
3)
Chronic inflammatory
states.
Generally, ptns commencing Preetx are also probably
have a more
education level, with
a higher socioeconomic standard, and usually evaluated by a nephrologist
earlier in their course of the CKD, all of these factors have been contributing to a better
survival after Tx. This has been further emphasized by the new payment
systems in the US rewarding
or penalizing the clinician performance in Preetx in the AAKHI.
Indications
for Preetx: The Preetx
has been advised for most ptns with ESKD
who are eligible candidate(s) for Tx. Preetx
is the best therapeutic option for ESRD ptns as it provides improved graft & ptns outcomes
if compared to Tx after a transitory
period of DX treatment:
o
Study: about
40,000 primary renal TR, those
undergoing Preetx had 25 & 27 % decline
in the RR for graft
loss for DDKT & LDKT, resp. Corresponding
risk (s) of ptns MR were declined
by 16 & 31 %.
o
Analysis: of 7948 ptns
chosen from the DNOTR, the 10-y survival was higher
among ptns commencing a Preetx LDKT as compared to
ptns receiving DDKT after an average
time of 3 ys on DX (73 vs 45 %,
resp). Comparing TR on W/L on DX, ptns longevity
benefits with Preetx was = 7.5-9.9 ys for 40-y-old ptns
& 4.3-6 ys for 70-y-old ptns.
The magnitude of timing spent on DX before Tx is directly related to a higher MR that may suggest
a dose-dependent impact of DX.
Despite the proven benefits, almost only 20 % of LDKT & 5 % of DDKT are proceeded as Preetx in the US. This can be attributed to the rapid rise in the potentially arranged Tx candidates with no a corresponding rise in the donors’ offers. So, the current waiting timing for a DDKT has dramatic rise over the elapsed 15 ys.
Exceptions to Preetx:
1)
Severe NS ptns may
benefit from DX before Tx with
expected Kru, and thus
nephrosis, will be significantly
declined. As severely
nephrotic ptns are H/C. H/C ptns preceding
to Tx are more prone
to thrombosis in the Tx kidney if
they perform Preetx. In
contrary, DX tends to limit
the thrombotic
tendency related to
NS. The
optimal module to limit severe nephrosis prior to KTx (e.g., Nc, embolization, or medical Nc) still
uncertain.
2)
TR receiving
their 2nd Tx after the 1st
Tx has been failed
within one y., may also gain benefits from a short timing of DX before commencing
the 2nd Tx.
GFR threshold for Tx:
Despite
that the general concept that Tx is
better to be mostly performed in ptns before
the requirement of DX, the exact
level of renal function (i.e. eGFR)
at which we perform Tx is not certain. Expert clinicians have a general consensus
that Tx should not be performed before
eGFR reaches <20 mL/min/1.73
m2 with existing evidence of a progressive/irreversible
decline in renal function along the last 6-12 mo. In the US, UNOS rules emphasize that the eGFR should
be 20
mL/min/1.73
m2 or less before Preetx
that is in agreement with the general guidelines of the CST. The eGFR
is generally calculated via the MDRD
equation.
Proceeding
to a KTx at a
higher eGFR has no
justification, even in case of an irreversible kidney disorder. As
ptns usually
have little Sns/Sms of ESKD requiring DX at this
level of renal dysfunction, and there is no more gains with performing a Tx prior to
its indication. This is best evident via analysing 19,461 1st -time,
Preetx observed
by the UNOS between
1995 & 2009. Analyzing this large report showed no detected difference in ptn
survival or DCGS among TR performed Tx at eGFRs <10, at 10-15,
at 15-20, & >20 mL/min/1.73
m2, resp. Once the eGFR declined < 20 mL/min/1.73
m2, deciding to proceed to an elective Preetx should be
primarily relying upon individual ptn (& donor) preference. In the contrary
to deciding to initiate chronic DX, the Tx should not
be postponed until emergent uremic Sms ensue.
Referring TR for assessment
by a Tx team
should undergone before this level of eGFR has been
reached. Ptn referral for Tx evaluation
with progressing CKD should be
at eGFR of <30 mL/min/1.73
m2. Assessment of a Tx candidate
and the recognition & evaluation of a potential donor is usually time
consuming. This earlier referring threshold may allow proper candidate to be W/L at the
timing the eGFR drop to 20 mL/min/1.73
m2 allowing more chance to the candidate avoiding DX before Tx. This attitude
is agreed with the NKF/KDOQI recommendations
that advise ptn referral for Tx assessment
at an eGFR <30 mL/min. However,
referring ptns at this level of renal function is usually not performed for many
reasons, as many clinicians do not consider the benefits provided by Preetx, and the ptns are usually
denying and reluctant to consider
any option of RRT until it
is currently mandated. Moreover, there’s a defect in direct accesses to pre-Tx assessment
in many areas.
