Kidney

OPTN/SRTR 2018 Annual Data Report: Kidney

Abstract

Despite the ongoing severe mismatch between organ need and supply, data from 2018 revealed some promising trends. For the fourth year in a row, the number of patients waiting for a kidney transplant in the US declined and numbers of both deceased and living donor kidney transplants increased. These encouraging trends are tempered by ongoing challenges, such as a large proportion of listed patients with dialysis time longer than 5 years. The proportion of candidates aged 65 years or older continued to rise, and the proportion undergoing transplant within 5 years of listing continued to vary dramatically nationwide, from 10% to nearly 80% across donation service areas. Increasing trends in the recovery of organs from hepatitis C positive donors and donors with anoxic brain injury warrant ongoing monitoring, as does the ongoing discard of nearly 20% of recovered organs. While the number of living donor transplants increased, racial disparities persisted in the proportion of living versus deceased donors. Strikingly, the total number of kidney transplant recipients alive with a functioning graft is on track to pass 250,000 in the next 1-2 years. The total number of pediatric kidney transplants remained steady at 756 in 2018. Deeply concerning to the pediatric community is the persistently low level of living donor kidney transplants, representing only 36.2% in 2018.

Introduction

Kidney transplant provides significant quality of life and mortality benefits over dialysis for the treatment of end-stage kidney disease, but optimizing access to kidney transplant and graft survival are ongoing challenges. The Annual Data Report is an opportunity to assess the state of kidney transplantation and examine the positive and unfavorable trends that warrant further monitoring and evaluation. Data are provided on adult and pediatric kidney transplant waiting lists, living donation, deceased donation, transplants, and outcomes.

Adults

Waiting List

Waitlist data from 2018 reveal encouraging trends. The number of patients on the kidney transplant waiting list declined for the fourth year in a row since its peak at nearly 100,000 in 2014 (Figure KI 2). The decline was less than in the previous year, but this was largely due to the greater number of patients added to the list, nearly 3000 more than in the previous 2 years (Figure KI 1, Table KI 5). Encouragingly, the decline in numbers of waitlisted candidates appeared to be due to further increases in both deceased and living donor transplants in 2018, rather than to increases in removals for other reasons; numbers of candidates removed from the list due to death or becoming too sick for transplant decreased.

Previous trends in the demographic characteristics of candidates on the waiting list did not change in 2018. The proportion aged 65 years or older continued to increase, comprising almost a quarter of the waiting list (Figure KI 3, Table KI 2). Approximately 60% of candidates were male (Figure KI 4), a proportion that changed little in the past decade. Similarly, while the proportion of Hispanic candidates has increased incrementally over the past decade, corresponding to a slight decrease in the proportion of white candidates, little has changed in the racial distribution (Figure KI 5). The metropolitan versus non-metropolitan candidate distribution also changed little over the past decade (Table KI 2). Diabetes remained the most common cause of kidney failure, with an ongoing upward trend to nearly 40% of listed candidates (Figure KI 6, Table KI 3). While still higher than it was 5 years ago, the proportion of candidates on the waiting list for more than 5 years did not increase for the first time in a decade (Figure KI 7, Table KI 4). Encouragingly, the 10-year trend in increased proportions of patients listed before starting dialysis continued, but those with more than 5 years on dialysis still comprised one-fifth of the waiting list. While the proportion of candidates with 6-10 years of dialysis time decreased slightly, possibly due to the new allocation policy in 2014 giving credit for time on dialysis, the large number of patients with long dialysis exposure prior to transplant remains a concern given deterioration in the benefits of transplant with longer dialysis exposure (Figure KI 8, Table KI 4).

Changes in willingness to accept a high kidney donor profile index (KDPI) (>85%) kidney are notable. With the new kidney allocation system (KAS), allocation of lower-KDPI kidneys with longer expected graft survival was prioritized for candidates with longer expected post-transplant survival, and as expected, transplant rates for older patients fell below the rates for younger patients (Figure KI 14). However, willingness to accept high-KDPI kidneys decreased after the new KAS among older patients, to a low of 60% in 2018. In 2018, reported willingness to accept high-KDPI kidneys was stable to slightly increased among older candidates for whom high-KDPI kidneys are likely the most beneficial (Figure KI 12). The coming years will reveal whether this single-year change represents a reversal of the previously concerning trend. Also notable is the year-over-year increase in willingness to accept a hepatitis C virus (HCV)-positive kidney (Figure KI 13). In a new era of effective HCV treatments, HCV-positive donors have the exciting potential to help ease the organ shortage, and a special chapter of the OPTN/SRTR 2018 Annual Data Report is devoted to further examining HCV-positive transplant.

