Kidney transplantation in adults: Timing of transplantation and issues related to dialysis

INTRODUCTION — Patients who receive a kidney transplant generally have decreased mortality compared with patients who are on dialysis. (See "Kidney transplantation in adults: Patient survival after kidney transplantation".)

Preemptive transplantation, defined as elective transplantation prior to the requirement for chronic dialysis, allows the patient to avoid dialysis completely. Preemptive transplantation improves patient survival compared with transplantation after initiation of dialysis. However, dialysis is often required by patients who are awaiting transplantation or who receive a transplant that does not work immediately.

This topic review discusses the timing of kidney transplantation and the optimal dialysis modality and prescription for patients who require dialysis either before or after transplantation. Dialysis issues in the patient with a failed kidney transplant are discussed elsewhere. (See "Kidney transplantation in adults: Management of the patient with a failed kidney transplant".)

TIMING OF TRANSPLANTATION

Patients not on dialysis

Preemptive transplantation — Preemptive transplantation is defined as elective transplantation prior to the initiation of chronic dialysis. For most patients with end-stage kidney disease (ESKD) who are suitable candidates for transplantation, we suggest preemptive transplantation rather than waiting until dialysis is initiated. The suitability of individuals for transplantation is discussed elsewhere. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)

Exceptions to universal preemptive transplantation include the following:

●Patients who have severe, symptomatic nephrotic syndrome. Severely nephrotic patients are hypercoagulable and may be at increased risk for thrombosis of the allograft or deep vein thrombosis and pulmonary emboli. Such patients may benefit from dialysis prior to transplantation, with the expectation that residual kidney function, and thus nephrosis, will decline significantly. Dialysis tends to decrease the thrombotic tendency associated with nephrotic syndrome. However, there is no high-quality evidence to support this approach. Thus, an individualized decision should be made, with careful attention paid to patients who have a prior history of venous thrombosis. The optimal method to decrease severe nephrosis before kidney transplantation (eg, nephrectomy, embolization, or medical nephrectomy) remains unclear. (See "Hypercoagulability in nephrotic syndrome", section on 'Pathogenesis'.)

●Patients who are undergoing a second transplant after the first transplanted kidney has failed within one year from transplantation. Such patients may benefit from a short period of dialysis prior to transplantation, as discussed elsewhere. (See "Kidney transplantation in adults: Management of the patient with a failed kidney transplant", section on 'Retransplantation'.)

Preemptive transplantation is generally preferred because it leads to substantial improvements in graft and patient survival when compared with transplantation after a period of dialysis therapy [1-4]. As examples:

●In a study of nearly 40,000 primary kidney transplant recipients, those undergoing preemptive transplantation had 25 and 27 percent reductions in the relative risk for graft loss for deceased- and living-donor transplants, respectively [1]. Corresponding risks for patient death were reduced by 16 and 31 percent.

●In an analysis of 7948 patients identified from the Dutch National Organ Transplant Registry, the 10-year survival was greater among patients who underwent a preemptive living-donor kidney transplant compared with patients who had a deceased-donor transplantation after a median time of three years on dialysis (73 versus 45 percent, respectively) [5]. Compared with waitlisting on dialysis, the survival benefit with preemptive transplantation was approximately 7.5 to 9.9 years for 40-year-old patients and 4.3 to 6 years for 70-year-old patients.

The amount of time that a patient spends on dialysis prior to transplantation is directly related to increased mortality, suggesting a dose-dependent effect of dialysis. (See 'Patients already on dialysis' below.)

Improved graft and patient survival associated with preemptive transplantation may be related to decreased rates of delayed graft function and biopsy-confirmed acute rejection for both deceased-donor and living-donor transplants [2,3,6]. In addition, relatively lower clearance provided by dialysis, compared with a transplanted kidney, may cause the accumulation of substances associated with atherosclerosis, malnutrition, and chronic inflammation [7].

