Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors.

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count ≥500 cells/µL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates.

Changes in Utilization and Discard of Hepatitis C-Infected Donor Livers in the Recent Era.

The impact of interferon (IFN)-free direct-acting antiviral (DAA) hepatitis C virus (HCV) treatments on utilization and outcomes associated with HCV-positive deceased donor liver transplantation (DDLT) is largely unknown. Using the Scientific Registry of Transplant Recipients, we identified 25 566 HCV-positive DDLT recipients from 2005 to 2015 and compared practices according to the introduction of DAA therapies using modified Poisson regression. The proportion of HCV-positive recipients who received HCV-positive livers increased from 6.9% in 2010 to 16.9% in 2015. HCV-positive recipients were 61% more likely to receive an HCV-positive liver after 2010 (early DAA/IFN era) (aRR:1.45 1.611.79 , p < 0.001) and almost three times more likely to receive one after 2013 (IFN-free DAA era) (aRR:2.58 2.853.16 , p < 0.001). Compared to HCV-negative livers, HCV-positive livers were 3 times more likely to be discarded from 2005 to 2010 (aRR:2.69 2.993.34 , p < 0.001), 2.2 times more likely after 2010 (aRR:1.80 2.162.58 , p < 0.001) and 1.7 times more likely after 2013 (aRR:1.37 1.682.04 , p < 0.001). Donor HCV status was not associated with increased risk of all-cause graft loss (p = 0.1), and this did not change over time (p = 0.8). Use of HCV-positive livers has increased dramatically, coinciding with the advent of DAAs. However, the discard rate remains nearly double that of HCV-negative livers. Further optimization of HCV-positive liver utilization is necessary to improve access for all candidates.

Induction Immunosuppression and Clinical Outcomes in Kidney Transplant Recipients Infected With Human Immunodeficiency Virus.

There is an increased risk of acute rejection (AR) in human immunodeficiency virus-positive (HIV+) kidney transplant (KT) recipients. Induction immunosuppression is standard of care for those at high risk of AR; however, use in HIV+ patients is controversial, given fears of increased infection rates. We sought to compare clinical outcomes between HIV+ KT recipients who were treated with (i) anti-thymocyte globulin (ATG), (ii) IL-2 receptor blocker, and (iii) no induction. We studied 830 HIV+ KT recipients between 2000 and 2014, as captured in the Scientific Registry of Transplant Recipients, and compared rates of delayed graft function (DGF), AR, graft loss and death. Infections and hospitalizations were ascertained by International Classification of Diseases, Ninth Revision codes in a subset of 308 patients with Medicare. Compared with no induction, neither induction agent was associated with an increased risk of infection (weighted hazard ratio [wHR] 0.80, 95% confidence interval [CI] 0.55-1.18). HIV+ recipients who received induction spent fewer days in the hospital (weighted relative risk [wRR] 0.70, 95% CI 0.52-0.95), had lower rates of DGF (wRR 0.66, 95% CI 0.51-0.84), less graft loss (wHR 0.47, 95% CI 0.24-0.89) and a trend toward lower mortality (wHR 0.60, 95% CI 0.24-1.28). Those who received induction with ATG had lower rates of AR (wRR 0.59, 95% CI 0.35-0.99). Induction in HIV+ KT recipients was not associated with increased infections; in fact, those receiving ATG, the most potent agent, had the lowest rates. In light of the high risk of AR in this population, induction therapy should be strongly considered.

Early Hospital Readmission After Simultaneous Pancreas-Kidney Transplantation: Patient and Center-Level Factors.

Early hospital readmission is associated with increased morbidity, mortality, and cost. Following simultaneous pancreas-kidney transplantation, rates of readmission and risk factors for readmission are unknown. We used United States Renal Data System data to study 3643 adult primary first-time simultaneous pancreas-kidney recipients from December 1, 1999 to October 31, 2011. Early hospital readmission was any hospitalization within 30 days of discharge. Modified Poisson regression was used to determine the association between readmission and patient-level factors. Empirical Bayes statistics were used to determine the variation attributable to center-level factors. The incidence of readmission was 55.5%. Each decade increase in age was associated with an 11% lower risk of readmission to age 40, beyond which there was no association. Donor African-American race was associated with a 13% higher risk of readmission. Each day increase in length of stay was associated with a 2% higher risk of readmission until 14 days, beyond which each day increase was associated with a 1% reduction in the risk of readmission. Center-level factors were not associated with readmission. The high incidence of early hospital readmission following simultaneous pancreas-kidney transplant may reflect clinical complexity rather than poor quality of care.

