Patients receiving a KTx have greatly declined mortalitiesas compared to Patients maintained on dialysis.
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.
TIMING OF TRANSPLANT
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