In general, patients undergoing preemptive transplantation are also likely to be more educated, come from a higher socioeconomic background, and be followed by a nephrologist earlier in the course of their chronic kidney disease (CKD), all factors that have been shown to confer better outcomes posttransplantation. This has been further highlighted by new payment models in the United States that reward or penalize nephrologist performance in preemptive kidney transplantation in the Advancing American Kidney Health initiative [8].

Despite the demonstrated benefit of preemptive kidney transplantation, only 20 percent of living-donor and 5 percent of deceased-donor transplants are performed preemptively in the United States [9]. This is primarily due to the rapid increase in the number of potential transplant candidates without a commensurate increase in the donor pool. As a result, the waiting time for a deceased-donor kidney has dramatically increased over the last 15 years.

Glomerular filtration rate threshold for transplantation — Although we believe that transplantation should be performed in most patients prior to the need for dialysis, the precise level of kidney function (ie, glomerular filtration rate [GFR]) at which to perform a transplant is not known.

Experts generally agree that transplantation should not be performed until the estimated GFR (eGFR) is <20 mL/min/1.73 m² with evidence of a progressive and irreversible decrease in kidney function over the previous 6 to 12 months. In the United States, United Network for Organ Sharing (UNOS) rules dictate that the eGFR needs to be 20 mL/min/1.73 m² or less prior to preemptive transplantation. This is consistent with the consensus guidelines from the Canadian Society of Transplantation [10]. We calculate the eGFR using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (calculator 1). (See "Assessment of kidney function".)

Performing kidney transplantation at a higher eGFR is not justified, even in the setting of irreversible kidney disease. This is because patients generally have few signs or symptoms of ESKD that require dialysis at this level of kidney function, and there is no benefit to be gained by performing a transplantation before it is required [11,12]. This was best shown by an analysis of 19,461 first-time, preemptive kidney transplant recipients reported to UNOS between 1995 and 2009 [12]. Analysis of this large cohort did not detect any difference in patient survival or death-censored graft survival among patients who were transplanted at eGFRs <10, between 10 and 15, between 15 and 20, and >20 mL/min/1.73 m², respectively.

Once the eGFR is below 20 mL/min/1.73 m², the decision to perform an elective preemptive transplant should be based upon individual patient (and donor) preferences. Unlike the decision to initiate chronic dialysis, the transplant should not be delayed until the emergence of uremic symptoms. (See "Indications for initiation of dialysis in chronic kidney disease".)

Referral for evaluation by a transplant team should take place before this eGFR is reached, as the process from initial encounter to either preemptive transplantation or deceased-donor listing can approach 6 to 12 months in many centers. We refer patients for transplant evaluation with a diagnosis of progressive CKD and an eGFR <30 mL/min/1.73 m². (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient", section on 'Timing of referral'.)

Patients already on dialysis — Patients who are already on dialysis and are suitable candidates for transplantation should be considered for transplantation as soon as possible. This is because the adverse effects of dialysis therapy on posttransplant outcomes are duration dependent. As noted above, transplantation is associated with better outcomes than dialysis for most patients. With approximately 17 percent of the United States' prevalent patients on dialysis in 2022 on a transplant waiting list, more opportunities exist [13,14]. (See "Kidney transplantation in adults: Patient survival after kidney transplantation".)

Analyses of the United States Renal Data Systems (USRDS) database have shown that pretransplant dialysis duration of six months or more is associated with decreased allograft survival [2,15]. In one study, dialysis duration for 36 months conferred a 68 percent increase in death-censored graft loss [2]. In another analysis, the 10-year adjusted graft survival for both deceased- and living-donor transplants was higher for patients transplanted preemptively compared with those who were on dialysis for two years prior to transplantation (69 and 75 for preemptive transplants versus 39 and 49 percent for dialysis followed by transplantation, respectively) [16].

The risk of death with a functioning allograft and all-cause mortality is also higher among patients who are dialyzed for more than six months before transplantation [2,15]. Among patients older than 65 years who are on dialysis for four or more years, there is no survival advantage seen with living- or deceased-donor transplantation compared with dialysis [17].