Landscape of Deceased Donors Labeled Increased Risk for Disease Transmission Under New Guidelines.

Deceased donors are labeled increased risk for disease transmission (IRD) if they meet certain criteria. New PHS guidelines were recently implemented; the impact of these changes remains unknown. We aimed to quantify the impact of the new guidelines on the proportion of deceased donors labeled IRD, as well as demographic and clinical characteristics. We used Poisson regression with an interaction term for era (new vs. old guidelines) to quantify changes. Under the new guidelines, 19.5% donors were labeled IRD, compared to 10.4%, 12.2%, and 12.3% in the 3 most recent years under the old guidelines (IRR = 1.45, p < 0.001). Increases were consistent across OPOs: 44/59 had an increase in the percent of donors labeled IRD, and 14 OPOs labeled 25% of their donors IRD under the new guidelines (vs. 5 OPOs under the old). African-Americans were 52% more likely to be labeled IRD under the new guidelines (RR = 1.52, p = 0.01). There has been a substantial increase in donors labeled IRD under the new PHS guidelines; it is important to understand the mechanism and consequences to ensure an optimal balance of patient safety and organ utilization is achieved.

Big data in organ transplantation: registries and administrative claims.

The field of organ transplantation benefits from large, comprehensive, transplant-specific national data sets available to researchers. In addition to the widely used Organ Procurement and Transplantation Network (OPTN)-based registries (the United Network for Organ Sharing and Scientific Registry of Transplant Recipients data sets) and United States Renal Data System (USRDS) data sets, there are other publicly available national data sets, not specific to transplantation, which have historically been underutilized in the field of transplantation. Of particular interest are the Nationwide Inpatient Sample and State Inpatient Databases, produced by the Agency for Healthcare Research and Quality. The USRDS database provides extensive data relevant to studies of kidney transplantation. Linkage of publicly available data sets to external data sources such as private claims or pharmacy data provides further resources for registry-based research. Although these resources can transcend some limitations of OPTN-based registry data, they come with their own limitations, which must be understood to avoid biased inference. This review discusses different registry-based data sources available in the United States, as well as the proper design and conduct of registry-based research.

Identifying appropriate recipients for CDC infectious risk donor kidneys.

Over 10% of deceased donors in 2011 met PHS/CDC criteria for infectious risk donor (IRD), and discard rates are significantly higher for kidneys from these donors. We hypothesized that patient phenotypes exist for whom the survival benefit outweighs the infectious risk associated with IRDs. A patient-oriented Markov decision process model was developed and validated, based on SRTR data and meta-analyses of window period risks among persons with IRD behaviors. The Markov model allows patients to see, for their phenotype, their estimated survival after accepting versus declining an IRD offer, graphed over a 5-year horizon. Estimated 5-year survival differences associated with accepting IRDs ranged from -6.4% to +67.3% for a variety of patient phenotypes. Factors most predictive of the survival difference with IRD transplantation were age, PRA, previous transplant, and the expected time until the next non-IRD deceased donor offer. This study suggests that survival benefit derived from IRD kidneys varies widely by patient phenotype. Furthermore, within the inherent limitations of model-based prediction, this study demonstrates that it is possible to identify those predicted to benefit from IRD kidneys, and illustrates how estimated survival curves based on a clinical decision can be presented to better inform patient and provider decision-making.

Disparities in provision of transplant education by profit status of the dialysis center.

Kidney transplant education is associated with higher transplantation rates; however national policies regarding optimal timing and content of transplant education are lacking. We aimed to characterize nephrologists' attitudes regarding kidney transplant education, and to compare practices between nephrologists at for-profit and nonprofit centers. We surveyed 906 nephrologist practicing in the United States. Most respondents (81%) felt the ideal time to spend on transplant education was >20 min, but only 43% reported actually doing so. Spending >20 min was associated with covering more topics, having one-on-one and repeated conversations, involving families in discussions and initiating discussions at CKD-stage 4. Providers at for-profit centers were significantly less likely to spend >20 min (RR = 0.89, 95%CI: 0.80-0.99) or involve families (RR = 0.57, 95%CI: 0.38-0.87); they reported that fewer of their patients received transplant counseling (RR = 0.58, 95%CI: 0.37-0.96), initiated transplant discussions (RR = 0.58, 95%CI: 0.38-0.88), or were eligible for transplantation (RR = 0.45, 95%CI: 0.30-0.68). Of nephrologists who spent ≤20 min, those at for-profit centers more often cited lack of reimbursement as a reason (30.0% vs. 18.9%, p = 0.02). Disparities in quality of education at for-profit centers might partially explain previously documented disparities in access to transplantation for patients at these centers. National policies detailing the optimal timing and content of transplant education are needed to improve equity.

