Components of Residential Neighborhood Deprivation and Their Impact on the Likelihood of Live-Donor and Preemptive Kidney Transplantation.

INTRODUCTION: Adults residing in deprived neighborhoods face various socioeconomic stressors, hindering their likelihood of receiving live-donor kidney transplantation (LDKT) and preemptive kidney transplantation (KT). We quantified the association between residential neighborhood deprivation index (NDI) and the likelihood of LDKT/preemptive KT, testing for a differential impact by race and ethnicity. METHODS: We studied 403 937 adults (age ≥ 18) KT candidates (national transplant registry; 2006-2021). NDI and its 10 components were averaged at the ZIP-code level. Cause-specific hazards models were used to quantify the adjusted hazard ratio (aHR) of LDKT and preemptive KT across tertiles of NDI and its 10 components. RESULTS: Candidates residing in high-deprivation neighborhoods were more likely to be female (40.1% vs. 36.2%) and Black (41.9% vs. 17.7%), and were less likely to receive both LDKT (aHR = 0.66, 95% confidence interval [CI]: 0.64-0.67) and preemptive KT (aHR = 0.60, 95% CI: 0.59-0.62) than those in low-deprivation neighborhoods. These associations differedby race and ethnicity (Black: aHRLDKT = 0.58, 95% CI: 0.55-0.62; aHRpreemptive KT = 0.68, 95% CI: 0.63-0.73; Pinteractions: LDKT < 0.001; Preemptive KT = 0.002). All deprivation components were associated with the likelihood of both LDKT and preemptive KT (except median home value): for example, higher median household income (LDKT: aHR = 1.08, 95% CI: 1.07-1.09; Preemptive KT: aHR = 1.10, 95% CI: 1.08-1.11) and educational attainments (≥high school [LDKT: aHR = 1.17, 95% CI: 1.15-1.18; Preemptive KT: aHR = 1.23, 95% CI: 1.21-1.25]). CONCLUSION: Residence in socioeconomically deprived neighborhoods is associated with a lower likelihood of LDKT and preemptive KT, differentially impacting minority candidates. Identifying and understanding which neighborhood-level socioeconomic status contributes to these racial disparities can be instrumental in tailoring interventions to achieve health equity in LDKT and preemptive KT.

Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease-a nationally representative study.

BACKGROUND: Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. METHODS: Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. RESULTS: Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. CONCLUSIONS: Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

Outcomes of Kidney Transplantation in Patients That Underwent Bariatric Surgery: A Systematic Review and Meta-analysis.

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes.

Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

Digital imaging software versus the "eyeball" method in quantifying steatosis in a liver biopsy.

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.

Characterizing the landscape and impact of infections following kidney transplantation.

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post-KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare-primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. The cumulative incidence of a post-KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five-year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5-year death-censored graft failure (DCGF) was 20.6% vs 10.1% (P < .001). This translated to a 2.22-fold higher mortality risk (adjusted hazard ratio [aHR]: 2.15 2.222.29 , P < .001) and 1.92-fold higher DCGF risk (aHR: 1.84 1.911.98 , P < .001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11-fold higher mortality risk for sepsis vs 1.62-fold for a UTI). Post-KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow-up to mitigate these risks.

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

Robotic Full Lobe Hepatectomy With Natural Orifice Extraction: Case Series Describing the Novel Technique of Robotic Major Hepatectomy and Transvaginal Specimen Extraction.

MINI-ABSTRACT: A minimally invasive approach to partial hepatectomy with transvaginal specimen extraction is safe and feasible with the potential to improve the cosmetic outcome, minimize postoperative narcotic utilization, and shorten hospital length of stay. This series describes the initial experience using this novel technique.

Survival benefit of accepting kidneys from older donation after cardiac death donors.