Increased duration of dialysis prior to transplantation may increase the risk of cancer [18]. In one registry study, patients on dialysis for more than 4.5 years before transplantation had a 60 percent greater risk of cancer compared with those on dialysis for less than 1.5 years [18].

DIALYSIS ISSUES

Before transplantation

Dialysis modality before transplantation — Despite the associated risks, many patients need dialysis prior to transplantation.

Available dialysis modalities include hemodialysis, either in a dialysis center or at home, or peritoneal dialysis. There are no good, objective data to inform decisions regarding the choice of dialysis modality prior to transplantation. Practice patterns are center specific, and the choice of therapy is determined on a case-by-case basis, with consideration of patient preference and medical factors. The choice of modality generally depends on factors that are unrelated to transplantation; these include availability and convenience, comorbid conditions, socioeconomic and dialysis-center factors, and others [19-25]. (See "Dialysis modality and patient outcome", section on 'Selection of dialysis modality'.)

Most studies that have compared pretransplant dialysis modalities on posttransplant outcomes have shown no clear benefit of one modality over others on overall graft or patient survival [26-37]. A meta-analysis of 26 observational studies including 269,715 transplant recipients found no significant difference in the risk of all-cause mortality (hazard ratio [HR] 0.98, 95% CI 0.85-1.01), death-censored graft failure (HR 0.98, 95% CI 0.85-1.14), graft vessel thrombosis, or posttransplant diabetes mellitus between pretransplant peritoneal dialysis and pretransplant hemodialysis [37]. Pretransplant peritoneal dialysis was associated with a lower risk for overall graft failure (HR 0.96, 95% CI 0.92-0.99) and delayed graft function (HR 0.73, 95% CI 0.70-0.76), but the strength of the evidence was rated very low to low.

Routine dialysis immediately prior to transplantation — For patients undergoing kidney transplant surgery, we suggest avoiding routine (ie, scheduled) dialysis in the 24 hours prior to transplantation. This recommendation differs from that for patients undergoing nontransplant surgery, for whom dialysis is generally recommended in the 24 hours prior to surgery. (See "Medical management of the dialysis patient undergoing surgery", section on 'Routine dialysis prior to surgery'.)

We avoid dialysis within 24 hours prior to transplantation because it may increase the risk of delayed graft function. The strong likelihood of kidney recovery after transplantation makes even small risks associated with dialysis less acceptable.

The effect of elective dialysis on short-term posttransplant outcomes is not certain [38,39]. One study suggested that dialysis within 24 hours of transplantation increased the risk of delayed graft function, especially if a bioincompatible filter was used and ultrafiltration was performed [38]. However, in a trial that randomly assigned 110 patients to receive hemodialysis (one three-hour session without ultrafiltration) or no hemodialysis immediately prior to transplantation, there was no difference in delayed graft function or estimated glomerular filtration rate (eGFR) five days posttransplant [39]. Thus, avoidance of ultrafiltration for 16 to 24 hours before transplantation may help to reduce the risk of delayed graft function.

In addition to a possible risk of delayed graft function, dialysis may contribute to electrolyte and fluid shifts, which require several hours to equilibrate, and could theoretically contribute to sudden death. Although not studied in the transplant perioperative period, in a retrospective study of 80 patients on chronic dialysis with documented sudden death, a 1.7-fold higher relative risk was observed in the 12-hour period beginning with the initiation of the dialysis treatment [40].

Among nontransplant patients with end-stage kidney disease (ESKD), this and other risks associated with dialysis are justified by the proven benefits provided by dialysis to patients with absent kidney function. By contrast, most patients undergoing transplantation have a rapid recovery of kidney function postoperatively. (See "Kidney replacement therapy (dialysis) in acute kidney injury: Metabolic and hemodynamic considerations", section on 'Mechanisms of hemodialysis-induced hypotension' and "Dialysis-related factors that may influence recovery of kidney function in acute kidney injury (acute renal failure)".)