Disparities in provision of transplant information affect access to kidney transplantation.

Recently Centers for Medicare and Medicaid Services (CMS) began asking providers on Form-2728 whether they informed patients about transplantation, and if not, to select a reason. The goals of this study were to describe national transplant education practices and analyze associations between practices and access to transplantation (ATT), based on United States Renal Data System (USRDS) data from 2005 to 2007. Multinomial logistic regression was used to examine factors associated with not being informed about transplantation, and modified Poisson regression to examine associations between not being informed and ATT (all models adjusted for demographics/comorbidities). Of 236,079 incident end-stage renal disease (ESRD) patients, 30.1% were not informed at time of 2728 filing, for reasons reported by providers as follows: 42.1% unassessed, 30.4% medically unfit, 16.9% unsuitable due to age, 3.1% psychologically unfit and 1.5% declined counsel. Older, obese, uninsured, Medicaid-insured and patients at for-profit centers were more likely to be unassessed. Women were more likely to be reported as unsuitable due to age, medically unfit and declined, and African Americans as psychologically unfit. Uninformed patients had a 53% lower rate of ATT, a disparity persisting in the subgroup of uninformed patients who were unassessed. Disparities in ATT may be partially explained by disparities in provision of transplant information; dialysis centers should ensure this critical intervention is offered equitably.

Pregnancy outcomes in kidney transplant recipients: a systematic review and meta-analysis.

Approximately 50,000 women of reproductive age in the United States are currently living after kidney transplantation (KT), and another 2800 undergo KT each year. Although KT improves reproductive function in women with ESRD, studies of post-KT pregnancies are limited to a few voluntary registry analyses and numerous single-center reports. To obtain more generalizable inferences, we performed a systematic review and meta-analysis of articles published between 2000 and 2010 that reported pregnancy-related outcomes among KT recipients. Of 1343 unique studies, 50 met inclusion criteria, representing 4706 pregnancies in 3570 KT recipients. The overall post-KT live birth rate of 73.5% (95%CI 72.1-74.9) was higher than the general US population (66.7%); similarly, the overall post-KT miscarriage rate of 14.0% (95%CI 12.9-15.1) was lower (17.1%). However, complications of preeclampsia (27.0%, 95%CI 25.2-28.9), gestational diabetes (8.0%, 95%CI 6.7-9.4), Cesarean section (56.9%, 95%CI 54.9-58.9) and preterm delivery (45.6%, 95%CI 43.7-47.5) were higher than the general US population (3.8%, 3.9%, 31.9% and 12.5%, respectively). Pregnancy outcomes were more favorable in studies with lower mean maternal ages; obstetrical complications were higher in studies with shorter mean interval between KT and pregnancy. Although post-KT pregnancy is feasible, complications are relatively high and should be considered in patient counseling and clinical decision making.

Risk of window period HIV infection in high infectious risk donors: systematic review and meta-analysis.

The OPTN defines high risk donors (HRDs), colloquially known as 'CDC high risk donors', as those thought to carry an increased risk of HIV window period (WP) infection prior to serologic detectability. However, the true risk of such infection remains unknown. To quantify the risk of WP infection in each HRD behavior category, we performed a systematic review and meta-analysis of studies of HIV prevalence and incidence. Of 3476 abstracts reviewed, 27 eligible studies of HIV infection in HRD populations were identified. Pooled HIV incidence estimates were calculated for each category of HRD behavior and used to calculate the risk of WP HIV infection. Risks ranged from 0.09-12.1 per 10 000 donors based on WP for ELISA and 0.04-4.9 based on nucleic acid testing (NAT), with NAT reducing WP risk by over 50% in each category. Injection drug users had the greatest risk of WP infection (4.9 per 10 000 donors by NAT WP), followed by men who have sex with men (4.2:10 000), commercial sex workers (2.7:10 000), incarcerated donors (0.9:10 000), donors exposed to HIV through blood (0.6:10 000), donors engaging in high-risk sex (0.3:10 000) and hemophiliacs (0.035:10 000). These estimates can help inform patient and provider decision making regarding HRDs.

Risk of window period hepatitis-C infection in high infectious risk donors: systematic review and meta-analysis.

