Kidney allograft offers: Predictors of turndown and the impact of late organ acceptance on allograft survival.

There is growing interest in understanding patterns of organ acceptance and reducing discard. Little is known about how donor factors, timing of procurement, and geographic location affect organ offer decisions. We performed a retrospective cohort study of 47 563 deceased donor kidney match-runs from 2007 to 2013. Several characteristics unrelated to allograft quality were independently associated with later acceptance in the match-run: Public Health Service increased-risk donor status (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 2.29-2.69), holiday or weekend procurement (aOR 1.11, 95% CI 1.07-1.16), shorter donor stature (aOR 1.53 for <150 cm vs reference >180 cm, 95% CI 1.28-1.94), and procurement in an area with higher intensity of market competition (aOR 1.71, 95% CI 1.62-1.78) and with the longest waiting times (aOR 1.41, 95% CI 1.34-1.49). Later acceptance in the match-run was associated with delayed graft function but not all-cause allograft failure (adjusted hazard ratio 1.01, 95% CI 0.96-1.07). Study limitations include a lack of match-run data for discarded organs and the possibility of sequence inaccuracies for some nonlocal matches. Interventions are needed to reduce turndowns of viable organs, especially when decisions are driven by infectious risk, weekend or holiday procurement, geography, or other donor characteristics unrelated to allograft quality.

Hemodialysis Clinic Social Networks, Sex Differences, and Renal Transplantation.

This study describes patient social networks within a new hemodialysis clinic and models the association between social network participation and kidney transplantation. Survey and observational data collected between August 2012 and February 2015 were used to observe the formation of a social network of 46 hemodialysis patients in a newly opened clinic. Thirty-two (70%) patients formed a social network, discussing health (59%) and transplantation (44%) with other patients. While transplant-eligible women participated in the network less often than men (56% vs. 90%, p = 0.02), women who participated discussed their health more often than men (90% vs. 45.5%, p = 0.02). Patients in the social network completed a median of two steps toward transplantation compared with a median of 0 for socially isolated patients (p = 0.003). Patients also completed more steps if network members were closely connected (ß = 2.23, 95% confidence interval [CI] 0.16-4.29, p = 0.03) and if network members themselves completed more steps (ß = 2.84, 95% CI 0.11-5.57, p = 0.04). The hemodialysis clinic patient social network had a net positive effect on completion of transplant steps, and patients who interacted with each other completed a similar number of steps.

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

Post-induction hypotension and early intraoperative hypotension associated with general anaesthesia.

BACKGROUND: We hypothesized that different phases of intraoperative hypotension should be differentiated because of different underlying causative mechanisms. We defined post-induction hypotension (PIH; i.e. arterial hypotension occurring during the first 20 min after anaesthesia induction) and early intraoperative hypotension (eIOH; i.e. arterial hypotension during the first 30 min of surgery). METHODS: In this retrospective study, we included 2037 adult patients who underwent general anaesthesia. Arterial hypotension was defined as a systolic arterial blood pressure (SAP) <90 mm Hg or a need for norepinephrine infusion at > 6 µg min -1 at least once during the phases of PIH and eIOH. Multivariate logistic regression analysis was used to test for association of clinical factors with PIH and eIOH. RESULTS: Independent variables significantly related to PIH were pre-induction SAP [odds ratio (OR) 0.97 (95% confidence interval 0.97-0.98)], age [OR 1.03 (1.02-1.04)], and emergency surgery [OR 1.75 (1.20-2.56); P <0.01 each]. Pre-induction SAP [OR 0.99 (0.98-0.99), P <0.01], age [OR 1.02 (1.02-1.03), P <0.01], emergency surgery [OR 1.83 (1.28-2.62), P <0.01], supplementary administration of spinal or epidural anaesthetic techniques [OR 3.57 (2.41-5.29), P <0.01], male sex [OR 1.41 (1.12-1.79), P <0.01], and ASA physical status IV [OR 2.18 (1.19-3.99), P =0.01] were significantly related to eIOH. CONCLUSIONS: We identified clinical factors associated with PIH and eIOH. The use of these factors to estimate the risk of PIH and eIOH might allow the avoidance or timely treatment of hypotensive episodes during general anaesthesia.