Indications for urgent dialysis before transplantation — Despite the anticipated recovery of kidney function, dialysis may be indicated in some transplant candidates to correct metabolic abnormalities that cannot be treated conservatively or pose unacceptable anesthesia risk. As with patients on maintenance dialysis undergoing nontransplant surgery, the major indications for urgent dialysis before transplant surgery are hyperkalemia and volume overload. (See "Medical management of the dialysis patient undergoing surgery", section on 'Indications for urgent preoperative dialysis'.)

Hyperkalemia is the most common reason for dialysis in the immediate pretransplant period. Mild hyperkalemia at baseline is common among patients with chronic kidney disease (CKD) and may be exacerbated during surgery. In most cases, hyperkalemia resulting from transplant surgery is mild and readily managed conservatively. We generally dialyze patients who have a potassium >5.4 mEq/L [41], but there is variability between centers. The threshold serum potassium at which it becomes unsafe to proceed with surgery without prior dialysis has not been evaluated among transplant patients, and there are no data that show that serum potassium should be normalized preoperatively [42,43]. (See "Medical management of the dialysis patient undergoing surgery", section on 'Hyperkalemia'.)

When dialysis is required, attention should be paid to the following dialysis prescription parameters:

●Ultrafiltration – Ultrafiltration (ie, fluid removal) should be avoided in most transplant candidates because there is evidence that fluid shifts are associated with delayed graft function, presumably due to the risk of inducing intravascular volume depletion with or without hypotension [39]. This may explain some of the observational data demonstrating lower delayed graft function in patients on peritoneal dialysis compared with patients on hemodialysis [35]. Some patients, however, require dialysis to treat volume overload. For such patients, we suggest using a relatively low rate of ultrafiltration (such as 5 to 10 mL/kg per hour), which allows for adequate plasma refill prior to surgery and may avoid intravascular volume depletion and hypotension during dialysis. Avoiding intravascular hypotension is particularly important because patients undergoing transplantation often receive intraoperative antibody preparations, which are associated with hypotension that could be exacerbated in a patient with recent, large ultrafiltration.

●Dialysis session length – The length of the dialysis session should be tailored to the individual patient based on the preoperative goal of the treatment. Generally, hyperkalemia can be treated safely with two hours of dialysis without the need for a low-potassium bath. Patients who require ultrafiltration may require longer treatments (three to four hours) to remove volume safely and without inducing hypotension. Unlike patients who are not undergoing transplantation, urea kinetic modelling (ie, Kt/V) should not be used to direct treatment, since there is an anticipation of kidney recovery and no data correlating urea Kt/V with transplant outcomes. (See "Acute hemodialysis prescription", section on 'Dialysis dose'.)

●Dialysate composition – The dialysate composition is the same as for nontransplant patients (see "Acute hemodialysis prescription", section on 'Dialysate composition'). However, the flux of calcium, magnesium, sodium, and glucose should be minimized during the treatment, and the choice of potassium and bicarbonate baths should be made carefully to minimize the development of hypokalemia and metabolic alkalosis. Dialysate temperature should also be tailored to each patient. We generally prefer a 3 mEq/L calcium, 1 mEq/L magnesium, 140 mEq/L constant sodium, and 100 mg/dL glucose dialysate bath. We adjust the dialysate temperature to typically be 0 to 1 degree Celsius below the patient's body temperature.

●Anticoagulation – Most outpatient dialysis treatments are performed with systemic anticoagulation utilizing heparin. It is preferred not to use heparin among patients who are undergoing transplantation with 24 hours of dialysis. The expected half-life of the usual 10 to 50 international units/kg bolus dose of heparin with hemodialysis is approximately 30 to 90 minutes, which is longer in a patient with ESKD than in a patient without ESKD and variable depending upon other facets of the dialysis treatment. Intraperitoneal heparin occasionally utilized for fibrin in peritoneal dialysis does not produce systemic anticoagulation.