The OPTN classifies high infectious risk donors (HRDs) based on criteria originally intended to identify people at risk for HIV infection. These donors are sometimes referred to as 'CDC high risk donors' in reference to the CDC-published guidelines adopted by the OPTN. However, these guidelines are also being used to identify deceased donors at increased risk of window period (WP) hepatitis C virus (HCV) infection, although not designed for this purpose. The actual risk of WP HCV infection in HRDs is unknown. We performed a systematic review of 3476 abstracts and identified 37 eligible estimates of HCV incidence in HRD populations in the United States/Canada. Pooled HCV incidence was derived and used to estimate the risk of WP infection for each HRD category. Risks ranged from 0.26 to 300.6 per 10,000 donors based on WP for ELISA and 0.027 to 32.4 based on nucleic acid testing (NAT). Injection drug users were at highest risk (32.4 per 10,000 donors by NAT WP), followed by commercial sex workers and donors exhibiting high risk sexual behavior (12.3 per 10,000), men who have sex with men (3.5 per 10,000), incarcerated donors (0.8 per 10,000), donors exposed to HIV infected blood (0.4 per 10,000) and hemophiliacs (0.027 per 10,000). NAT reduced WP risk by approximately 10-fold in each category.

Underutilization of hepatitis C-positive kidneys for hepatitis C-positive recipients.

Hepatitis C-positive (HCV(+)) candidates likely derive survival benefit from transplantation with HCV(+) kidneys, yet evidence remains inconclusive. We hypothesized that lack of good survival benefit data has led to wide practice variation. Our goal was to characterize national utilization of HCV(+) kidneys for HCV(+) recipients, and to quantify the risks/benefits of this practice. Of 93,825 deceased donors between 1995 and 2009, HCV(+) kidneys were 2.60-times more likely to be discarded (p < 0.001). However, of 6830 HCV(+) recipients, only 29% received HCV(+) kidneys. Patients over 60 relative rate (RR 0.86), women (RR 0.73) and highly sensitized patients (RR 0.42) were less likely to receive HCV(+) kidneys, while African Americans (RR 1.56), diabetics (RR 1.29) and those at centers with long waiting times (RR 1.19) were more likely to receive them. HCV(+) recipients of HCV(+) kidneys waited 310 days less than the average waiting time at their center, and 395 days less than their counterparts at the same center who waited for HCV(-) kidneys, likely offsetting the slightly higher patient (HR 1.29) and graft loss (HR 1.18) associated with HCV(+) kidneys. A better understanding of the risks and benefits of transplanting HCV(+) recipients with HCV(+) kidneys will hopefully improve utilization of these kidneys in an evidence-based manner.

Impact of Medicare coverage on disparities in access to simultaneous pancreas and kidney transplantation.

In the setting of disparities in access to simultaneous pancreas and kidney transplantation (SPKT), Medicare coverage for this procedure was initiated July 1999. The impact of this change has not yet been studied. A national cohort of 22 190 type 1 diabetic candidates aged 18-55 for kidney transplantation (KT) alone or SPKT was analyzed. Before Medicare coverage, 57% of Caucasian, 36% of African American and 38% of Hispanic type 1 diabetics were registered for SPKT versus KT alone. After Medicare coverage, these proportions increased to 68%, 45% and 43%, respectively. The overall increase in SPKT registration rate was 27% (95% CI 1.16-1.38). As expected, the increase was more substantial in patients with Medicare primary insurance than those with private insurance (Relative Rate 1.18, 95% CI 1.09-1.28). However, racial disparities were unaffected by this policy change (African American vs. Caucasian: 0.97, 95% CI 0.87-1.09; Hispanic vs. Caucasian: 0.94, 95% CI 0.78-1.05). Even after Medicare coverage, African Americans and Hispanics had almost 30% lower SPKT registration rates than their Caucasian counterparts (95% CI 0.66-0.79 and 0.59-0.80, respectively). Medicare coverage for SPKT succeeded in increasing access for patients with Medicare, but did not affect the substantial racial disparities in access to this procedure.

Provider utilization of high-risk donor organs and nucleic acid testing: results of two national surveys.

