Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities.

Background: Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities. Methods: We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death. Results: We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10). Conclusions: Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

Using Relative Survival to Estimate the Burden of Kidney Failure.

RATIONALE & OBJECTIVE: Estimates of mortality from kidney failure are misleading because the mortality from kidney failure is inseparable from the mortality attributed to comorbid conditions. We sought to develop an alternative method to reduce the bias in estimating mortality due to kidney failure using life table methods. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: Using data from the US Renal Data System and the Medicare 5% sample, we identified an incident cohort of patients, age 66+, who first had kidney failure in 2009 and a similar general population cohort without kidney failure. EXPOSURE: Kidney failure. OUTCOME: Death. ANALYTICAL APPROACH: We created comorbidity, age, sex, race, and year-specific life tables to estimate relative survival of patients with incident kidney failure and to attain an estimate of excess kidney failure-related deaths. Estimates were compared with those based on standard life tables (not adjusted for comorbidity). RESULTS: The analysis included 31,944 adults with kidney failure with a mean age of 77±7 years. The 5-year relative survival was 31% using standard life tables (adjusted for age, sex, race, and year) versus 36% using life tables also adjusted for comorbidities. Compared with other chronic diseases, patients with kidney failure have among the lowest relative survival. Patients with incident kidney failure ages 66-70 and 76-80 have a survival comparable to adults without kidney failure roughly 86-90 and 91-95 years old, respectively. LIMITATIONS: Relative survival estimates can be improved by narrowing the specificity of the covariates collected (eg, disease severity and ethnicity). CONCLUSIONS: Estimates of survival relative to a matched general population partition the mortality due to kidney failure from other causes of death. Results highlight the immense burden of kidney failure on mortality and the importance of disease prevention efforts among older adults. PLAIN-LANGUAGE SUMMARY: Estimates of death due to kidney failure can be misleading because death information from kidney failure is intertwined with death due to aging and other chronic diseases. Life tables are an old method, commonly used by actuaries and demographers to describe the life expectancy of a population. We developed life tables specific to a patient's age, sex, year, race, and comorbidity. Survival is derived from the life tables as the percentage of patients who are still alive in a specified period. By comparing survival of patients with kidney failure to the survival of people from the general population, we estimate that patients with kidney failure have one-third the chance of survival in 5 years compared with people with similar demographics and comorbidity but without kidney failure. The importance of this measure is that it provides a quantifiable estimate of the immense mortality burden of kidney failure.

Endovascular versus Surgical Lower Extremity Revascularization among Patients with Chronic Kidney Disease.

Introduction: Patients with chronic kidney disease (CKD) have a high prevalence of peripheral artery disease. How best to manage lower extremity peripheral artery disease remains unclear in this patient population. We therefore sought to compare the outcomes after endovascular versus surgical lower extremity revascularization among patients with CKD. Methods: We used data from Optum's de-identifed Clinformatics® Data Mart Database, a nationwide database of commercially insured persons in the United States to study patients with CKD who underwent lower extremity endovascular or surgical revascularization. We used inverse probability of treatment weighting to balance covariates. We employed proportional hazard regression to study the primary outcome of major adverse limb events (MALE), defined as a repeat revascularization or amputation. We also studied each of these events separately and death from any cause. Results: In our cohort, 60,057 patients underwent endovascular revascularization and 9,338 patients underwent surgical revascularization. Endovascular revascularization compared with surgical revascularization was associated with a higher adjusted hazard of MALE (hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.46-1.59). Endovascular revascularization was also associated with a higher adjusted hazard of repeat revascularization (HR 1.65; 95% CI 1.57-1.72) but a lower adjusted risk of amputation (HR 0.71; CI 0.73-0.89). Patients undergoing endovascular revascularization also had a lower adjusted hazard for death from any cause (0.85; CI 0.82-0.88). Conclusions: In this analysis of patients with CKD undergoing lower extremity revascularization, an endovascular approach was associated with a higher rate of repeated revascularization but a lower risk of subsequent amputation and death compared with surgical revascularization. Multiple factors must be considered when counseling patients with CKD, who have a high burden of comorbid conditions. Clinical trials should include more patients with kidney disease, who are often otherwise excluded from participation, to better understand the most effective treatment strategies for this vulnerable patient population.

Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes.

Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear. Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI). Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes. Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant. Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant. Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P < .001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%). Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

Serum testosterone concentrations and outcomes in hemodialysis patients enrolled in the EVOLVE trial.

BACKGROUND: Hypogonadism is common in end-stage kidney disease and may contribute to morbidity and mortality. METHODS: Using data from the randomized controlled Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial of cinacalcet, we analyzed the associations of total testosterone, free testosterone and sex hormone-binding globulin (SHBG) serum concentrations with mortality and major cardiovascular events in 1692 men and 1059 women receiving hemodialysis. We also describe the effect of cinacalcet treatment on serum concentrations of testosterone. RESULTS: Among men, lower serum free testosterone [odds ratio (OR) 0.18, 95% confidence interval (CI) 0.04-0.82, P = .026] and higher SHBG (OR 1.05 per 10 nmol/L, 95% CI 1.01-1.10, P = .012), but not total testosterone, were associated with higher risk of death or cardiovascular event. Only SHBG was associated with all-cause mortality (OR 1.07 per 10 nmol/L, 95% CI 1.02-1.12, P = .0073). Among women, neither total nor free testosterone, nor SHBG were associated with outcomes. We found no statistically significant effect of cinacalcet treatment on SHBG, free or total testosterone. CONCLUSIONS: Lower free testosterone and higher SHBG in serum are associated with higher risk of death or cardiovascular event in men undergoing chronic hemodialysis.

National Imaging Trends for Suspected Urinary Stone Disease in the Emergency Department.

This cohort study examines the use of an ultrasonography-first strategy for urinary stone disease.

Trends in Coronary Artery Disease Screening before Kidney Transplantation.

Background: Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. In this study we describe temporal trends in CAD screening before kidney transplant in the United States. Methods: Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis on the basis of whether the patient's comorbidity burden met guideline definitions of high risk for CAD. We examined temporal trends in nonurgent CAD tests within the year before transplant and the composite of death and nonfatal myocardial infarction in the 30 days after transplant. Results: Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one nonurgent CAD test in the 1 year before transplant. From 2000 to 2015, the transplant program waitlist volume had increased as transplant volume stayed constant, whereas patients in the later eras had a slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year before transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in patients who were high risk but remained constant in patients who were low risk after 2008. Death or nonfatal myocardial infarction within 30 days after transplant decreased from 3% in 2000 to 2% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout the examined time periods. Conclusions: CAD testing rates before kidney transplantation have remained constant from 2000 through 2015, despite widespread changes in cardiology guidelines and practice.

Karnofsky Performance Score-Failure to Thrive as a Frailty Proxy?

Among patients listed for kidney transplantation, the Karnofsky Performance Status (KPS) Scale has been used as a proxy for frailty and proposed as a predictor of long-term posttransplant outcomes. The KPS is required by the Organ Procurement and Transplantation Network for all transplants; however, the interrater reliability of KPS reporting in kidney transplant candidates has not been well investigated, and there is concern regarding limitations of using KPS that may influence transplant eligibility. METHODS: We performed an observational study using existing Scientific Registry of Transplant Recipients data from 2006 to 2020 to examine the variability, reliability, and trends in the KPS among patients on the kidney transplant waitlist. RESULTS: Our analysis included 8197 kidney transplant candidates with >1 KPS in a 3-mo period. We observed 2-7 scores per patient with an average score of 78.9 (SD = 12, 95% confidence interval, 78.8-79.1). We found substantial variability in KPS reporting, in which 27% of the patients had scores that varied widely with 20-80 points in difference. Interrater reliability in the 10-point scale was poor (30%). When using a condensed 4-category scale (disabled, requires assistance, capable of self-care, normal activity), 38% of patients experienced at least a 1-category shift in their score. CONCLUSIONS: The lack of reliability in KPS reporting raises concerns when applying the KPS as a proxy for frailty and a metric to be considered when evaluating candidacy for kidney transplantation.

Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates.