Assessing the Acceptability, Feasibility, and Effectiveness of a Tablet-Based Cervical Cancer Educational Intervention.

Cervical cancer is a common and deadly disease, especially in developing countries. We developed and implemented an interactive, tablet-based educational intervention to improve cervical cancer knowledge among women in rural Malawi. Chichewa-speaking adult women in six rural villages participated. Each woman took a pretest, participated in the lesson, and then took a posttest. The lesson included information on cervical cancer symptoms, causes, risk factors, prevention, and treatment. Over the 6-month study period, 243 women participated. Women ranged in age from 18 to 77 years. Only 15 % had education beyond primary school. Nearly half of participants (48 %) had heard of cervical cancer prior to viewing the lesson. For these women, the median number of correct responses on the pretest was 11 out of 20; after the lesson, they had a median of 18 correct responses (p < 0.001). After the intervention, 93 % of women indicated a desire for cervical cancer screening. Despite lack of familiarity with computers (96 %), most women (94 %) found the tablet easy to use. A tablet-based educational program was an effective, feasible, and acceptable strategy to disseminate cervical cancer information to women with low education in rural Malawi. This method may be appropriate to distribute health information about other health topics in low-resource settings.

The Ethics of Promoting Living Kidney Donation Using Nonargumentative Influence: Applications, Concerns, and Future Directions.

Recommendations from the 2014 Consensus Conference on Best Practices in Living Kidney Donation reflect increasing attention to overcoming barriers to donation as a means of expanding access to living donor kidney transplantation. "High priority" initiatives include empowering transplant candidates and their loved ones in their search for a living kidney donor. Transplant programs are assuming an unprecedented role as facilitators of patients' solicitation for donors, and nonprofits are promoting living kidney donation (LKD) in the community. New strategies to promote LKD incorporate "nonargumentative" forms of influence (i.e. approaches to shaping behavior that do not attempt to persuade through reason) such as appeals to emotion, messenger effects and social norms. These approaches have raised ethical concerns in other settings but have received little attention in the transplantation literature despite their increasing relevance. Previous work on using nonargumentative influence to shape patient behavior has highlighted implications for (1) the relationship between influencer and influenced and (2) patient autonomy. We argue that using nonargumentative influence to promote LKD is a promising strategy that can be compatible with ethical standards. We also outline potential concerns and solutions to be implemented in practice.

Donor Hemodynamics as a Predictor of Outcomes After Kidney Transplantation From Donors After Cardiac Death.

Donation after cardiac death is an important source of transplantable organs, but evidence suggests donor warm ischemia contributes to inferior outcomes. Attempts to predict recipient outcome using donor hemodynamic measurements have not yielded statistically significant results. We evaluated novel measures of donor hemodynamics as predictors of delayed graft function and graft failure in a cohort of 1050 kidneys from 566 donors. Hemodynamics were described using regression line slopes, areas under the curve, and time beyond thresholds for systolic blood pressure, oxygen saturation, and shock index (heart rate divided by systolic blood pressure). A logistic generalized estimation equation model showed that area under the curve for systolic blood pressure was predictive of delayed graft function (above median: odds ratio 1.42, 95% confidence interval [CI] 1.06-1.90). Multivariable Cox regression demonstrated that slope of oxygen saturation during the first 10 minutes after extubation was associated with graft failure (below median: hazard ratio 1.30, 95% CI 1.03-1.64), with 5-year graft survival of 70.0% (95%CI 64.5%-74.8%) for donors above the median versus 61.4% (95%CI 55.5%-66.7%) for those below the median. Among older donors, increased shock index slope was associated with increased hazard of graft failure. Validation of these findings is necessary to determine the utility of characterizing donor warm ischemia to predict recipient outcome.

Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function.

Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1, IL-18 and liver-type fatty acid-binding protein [L-FABP]) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6-mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1-h flow was inversely associated with DGF. Higher NGAL or L-FABP concentrations and increased resistance were inversely associated with 6-mo eGFR, whereas higher flow was associated with higher adjusted 6-mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated "undesirable" biomarker levels or HMP parameters experienced acceptable 6-mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality.

Development of a Donor-Centered Approach to Risk Assessment: Rebalancing Nonmaleficence and Autonomy.

Living kidney donors are often excluded from the shared decision making and patient-centered models that are advocated in medical practice. Thresholds for acceptable risk vary between transplant centers, and between clinicians and donors. Although donor selection committees commonly focus on medical risks, potential donors also consider nonmedical risks and burdens, which may alter their assessment of an acceptable level of medical risk. Thus, transplant centers may encounter ethical tensions between nonmaleficence and respect for donor autonomy. A donor-centered model of risk assessment and risk reconciliation would integrate the donor's values and preferences in a shared decision about their eligibility to donate. This paper argues for shifting to a donor-centered model of risk assessment, and presents a research agenda to facilitate the greater participation of donors in their own evaluation and approval processes.

Associations of deceased donor kidney injury with kidney discard and function after transplantation.

Deceased donor kidneys with acute kidney injury (AKI) are often discarded due to fear of poor outcomes. We performed a multicenter study to determine associations of AKI (increasing admission-to-terminal serum creatinine by AKI Network stages) with kidney discard, delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). In 1632 donors, kidney discard risk increased for AKI stages 1, 2 and 3 (compared to no AKI) with adjusted relative risks of 1.28 (1.08-1.52), 1.82 (1.45-2.30) and 2.74 (2.0-3.75), respectively. Adjusted relative risk for DGF also increased by donor AKI stage: 1.27 (1.09-1.49), 1.70 (1.37-2.12) and 2.25 (1.74-2.91), respectively. Six-month eGFR, however, was similar across AKI categories but was lower for recipients with DGF (48 [interquartile range: 31-61] vs. 58 [45-75] ml/min/1.73m(2) for no DGF, p < 0.001). There was significant favorable interaction between donor AKI and DGF such that 6-month eGFR was progressively better for DGF kidneys with increasing donor AKI (46 [29-60], 49 [32-64], 52 [36-59] and 58 [39-71] ml/min/1.73m(2) for no AKI, stage 1, 2 and 3, respectively; interaction p = 0.05). Donor AKI is associated with kidney discard and DGF, but given acceptable 6-month allograft function, clinicians should consider cautious expansion into this donor pool.

An Assessment of HIV-Infected Patients Dying in Care for Deceased Organ Donation in a United States Urban Center.

Organ transplantation is an acceptable option for human immunodeficiency virus (HIV)-infected patients with end-stage kidney or liver disease. With worse outcomes on the waitlist, HIV-infected patients may actually be disproportionately affected by the organ shortage in the United States. One potential solution is the use of HIV-infected deceased donors (HIVDD), recently legalized by the HIV Organ Policy Equity (HOPE) Act. This is the first analysis of patient-specific data from potential HIVDD, retrospectively examining charts of HIV-infected patients dying in care at six HIV clinics in Philadelphia, Pennsylvania from January 1, 2009 to June 30, 2014. Our data suggest that there are four to five potential HIVDD dying in Philadelphia annually who might yield two to three kidneys and three to five livers for transplant. Extrapolated nationally, this would approximate 356 potential HIVDD yielding 192 kidneys and 247 livers annually. However, several donor risk indices raise concerns about the quality of kidneys that could be recovered from HIVDD as a result of older donor age and comorbidities. On the other hand, livers from these potential HIVDD are of similar quality to HIV-negative donors dying locally, although there is a high prevalence of positive hepatitis C antibody.

