Perioperative Considerations in Older Kidney and Liver Transplant Recipients: A Review.

With the growth of the older adult population, the number of older adults waitlisted for and undergoing kidney and liver transplantation has increased. Transplantation is an important and definitive treatment for this population. We present a contemporary review of the unique preoperative, intraoperative, and postoperative issues that patients older than 65 y face when they undergo kidney or liver transplantation. We focus on geriatric syndromes that are common in older patients listed for kidney or liver transplantation including frailty, sarcopenia, and cognitive dysfunction; discuss important considerations for older transplant recipients, which may impact preoperative risk stratification; and describe unique challenges in intraoperative and postoperative management for older patients. Intraoperative challenges in the older adult include using evidence-based best anesthetic practices, maintaining adequate perfusion pressure, and using minimally invasive surgical techniques. Postoperative concerns include controlling acute postoperative pain; preventing cardiovascular complications and delirium; optimizing immunosuppression; preventing perioperative kidney injury; and avoiding nephrotoxicity and rehabilitation. Future studies are needed throughout the perioperative period to identify interventions that will improve patients' preoperative physiologic status, prevent postoperative medical complications, and improve medical and patient-centered outcomes in this vulnerable patient population.

Safety and Efficacy of Drug Eluting Stents for Treatment of Transplant Renal Artery Stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) after renal transplantation is a common cause of graft dysfunction and failure. Endovascular intervention in the form of percutaneous transluminal angioplasty (PTA) and stenting has rapidly become the dominant treatment modality for the TRAS. There is a paucity of clinical data on the use of drug-eluting stent (DES) for TRAS. We investigated the outcomes of patients with clinically significant TRAS undergoing DES placement. METHODS: A retrospective review of patients with clinically significant TRAS undergoing PTA with DES placement from June 2014 to April 2021 was conducted. Patients treated for TRAS exhibited uncontrolled hypertension and/or unexplained allograft dysfunction. Patient demographics, procedural details, and follow-up outcomes were collected. Primary endpoints were the in-stent primary patency and graft survival. Secondary endpoints were freedom from reintervention, primary-assisted patency, and access-related complications. RESULTS: Thirteen TRAS in 12 patients with graft function alteration were treated with DES. The median age was 57 years (interquartile range (IQR), 48-63 years), and 9 (70%) patients were male. The median follow-up was 9 months (IQR, 4-52 months). The most common comorbidity was hypertension (100%), coronary artery disease (83%), and diabetes. The median time from deceased donor transplant to intervention was 5.8 months (IQR, 3.5-6.7 months). TRAS was most commonly found at the juxta-ostial segment (77%). The procedure was performed with carbon dioxide angiography with minimal amount of iodinated contrast (median, 3 mL) under local anesthesia in 9 (69%), and general anesthesia in 4 (31%) patients. The median stent diameter was 4.5 mm (IQR, 4-5 mm), and the median stent length was 15 mm (IQR, 15-18 mm). No intraoperative complications occurred. The rates of stenosis-free primary patency of the DES and graft survival were 76% and 100%, respectively. All 3 reinterventions for restenosis resulted from the kinking of the transplant renal artery proximal to the DES, which were treated by extending the stent more proximally 1-2 mm into the external iliac artery. There were no access-related complications. The median time to reintervention was 0.9 months (range, 0.23-2 months). Freedom from reintervention and primary-assisted patency were 76% and 100%, respectively. CONCLUSIONS: Our study demonstrates that DES is a safe and effective treatment modality in patients with TRAS at short to mid-term follow-up. As all reinterventions after DES were performed due to kinking of the transplant renal artery proximal to the stent, bridging of the DES 1-2 mm into the external iliac artery is recommended.

Clinical and Financial Implications of 2 Treatment Strategies for Donor-derived Hepatitis C Infections.

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays. METHODS: At our institution, 2 strategies for providing DAA therapy to HCV- recipients of HCV+ transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies. RESULTS: One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2-7] vs 10 [IQR, 8-13]; P < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12-29] vs 36 [IQR, 30-47]; P < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients. CONCLUSIONS: Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group.

Long term outcomes of patients transplanted for hepatocellular carcinoma with human immunodeficiency virus infection.