In addition to deceased donor transplant rate changes for older patients, rates changed for several key groups after the new KAS, and these trends continued in 2018. Disparities in deceased donor transplant rates between whites and other races decreased after the new KAS, and this trend continued in 2018, although rates for Asians remained slightly lower compared with rates for other racial groups (Figure KI 15). After a dramatic spike immediately post-KAS in transplant rates among patients with calculated panel-reactive antibody (cPRA) above 98%, rates leveled off and in 2018 remained similar to rates for lower-cPRA candidates with, the exception of candidates with cPRA 80%-98%, for whom rates remain slightly higher (Figure KI 17). The long-term effects of these allocation policy changes on allograft survival will need to be monitored. Despite the KAS provision allowing for allocation of blood type A2 and A2B kidneys to B recipients, transplant rates among blood type B candidates have not increased markedly. In fact, post-KAS transplant rates increased most among blood type AB candidates, a trend that may warrant further study (Figure KI 18). Transplant rates also rose markedly among patients with less than 1 year on the waiting list post-KAS, again possibly due to credit given for time on dialysis, which resulted in many new patients with long dialysis times moving to the top of the waiting list immediately after listing. This trend continued in 2018, although the rate of increase appears to be plateauing (Figure KI 19). Transplant rates by metropolitan vs. non-metropolitan areas remained similar and relatively unchanged (Figure KI 20, Figure KI 21).

Overall, 40% of patients listed for transplant in 2015 were still waiting in 2018, while approximately 40% underwent transplant and 20% died or were removed from the list for other reasons (Figure KI 22). The 6-month mortality rate for candidates removed from the list remained stable, suggesting that standards for removing patients deemed too sick to undergo transplant have not changed substantially (Figure KI 34). For candidates who did not undergo living donor transplant, 30% underwent transplant within 3 years and less than 40% within 5 years. Nationally, median time to deceased donor transplant for a newly listed candidate has not been calculable for a decade, as 2008 was the last listing year in which more than 50% of the waiting list underwent transplant. The proportion of candidates who undergo transplant within 5 years of listing continued to vary dramatically nationwide, from 10% to 80% across donation service areas (DSA) (Figure KI 24, Figure KI 25). Despite this ongoing mismatch between organ need and supply, a small but positive trend is notable in waitlist survival across age groups, although disparities between white candidates and black, Hispanic, and Asian candidates persisted (Figure KI 26, Figure KI 27, Figure KI 28, Figure KI 29, Figure KI 30, Figure KI 31). Not surprisingly given the large variation in transplant rates, waitlist mortality also varied dramatically by DSA, with rates more than five times higher in some DSAs (Figure KI 32). Resolving this persistent geographic disparity in mortality and access to transplant warrants further investigation.

Deceased Donation

Deceased kidney donation trends were largely unchanged in 2018 with a few notable exceptions (Figure KI 37, Figure KI 38, Figure KI 39). While the distribution of deceased donor kidneys by age, race, and sex has been stable, the total number of kidneys recovered from donors aged 18-64 years rose steadily over the past decade (Figure KI 35). This may be due to a general increase in recovery by organ procurement organizations, but the opioid epidemic may also play a role, as evidenced by the corresponding rise in proportions of kidneys donated after anoxic brain injury (Figure KI 55). The number of HCV-antibody-positive kidneys recovered also increased, albeit only slightly, while the proportion of recovered HCV-positive organs discarded decreased substantially (Figure KI 48), suggesting an increase in demand for these organs in the era of better treatment options (Figure KI 36, Figure KI 40). Nearly 20% of recovered kidneys were not transplanted. Discarded kidneys are more commonly from older donors, donors with diabetes, hypertension, and/or terminal creatinine above 1.5 mg/dL (Figure KI 42, Figure KI 43, Figure KI 44, Figure KI 45). Discarded kidneys were also more likely to have been biopsied (Figure KI 46). Given that the average kidney donor risk index (KDRI) of biopsied kidneys also decreased (Figure KI 54), this trend again raises concern that biopsy findings may not correspond to significantly decreased graft survival and may lead to the discard of potentially beneficial kidneys. Interestingly, kidneys from donors designated as Public Health Service increased risk for transmission of infectious disease were discarded less than standard infectious risk kidneys, although given that these kidneys often have substantially lower KDPI, this may still reflect discard of potentially beneficial kidneys. Nearly 60% of kidneys recovered with KDPI above 85% were not transplanted (Figure KI 51). Given that KDPI is based on the previous years’ recovered kidneys, discard of high-KDRI kidneys could result in a drift in the KDPI score such that a given KDPI corresponds to a lower KDRI; it is reassuring that after several years of decline, the average KDRI of discarded kidneys increased after 2016 (Figure KI 53).

