B. L. Kasiske

OPTN/SRTR 2015 Annual Data Report: Kidney

The first full year of data after implementation of the new kidney allocation system reveals an increase in deceased donor kidney transplants among black candidates and those with calculated panel‐reactive antibodies 98%–100%, but a decrease among candidates aged 65 years or older. Data from 2015 also demonstrate ongoing positive trends in graft and patient survival for both deceased and living donor kidney transplants, but the challenges of a limited supply of kidneys in the setting of increasing demand remain evident. While the total number of patients on the waiting list decreased for the first time in a decade, this was due to a combination of a decrease in the number of candidates added to the list and an increase in the number of candidates removed from the list due to deteriorating medical condition, as well as an increase in total transplants. Deaths on the waiting list remained flat, but this was likely because of an increasing trend toward removing inactive candidates too sick to undergo transplant.

OPTN/SRTR 2015 Annual Data Report: Liver.

ABSTRACT  The current liver allocation system, introduced in 2002, decreased the importance of waiting time for allocation priorities; the number of active wait‐listed candidates and median waiting times were immediately reduced. However, the total number of adult wait‐listed candidates has increased since 2002, and median waiting time has increased since 2006. Pretransplant mortality rates have been stable, but the number of candidates withdrawn from the list as being too sick to undergo transplant nearly doubled between 2009 and 2011. Deceased donation rates have remained stable, with an increasing proportion of expanded criteria donors. Living donation has decreased over the past 10 years. Transplant outcomes remain robust, with continuously improving graft survival rates for deceased donor, living donor, and donation after circulatory death livers. Numbers of new and prevalent pediatric candidates on the waiting list have decreased. Pediatric pretransplant mortality has decreased, most dramatically for candidates aged less than 1 year. The transplant rate has increased since 2002, and is highest in candidates aged less than 1 year. Graft survival continues to improve for pediatric recipients of deceased donor and living donor livers. Incidence of acute rejections increases with time after transplant. Posttransplant lymphoproliferative disorder remains an important concern in pediatric recipients.

Evidence for antibody-mediated injury as a Major determinant of late kidney allograft failure

Background. Late graft failure (LGF) is believed to be the consequence of immunologic and nonimmunologic insults leading to progressive deterioration in kidney function. We studied recipients with new onset late kidney graft dysfunction (n=173) to determine the importance of C4d staining and circulating donor-specific antibody (DSA) in subsequent LGF. Methods. One hundred seventy-three subjects transplanted before October 1, 2005 (mean time after transplant 7.3±6.0 years) had a baseline serum creatinine level of 1.4±0.3 mg/dL before January 1, 2006 and underwent biopsy for new onset graft dysfunction after that date (mean creatinine at biopsy 2.7±1.6 mg/dL). Statistical analysis was based on central DSA and blinded pathology determinations. Results. Subjects were divided into four groups based on C4d and DSA: no C4d, no DSA (group A; n=74); only DSA (group B; n=31); only C4d (group C; n=28); and both C4d and DSA (group D; n=40). Among DSA+ recipients (groups B and D), group D had broader reactivity and a stronger DSA response. After 2 years, groups C and D (C4d+) were at significantly greater risk for LGF than groups A and B. Adjusting for inflammation (Banff i, t, g, and ptc scores) did not change the outcome. Local diagnosis of calcineurin inhibitor nephrotoxicity was spread across all four subgroups and did not impact risk of LGF. Conclusions. Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