INTRODUCTION: Current screening algorithms for coronary artery disease (CAD) before kidney transplantation result in many tests but few interventions. OBJECTIVE: The aim of this study was to study the utility of 6-minute walk test (6MWT), an office-based test of cardiorespiratory fitness, for risk stratification in this setting. METHODS: We enrolled 360 patients who are near the top of the kidney transplant waitlist at our institution. All patients underwent CAD evaluation irrespective of 6MWT results. We examined the association between 6MWT and time to CAD-related events (defined as cardiac death, revascularization, nonfatal myocardial infarction, and removal from the waitlist for CAD), treating noncardiac death and waitlist removal for non-CAD reasons as competing events. RESULTS: The 6MWT-based approach designated approximately 45% of patients as "low risk," whereas a risk factor- or symptom-based approach designated 14 and 81% of patients as "low risk," respectively. The 6MWT-based approach was not significantly associated with CAD-related events within 1 year (subproportional hazard ratio [sHR] 1.00 [0.90-1.11] per 50 m) but was significantly associated with competing events (sHR 0.70 [0.66-0.75] per 50 m). In a companion analysis, removing waitlist status from consideration, 6MWT result was associated with the development of CAD-related events (sHR 0.92 [0.84-1.00] per 50 m). CONCLUSIONS: The 6MWT designates fewer patients as high risk and in need of further testing (compared to risk factor-based approaches), but its utility as a pure CAD risk stratification tool is modulated by the background waitlist removal rate. CAD screening before kidney transplant should be tailored according to a patient's actual chance of receiving a transplant.

And Then There Were Three: Effects of Pretransplant Dialysis on Multiorgan Transplantation.

BACKGROUND: Simultaneous liver-kidney (SLK) and simultaneous heart-kidney (SHK) transplantation currently utilize 6% of deceased donor kidneys in the United States. To what extent residual kidney function accounts for apparent kidney allograft survival is unknown. METHODS: We examined all adult SLK and SHK transplants in the United States during 1995-2014. We considered the duration of dialysis preceding SLK or SHK (≥90 d, 1-89 d, or none) as a proxy of residual kidney function. We used multinomial logistic regression to estimate the difference in the adjusted likelihood of 6- and 12-month apparent kidney allograft failure between the no dialysis versus ≥90 days dialysis groups. RESULTS: Of 4875 SLK and 848 SHK recipients, 1775 (36%) SLK and 449 (53%) SHK recipients received no dialysis before transplant. The likelihood of apparent kidney allograft failure was 1%-3% lower at 12 months in SLK and SHK recipients who did not require pretransplant dialysis relative to recipients who required ≥90 days of pretransplant dialysis. Among 3978 SLK recipients who survived to 1 year, no pretransplant dialysis was associated with a lower risk of apparent kidney allograft failure over a median follow-up of 5.7 years (adjusted hazard ratio 0.73 [0.55-0.96]). CONCLUSIONS: Patients with residual kidney function at the time of multiorgan transplantation are less likely to have apparent failure of the kidney allograft. Whether residual kidney function facilitates function of the allograft or whether some SLK and SHK recipients have 3 functional kidneys is unknown. Sustained kidney function after SLK and SHK transplants does not necessarily indicate successful MOT.

Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates.

Frailty is associated with adverse kidney transplant outcomes and can be assessed by subjective and objective metrics. There is increasing recognition of the value of metrics obtainable remotely. We compared the self-reported SF-36 physical functioning subscale score (SF-36 PF) with in-person physical performance tests (6-min walk and sit-to-stand) in a prospective cohort of kidney transplant candidates. We assessed each metric's ability to predict time to the composite outcome of waitlist removal or death, censoring at transplant. We built time-dependent receiver operating characteristic curves and calculated the area under the curve [AUC(t)] at 1 year, using bootstrapping for internal validation. In 199 patients followed for a median of 346 days, 41 reached the composite endpoint. Lower SF-36 PF scores were associated with higher risk of waitlist removal/death, with every 10-point decrease corresponding to a 16% increase in risk. All models showed an AUC(t) of 0.83-0.84 that did not contract substantially after internal validation. Among kidney transplant candidates, SF-36 PF, obtainable remotely, can help to stratify the risk of waitlist removal or death, and may be used as a screening tool for poor physical functioning in ongoing candidate evaluation, particularly where travel, increasing patient volume, or other restrictions challenge in-person assessment.

Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT).

SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.

Physical Performance Testing in Kidney Transplant Candidates at the Top of the Waitlist.