What are the harms of refusing to allow living kidney donation? An expanded view of risks and benefits.

Recent Organ Procurement and Transplantation Network policies relating to living kidney donation (LKD)warrant renewed attention to the ethics of transplantation from living donors. These policies focus on risks related to potential donor evaluation, informed consent and follow-up. The ethical basis of living donation is a favorable risk/benefit ratio for the donor, but regulations and research have given less attention to the benefits of donation. Relatedly, the transplant field has also failed to consider potential harms from denying patients the opportunity to donate. These harms may be substantial in the setting of directed kidney donation to a spouse/partner, sibling or child.We argue that complete assessment of donor risks and benefits demands consideration of not only the risks and benefits of donation, but also those of refusing a donor. In contrast to the ever-expanding literature on risks of donation, there are no data describing outcomes for individuals who were turned down as kidney donors. We consider factors contributing to this omission in the transplant literature, argue that current regulations may perpetuate a narrow understanding of relevant risks and benefits in LKD, and identify areas for improvement in research and clinical practice.

Revisiting multi-organ transplantation in the setting of scarcity.

In the setting of organ scarcity, the ethics of multi-organ transplantation (MOT) deserve new examination. MOT offers substantial benefits to certain recipients, including avoiding serial surgeries. However, MOT candidates in the United States commonly receive priority for their nonprimary organ over many individuals who need that organ, which may undermine equity. The absence of standard criteria for MOT eligibility also enables large and unfair regional variation in MOT, such as simultaneous liver-kidney transplantation. Unfortunately, MOT may also undermine utility (optimal patient and graft survival) in circumstances where providing multiple organs to one person fails to achieve the greater collective benefit attained by providing transplants to multiple people. Policy reforms should include the adoption of minimal clinical criteria for MOT candidacy with the attendant goal of decreasing regional variation in MOT. In the future, these minimal criteria can be revised to accommodate new research about which patients derive the most benefit from MOT. Incentives to perform MOT should also be reduced, such as by including MOT outcomes in center-specific reports. These reforms run the risk that the transplant community could be perceived as abandoning MOT candidates, but offer an opportunity to align transplant practice and ethical principles.

Effect of dialysis initiation for preemptively listed candidates in the revised kidney allocation policy.

The new allocation policy for deceased donor kidneys in the United States is expected to begin in late 2014. As part of this policy, prioritization to the highest quality deceased donor kidneys is dependent on candidate's estimated posttransplant survival (EPTS) score. In particular, candidates with low (≤20%) EPTS (indicating better estimated survival) will have greater access to donor offers. We evaluated the effect of dialysis initiation on preemptively listed candidates' EPTS score. Using current estimates, approximately 10% (n = 19,406) of candidates placed on the waiting list between 2008 and 2013 were listed preemptively and would have qualified for top 20% status. These patients were more likely younger, female, Caucasian and nondiabetic compared to other candidates. Among nondiabetic preemptively listed candidates, dialysis initiation decreases EPTS score (indicating better estimated survival and higher allocation priority) for approximately 5 months. In contrast, diabetic patients' EPTS score significantly increases (approximately 6%) immediately upon dialysis initiation. Our results reveal a counterintuitive aberration in the EPTS formula, which is important for decision making regarding organ selection and timing of dialysis initiation in the new allocation system. Revision of the EPTS formula should be considered to address these findings and further understanding of the impact of the new allocation system on candidates' prognosis is important.

Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function.

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

Mortality and cardiovascular disease among older live kidney donors.

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation.

Eryngial (trans-2-dodecenal), a bioactive compound from Eryngium foetidum: its identification, chemical isolation, characterization and comparison with ivermectin in vitro.

