Patients receiving a KTx have greatly declined mortalitiesas compared to Patients maintained on dialysis.
Abbreviations (read twice please):
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:
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 % decline in the RR for graft loss for DDKT & LDKT, resp. Corresponding risk (s) of ptns MR were declined by %.
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 ( %, resp). Comparing TR on W/L on DX, ptns longevity benefits with Preetx was = ys for 40-y-old ptns & 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:
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 mL/min/1.73 m2 with existing evidence of a progressive/irreversible decline in renal function along the last US, UNOS rules emphasize that the eGFR should be mo. In the 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.
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 < 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 < 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 % 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 % 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 ( for Preetx vs % 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
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 , 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 , 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 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 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+ > 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., 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 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 IU/kg bolus heparin dosing within HDX is almost 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 DX after Tx. The requirement for DX in the 1st post-operative week after Tx is currently named , whatever the cause of renal dysfunction. DGF has been independently complicated with about % of ptns may need temporary fold rises in:
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 kg of the ptn's known dry Wt with fluid removing not exceeding 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 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:
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.