●Dialyzer membrane – A biocompatible membrane should be used for all patients who are undergoing dialysis prior to transplantation. Complement-activating or bioincompatible membrane dialyzers (eg, cuprophane dialyzers) have been associated with delayed graft function. As an example, in a study of 44 allograft recipients who were dialyzed within 24 hours prior to transplantation, recovery of kidney function was higher among those dialyzed with biocompatible membranes compared with bioincompatible ones [38].

After transplantation

Dialysis immediately after transplantation — Approximately 20 percent of patients require temporary dialysis after transplantation [44-46]. The need for dialysis in the first postoperative week after transplantation is called delayed graft function, regardless of the cause of kidney dysfunction. Delayed graft function has been independently associated with nearly two- to threefold increases in patient death, graft failure, and death-censored graft failure [35,45,47]. The risk of delayed graft function may be assessed using a nomogram that has been evaluated in multiple studies [44].

The indications for acute dialysis among patients in the immediate transplant period are the same as among nontransplant patients who develop acute kidney injury. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Urgent indications'.)

The optimal dialysis modality in the postoperative period is not well studied. We, and most nephrologists, perform hemodialysis after transplantation. This is because of the concern that the peritoneal membrane has been disrupted during transplant surgery, with the potential for leakage of glucose-containing peritoneal dialysate fluid and infection [48]. Some authors have suggested removing the peritoneal dialysis catheter at the time of transplant surgery to avoid the approximately 5 percent or greater risk of peritonitis even in patients who do not perform dialysis [49]. However, peritoneal dialysis has been used successfully in some patients with delayed graft function [50,51], with some clinicians prescribing low-volume (approximately 15 mL/kg or less) supine exchanges [52]. Generally, there is no indication for continuous kidney replacement therapies. (See "Continuous kidney replacement therapy in acute kidney injury".)

The dialysis prescription is generally the same as for nontransplantation patients. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Intermittent hemodialysis'.)

Excessive ultrafiltration should be avoided in order to limit the possibility of ischemic injury to the allograft. We generally target a weight (as a parameter of volume) that is within 1 to 2 kilograms of the patient's known dry weight with fluid removal not greater than 10 mL/kg/hour.

Removal of peritoneal dialysis catheter — The optimal timing of peritoneal dialysis catheter removal after kidney transplantation is unclear [53]. For living-donor recipients, most centers base the decision to remove the catheter during transplant surgery on the immediate status of the allograft after the kidney is reperfused. If the allograft demonstrates satisfactory perfusion and diuresis intraoperatively, transplant surgeons usually will remove the peritoneal dialysis catheter during the operation. For marginal allograft appearance and/or delayed diuresis, the peritoneal dialysis catheter remains in place in case peritoneal dialysis is necessary postoperatively. For deceased-donor recipients, the approach to catheter removal intraoperatively is more varied; for centers with higher rates of delayed graft function the catheter may be left in, even in cases in which adequate allograft perfusion and diuresis are observed.

Infrequently, the catheter is removed intraoperatively after inadvertent, large incisions in the peritoneum are made during the transplant procedure. Large peritoneal disruptions in this setting generally require at least a temporary transition from peritoneal dialysis to intermittent hemodialysis, should dialysis be required in the postoperative period.

Patients at high risk for peritonitis may benefit from earlier catheter removal. As an example, one retrospective study of 232 patients on peritoneal dialysis found that a significantly increased incidence of peritonitis occurred in those with the following clinical characteristics [54]:

●An increased number of peritonitis episodes prior to surgery (median of three)

●Previous peritonitis episodes due to Staphylococcus aureus

●Male sex

●Technical problems at surgery

●More than two rejection episodes

●Permanent graft nonfunction

●Urinary leak

Dialysis after graft failure — Patients may require dialysis after their transplanted kidney has failed. This is discussed in detail elsewhere. (See "Kidney transplantation in adults: Management of the patient with a failed kidney transplant", section on 'Dialysis after graft failure'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)