Methanol-water (4:1, v/v) crude extracts (50 mg mL(-1)) of 25 Jamaican medicinal plants were screened in vitro for anthelmintic activity using infective third-stage larvae of Strongyloides stercoralis. The most effective extract was further chemically scrutinized to isolate and identify the source of the bioactivity, and the efficacy of this compound was compared with ivermectin. Eosin exclusion (0.1 mg mL(-1)) served as the indicator of mortality in all bioassays. A crude extract of Eryngium foetidum (Apiaceae) was significantly (Probit Analysis, P<0.05) more potent than the other plant extracts, taking 18.9 h to kill 50% (LT50) of the larvae. Further, the petrol extract of E. foetidum was significantly more effective (Probit Analysis, P<0.05) at killing the larvae (LT50, 4.7 h) than either its methanol-water or dichloromethane extract. The latter two effected less than 1% larval mortality after 120 h. With bioassay-driven column chromatography of the petrol extract, trans-2-dodecenal (eryngial) was identified and chemically isolated as the main anthelmintic compound in E. foetidum. There was a significant difference between the 24 h LD50 values (mm) of trans-2-dodecenal (0.461) and ivermectin (2.251) but there was none between the 48 h LD50 values (mm): trans-2-dodecenal (0.411) and ivermectin (0.499) in vitro.

Allowing HIV-positive organ donation: ethical, legal and operational considerations.

Case reports of kidney transplantation using HIV-positive (HIV+) donors in South Africa and advances in the clinical care of HIV+ transplant recipients have drawn attention to the legal prohibition of transplanting organs from HIV+ donors in the United States. For HIV+ transplant candidates, who face high barriers to transplant access, this prohibition violates beneficence by placing an unjustified limitation on the organ supply. However, transplanting HIV+ organs raises nonmaleficence concerns given limited data on recipient outcomes. Informed consent and careful monitoring of outcome data should mitigate these concerns, even in the rare circumstance when an HIV+ organ is intentionally transplanted into an HIV-negative recipient. For potential donors, the federal ban on transplanting HIV+ organs raises justice concerns. While in practice there are a number of medical criteria that preclude organ donation, only HIV+ status is singled out as a mandated exclusion to donation under the National Organ Transplant Act (NOTA). Operational objections could be addressed by adapting existing approaches used for organ donors with hepatitis. Center-specific outcomes should be adjusted for HIV donor and recipient status. In summary, transplant professionals should advocate for eliminating the ban on HIV+ organ donation and funding studies to determine outcomes after transplantation of these organs.

Early rehospitalization after kidney transplantation: assessing preventability and prognosis.

Early rehospitalization after kidney transplantation (KT) is common and may predict future adverse outcomes. Previous studies using claims data have been limited in identifying preventable rehospitalizations. We assembled a cohort of 753 adults at our institution undergoing KT from January 1, 2003 to December 31, 2007. Two physicians independently reviewed medical records of 237 patients (32%) with early rehospitalization and identified (1) primary reason for and (2) preventability of rehospitalization. Mortality and graft failure were ascertained through linkage to the Scientific Registry of Transplant Recipients. Leading reasons for rehospitalization included surgical complications (15%), rejection (14%), volume shifts (11%) and systemic and surgical wound infections (11% and 2.5%). Reviewer agreement on primary reason (85% of cases) was strong (kappa = 0.78). Only 19 rehospitalizations (8%) met preventability criteria. Using logistic regression, weekend discharge (odds ratio [OR] 1.59, p = 0.01), waitlist time (OR 1.10, p = 0.04) and longer initial length of stay (OR 1.42, p = 0.03) were associated with early rehospitalization. Using Cox regression, early rehospitalization was associated with mortality (hazard ratio [HR] 1.55; p = 0.03) but not graft loss (HR 1.33; p = 0.09). Early rehospitalization has diverse causes and presents challenges as a quality metric after KT. These results should be validated prospectively at multiple centers to identify vulnerable patients and modifiable processes-of-care.