Faculty Bibliography

BACKGROUND:Induction immunosuppression is a mainstay of rejection prevention after transplantation. Studies have suggested a connection between antibody induction agents and cancer development, potentially limiting important immunosuppression protocols. METHODS:We used a linkage of U.S. transplantation data and cancer registries to explore the relationship between induction and cancer after transplantation. A total of 111,857 kidney recipients (1987-2009) in the Transplant Cancer Match Study, which links the Scientific Registry for Transplant Recipients and U.S. Cancer Registries, were included. Poisson regression models were used to estimate adjusted incidence rate ratios (aIRR) of non-Hodgkin lymphoma (NHL) and other cancers with increased incidence after transplantation (lung, colorectal, kidney, and thyroid cancers, plus melanoma). RESULTS:Two thousand seven hundred sixty-three cancers of interest were identified. Muromonab-CD3 was associated with increased NHL (aIRR, 1.37; 95% CI, 1.06-1.76). Alemtuzumab was associated with increased NHL (aIRR, 1.79; 95% CI, 1.02-3.14), colorectal cancer (aIRR, 2.46; 95% CI, 1.03-5.91), and thyroid cancer (aIRR, 3.37; 95% CI, 1.55-7.33). Polyclonal induction was associated with increased melanoma (aIRR, 1.50; 95% CI, 1.06-2.14). CONCLUSION/CONCLUSIONS:Our findings highlight the relative safety with regard to cancer risk of the most common induction therapies, the need for surveillance of patients treated with alemtuzumab, and the possible role for increased melanoma screening for those patients treated with polyclonal anti-T-cell induction.

IMPORTANCE/OBJECTIVE:Based on evidence of survival benefit when initiating hemodialysis (HD) via arteriovenous fistula (AVF) or arteriovenous graft (AVG) vs hemodialysis catheter (HC), the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative published practice guidelines in 1997 recommending 50% or greater AVF rates in incident HD patients. A decade after, lapses exist and the impact on HD outcomes is uncertain. OBJECTIVE:To assess the achievement of the practice goals for incident vascular access and the effects on HD outcomes. DESIGN, SETTING, AND PARTICIPANTS/METHODS:This retrospective cohort study was conducted using the US Renal Data System. All patients with end-stage renal disease in the United States without prior renal replacement therapy who had incident vascular access for HD created between January 1, 2006, and December 31, 2010 (N = 510 000) were included. MAIN OUTCOMES AND MEASURES/METHODS:Incident vascular access use rates and mortality. Relative mortality was quantified using multivariable Cox proportional hazard models. Coarsened exact matching and propensity score-matching techniques were used to better account for confounding by indication. RESULTS:Of 510 000 patients included in this study, 82.6% initiated HD via HC, 14.0% via AVF, and 3.4% via AVG. Arteriovenous fistula use increased only minimally, from 12.2% in 2006 to 15.0% in 2010. Patients initiating HD with AVF had 35% lower mortality than those with HC (adjusted hazard ratio, 0.65; 95% CI, 0.64-0.66; P < .001). Those initiating HD with AVF had 23% lower mortality than those initiating with an HC while awaiting maturation of an AVF (adjusted hazard ratio, 0.77; 95% CI, 0.76-0.79; P < .001). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Current incident AVF practice falls exceedingly short years after recommendations were made in 1997. The impact of this shortcoming on mortality for patients with end-stage renal disease is enormous. Functioning permanent access at initiation of HD confers lower mortality even compared with patients temporized with an HC while awaiting maturation of permanent access. A change of current policies and structured multidisciplinary efforts are required to establish matured fistulae prior to HD to ameliorate this deficit in delivering care.

Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly.

BACKGROUND:Frailty, a validated measure of physiologic reserve, predicts adverse health outcomes among adults with end-stage renal disease. Frailty typically is not measured clinically; instead, a surrogate-perceived frailty-is used to inform clinical decision-making. Because correlations between perceived and measured frailty remain unknown, the aim of this study was to assess their relationship. METHODS:146 adults undergoing hemodialysis were recruited from a single dialysis center in Baltimore, Maryland. Patient characteristics associated with perceived (reported by nephrologists, nurse practitioners (NPs), or patients) or measured frailty (using the Fried criteria) were identified using ordered logistic regression. The relationship between perceived and measured frailty was assessed using percent agreement, kappa statistic, Pearson's correlation coefficient, and prevalence of misclassification of frailty. Patient characteristics associated with misclassification were determined using Fisher's exact tests, t-tests, or median tests. RESULTS:Older age (adjusted OR [aOR] = 1.36, 95%CI:1.11-1.68, P = 0.003 per 5-years older) and comorbidity (aOR = 1.49, 95%CI:1.27-1.75, P < 0.001 per additional comorbidity) were associated with greater likelihood of nephrologist-perceived frailty. Being non-African American was associated with greater likelihood of NP- (aOR = 5.51, 95%CI:3.21-9.48, P = 0.003) and patient- (aOR = 4.20, 95%CI:1.61-10.9, P = 0.003) perceived frailty. Percent agreement between perceived and measured frailty was poor (nephrologist, NP, and patient: 64.1%, 67.0%, and 55.5%). Among non-frail participants, 34.4%, 30.0%, and 31.6% were perceived as frail by a nephrologist, NP, or themselves. Older adults (P < 0.001) were more likely to be misclassified as frail by a nephrologist; women (P = 0.04) and non-African Americans (P = 0.02) were more likely to be misclassified by an NP. Neither age, sex, nor race was associated with patient misclassification. CONCLUSIONS:Perceived frailty is an inadequate proxy for measured frailty among patients undergoing hemodialysis.