OPTN/SRTR 2013 Annual Data Report: Kidney: OPTN/SRTR 2013 Annual Data Report

A new kidney allocation system, expected to be implemented in late 2014, will characterize donors on a percent scale (0%‐100%) using the kidney donor profile index (KDPI). The 20% of deceased donor kidneys with the greatest expected posttransplant longevity will be allocated first to the 20% of candidates with the best expected posttransplant survival; kidneys that are not accepted will then be offered to remaining 80% of candidates. Waiting time will start at the time of maintenance dialysis initiation (even if before listing) or at the time of listing with an estimated glomerular filtration rate of 20 mL/min/1.73 m2 or less. Under the current system, the number of candidates on the waiting list continues to increase, as each year more candidates are added than are removed. Median waiting times for adults increased from 3 years in 2003 to more than 4.5 years in 2009. Donation rates have not increased. Short‐term outcomes continue to improve; death‐censored graft survival at 90 days posttransplant was 97% or higher for deceased donor transplants and over 99% for living donor transplants. In 2013, 883 pediatric candidates were added to the waiting list; 65.8% of pediatric candidates on the list in 2013 underwent deceased donor transplant. Five‐year graft survival was highest for living donor recipients aged younger than 11 years (89%) and lowest for deceased donor recipients aged 11 to 17 years (68%).

OPTN/SRTR 2012 Annual Data Report: Pancreas: OPTN & SRTR Annual Data Report 2012

For most end‐stage renal disease patients, successful kidney transplant provides substantially longer survival and better quality of life than dialysis, and preemptive transplant is associated with better outcomes than transplants occurring after dialysis initiation. However, kidney transplant numbers in the us have not changed for a decade. Since 2004, the total number of candidates on the waiting list has increased annually. Median time to transplant for wait‐listed adult patients increased from 2.7 years in 1998 to 4.2 years in 2008. The discard rate of deceased donor kidneys has also increased, and the annual number of living donor transplants has decreased. The number of pediatric transplants peaked at 899 in 2005, and has remained steady at approximately 750 over the past 3 years; 40.9% of pediatric candidates undergo transplant within 1 year of wait‐listing. Graft survival continues to improve for both adult and pediatric recipients. Kidney transplant is one of the most cost‐effective surgical interventions; however, average reimbursement for recipients with primary Medicare coverage from transplant through 1 year posttransplant was comparable to the 1‐year cost of care for a dialysis patient. Rates of rehospitalization are high in the first year posttransplant; annual costs after the first year are lower.

OPTN/SRTR 2013 Annual Data Report: Liver: OPTN/SRTR 2013 Annual Data Report: Liver

During 2013, 10,479 adult candidates were added to the liver transplant waiting list, compared with 10,185 in 2012; 5921 liver transplants were performed, and 211 of the transplanted organs were from living donors. As of December 31, 2013, 15,027 candidates were registered on the waiting list, including 12,407 in active status. The most significant change in allocation policy affecting liver waitlist trends in 2013 was the Share 35 policy, whereby organs from an entire region are available to candidates with model for end‐stage liver disease scores of 35 or higher. Median waiting time for such candidates decreased dramatically, from 14.0 months in 2012 to 1.4 months in 2013, but the effect on waitlist mortality is unknown. The number of new active pediatric candidates added to the liver transplant waiting list increased to 693 in 2013. Transplant rates were highest for candidates aged younger than 1 year (275.6 per 100 waitlist years) and lowest for candidates aged 11 to 17 years (97.0 per 100 waitlist years). Five‐year graft survival was 71.7% for recipients aged younger than 1 year, 74.9% for ages 1 to 5 years, 78.9% ages 6 to 10 years, and 77.4% for ages 11 to 17 years.

OPTN/SRTR 2011 Annual Data Report: Lung

ABSTRACT  Lungs are allocated in part based on the Lung Allocation Score (LAS), which considers risk of death without transplant and posttransplant. Wait‐list additions have been increasing steadily after an initial decline following LAS implementation. In 2011, the largest number of adult candidates were added to the waiting list in a single year since 1998; donation and transplant rates have been unable to keep pace with wait‐list additions. Candidates aged 65 years or older have been added faster than candidates in other age groups. After an initial decline following LAS implementation, wait‐list mortality increased to 15.7 per 100 wait‐list years in 2011. Short‐ and long‐term graft survival improved in 2011; 10‐year graft failure fell to an all‐time low. Since 1998, the number of new pediatric (aged 0–11 years) candidates added yearly to the waiting list has declined. In 2011, 19 pediatric lung transplants were performed, a transplant rate of 34.7 per 100 wait‐list years. The percentage of patients hospitalized before transplant has not changed. Both graft and patient survival have continued to improve over the past decade. Posttransplant complications for pediatric lung transplant recipients, similar to complications for adult recipients, include hypertension, renal dysfunction, diabetes, bronchiolitis obliterans syndrome, and malignancy.