BACKGROUND: We aimed to study outcomes in HIV + patients with HCC in the US following Liver Transplantation (LT) using the UNOS dataset. METHODS: The database was queried from 2003 to 2016 for patients undergoing LT with HCC, HIV+, and HCC/HIV+. RESULTS: Out of 17,397 LT performed for HCC during the study period, 113 were transplanted for HCC with HIV infection (91 isolated livers). Patients transplanted for HCC/HIV+ were younger (55.54 ± 5.89 vs 58.80 ± 7.37, p < 0.001), had lower total bilirubin (1.20 vs 1.60, p = 0.042) significantly lower BMI (25.35 ± 4.43 vs 28.39 ± 5.17, p < 0.001) and were more likely to be co-infected with HBV (25.3% vs 8.2% p < 0.001) than those transplanted for HCC alone. HCC/HIV + patients were found to have a 3.8 fold increased risk of peri-operative mortality at 90 days after matching. HCC/HIV + recipients had 54% decreased long-term survival within the HCC cohort. Our initial analysis of overall graft and patient survival found significant differences between HCC/HIV and HCC/HIV + recipients. However, these variances were lost after case-matching. Recurrence and disease free survival were similar in HCC alone vs HCC/HIV + recipients. CONCLUSIONS: Our analysis suggests that excellent outcomes can be achieved in selected patients with HCC/HIV+.

Electronic messaging and communication with living kidney donors.

New regulations require living kidney donor (LKD) follow-up for 2 years, but donor retention remains poor. Electronic communication (eg, text messaging and e-mail) might improve donor retention. To explore the possible impact of electronic communication, we recruited LKDs to participate in an exploratory study of communication via telephone, e-mail, or text messaging postdonation; communication through this study was purely optional and did not replace standard follow-up. Of 69 LKDs recruited, 3% requested telephone call, 52% e-mail, and 45% text messaging. Telephone response rate was 0%; these LKDs were subsequently excluded from analysis. Overall response rates with e-mail or text messaging at 1 week, 1 month, 6 months, 1 year, and 2 years were 94%, 87%, 81%, 72%, and 72%. Lower response rates were seen in African Americans, even after adjusting for age, sex, and contact method (incidence rate ratio (IRR) nonresponse 2.07 5.8116.36 , P = .001). Text messaging had higher response rates than e-mail (IRR nonresponse 0.11 0.280.71 , P = .007). Rates of nonresponse were similar by sex (IRR 0.68, P = .4) and age (IRR 1.00, P > .9). In summary, LKDs strongly preferred electronic messaging over telephone and were highly responsive 2 years postdonation, even in this nonrequired, nonincentivized exploratory research study. These electronic communication tools can be automated and may improve regulatory compliance and postdonation care.

Socioeconomic factors as predictors of organ donation.

BACKGROUND: Despite numerous initiatives to increase solid organs for transplant, the gap between donors and recipients widens. There is little in the literature identifying socioeconomic predictors for donation. We evaluate the correlation between socioeconomic factors and familial authorization for donation. METHODS: A retrospective analysis of adult potential donor referrals between 2007 and 2012 to our organ procurement organization (OPO) was performed. Potential donor information was obtained from the OPO database, death certificates, and the US Census Report. Data on demographics, education, residence, income, registry status, cause and manner of death, as well as OPO assessments and approach for donation were collected. End point was familial authorization for donation. RESULTS: A total of 1059 potential donors were included, with an overall authorization rate of 47%. The majority was not on the donor registry (73%). Younger donors (18-39 y: odds ratio [OR] = 4.9, P < 0.001; 40-60 y: OR = 2.1, P < 0.001), higher levels of education (college: OR = 2.5, P = 0.005; graduate studies: OR = 3.9, P = 0.002), prior listing on the donor registry (OR = 10.3, P < 0.001), and residence in counties with lower poverty rates than the US rates (OR = 1.7, P = 0.02) were independently associated with higher authorization rates. Decoupling (OR = 3.1, P < 0.001) and donation first mentioned by the local health care provider (OR = 1.8, P = 0.01) were also independently associated with higher authorization rates. CONCLUSIONS: Donor registration correlated most strongly with the highest authorization rates. These results indicate that public educational efforts in populations with unfavorable socioeconomic considerations may be beneficial in improving donor registration. Collaborations with local providers as well as OPO in-hospital assessments and approach techniques can help with improving authorization rates.

Perioperative complications after live-donor hepatectomy.

