INTRODUCTION — Kidney transplantation is the treatment of choice for selected patients with end-stage kidney disease (ESKD) [1]. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients when compared with maintenance dialysis [2-4]. Survival rates posttransplantation are similar for both hemodialysis and peritoneal dialysis patients [5].
The following discussion will review the data relating to patient survival in adult patients undergoing kidney transplantation. Patient survival in children undergoing kidney transplantation and the determinants of short-term and long-term graft survival are discussed separately:
●(See "Kidney transplantation in children: Outcomes", section on 'Patient survival'.)
●(See "Kidney transplantation in adults: Risk factors for graft failure".)
OVERVIEW — Graft and patient survival after kidney transplantation have improved over the past decade (table 1 and figure 1). For deceased-donor kidney transplant recipients who were transplanted in 2006, 10-year all-cause graft failure declined to 51.6 percent, compared with 57.2 percent for transplants performed in 1998, and 10-year death-censored graft failure declined from 33.7 to 26.2 percent [6]. Living-donor recipients transplanted in 2006 had a 34.2 percent 10-year all-cause and an 18 percent death-censored graft failure rate [6]. In a large Scientific Registry of Transplant Recipients (SRTR) analysis comparing average one-year posttransplant estimated glomerular filtration rate (eGFR) between the 2001 to 2005 period and the 2011 to 2013 period, eGFR (a proxy for long-term graft survival) remained essentially unchanged despite the use of more marginal organs and transplanting older recipients; the stability of graft dysfunction was attributed to improvements in immunosuppression during this time period [7]. Death-censored graft survival in particular has improved, while death with a functioning graft has increased over the decade, mitigating improvements in overall graft survival. This is likely a reflection of better immunosuppression in the former and an older patient population with greater comorbidities in the latter.
The long-term advantages of living-donor versus deceased-donor kidney transplant are best appreciated in those with long expected longevity and fewer comorbidities, such as the pediatric population.
Among adults, both early graft loss within 90 days from transplant and estimated glomerular filtration rate (GFR) at one year following transplant improved over the last decade. A retrospective study comparing transplant outcomes (from all donor types; n = 202 expanded criteria, 642 standard criteria, and 673 living-donor transplants) to outcomes of 173 patients in an intensive home hemodialysis program (16 hours per week) in Canada demonstrated the advantage of transplantation, with a reduction in risk of mortality and treatment failure (defined as either permanent switch to alternative dialysis modality or graft loss) of over 50 percent among those transplanted, despite a higher rate of hospitalizations in the transplant cohort within the first three months [8].
The widely perceived success of transplantation must be tempered by the realization that organ demand far exceeds organ supply [9,10]. In addition, despite significant improvements in one-year graft survival, the rate of chronic graft loss after the first year remains substantial.
SURVIVAL COMPARED WITH DIALYSIS — The claim of many early studies that a lower mortality is found among kidney transplant recipients compared with dialysis patients has been criticized because the design of most such studies was flawed. These reports frequently failed to adequately account for the higher number and/or severity of comorbid conditions among dialysis patients. As an example, some of the benefit associated with transplantation is related to patient selection. Those treated with dialysis are usually older (mean 57 years versus 44 years for those transplanted in one study) and more likely to have type 2 diabetes and extrarenal vascular disease [11].
Given that many dialysis patients are inappropriate candidates for kidney transplantation because of severe multiorgan disease and/or age, the assessment of relative mortality is best performed by comparing the survival rates between patients accepted for kidney transplantation who have undergone surgery with those accepted for transplantation but who have not yet received a kidney allograft (waiting-list patients).
Multiple studies using these two comparative groups have found that patient survival is clearly better with kidney transplantation than with dialysis [2-4,12-16]. In one of the largest, most comprehensive studies to date, survival analysis using data from the United States Renal Data System (USRDS) was performed on nearly 230,000 dialysis patients [12]; among the 46,000 placed on a waiting list for transplantation, 23,000 subsequently underwent a first cadaveric transplant. The following results were reported:
●The annual death rate was significantly lower among transplant patients compared with waiting-list patients (3.8 versus 6.3/100 patient-years).
●After the first two weeks posttransplantation, the risk of death was lower among transplant recipients compared with waiting-list patients. As an example, the mortality risk at three to four years was nearly 70 percent lower among transplant recipients (relative risk [RR] 0.32). Because of the initially higher risk with transplant surgery, the likelihood of survival only became equal among the two patient groups at day 244 posttransplantation.