Ptns already on DX: Ptns already
commencing DX and are suitable
candidates for Tx should be prepared
for Tx as early as possible. As the adverse drawbacks of DX treatment on post-Tx survival
are currently duration dependent. As mentioned
before, Tx is associated with better survival
than DX mostly among all ptns. With
only 19 % of the US' DX ptns in
2019 ordered on a Tx W/L,
more options still existing.
Analyses of the USRDS data bases
have reported that pre-Tx DX duration of 6 mo or
more declines allograft survival. One study: DX duration
for 36 mo conferred a 68 % elevation in DCGL. Another
analysis: the 10-y
adjusted graft longevity for both DDKT & LDKT was higher
for TR commencing
Preetx as compared
to those maintained on DX for 2 ys before Tx (69 & 75 for Preetx vs 39 & 49 % for DX followed
by Tx, resp). The
observed risk of mortality with a functioning allograft and all-cause MR is also greater among ptns who were
dialyzing > 6 mo prior
to Tx. The
duration of DX before Tx may also
trigger the risk of cancer. One study: ptns on DX for > 4.5 ys prior
to Tx had a 60 % higher risk
of cancer as compared to ptns on DX for < 1.5 ys.
DX MODALITY BEFORE
TX
In spite
the current risks, many ptns may require DX before Tx. The current DX modalities may include HDX, either
in a DX center or
home DX, or PD. There
are no precise, objective data to suggest a decision in regard to the choosing DX modality before
Tx. Practice
attitudes are usually center related, and the option of therapy is recognized
on an individual basis considering ptn preference and co-morbid disorders. Choosing
a DX modality
generally rely upon factors not related to Tx; these may
include center facilities and convenience, co-morbid disorders, socioeconomic standard
and other DX-center
related conditions. Several reports comparing the pre-Tx DX modality
on post-Tx outcome
have observed NO clear
benefit of one
modality over others on total allograft or ptn longevity. One study: about
23,000 primary renal TR showed 15 % higher risk of DCGF among PD-treated ptns than those
ptns maintained on HDX before Tx, with the
risk mostly limited to the earlier Tx period. If
the analysis was confined to the 1st 3 mo after Tx, the RR for allograft
loss related to PD was 33 % greater
than that for HDX. However,
this finding was not confirmed by other recent reports. The etiology of greater
allograft loss associating pre-Tx PD, is not clear.
However, limited data suggesting allograft thrombosis rates may be greater
among ptns on PD before Tx. The
mechanism by which PD induces graft
thrombosis still uncertain.
IMMEDIATE
DX BEFORE TX: Routinely performed (i.e., scheduled) DX should be prohibited in the last 24 hs before Tx. This recommendation is differing from that
provided for ptns commencing non-Tx surgery,
for whom DX is usually advised in the
last 24 hs before surgery. Avoiding DX
within 24 hs before Tx is advised as
it may trigger the risk of DGF. The robust
likelihood of renal function recovery after Tx made minute risks associating DX less accepted. The impact of elective DX on the short-term post-Tx outcome still uncertain. One study: observed
that DX within 24 hs prior to Tx may trigger the risk of DGF, particularly if a Binc diayzer was utilized and UF was undergone. However, trial:
random assignment of 110 ptns receiving HDX (one 3-h. session with no UF)
or no immediate HDX before Tx, NO differences in DGF or eGFR
rates 5 d.s after Tx.
Thus, avoiding the UF for 16-24 hs prior
to Tx may help reducing the DGF risk.
Added to the
potential risk of DGF, DX may induce
electrolyte/fluid alterations that need several hours to be balanced, and may
theoretically contributing to a sudden death. Despite the lack of
enough studies in the perioperative Tx timing, a retrospective
study: 80
chronic DX ptns with reported
sudden death, a 1.7 RR was seen in the 12-h period starting with the beginning of the DX ttt. Among
non-Tx ESKD ptns,
this risk and other associated risks with DX can be
justified by the well-known proven benefit (s) given by DX to ptns
with lack kidney function. In contrary, most ptns proceeding
to Tx will
develop a rapid
recovery of renal
function in the immediate post-operative period.
However,
despite the predicted renal recovery, DX
may be required in some Tx ptns to control metabolic alterations difficult
to be managed by conservative means or considered unacceptable risk for the
ptns to be anaesthetized. Hyper-k+
is the most considerable reason for DX
immediately before Tx. Mild hyper-k+ is commonly observed among CKD ptns with
expected exacerbation intraoperatively. Hyper-k+
resulting from Tx surgery is mostly mild and can be controlled
conservatively. TR having k+
> 5.4 mEq/L
are generally dialyzed, with variable policies
between Tx
centers. The optimal threshold s. k+
considered safely to proceed with surgery with no prior DX has not been properly assessed among Tx ptns, and there are no available data recommended
that s k+ should be
normalized prior to surgery. Volume overloaded TR
can be also indicated to commence DX.