OPTN/SRTR 2015 Annual Data Report: Heart

The number of heart transplant candidates and transplants performed continued to rise each year. In 2015, 2819 heart transplants were performed. In addition, the number of new adult candidates on the waiting list increased 51% since 2004. The number of adult heart transplant survivors continued to increase, and in 2015, 29,172 recipients were living with heart transplants. Patient mortality following transplant has declined. The number of pediatric candidates and transplants performed also increased. New listings for pediatric heart transplants increased from 451 in 2004 to 644 in 2015. The number of pediatric heart transplants performed each year increased from 297 in 2004 to 460 in 2015. Among pediatric patients who underwent transplant in 2014, death occurred in 7.2% at 6 months and 9.6% at 1 year.

OPTN/SRTR 2012 Annual Data Report

Lung transplants are increasingly used as treatment for end‐stage lung diseases not amenable to other medical and surgical therapies. Lungs are allocated to adult and adolescent transplant candidates on the basis of age, geography, blood type compatibility, and the Lung Allocation Score, which reflects risk of wait‐list mortality and probability of posttransplant survival. The overall median waiting time in 2012 was 4 months, and 65.3% of candidates underwent transplant within 1 year of listing; however, this proportion varied greatly by donation service area. Unadjusted median survival of lung transplant recipients was 5.3 years in 2012, and median survival conditional on living for 1 year posttransplant was 6.7 years. Among pediatric lung candidates in 2012, 32.1% were wait‐listed for less than 1 year, 17.9% for 1 to less than 2 years, 16.7% for 2 to less than 4 years, and 33.3% for 4 or more years. Both graft and patient survival have continued to improve; survival rates for recipients aged 6‐11 years are better than for younger recipients. Compared with recipients of other solid organ transplants, lung transplant recipients experienced the highest rates of rehospitalization for transplant complications: 43.7 per 100 patients in year 1 and 36.0 in year 2.

Inflammation in Areas of Tubular Atrophy in Kidney Allograft Biopsies: A Potent Predictor of Allograft Failure

The Banff scoring schema provides a common ground to analyze kidney transplant biopsies. Interstitial inflammation (i) and tubulitis (t) in areas of viable tissue are features in scoring acute rejection, but are excluded in areas of tubular atrophy (TA). We studied inflammation and tubulitis in a cohort of kidney transplant recipients undergoing allograft biopsy for new‐onset late graft dysfunction (N = 337). We found inflammation (‘iatr’) and tubulitis (‘tatr’) in regions of fibrosis and atrophy to be strongly correlated with each other (p < 0.0001). Moreover, iatr was strongly associated with death‐censored graft failure when compared to recipients whose biopsies had no inflammation, even after adjusting for the presence of interstitial fibrosis (Hazard Ratio = 2.31, [1.10–4.83]; p = 0.0262) or TA (hazard ratio = 2.42, [1.16–5.08]; p = 0.191), serum creatinine at the time of biopsy, time to biopsy and i score. Further, these results did not qualitatively change after additional adjustments for C4d staining or donor specific antibody. Stepwise regression identified the most significant markers of graft failure which include iatr score. We propose that a more global assessment of inflammation in kidney allograft biopsies to include inflammation in atrophic areas may provide better prognostic information. Phenotypic characterization of these inflammatory cells and appropriate treatment may ameliorate late allograft failure.