RATIONALE & OBJECTIVE: Frailty and poor physical function are associated with adverse kidney transplant outcomes, but how to incorporate this knowledge into clinical practice is uncertain. We studied the association between measured physical performance and clinical outcomes among patients on kidney transplant waitlists. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We studied consecutive patients evaluated in our Transplant Readiness Assessment Clinic, a top-of-the-waitlist management program, from May 2017 through December 2018 (N=305). We incorporated physical performance testing, including the 6-minute walk test (6MWT) and the sit-to-stand (STS) test, into routine clinical assessments. EXPOSURES: 6MWT and STS test results. OUTCOMES: The primary outcome was time to adverse waitlist outcomes (removal from waitlist or death); secondary outcomes were time to transplantation and time to death. ANALYTICAL APPROACH: We used linear regression to examine the relationship between clinical characteristics and physical performance test results. We used subdistribution hazards models to examine the association between physical performance test results and outcomes. RESULTS: Median 6MWT and STS results were 393 (IQR, 305-455) m and 17 (IQR, 12-21) repetitions, respectively. Clinical characteristics and Estimated Post-Transplant Survival scores accounted for only 14% to 21% of the variance in 6MWT/STS results. Physical performance test results were associated with adverse waitlist outcomes (adjusted subdistribution hazard ratio [sHR] of 1.42 [95% CI, 1.30-1.56] per 50-m lower 6MWT test result and 1.53 [95% CI, 1.33-1.75] per 5-repetition lower STS test result) and with transplantation (adjusted sHR of 0.80 [95% CI, 0.72-0.88] per 50-m lower 6MWT test result and 0.80 [95% CI, 0.71-0.89] per 5-repetition lower STS test result). Addition of either STS or 6MWT to survival models containing clinical characteristics enhanced fit (likelihood ratio test P<0.001). LIMITATIONS: Single-center observational study. Other measures of global health status (eg, Fried Frailty Index or Short Physical Performance Battery) were not examined. CONCLUSIONS: Among waitlisted kidney transplant candidates with high kidney allocation scores, standardized and easily performed physical performance test results are associated with waitlist outcomes and contain information beyond what is currently routinely collected in clinical practice.

Impact of Pretransplant Donor BK Viruria in Kidney Transplant Recipients.

BACKGROUND: BK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients. METHODS: We prospectively collected pretransplant plasma and urine samples from living and deceased kidney donors and performed BKV polymerase chain reaction (PCR) and immunoglobulin G (IgG) testing on pretransplant and serially collected posttransplant samples in kidney transplant recipients. RESULTS: Among deceased donors, 8.1% (17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4% (6/39) of living donors and 8.5% (4/47) of deceased donors of recipients at our institution (P = .50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6% vs 7.8%; P < .001) and viremia (66.6% vs 8.9%; P < .001) with a shorter time to onset (log-rank test, P < .001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pretransplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (P = .31, P = .75, and P = .51, respectively). CONCLUSIONS: Donor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at risk for BKV complications.

Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Trimethylamine N-oxide (TMAO), a compound derived from byproducts of intestinal bacteria, has been shown to accelerate atherosclerosis in rodents. To date, there are conflicting data regarding the association of serum TMAO with cardiovascular outcomes in patients with ESKD, a population exhibiting both high serum TMAO and excessive atherosclerosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured baseline serum TMAO concentrations in a subset of participants (n=1243) from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial and conducted post hoc analyses evaluating the association between baseline serum TMAO and cardiovascular outcomes. RESULTS: We observed a wide distribution of serum TMAO in our cohort, with approximately 80% of participants exhibiting TMAO concentrations ≥56 µM and a maximum TMAO concentration of 1103.1 µM. We found no association between TMAO and our primary outcome, a composite of cardiovascular mortality, myocardial infarction, peripheral vascular event, stroke, and hospitalization for unstable angina. Moreover, in unadjusted and adjusted analyses, we observed no relation between TMAO and all-cause mortality, the independent components of our composite outcome, or the original EVOLVE primary outcome. Although we did observe higher TMAO concentrations in white participants, further subgroup analyses did not confirm the previously identified interaction between TMAO and race observed in a prior study in patients receiving dialysis. CONCLUSIONS: We found no evidence linking TMAO to adverse clinical outcomes in patients receiving maintenance hemodialysis with moderate to severe secondary hyperparathyroidism.