Current studies of complications following donor hepatectomy may not be generalizable to all hospitals performing this procedure. To address this, live liver donors were identified in the Nationwide Inpatient Sample (2000-2008). Complications after donor hepatectomy were categorized using International Classification of Diseases, Ninth Revision codes and risk factors for complications were tested using logistic regression. Negative binomial regression models were used to estimate the increase in length of stay and hospital charge associated with complications. Among 555 donors (representing 2783 donors nationwide), 23% had 1 or more complications and 5% had a major complication. The most common complications were ileus (27%) and atelectasis (26%). No patient or hospital factors were associated with complications. Having any complication was associated with increased length of stay (incidence rate ratio, 1.36; 95% CI, 1.16-1.58; P < .001) and hospital charge (incidence rate ratio, 1.25; 95% CI, 1.09-1.44; P = .002). Approximately 25% of liver donors have complications immediately postoperatively but most are minor, lending support to current practices in live liver donation and donor selection.

Live donor champion: finding live kidney donors by separating the advocate from the patient.

BACKGROUND: Lack of education and reluctance to initiate a conversation about live donor kidney transplantation is a common barrier to finding a donor. Although transplant candidates are often hesitant to discuss their illness, friends or family members are often eager to spread awareness and are empowered by advocating for the candidates. We hypothesized that separating the advocate from the patient is important in identifying live donors. METHODS: We developed an intervention to train a live donor champion (LDC; a friend, family member, or community member willing to advocate for the candidate) for this advocacy role. We compared outcomes of 15 adult kidney transplant candidates who had no prospective donors and underwent the LDC intervention with 15 matched controls from our waiting list. RESULTS: Comfort in initiating a conversation about transplantation increased over time for LDCs. Twenty-five potential donors contacted our center on behalf of LDC participants; four participants achieved live donor kidney transplantation and three additional participants have donors in evaluation, compared with zero among matched controls (P < 0.001). CONCLUSIONS: Transplant candidates are ill equipped to seek live donors; by separating the advocate from the patient, understandable concerns about initiating conversations are reduced.

Outcomes of ABO-incompatible kidney transplantation in the United States.

BACKGROUND: ABO incompatible (ABOi) kidney transplantation is an important modality to facilitate living donor transplant for incompatible pairs. To date, reports of the outcomes from this practice in the United States have been limited to single-center studies. METHODS: Using the Scientific Registry of Transplant Recipients, we identified 738 patients who underwent live-donor ABOi kidney transplantation between January 1, 1995, and March 31, 2010. These were compared with matched controls that underwent ABO compatible live-donor kidney transplantation. Subgroup analyses among ABOi recipients were performed according to donor blood type, recipient blood type, and transplant center ABOi volume. RESULTS: When compared with ABO compatible-matched controls, long-term patient survival of ABOi recipients was not significantly different between the cohorts (P=0.2). However, graft loss was significantly higher, particularly in the first 14 days posttransplant (subhazard ratio, 2.34; 95% confidence interval, 1.43-3.84; P=0.001), with little to no difference beyond day 14 (subhazard ratio, 1.28; 95% confidence interval, 0.99-1.54; P=0.058). In subgroup analyses among ABOi recipients, no differences in survival were seen by donor blood type, recipient blood type, or transplant center ABOi volume. CONCLUSIONS: These results support the use and dissemination of ABOi transplantation when a compatible live donor is not available, but caution that the highest period of risk is immediately posttransplant.

Frailty and delayed graft function in kidney transplant recipients.

The ability to predict outcomes following a kidney transplant is limited by the complex physiologic decline of kidney failure, a latent factor that is difficult to capture using conventional comorbidity assessment. The frailty phenotype is a recently described inflammatory state of increased vulnerability to stressors resulting from decreased physiologic reserve and dysregulation of multiple physiologic systems. We hypothesized that frailty would be associated with delayed graft function, based on putative associations between inflammatory cytokines and graft dysfunction. We prospectively measured frailty in 183 kidney transplant recipients between December 2008 and April 2010. Independent associations between frailty and delayed graft function were analyzed using modified Poisson regression. Preoperative frailty was independently associated with a 1.94-fold increased risk for delayed graft function (95% CI, 1.13-3.36; P = .02). The assessment of frailty may provide further insights into the pathophysiology of allograft dysfunction and may improve our ability to preoperatively risk-stratify kidney transplant recipients.

Center-level factors and racial disparities in living donor kidney transplantation.