●Improved survival with transplantation was observed among diabetics, African Americans, and in all age groups, including those 60 to 74 years old.
Similar survival benefits associated with transplantation were observed in a second study of over 100,000 patients in the United States placed on the transplant waiting list between 1988 and 1996, of whom nearly 74,000 eventually received a kidney allograft [14]. Although the RR for death decreased over time in both groups, the annual death rate remained significantly lower for transplant recipients. In addition, a report from the same group using a strategy of analyzing survival of paired kidneys from those with end-stage kidney disease (ESKD) for more than two years versus less than six months found a survival advantage with less time on the transplant waiting list [17].
A survival benefit with transplantation has also been reported in patient populations outside of the United States. In Scotland, for example, one study reported the survival of 1732 patients waitlisted for a first kidney transplant in 1999 [15]. After an increased initial risk of death postsurgery, the long-term risk of death was markedly lower with kidney transplantation (RR at 18 months 0.18, 95% CI 0.08-0.42). Projected life expectancy was significantly higher in those who underwent transplantation (17.2 versus 5.8 years).
A significant survival advantage is also observed among recipients of marginal kidneys defined either by expanded-criteria-donor definitions or kidney donor profile index (KDPI) >85 percent (see "Kidney transplantation in adults: Organ sharing"), including kidneys donated after cardiac death [18-20]:
●In one study, the survival of patients who received an expanded-criteria-donor kidney was compared with those who received standard therapy, which consisted of remaining on the waiting list and receiving an ideal donor kidney [19]. At three years, mortality was 17 percent lower for those who received an extended-criteria-donor kidney; in particular, significant benefits were observed in patients >40 years of age, non-Hispanic patients, unsensitized patients, and those with diabetes or hypertension. This benefit with marginal kidneys is particularly significant for older and frailer transplant candidates [21].
●An observational cohort study of 2575 kidney transplant waitlist patients evaluated the mortality risk of those who received a standard-criteria kidney donated after cardiac death versus patients who continued on dialysis and waited for a standard-criteria kidney donated after brain death [20]. Compared with those who remained on dialysis, mortality was significantly lower among patients who received a kidney donated after cardiac death (hazard ratio [HR] 0.44, 95% CI 0.24-0.80).
Repeat kidney transplantation after a failed primary transplant also may confer a survival benefit [22,23]. In a large series of over 19,000 kidney transplant recipients with primary allograft failure, repeat kidney transplantation was associated with a 45 and 23 percent reduction in mortality at five years for patients with type 1 diabetes mellitus and those without diabetes, respectively, compared with those remaining on the waiting list [22]. Since patients with a failed primary transplant may comprise nearly 30 percent of current waiting lists, these added survival benefits with repeat transplantation have a significant impact upon overall mortality from ESKD.
However, these data need to be interpreted with caution. Although the authors of the last study attempted to utilize a "control" group (ie, those listed for transplantation who did not actually receive a transplant), selection bias almost certainly played some role in these results. Patients listed for transplantation may not have been transplanted, due to the development of intercurrent disease that led to death. This is a limitation common to all studies that rely upon the review of registry data.
Despite some concerns about surgical risk, patients with obesity undergoing dialysis also derive a survival advantage with transplantation. In an analysis of data from the USRDS, significantly improved survival was observed among recipients with obesity (body mass index [BMI] of ≥30 kg/m2) who received cadaveric or living-donor kidneys (HRs 0.39 and 0.23, respectively), compared with waiting-list patients with obesity [24].
The reduction in mortality among transplant recipients, compared with dialysis patients, is due in part to a decrease in cardiovascular events, especially among diabetic patients. Transplantation reduces the risk of fatal and nonfatal cardiovascular complications, compared with long-term dialysis, among patients selected to be suitable transplant candidates [25-29].
Reasons for improved survival — The underlying reasons for improved survival with kidney transplantation, compared with dialysis, are unclear. However, since a functioning kidney allograft more closely resembles a normal kidney than does maintenance dialysis therapy, it is possible that the survival benefit may result in part from improved clearance of uremic toxins.
A possibility is that the recovery of kidney function with a functional kidney allograft lowers the inflammatory and/or oxidative state found in patients undergoing chronic dialysis. This has been reported in some studies for levels of C-reactive protein, tumor necrosis factor (TNF)-alpha, and interleukin-6 [30,31]. Some have postulated that this reduction is due in part to the chronic administration of antiinflammatory drugs [32]. (See "Inflammation in patients with kidney function impairment".)