If DX is indicated, UF (i.e., removing fluids) should be discouraged in most Tx centers as there is evidence that fluid shifting can be complicated by DGF, probably related to the risk of resultant intravascular depleted volume with/without Hpt that may elucidate the findings of some observational reports showing lower DGF in PD ptns as compared to HDX ptns. Some ptns, however, may need DX to control their volume overload. For those ptns, we may use a relatively lower rate of UF (e.g., 5-10 mL/kg/h) allowing adequate plasma refill before surgery and avoiding intravascular depleted volume & Hpt during DX treatment. Prevention of intravascular Hpt is particularly crucial as ptns proceeding to Tx usually receiving intraoperative AB medications that are usually inducing Hpt that may be deteriorated in a TR performing recent, large UF amount.
The duration
of the DX session
should be adjusted and individualized according to the preoperative target of
the ttt.
Generally, hyper-k+
can be managed safely within 2 hs of DX with no
need to provide a lower-k+ bath. Ptns requiring UF may need prolonged
ttt (3-4 hs) for safe
fluid removal and with no expected Hpt. Unlike non-Tx ptns cohort, Kt/V, should NOT
be utilized to manage ttt, as there
is an expected kidney
function recovery and there
is no available data that correlate the Kt/V with Tx outcome. Dialysate
constituents is usually similar to that for non-Tx ptns.
However, Ca+, Mg+, Na+, &
glucose efflux should be limited during the ttt, and the
choice of k+
& HCO3 baths should be optimized to limit the evolution of
hypo-k+ & metabolic alkalosis.
Dialysate C0
should be also adjusted for every ptn. A preferable
level of 3 mEq/L Ca+, 1 mEq/L Mg+, 140 mEq/L constant Na+, & 100 mg/dL glucose dialysate
bath. We adjust the dialysate C0 to typically be 0-1 degrees
Celsius below the ptn's body C0.
The
out-ptn DX ttt mostly running with systemic
anticoagulation using heparin
infusion. So, it is preferable not using heparin among the TR proceeding
to Tx within 24 hs of DX. The normal ½-life of the commonly used 10-50 IU/kg
bolus heparin dosing within HDX is almost
30-90 min. that is
prolonged in an ESKD ptn than a non-ESKD ptn and may vary according to other settings of
the DX ttt.
The current utilization of intraperitoneal
heparin sometimes used for fibrin management
in PD does not induce systemic
anticoagulation.
A
Bic membrane
should be utilized for all TR who’re undergoing DX
before Tx. C -activating or Binc membrane dialyzers (e.g., cuprophane dialyzer)
have been complicated with DGF. Study:
44 graft TR
were dialyzed within a 24-h interval before
Tx, the recovery
of renal function was greater
among ptns dialyzed with the Bic membrane
compared with a Binc one.
IMMEDIATE
DX AFTER
TX
Almost
20 % of ptns may
need temporary DX after Tx. The requirement for DX in the 1st post-operative week
after Tx is currently named DGF,
whatever the cause of renal dysfunction. DGF
has been independently complicated with about 2-3 fold rises in:
1)
DCGF.
2)
TR mortality, &
3)
Allograft
failure.
The
DGF risk can be evaluated via a nomogram in
several studies. The prescribed indications for acute DX among TR in the immediate Tx period are similar to that in non-Tx ptns developing AKI.
However,
the optimal DX modality required postoperatively
is not certain. Most clinician, use HDX
after Tx, considering the disruption
of peritoneal membrane during Tx surgery, with possible leaking of glucose-rich peritoneal dialysate with higher rates of infection. Some clinicians usually
remove the PD catheter at the timing
of Tx surgery avoiding about 5 % or higher risk of
peritonitis
even in ptns not performing DX. However, PD
has been utilized successfully in some ptns with
DGF. Generally, there’s no current indication
for CRRT. The DX prescription is generally similar to that
in non-Tx
ptns. Greater amounts of UF should
be discouraged in order to prevent the likelihood of ischemic injury to the graft.
We are usually targeting a Wt (= volume indicator) within 1-2 kg of the ptn's
known dry Wt
with fluid removing not exceeding 10 mL/kg/h.
Post-Tx PD
CATHETER REMOVAL:
Optimal
timing of PD
catheter removal after KTx still uncertain. Unless indicated for any reason and
in spite the higher risk of peritonitis, some physicians may wait
3-4
mo after surgery, as considerable number of ptns may
require either transient/permanent DX
after Tx. However, many ptns at higher
risk for peritonitis may get beneficial effects from early catheter removal. Retrospective study: 232 PD ptns found
significant higher incidence of peritonitis observed with the
following criteria:
o
Urine leak
o
Male sex
o
> 2 rejection
attacks
o
Surgical technical issues
o
Permanently
non-functioning graft.
o
Staphylococcus aureus-related peritonitis
o
Higher episodes
of peritonitis before
surgery (median 3).
PD catheter is currently removed within one mo
after Tx, unless there is a highly
suspicious indication for the need for DX.
Catheter removal in certain centers may be at the timing of or within the 1st
post-surgical week.
COMMENTS