BACKGROUND: On average, African Americans attain living donor kidney transplantation (LDKT) at decreased rates compared with their non-African American counterparts. However, center-level variations in this disparity or the role of center-level factors is unknown. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 247,707 adults registered for first-time kidney transplants from 1995-2007 as reported by the Scientific Registry of Transplant Recipients. PREDICTORS: Patient-level factors (age, sex, body mass index, insurance status, education, blood type, and panel-reactive antibody level) were adjusted for in all models. The association of center-level characteristics (number of candidates, transplant volume, LDKT volume, median time to transplant, percentage of African American candidates, percentage of prelisted candidates, and percentage of LDKT) and degree of racial disparity in LDKT was quantified. OUTCOMES: Hierarchical multivariate logistic regression models were used to derive center-specific estimates of LDKT attainment in African American versus non-African American candidates. RESULTS: Racial parity was not seen at any of the 275 transplant centers in the United States. At centers with the least racial disparity, African Americans had 35% lower odds of receiving LDKT; at centers with the most disparity, African Americans had 76% lower odds. Higher percentages of African American candidates (interaction term, 0.86; P = 0.03) and prelisted candidates (interaction term, 0.80; P = 0.001) at a given center were associated with increased racial disparity at that center. Higher rates of LDKT (interaction term, 1.25; P < 0.001) were associated with less racial disparity. LIMITATIONS: Some patient-level factors are not captured, including a given patient's pool of potential donors. Geographic disparities in deceased donor availability might affect LDKT rates. Center-level policies and practices are not captured. CONCLUSIONS: Racial disparity in attainment of LDKT exists at every transplant center in the country. Centers with higher rates of LDKT attainment for all races had less disparity; these high-performing centers might provide insights into policies that might help address this disparity.

Living kidney donors ages 70 and older: recipient and donor outcomes.

BACKGROUND AND OBJECTIVES: The profound organ shortage has resulted in longer waiting times and increased mortality for those awaiting kidney transplantation. Consequently, patients are turning to older living donors. It is unclear if an upper age limit for donation should exist, both in terms of recipient and donor outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the United States, 219 healthy adults aged ≥70 have donated kidneys at 80 of 279 transplant centers. Competing risks models with matched controls were used to study the independent association between older donor age and allograft survival, accounting for the competing risk of recipient mortality as well as other transplant factors. RESULTS: Among recipients of older live donor allografts, graft loss was significantly higher than matched 50-to 59-year-old live donor allografts (subhazard ratio [SHR] 1.62, 95% confidence interval [CI] 1.16 to 2.28, P = 0.005) but similar to matched nonextended criteria 50-to 59-year-old deceased donor allografts (SHR 1.19, 95% CI 0.87 to 1.63, P = 0.3). Mortality among living kidney donors aged ≥70 was no higher than healthy matched controls drawn from the NHANES-III cohort; in fact, mortality was lower, probably reflecting higher selectivity among older live donors than could be captured in National Health and Nutrition Examination Survey III (NHANES-III; HR 0.37, 95% CI 0.21 to 0.65, P < 0.001). CONCLUSIONS: These findings support living donation among older adults but highlight the advantages of finding a younger donor, particularly for younger recipients.

Effect of eliminating priority points for HLA-B matching on racial disparities in kidney transplant rates.

BACKGROUND: African Americans have lower rates of obtaining a deceased donor kidney transplant (DDKT) compared with their white counterparts. One proposed mechanism is differential HLA distributions between African Americans and whites. In May 2003, the United Network for Organ Sharing/Organ Procurement and Transplantation Network changed kidney allocation policy to eliminate priority based on HLA-B matching in an effort to address this disparity. The objective of this study was to quantify the effect of the change in policy regarding priority points for HLA-B matching. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A cohort of 178,902 patients registered for a DDKT between January 2000 and August 2009. FACTORS: African Americans versus whites before and after the policy change. Cox models were adjusted for age, sex, diabetes, dialysis type, insurance status, education, panel-reactive antibody level, and blood type. OUTCOMES: Adjusted relative rates (aRRs) of deceased donor kidney transplant for African Americans compared with whites. MEASUREMENTS: Time from initial active wait listing to DDKT, censored for living donor kidney transplant and death. RESULTS: Before the policy change, African Americans had 37% lower rates of DDKT (aRR, 0.63; 95% CI, 0.60-0.65; P < 0.001). After the policy change, African Americans had 23% lower rates of DDKT (aRR, 0.77; 95% CI, 0.76-0.79; P < 0.001). There was a 23% reduction in the disparity between African Americans and whites after the policy change (interaction aRR, 1.23; 95% CI, 1.18-1.29; P < 0.001). LIMITATIONS: As an observational study, findings could have been affected by residual confounding or other changes in practice patterns. CONCLUSIONS: Racial disparity in rates of DDKT was decreased by the HLA-B policy change, but parity was not achieved. There are unaddressed factors in kidney allocation that lead to continued disparity on the kidney transplant waiting list.