Among diabetics, the restoration of near-normal kidney function following transplantation also retards the progression of microvascular disease by reducing the circulating levels of advanced glycosylation end products [33]. These compounds accumulate in diabetic patients with kidney failure and may contribute to the development of vascular disease, in part by crosslinking with collagen. (See "Glycemic control and vascular complications in type 1 diabetes mellitus", section on 'Pathogenesis'.)
Another contributing factor may be that left ventricular hypertrophy tends to lessen after transplantation. Such improvement may decrease the risk of mortality from coronary heart disease [34,35]. Decreased ongoing general inflammation and oxidative stress, which are associated with an increased risk of cardiovascular disease, may also contribute [36].
FACTORS ASSOCIATED WITH PATIENT SURVIVAL — Patient survival after kidney transplantation varies based upon the source of the allograft, patient age, and the presence and degree of severity of comorbid conditions. Other possible contributing factors include sex, race, and degree of immunosuppression. One European study evaluated the determinants of patient survival after kidney transplantation among 86 living-donor transplant recipients and 916 deceased-donor recipients [37]. After the first year posttransplantation, an increased risk of death was observed among patients >40 years of age, men, deceased-donor recipients, those with diabetes or hypertension, and smokers. Similar adverse outcomes with smoking, including those who have ever smoked, were noted in a second study [38].
Although transplantation confers the highest survival benefit among all of the different kidney replacement therapies, kidney allograft recipients still have a high mortality rate compared with population controls. In the previously mentioned European study, for example, the mortality of recipients of first kidney transplants was 14 times higher than the age-matched population without kidney failure during the first year after transplantation and was four times higher after this period [37].
Allograft source — The survival of patients receiving an allograft from a living donor is superior to those who receive a kidney from a deceased donor, including both nonexpanded-criteria and expanded-criteria donors [39,40]:
●For recipients of a living-donor kidney, patient survival rate at five years posttransplantation is 91 percent.
●For those who receive a deceased, nonexpanded-criteria donor transplant, the survival rate is 84 percent.
●For those who receive a deceased, expanded-criteria donor transplants, the respective value is 70 percent.
The kidney donor profile index (KDPI) >85 percent has largely replaced the expanded-donor-criteria terminology based on the observation that many factors impact organ quality and outcomes (see "Kidney transplantation in adults: Organ sharing"). The outcomes of recipients who receive such kidneys with higher KDPIs decline slowly until KDPI exceeds 85 percent. Kidneys with a KDPI >85 percent approximate the prior expanded-donor-criteria definitions, if imperfectly. The outcomes of such transplants were evaluated in a study that compared the survival of candidates older than 60 years who either received a KDPI >85 percent allograft or remained on dialysis [41]. Mortality after the first posttransplant year was markedly reduced in those who received such higher-risk kidneys (either preemptively before the need for dialysis or nonpreemptively after dialysis initiation) compared with those who were listed but never transplanted.
Recipient and deceased-donor age — Patients of increasing age who undergo kidney transplantation have a higher mortality rate than younger recipients [42]. In the 2003 Scientific Registry of Transplant Recipients (SRTR) report on the state of transplantation, for example, the one- and five-year survival rates for children age 6 to 10 years who received a living-donor kidney were 96 and 85 percent, respectively [43]. For same-age children who received deceased-donor kidneys, it was 95 and 77 percent, respectively.
Although lower than in children, survival of the older transplant recipient is currently excellent. With present therapy, the survival at one and five years of patients >65 years of age is approximately 90 and 70 percent, respectively [44]. As a result, the older dialysis patient should not be excluded as a possible transplant recipient based upon age alone. (See "Kidney transplantation in adults: Kidney transplantation and the older adult patient".)
Among recipients of any age, survival is inversely correlated with the age of the deceased donor. This was reported in a review of over 50,000 kidney transplant recipients from the United Network of Organ Sharing (UNOS) database [45]. Among recipients >55 years of age, donor age groups 0 to 17, 18 to 29, 30 to 41, 42 to 54, and >55 years of age were associated with an adjusted 10-year patient survival of 48, 46, 45, 37, and 35 percent, respectively.