Living Donation

After a steady decline in living donor transplants for more than a decade, their number increased in 2018 for the second year in a row (Figure KI 56). Living donor transplants continued to represent a small proportion of transplants relative to the size of the waiting list, and compared with their peak in 2004; coming years will reveal whether this positive trend continues. The number and proportion of donors aged older than 50 years continued to rise, corresponding to improved procedural safety and increased concern regarding the long-term risk of kidney donation (Figure KI 57). Living kidney donors remained predominantly female and mostly white (Figure KI 58, Figure KI 59). Reported complications and hospitalizations were uncommon, but loss to follow-up at even 1 year was high (Figure KI 61, Figure KI 62).

Transplants

The total number of kidney transplants increased in 2018 for the fourth year in a row, having been relatively stagnant for many years prior (Figure KI 64). The increase occurred across age groups (except ages <18 years), sex, race, and cause of kidney disease (Figure KI 65, Figure KI 66, Figure KI 67, Figure KI 68). Important demographic differences in transplant recipients are worth noting. White recipients continued to represent a disproportionately large share of living donor transplants, 64.7%, despite making up only 45.9% of all transplants. The racial disparity in living donor transplant was most notable among African American recipients, who accounted for 12.5% of living donor transplants despite making up 26.9% of all transplants (Table KI 8). Most living donor recipients had private insurance at the time of transplant, while most deceased donor recipients had Medicare. Rates of deceased versus living transplant were similar by metropolitan/non-metropolitan breakdown and distance from transplant programs (Table KI 8). Not surprisingly, living donor recipients tended to have less dialysis time and lower cPRA (Table KI 9). About 90% of deceased and of living donor transplants were first-time transplants (Table KI 10), and approximately 18% of each were cytomegalovirus donor-positive/recipient-negative (Table KI 11, Table KI 12).

The proportion of low-KDPI transplanted kidneys decreased slightly, a trend that may warrant investigation, and may reflect discards of increased infectious risk (but often low-KDPI) kidneys in the setting of the opioid epidemic (Figure KI 69). T-cell depleting agents remained the most common induction agent, as most patients continued on a tacrolimus and mycophenolate mofetil (MMF)-based regimen. Approximately 30% were on steroid-free regimens, a relatively stable proportion over the past decade. As noted previously, the proportion of deceased donor transplants in recipients with cPRA 98-100 increased notably after the 2014 KAS, and has since leveled off (Figure KI 72). The increased numbers of transplants occurred in larger transplant programs, at or above the median size, performing at least 250 transplants per year (Figure KI 75, Figure KI 76).

Outcomes

Overall, short- and long-term all-cause and death-censored graft failure after deceased donor transplant continued to decline, although 3-year graft failure increased slightly after 2015 after many years of decline (Figure KI 77, Figure KI 78). This small change corresponds to the new KAS, and given concerns about increased long-term graft failure with increased cold ischemia time and high-cPRA transplants, this trend should be closely monitored. Short- and long-term living donor graft failure continued to decline (Figure KI 80, Figure KI 81). Graft survival remained lowest among patients with diabetes or hypertension as a cause of kidney disease compared with other diagnoses (Figure KI 83), or with higher KDPI; 5-year graft survival was approximately 65% among deceased donor kidneys with KDPI above 85% (Figure KI 84). Five-year unadjusted graft survival did not differ by donation after circulatory death status (Figure KI 85). Unadjusted graft survival was lower for kidneys that were biopsied at the time of transplant (Figure KI 86); as noted previously, the utility of biopsy in procurement is a question that warrants further study. Unadjusted graft survival was not worse in non-metropolitan compared with metropolitan zip codes, and actually improved with greater distance from transplant programs (Figure KI 87, Figure KI 88).

Graft survival also continued to improve after living donor transplant, with 5-year graft survival nearly 90% in 2018 (Figure KI 89). Five-year unadjusted living donor graft survival was best among Asians and worst among African Americans (Figure KI 90) and recipients with diabetes (Figure KI 91). Estimated glomerular filtration rate at 12 months improved slightly over the past decade, and was 45-90 mL/min/1.73m² for nearly 70% of deceased donor recipients (Figure KI 94). The total number of kidney transplant recipients alive with a functioning graft is on track to pass 250,000 in the next 1-2 years, and trends in patient survival closely mirror those in graft survival (Figure KI 103, Figure KI 104, Figure KI 105, Figure KI 106, Figure KI 107, Figure KI 108, Figure KI 109, Figure KI 110, Figure KI 111, Figure KI 112, Figure KI 113).