SUMMARY AND RECOMMENDATIONS

●Timing of transplantation

•Patients not on dialysis – For most patients with end-stage kidney disease (ESKD) who are suitable candidates for transplantation, we suggest preemptive transplantation rather than waiting until dialysis is initiated (Grade 2C). Preemptive transplantation is associated with improved graft and patient survival when compared with transplantation after a period of dialysis therapy. Exceptions to preemptive transplantation include patients who have severe, symptomatic nephrotic syndrome and those undergoing a second transplant after the first transplanted kidney failed within one year from transplantation. Such patients may benefit from a short period of dialysis prior to transplantation. (See 'Preemptive transplantation' above.)

Transplantation should not be performed until the estimated glomerular filtration rate (eGFR) is <20 mL/min/1.73 m² and evidence exists of a progressive and irreversible decrease in kidney function over the previous 6 to 12 months. (See 'Glomerular filtration rate threshold for transplantation' above.)

•Patients on dialysis – Patients who are already on dialysis and are suitable candidates for transplantation should be considered for transplantation as soon as possible. This is because the adverse effects of dialysis therapy on posttransplant outcomes are duration dependent. (See 'Patients already on dialysis' above.)

●Dialysis issues before transplantation

•Modality before transplantation – Most studies have found similar risks of mortality with peritoneal dialysis or hemodialysis prior to transplantation. The choice of modality generally depends on factors that are unrelated to transplantation; these include availability and convenience, comorbid conditions, and socioeconomic and dialysis-center factors. (See 'Dialysis modality before transplantation' above.)

•Routine dialysis prior to transplant – For patients undergoing kidney transplant surgery, we suggest avoiding routine (ie, scheduled) dialysis in the 24 hours prior to transplantation (Grade 2C). This recommendation differs from that for patients undergoing nontransplant surgery, for whom dialysis is generally recommended in the 24 hours prior to surgery. Dialysis within 24 hours prior to transplantation may increase the risk of delayed graft function. (See 'Routine dialysis immediately prior to transplantation' above.)

•Indications for urgent dialysis – As with patients on maintenance dialysis undergoing nontransplant surgery, the major indications for urgent dialysis before transplant surgery are hyperkalemia and volume overload. (See 'Indications for urgent dialysis before transplantation' above.)

●Dialysis issues after transplantation

•Dialysis immediately posttransplant – The need for dialysis in the first postoperative week after transplantation is called delayed graft function, regardless of the cause of kidney dysfunction. The indications for dialysis are the same for such patients as for nontransplant patients with acute kidney injury. Excessive ultrafiltration should be avoided, if possible, in order to limit the possibility of ischemic injury to the allograft. (See 'Dialysis immediately after transplantation' above.)

•Removal of the peritoneal dialysis catheter – The optimal timing of peritoneal dialysis catheter removal after kidney transplantation is unclear. For living-donor recipients, most centers base the decision to remove the catheter during transplant surgery on the immediate status of the allograft after the kidney is reperfused. If the allograft demonstrates satisfactory perfusion and diuresis intraoperatively, transplant surgeons usually will remove the peritoneal dialysis catheter during the operation. For marginal allograft appearance and/or delayed diuresis, the peritoneal dialysis catheter remains in place in case peritoneal dialysis is necessary postoperatively. For deceased-donor recipients, the approach to catheter removal intraoperatively is more varied; for centers with higher rates of delayed graft function the catheter may be left in, even in cases in which adequate allograft perfusion and diuresis are observed. (See 'Removal of peritoneal dialysis catheter' above.)

•Dialysis after graft failure – Patients may require dialysis after their transplanted kidney has failed. This is discussed in detail elsewhere. (See "Kidney transplantation in adults: Management of the patient with a failed kidney transplant", section on 'Dialysis after graft failure'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Vijaya Venkataraman, MD, who contributed to an earlier version of this topic review.