Comorbid conditions — The presence of systemic disorders, particularly vascular disease, is associated with poorer long-term patient survival after kidney transplantation. In a single-center study, high comorbidity (as assessed by the Charlson comorbidity index) correlated with an increased risk of death in both the perioperative period (hazard ratio [HR] 3.20) and more than three months after transplantation [46].
Patients with disease primarily affecting the kidney, such as autosomal dominant polycystic kidney disease and glomerulonephritis, have better long-term survival than those with systemic disorders, such as hypertension and diabetes. Obesity is also associated with an increased risk of death [24,47].
Cardiovascular disease — Fifty to 60 percent of deaths among kidney transplant recipients are directly attributable to cardiovascular disease, which has a reported incidence of approximately 1 per 100 person-years at risk [48,49]. Death from cardiovascular disease is also the most common cause of graft loss, accounting for 30 percent of graft loss from death overall, with the greatest rates early after transplant [50]. However, one must keep in mind that most of the deaths attributable to cardiovascular disease are among those with diabetes, whereas infection, malignancy, and others are more commonly the cause of death among those without diabetes [29].
Since cardiovascular disease is the leading cause of death for adult kidney allograft recipients, it is important to evaluate the extent and severity of coronary disease prior to transplantation (see "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient"). Nearly one-third of all such deaths are due to acute myocardial infarction (MI), with diabetic patients having the worst survival post-MI [25,51].
Among those who require intervention for coronary artery disease after transplantation, myocardial revascularization is associated with acceptable immediate and long-term survival and similar outcomes with percutaneous and surgical techniques:
●In a retrospective study of kidney transplant recipients who underwent a first coronary revascularization procedure from 1995 to 1999, in-hospital mortality was 2.3, 4,3, 9.4, and 5 percent for 909 stent patients, 652 percutaneous coronary angioplasty (PTCA) patients, 288 coronary artery bypass graft (CABG; without internal mammary grafting), and 812 CABG (with internal mammary grafting) patients, respectively [52]. At two years, all-cause survival was 83, 82, 74, and 83 percent for the stent, PTCA, CABG (without internal mammary grafting), and CABG (with internal mammary grafting) groups, respectively.
Compared with PTCA, the relative risk (RR) of death or acute MI for stent, CABG (without internal mammary grafting), and CABG (with internal mammary grafting) was 0.90, 0.80, and 0.57 (95% CI 0.42-0.76), respectively. Thus, similar long-term survival has been reported with surgical and percutaneous techniques, with the best survival being observed with CABG with an internal mammary graft. (See "Coronary artery bypass graft surgery: Graft choices".)
●In one study of nearly 3000 kidney transplant recipients at one institution, survival of the 83 who required either bypass surgery or angioplasty was 89, 77, and 65 percent at one, three, and five years postprocedure, respectively [53].
De novo heart failure, a common condition among patients after kidney transplantation, is associated with poor survival. Based upon registry data from the United States Renal Data System (USRDS), the onset of heart failure increased the risk of death (adjusted HR [aHR] 2.6, 95% CI 2.4-2.9) and death-censored graft failure (aHR 2.7, 95% CI 2.4-3.0) [26]. Similarly, the development of atrial fibrillation increases the risk of death (aHR 3.2, 95% CI 2.9-3.6) and death-censored graft failure (aHR 1.9, 95% CI 1.6-2.3) [54].
Diabetes mellitus — Survival of diabetic patients after kidney transplantation (75 to 80 percent at five years) is lower than that reported in nondiabetic patients [55,56]. However, these results, due largely to extrarenal vascular disease, are still markedly better than those seen with dialysis, where the five-year patient survival rate is approximately 30 percent. (See "Kidney transplantation in diabetic kidney disease".)
Overall immunosuppression — The level of overall immunosuppression used for induction therapy, maintenance therapy, and the treatment of acute rejection episodes is a major risk factor for posttransplant infection, rather than the use of a specific immunosuppressive agent. Since infections are the leading cause of mortality in the early posttransplant period, infection and allograft dysfunction caused by rejection are closely interrelated through the use of immunosuppressive therapy [57,58]. (See "Kidney transplantation in adults: Induction immunosuppressive therapy" and "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
Allograft function — Although early kidney dysfunction has a clear, adverse effect upon long-term allograft survival, a paucity of data exists concerning the relationship between graft function and patient survival. In a retrospective study of nearly 600 recipients of first deceased-donor allografts, significantly increased mortality was observed in patients with a primary nonfunctioning graft (ie, a graft that never functions) compared with those with less severe graft dysfunction (45 versus 20 percent at six years) [59]. The predominant cause of death was cardiovascular disease. (See "Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction".)