Pediatric Kidney Transplant

Waiting List

In 2018, 966 pediatric candidates were added to the kidney transplant waiting list, with 336 (34.8%) as active status (Figure KI 114). The number of prevalent pediatric candidates (listed at age <18 years and on the list on December 31 of the given year) has been steadily increasing and reached 1585 on December 31, 2018, with 510 (32%) as active status (Figure KI 115). The most common reason for inactive status among newly listed pediatric candidates in 2018 was incomplete work-up (51.4%), followed by living donor candidate status (15.6%), and too well to need transplant (14.2%) (Table KI 13). Over the past decade, the age of pediatric candidates on the waiting list shifted, with an increase in those aged 1-5 and 6-10 years and a decrease in those aged 11-17 years (63.4% to 56.6%) (Table KI 14). Proportions of candidates with congenital anomalies of the kidney and urinary tract (CAKUT) as primary cause of disease increased from 25.9% in 2008 to 36.7% in 2018, and proportions with glomerulonephritis and focal segmental glomerulosclerosis (FSGS) decreased (Table KI 15). By cause of end-stage renal disease (ESRD) and age, CAKUT was most common among candidates aged younger than 6 years, while FSGS and glomerulonephritis were more common among older children (Figure KI 122). For most candidates waiting as of December 31, 2018 (69.8%), cPRA was less than 1% (Table KI 15). The proportion of pediatric candidates waiting for re-transplant decreased from 26.8% in 2008 to 14.4% in 2018. Multi-organ listing remained uncommon; only 1.7% of pediatric candidates were awaiting multi-organ transplant at the end of 2018 (Table KI 16).

Of the 996 pediatric candidates removed from the waiting list in 2018, 596 (59.8%) received a deceased donor kidney, 301 (30.2%) received a living donor kidney, 25 (2.5%) died, 10 (1.0%) were removed from the list because their condition improved, and nine (0.9%) were considered too sick to undergo transplant (Table KI 17, Table KI 18). Among patients newly listed in 2015, 54.5% underwent deceased donor transplant within 3 years, 27.0% underwent living donor transplant, 15.0% were still waiting, 2.1% were removed from the list for other reasons, and 1.5% died (Figure KI 123). The rate of deceased donor transplant among pediatric waitlisted candidates decreased over the past decade and was 37.9 transplants per 100 waitlist-years in 2018, compared with a peak of 52.0 transplants in 2009 (Figure KI 124). Post-KAS, transplant rates changed based on recipient age (Figure KI 124). In 2018, transplant rates were highest for candidates aged 11-17 years (48.1 per 100 waitlist-years), followed by candidates aged 6-10 years (42.9) and candidates aged younger than 6 years (38.7). As expected, transplant rates remained higher than pre-KAS rates for highly sensitized (=98%) candidates, reflecting KAS priority; the transplant rate increased from 6.6 transplants per 100 waitlist-years in 2014 to 15.1 in 2018 (Figure KI 125). Transplant rates for pediatric candidates with cPRA 80%-97% initially declined to 17.1 post-KAS in 2015, but increased to 21.9 in 2018 (Figure KI 125), similar to rates in the adult population. In contrast to mortality among candidates waiting for other organs, pretransplant mortality among pediatric candidates waiting for kidney transplant remained low: 1.3 per 100 waitlist-years in 2018, but varying by age; rates were 2.1 for ages younger than 6 years, 0.4 for 6-10 years, and 0.6 for 11-17 years (Figure KI 128).

Transplant

The total number of pediatric kidney transplants remained steady at 756 in 2018 (Figure KI 131). Deeply concerning to the pediatric community is the persistently low level of living donor kidney transplants, representing only 36.2% in 2018. The number of related living donors decreased dramatically over the past decade (Figure KI 132), but the number of unrelated directed transplants performed in pediatric candidates reached its highest at 66 in 2018 (Figure KI 132). Children aged younger than 6 years made up the largest group of living donor kidney recipients (49.1%) (Figure KI 133).

In 2018, 36 programs were performing only pediatric kidney transplants, compared with 150 performing only adult or late teenage (ages 15-17 years) transplants and 53 performing transplants in both adults and children (Figure KI 134). In 2018, 16.4% of transplants in candidates aged younger than 18 years were performed at programs with volume of five or fewer pediatric transplants in that year (Figure KI 135). Most pediatric recipients who underwent transplant between 2016 and 2018 were aged 11-17 years, 61.4% among deceased donor recipients and 51.5% among living donor recipients (Table KI 19). A higher proportion of living donor transplants were performed in recipients aged 1-5 years; this group accounted for 29.9% of pediatric living donor transplants and 19.2% of pediatric deceased donor transplants (Table KI 19).The racial distribution differed for deceased and living donor transplant recipients; a higher proportion of living than deceased donor recipients were white (69.4% vs. 37.4%). Private insurance was more common among living donor recipients (55.3% vs. 26.5%) and Medicare/Medicaid among deceased donor recipients. Most deceased donor recipients (95.2%) underwent transplant with a kidney from a donor with KDPI less than 35% (Table KI 21).