Incompatible live-donor kidney transplantation in the United States: results of a national survey.

BACKGROUND AND OBJECTIVES: Use of incompatible kidney transplantation (IKT) is growing as a response to the organ shortage and the increase in sensitization among candidates. However, recent regulatory mandates possibly threaten IKT, and the potential effect of these mandates cannot be estimated because dissemination of this modality remains unknown. The goal of this study was to better understand practice patterns of IKT in the United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Directors from all 187 unique active adult kidney transplant programs were queried about transplantation across the following antibody barriers: positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); positive cytotoxic crossmatch (PCC); and ABO incompatible (ABOi). RESULTS: Responses from 125 centers represented 84% of the live-donor transplant volume in the United States. Barriers of PLNF, PFNC, PCC, and ABOi are being crossed in 70%, 51%, 18%, and 24%, respectively, of transplant centers that responded. Desensitization was performed in 58% of PLNF, 76% of PFNC, 100% of PCC, and 80% of ABOi using plasmapheresis and low-dose intravenous Ig (IVIg) in 71% to 83% and high-dose IVIg in 29% to 46%. CONCLUSIONS: A higher proportion of centers perform IKT than might be inferred from the literature. The rapid dissemination of these protocols despite adequate evidence of a clear advantage of IKT transplants argues for the creation of a national registry and randomized studies.

Metastasis suppressor genes: from gene identification to protein function and regulation.

In the past decade, findings from various disciplines of research have stimulated a reevaluation of fundamental concepts of the biology of metastasis. The convergence of two avenues of research has largely been responsible for this shift. First, clinical and experimental studies of specific steps of the metastatic cascade have shown that cancer cells often disseminate early in the natural history of disease and can persist at secondary sites for extended periods of time. These findings suggest that disseminated cells remain subject to growth regulation at distant sites as "dormant" single cells or microscopic metastases consisting of small numbers of cells. Second, complementary functional, biochemical, and signal transduction studies have identified a specific class of proteins that suppress the formation of overt metastases. These proteins are encoded by metastasis suppressor genes, which are operationally defined as genes that suppress in vivo metastasis without inhibiting primary tumor growth when expressed ectopically in metastatic cell lines. While metastasis suppressor proteins may affect many steps in metastatic development, recent evidence specifically implicates several of these proteins in the regulation of growth of disseminated cells at secondary sites. This review describes the evolving understanding of rate-limiting steps of metastatic growth, and the role of metastasis suppressor proteins in the regulation of these processes. We will give an overview of the studies of metastasis suppressor protein function, which have shifted our attention toward mechanisms of growth control at the secondary site (i.e., "metastatic colonization"). Emphasis is placed upon the complimentary research in the fields of metastasis and signal transduction that has identified signaling pathways controlling metastatic colonization. We also discuss the regulation of metastasis suppressor proteins and the potential biological and biochemical mechanisms responsible for their organ-type specificity. Finally, the implication of these emerging concepts on the development of therapeutic strategies will be presented.

Metastasis suppressor genes: signal transduction, cross-talk and the potential for modulating the behavior of metastatic cells.

In the past decade, research from various disciplines has stimulated a re-evaluation of our ideas of how cancers metastasize. Two important findings have been fundamental to this re-evaluation: that cancer cells are subject to growth regulation at the secondary site and that a specific class of proteins suppresses the metastatic phenotype. These proteins are encoded by metastasis suppressor genes, which are operationally defined as genes that suppress in vivo metastasis without inhibiting primary tumor growth when transfected into metastatic cell lines and injected into experimental animals. Recent biochemical studies have shown that certain metastasis suppressor proteins participate in highly conserved signal transduction cascades that mediate cellular responses to growth factors, cytokines and cellular stresses. Further elucidation of the biochemical foundations of these pathways coupled with strong in vivo studies should give us insight into the mechanisms of cancer metastasis, and may hold important implications for the future of cancer staging and therapy, using both existing and novel modalities.