Patient survival is high among those with persistent, long-term graft function. In one survey of over 86,000 patients, of whom nearly 18,500 died over a 10-year period, survival at 1, 5, and 10 years was 97, 91, and 86 percent, respectively, among those with continued kidney allograft function [60].
Despite decreasing early acute rejection rates, long-term allograft survival rates have changed little over time. This is due to a statistically significant trend toward increasing death-censored allograft survival [61]. Although the underlying reasons for this trend are unclear, this may be related to a higher proportion of acute rejection episodes that fail to recover to previous baseline function.
CAUSES OF DEATH — Atherosclerotic cardiovascular disease continues to be the overall major cause of death after kidney transplantation. The causes of death among transplant recipients have changed over time and vary with age [62,63]. In a single-center study, for example, cardiac disease, cancer, and stroke as causes of death increased from 9.6, 1.2, and 2.4 percent, respectively, for the period 1970 to 1979 to 30.3, 13.2, and 8 percent for 1990 to 1999 [63].
In addition, death from cardiovascular disease is much less common among younger than older individuals [64]. Among prevalent transplant patients from 1994 to 1996, the following were the percentage of deaths due to the most significant life-threatening disorders:
●All cardiac causes accounted for 18, 33, and 37 percent of deaths for those aged 0 to 19, 20 to 44, and 45 to 64, respectively.
●Infection accounted for 25, 17, and 19 percent, respectively.
●Malignancy accounted for 16, 8, and 11 percent, respectively.
●Other known causes accounted for 41, 24, and 18 percent, respectively.
ESTIMATED POSTTRANSPLANT SURVIVAL — When a candidate is offered a kidney for transplant, available information about the candidate at the time of the organ offer will be used by the United Network for Organ Sharing (UNOS) to determine the candidate's estimated posttransplant survival (EPTS). The calculation for EPTS is based on four factors:
●Candidate age
●Length of time on dialysis
●Any prior organ transplant
●Diabetes status
The 20 percent of adult candidates with the longest EPTS will receive priority for kidneys from the highest-quality donors (as defined by Kidney Donor Profile Index [KDPI] scores in the top 20 percent) [65]. (See "Kidney transplantation in adults: Organ sharing", section on 'National deceased-donor kidney allocation policy'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Kidney transplant (The Basics)" and "Patient education: Planning for a kidney transplant (The Basics)")
SUMMARY
●Kidney transplantation is the treatment of choice for selected patients with end-stage kidney disease (ESKD). Transplantation confers the highest survival benefit among all of the different kidney replacement therapies. A survival benefit has been observed among diabetic patients, African Americans, patients with obesity, and patients in all age groups, as well as in those who are recipients of marginal kidneys. The reasons for improved survival with kidney transplantation, compared with dialysis, are unclear. (See 'Introduction' above and 'Factors associated with patient survival' above and 'Survival compared with dialysis' above.)
●Despite the survival benefit conferred by transplantation compared with dialysis, kidney allograft recipients still have a high mortality rate compared with population controls. Posttransplantation survival rates vary based upon the source of the allograft, patient age, and the presence and degree of severity of comorbid conditions. Other factors that may contribute to survival rates include sex, race, and degree of immunosuppression. (See 'Factors associated with patient survival' above.)
●Cardiovascular disease is the leading cause of death for adult kidney allograft recipients. De novo heart failure is also common among patients after kidney transplantation and is associated with poor survival. Among those who require intervention for coronary artery disease after transplantation, myocardial revascularization is associated with acceptable immediate and long-term survival and similar outcomes with percutaneous and surgical techniques. (See 'Cardiovascular disease' above.)
●The survival of diabetic patients after kidney transplantation is lower than that reported for nondiabetic patients due to the prevalence of extrarenal vascular disease. However, survival among diabetic patients who have a transplant is still markedly better than that seen with dialysis. (See 'Diabetes mellitus' above and "Kidney transplantation in diabetic kidney disease".)
●Infections are the leading cause of mortality in the early posttransplant period and are related to the level of overall immunosuppression rather than the use of a specific immunosuppressive agent. (See 'Overall immunosuppression' above.)
●The causes of death among transplant recipients have changed over time and vary with age. In one single-center study, the percentages of deaths caused by cardiac disease, cancer, and stroke appear to have increased. (See 'Causes of death' above.)