Longitudinal changes in kidney function following heart transplantation: Stanford experience.

Many heart transplant recipients experience declining kidney function following transplantation. We aimed to quantify change in kidney function in heart transplant recipients stratified by pre-transplant kidney function. A total of 230 adult heart transplant recipients between May 1, 2008, and December 31, 2014, were evaluated for up to 5 years post-transplant (median 1 year). Using 19 398 total estimated glomerular filtration rate (eGFR) assessments, we evaluated trends in eGFR in recipients with normal/near-normal (eGFR ≥45 mL/min/1.73 m2 ) vs impaired (eGFR <45 mL/min/1.73 m2 ) kidney function and the likelihood of reaching an eGFR of 20 mL/min/1.73 m2 after heart transplant. Baseline characteristics were similar. Immediately following heart transplant, the impaired pre-transplant kidney function group showed a mean eGFR gain of 9.5 mL/min/1.73 m2 (n = 193) vs a mean decline of 4.9 mL/min/1.73 m2 (n = 37) in the normal/near-normal group. Subsequent rates of eGFR decline were 2.2 mL/min/1.73 m2 /y vs 2.9 mL/min/1.73 m2 /y, respectively. The probability of reaching an eGFR of 20 mL/min/1.73 m2 or less at 1, 5, and 10 years following heart transplant was 1%, 4%, and 30% in the impaired group, and <1%, <1%, and 10% in the normal/near-normal group. Estimates of expected recovery in kidney function and its decline over time will help inform decision making about kidney care after heart transplantation.

Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation.

BACKGROUND: Simultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice. METHODS: Using data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors. RESULTS: The adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21). CONCLUSIONS: SLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.

Adolescent and young adult cancer survival.

Adolescent and young adults (AYAs) face challenges in having their cancers recognized, diagnosed, treated, and monitored. Monitoring AYA cancer survival is of interest because of the lack of improvement in outcome previously documented for these patients as compared with younger and older patient outcomes. AYA patients 15-39 years old, diagnosed during 2000-2008 with malignant cancers were selected from the SEER 17 registries data. Selected cancers were analyzed for incidence and five-year relative survival by histology, stage, and receptor subtypes. Hazard ratios were estimated for cancer death risk among younger and older ages relative to the AYA group. AYA survival was worse for female breast cancer (regardless of estrogen receptor status), acute lymphoid leukemia (ALL), and acute myeloid leukemia (AML). AYA survival for AML was lowest for a subtype associated with a mutation of the nucleophosmin 1 gene (NPM1). AYA survival for breast cancer and leukemia remain poor as compared with younger and older survivors. Research is needed to address disparities and improve survival in this age group.

Current estimates of the cure fraction: a feasibility study of statistical cure for breast and colorectal cancer.

BACKGROUND: The probability of cure is a long-term prognostic measure of cancer survival. Estimates of the cure fraction, the proportion of patients "cured" of the disease, are based on extrapolating survival models beyond the range of data. The objective of this work is to evaluate the sensitivity of cure fraction estimates to model choice and study design. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER)-9 registries to construct a cohort of breast and colorectal cancer patients diagnosed from 1975 to 1985. In a sensitivity analysis, cure fraction estimates are compared from different study designs with short- and long-term follow-up. Methods tested include: cause-specific and relative survival, parametric mixture, and flexible models. In a separate analysis, estimates are projected for 2008 diagnoses using study designs including the full cohort (1975-2008 diagnoses) and restricted to recent diagnoses (1998-2008) with follow-up to 2009. RESULTS: We show that flexible models often provide higher estimates of the cure fraction compared to parametric mixture models. Log normal models generate lower estimates than Weibull parametric models. In general, 12 years is enough follow-up time to estimate the cure fraction for regional and distant stage colorectal cancer but not for breast cancer. 2008 colorectal cure projections show a 15% increase in the cure fraction since 1985. DISCUSSION: Estimates of the cure fraction are model and study design dependent. It is best to compare results from multiple models and examine model fit to determine the reliability of the estimate. Early-stage cancers are sensitive to survival type and follow-up time because of their longer survival. More flexible models are susceptible to slight fluctuations in the shape of the survival curve which can influence the stability of the estimate; however, stability may be improved by lengthening follow-up and restricting the cohort to reduce heterogeneity in the data.