The combination of a donor who was positive for cytomegalovirus and a pediatric recipient who was negative occurred in 39.0% of deceased donor transplants and in 28.9% of living donor transplants (Table KI 22, Table KI 23). The combination of a donor who was positive for Epstein-Barr virus (EBV) and a recipient who was negative occurred in 37.4% of deceased donor transplants and in 51.5% of living donor transplants.

Immunosuppressive Medication Use

Use of T-cell depleting agents continued to increase, reaching 63.6% in 2018. IL-2-RA therapy remained stable at 35.1% (Figure KI 136). In 2018, the most common initial immunosuppression regimens were tacrolimus, MMF, and steroids in 57.8% of recipients, followed by tacrolimus and MMF in 37.5% (Figure KI 137). T-cell depleting agents were more common with increasing cPRA and IL-2-RA use with decreasing cPRA (Figure KI 138).

Outcomes

All-cause graft failure after kidney-alone deceased donor transplant in pediatric recipients was 1.6% at 6 months and 2.2% at 1 year for transplants in 2016-2017, 8.3% at 3 years for transplants in 2014-2015, 17.4 at 5 years for transplants in 2012-2013, and 39.4% at 10 years for transplants in 2008-2009 (Figure KI 142). Corresponding graft failure after living donor transplant was 0.8% at 6 months and 0.8% at 1 year for transplants in 2016-2017, 5.3% at 3 years for transplants in 2014-2015, 8.8% at 5 years for transplants in 2012-2013, and 29.7% at 10 years for transplants in 2008-2009 (Figure KI 145). For the cohort of recipients who underwent transplant in 2009-2013, graft survival was highest for living donor recipients aged younger than 11 years (93.1% at 5 years) and lowest for deceased donor recipients aged 11-17 years (77.2% at 5 years) (Figure KI 148). In the 2016-2017 cohort, the overall incidence of acute rejection within the first year was 11.4%, with some variation by age: highest for ages younger than 6 years (12.5%) and lowest for ages 6-10 years (7.9%) (Figure KI 149). Short-term renal function, measured by eGFR, improved substantially over the past decade. Proportions of living donor and deceased donor recipients with eGFR 90 mL/min/1.73 m² or higher at 12 months posttransplant were 31.3% (increased from 19.7% in 2008) and 28.5 % (increased from 22.3%), respectively (Figure KI 140,141). Incidence of posttransplant lymphoproliferative disorder among EBV-negative recipients from 2006-2016 was 3.1% at 5 years posttransplant, compared with 0.8% among EBV-positive recipients (Figure KI 151). Overall 5-year patient survival among pediatric kidney transplant recipients in 2009-2013 was very high, at 98.4% (Figure KI 152).

Figure List

Waiting list

Deceased donation

Living donation

Figure KI 56. Kidney transplants from living donors by donor relation
Figure KI 57. Living kidney donors by age
Figure KI 58. Living kidney donors by sex
Figure KI 59. Living kidney donors by race
Figure KI 60. Intended living kidney donor procedure type
Figure KI 61. Rehospitalization among living kidney donors, 2013-2017
Figure KI 62. Kidney complications among living kidney donors, 2013-2017
Figure KI 63. BMI among living kidney donors

Transplant

Figure KI 64. Total kidney transplants
Figure KI 65. Total kidney transplants by age
Figure KI 66. Total kidney transplants by sex
Figure KI 67. Total kidney transplants by race
Figure KI 68. Total kidney transplants by diagnosis
Figure KI 69. Kidney transplants by kidney donor profile index (KDPI)
Figure KI 70. Induction agent use in adult kidney transplant recipients
Figure KI 71. Immunosuppression regimen use in adult kidney transplant recipients
Figure KI 72. C/PRA at time of kidney transplant in adult deceased donor recipients
Figure KI 73. C/PRA at time of kidney transplant in adult living donor recipients
Figure KI 74. Total HLA A, B, and DR mismatches among adult kidney transplant recipients, 2014-2018
Figure KI 75. Annual adult kidney transplant center volumes, by percentile
Figure KI 76. Distribution of adult kidney transplants by annual center volume

Outcomes

Pediatric transplant

Table List