BACKGROUND:Disparities in access to kidney transplantation (KT) remain inadequately understood and addressed. Detailed descriptions of patient attitudes may provide insight into mechanisms of disparity. The aims of this study were to explore perceptions of dialysis and KT among African American adults undergoing hemodialysis, with particular attention to age- and sex-specific concerns. METHODS:Qualitative data on experiences with hemodialysis and views about KT were collected through four age- and sex-stratified (males <65, males ≥65, females <65, and females ≥65 years) focus group discussions with 36 African American adults recruited from seven urban dialysis centers in Baltimore, Maryland. RESULTS:Four themes emerged from thematic content analysis: 1) current health and perceptions of dialysis, 2) support while undergoing dialysis, 3) interactions with medical professionals, and 4) concerns about KT. Females and older males tended to be more positive about dialysis experiences. Younger males expressed a lack of support from friends and family. All participants shared feelings of being treated poorly by medical professionals and lacking information about renal disease and treatment options. Common concerns about pursuing KT were increased medication burden, fear of surgery, fear of organ rejection, and older age (among older participants). CONCLUSIONS:These perceptions may contribute to disparities in access to KT, motivating granular studies based on the themes identified.

BACKGROUND:Mycophenolate mofetil (MMF) side effects often prompt dose reduction or discontinuation, and this MMF dose reduction (MDR) can lead to rejection and possibly graft loss. Unfortunately, little is known about what factors might cause or contribute to MDR. Frailty, a measure of physiologic reserve, is emerging as an important, novel domain of risk in kidney transplantation recipients. We hypothesized that frailty, an inflammatory phenotype, might be associated with MDR. METHODS:We measured frailty (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed), other patient and donor characteristics, longitudinal MMF doses, and graft loss in 525 kidney transplantation recipients. Time-to-MDR was quantified using an adjusted Cox proportional hazards model. RESULTS:By 2 years after transplantation, 54% of frail recipients and 45% of nonfrail recipients experienced MDR; by 4 years, incidence was 67% and 51%. Frail recipients were 1.29 times (95% confidence interval [95% CI], 1.01-1.66; P = 0.04) more likely to experience MDR, as were deceased donor recipients (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.44-2.54, P < 0.001) and older adults (age ≥ 65 vs <65; aHR, 1.47; 95% CI, 1.10-1.96, P = 0.01). Mycophenolate mofetil dose reduction was independently associated with a substantially increased risk of death-censored graft loss (aHR, 5.24; 95% CI, 1.97-13.98, P = 0.001). CONCLUSION/CONCLUSIONS:A better understanding of risk factors for MMF intolerance might help in planning alternate strategies to maintain adequate immunosuppression and prolong allograft survival.

There is significant variability amongst transplant centers, Organ Procurement Organizations (OPO), members of public, and patients about organs from Public Health Service increased risk donors. This has therefore required regulatory bodies like Centers for Disease Control and Prevention to formulate policies for transplant centers and OPOs to minimize risk of infectious transmission to recipients of solid-organ transplants from such donors.

In June 2013, a change to the liver waitlist priority algorithm was implemented. Under Share 35, regional candidates with MELD ≥ 35 receive higher priority than local candidates with MELD < 35. We compared liver distribution and mortality in the first 12 months of Share 35 to an equivalent time period before. Under Share 35, new listings with MELD ≥ 35 increased slightly from 752 (9.2% of listings) to 820 (9.7%, p = 0.3), but the proportion of deceased-donor liver transplants (DDLTs) allocated to recipients with MELD ≥ 35 increased from 23.1% to 30.1% (p < 0.001). The proportion of regional shares increased from 18.9% to 30.4% (p < 0.001). Sharing of exports was less clustered among a handful of centers (Gini coefficient decreased from 0.49 to 0.34), but there was no evidence of change in CIT (p = 0.8). Total adult DDLT volume increased from 4133 to 4369, and adjusted odds of discard decreased by 14% (p = 0.03). Waitlist mortality decreased by 30% among patients with baseline MELD > 30 (SHR = 0.70, p < 0.001) with no change for patients with lower baseline MELD (p = 0.9). Posttransplant length-of-stay (p = 0.2) and posttransplant mortality (p = 0.9) remained unchanged. In the first 12 months, Share 35 was associated with more transplants, fewer discards, and lower waitlist mortality, but not at the expense of CIT or early posttransplant outcomes.

Whether the liver allocation system shifts organs from better performing organ procurement organizations (OPOs) to poorer performing OPOs has been debated for many years. Models of OPO performance from the Scientific Registry of Transplant Recipients make it possible to study this question in a data-driven manner. We investigated whether each OPO's net liver import was correlated with 2 performance metrics [observed to expected (O:E) liver yield and liver donor conversion ratio] as well as 2 alternative explanations [eligible deaths and incident listings above a Model for End-Stage Liver Disease (MELD) score of 15]. We found no evidence to support the hypothesis that the allocation system transfers livers from better performing OPOs to centers with poorer performing OPOs. Also, having fewer eligible deaths was not associated with a net import. However, having more incident listings was strongly correlated with the net import, both before and after Share 35. Most importantly, the magnitude of the variation in OPO performance was much lower than the variation in demand: although the poorest performing OPOs differed from the best ones by less than 2-fold in the O:E liver yield, incident listings above a MELD score of 15 varied nearly 14-fold. Although it is imperative that all OPOs achieve the best possible results, the flow of livers is not explained by OPO performance metrics, and instead, it appears to be strongly related to differences in demand.