Fears of infectious transmission from CDC high-risk donors (HRDs) remain a significant disincentive, and the potential for human immunodeficiency virus/hepatitis C virus (HIV/HCV) nucleic acid testing (NAT) to allay these fears remains unstudied. We hypothesized that NAT, which narrows the window period between infection and detectability compared to the standard ELISA, might lead to increased provider willingness to use HRDs. Between January and April 2008, we performed two national surveys: one of current NAT practice among organ procurement organizations (OPOs); a second of HRD use among transplant surgeons. Surgeons who reported accepting 10% or more offers for a given HRD behavior and organ type were classified as 'high utilizers' of that subgroup. We built hierarchical models to examine associations between OPO NAT performance and provider utilization. Providers who ranked medical risks of HIV or HCV as important disincentives to HRD use had significantly lower odds of being high utilizers (HIV odds ratio 0.22, HCV odds ratio 0.41, p < 0.005). Furthermore, both HIV and HCV NAT performance were associated with significantly higher odds of being high utilizers (HIV odds ratio 1.58, HCV 2.69, p < 0.005). The demonstrated associations between OPO NAT performance and high provider utilization of HRDs should be considered in the ongoing debate about NAT in transplantation.

Formal policies and special informed consent are associated with higher provider utilization of CDC high-risk donor organs.

A new United Network for Organ Sharing (UNOS) policy mandates special informed consent (SIC) before transplanting organs from donors classified by the Public Health Service/Center for Disease Control (PHS/CDC) as high-risk donors (HRDs); however, concerns remain that this policy may cause suboptimal organ utilization. Currently, consent and disclosure policy is determined by individual centers or surgeons; as such, little is known about current practices. The goals of this study were to quantify consent and disclosure practices for HRDs in the United States, identify factors associated with SIC use and analyze associations between SIC use and HRD organ utilization. We surveyed 422 transplant surgeons about their use of HRD organs and their associated consent and disclosure practices. In total, 52.7% of surgeons use SIC, but there is a high variation in use within centers, between centers and by donor behavior. A defined HRD policy at a transplant center is strongly associated with SIC use at that center (OR = 4.68, p < 0.001 by multivariate hierarchical logistic regression). SIC use is associated with higher utilization of HRD livers (OR 3.37), and a trend toward higher utilization of HRD kidneys (OR 1.74) and pancreata (OR 1.28). We believe our findings support a formalized national policy and suggest that this policy will not result in decreased utilization.

Viral nucleic acid testing (NAT) and OPO-level disposition of high-risk donor organs.

The use of Public Health Service/Centers for Disease Control and Prevention (PHS/CDC) high-risk donor (HRD) organs remains controversial, especially in light of a recent high-profile case of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission. Nucleic acid testing (NAT), while more expensive and time consuming, reduces infectious risk by shortening the period between infection and detectability. The purpose of this study was to characterize HRDs and disposition of their organs by organ procurement organization (OPO), to measure NAT practices by OPO and to examine associations between NAT practices and use of HRD organs. We analyzed 29 950 deceased donors (2574 HRDs) reported to UNOS since July 1, 2004 and May 8, 2008. We then surveyed all OPO clinical directors about their use of NAT, average time to receive NAT results, locations where NAT is performed and percentage of the time NAT results are available for allocation decisions. In total, 51.7% of OPOs always perform HIV NAT, while 24.1% never do. A similar pattern is seen for HCV NAT performance, while the majority (65.6%) never perform HBV NAT. AIDS prevalence in an OPO service area is not associated with NAT practice. OPOs that perform HIV NAT are less likely to export organs outside of their region. The wide variation of current practice and the possibility that NAT would improve organ utilization support consideration for a national policy.

Effect modification in liver allografts with prolonged cold ischemic time.

Although prolonged cold ischemia time (PCIT) is generally associated with worse outcomes following liver transplantation, evidence suggests that some recipients and some donors might be more sensitive to PCIT than others. The purpose of this study was to identify factors that predict a higher risk of graft loss after a transplant with PCIT when compared with a similar transplant with average CIT (ACIT). 14 637 recipients reported to United Network for Organ Sharing (UNOS) in the model for end-stage liver disease (MELD) era were studied by interaction term analysis in proportional hazards models. Recipient diabetes, obesity and donor African American (AA) ethnicity were found to significantly amplify the adverse effects of PCIT. Graft loss was 1.85-fold higher in diabetic or obese PCIT recipients compared with diabetic or obese ACIT recipients, (vs. 1.17 for the same comparison in non-diabetic non-obese recipients). Similarly, graft loss was 1.80-fold higher in AA PCIT donors compared with AA ACIT donors, (vs. 1.31 for the same comparison in non-AA donors). Other factors may also exist, but current clinical practices might already mitigate the risks from those factors. As such, we recommend expanding clinical practice to include our findings, but not abandoning current judgment based on factors already perceived to amplify the adverse effects of PCIT.