Kidneys from older (age ≥50 years) donation after cardiac death (DCD50) donors are less likely to be transplanted due to inferior posttransplant outcomes. However, candidates who decline a DCD50 offer must wait for an uncertain future offer. To characterize the survival benefit of accepting DCD50 kidneys, we used 2010-2018 Scientific Registry for Transplant Recipients (SRTR) data to identify 92 081 adult kidney transplantation candidates who were offered a DCD50 kidney that was eventually accepted for transplantation. DCD50 kidneys offered to candidates increased from 590 in 2010 to 1441 in 2018. However, 34.6% of DCD50 kidneys were discarded. Candidates who accepted DCD50 offers had 49% decreased mortality risk (adjusted hazard ratio [aHR] 0.46 0.510.55 , cumulative mortality at 6-year 23.3% vs 34.0%, P < .001) compared with those who declined the same offer (decliners). Six years after their initial DCD50 offer decline, 43.0% of decliners received a deceased donor kidney transplant (DDKT), 6.3% received living donor kidney transplant (LDKT), 22.6% died, 22.0% were removed for other reasons, and 6.0% were still on the waitlist. Comparable survival benefit was observed even with DCD donors age ≥60 (aHR: 0.42 0.520.65 , P < .001). Accepting DCD50 kidneys was associated with a substantial survival benefit; providers and patients should consider these benefits when evaluating offers.

Minimizing Risks of Liver Transplantation With Steatotic Donor Livers by Preferred Recipient Matching.

BACKGROUND: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts. METHODS: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression. RESULTS: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers. CONCLUSIONS: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

Outcomes After Declining a Steatotic Donor Liver for Liver Transplant Candidates in the United States.

BACKGROUND: Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer. METHODS: We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted). RESULTS: Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03). CONCLUSIONS: Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

Physical Impairment and Access to Kidney Transplantation.

BACKGROUND: The short physical performance battery (SPPB) test is an objective measurement of lower extremity function (walk speed, balance, chair stands). SPPB impairment is associated with longer length of stay and increased mortality in kidney transplant (KT) recipients. Furthermore, the SPPB test may represent an objective quantification of the "foot of the bed test" utilized by clinicians; therefore, impairment may translate with decreased access to KT. METHODS: We studied 3255 participants (2009-2018) at 2 KT centers. SPPB impairment was defined as a score of ≤10. We estimated time to listing, waitlist mortality, and transplant rate by SPPB impairment status using Cox proportional hazards, competing risks, and Poisson regression. RESULTS: The mean age was 54 years (SD = 14; range 18-89) and 54% had SPPB impairment. Impaired participants were less likely to be listed for KT (adjusted hazard ratio: 0.70, 95% CI: 0.64-0.77, P < 0.001). Also, once listed, impaired candidates had a 1.6-fold increased risk of waitlist mortality (adjusted subhazard ratio: 1.56, 95% CI: 1.18-2.06, P = 0.002). Furthermore, impaired candidates were transplanted 16% less frequently (adjusted incidence rate ratio: 0.84, 95% CI: 0.73-0.98, P = 0.02). CONCLUSIONS: SPPB impairment was highly prevalent in KT candidates. Impaired candidates had decreased chance of listing, increased risk of waitlist mortality, and decreased rate of KT. Identification of robust KT candidates and improvement in lower extremity function are potential ways to improve survival on the waitlist and access to KT.

Temporal trends in utilization and outcomes of steatotic donor livers in the United States.

Steatotic donor livers (SDLs) (macrosteatosis ≥30%) represent a possible donor pool expansion, but are frequently discarded due to a historical association with mortality and graft loss. However, changes in recipient/donor demographics, allocation policy, and clinical protocols might have altered utilization and outcomes of SDLs. We used Scientific Registry of Transplant Recipients data from 2005 to 2017 and adjusted multilevel regression to quantify temporal trends in discard rates (logistic) and posttransplant outcomes (Cox) of SDLs, accounting for Organ Procurement Organization-level variation. Of 4346 recovered SDLs, 58.0% were discarded in 2005, versus only 43.1% in 2017 (P < .001). SDLs were always substantially more likely discarded versus non-SDLs, although this difference decreased over time (adjusted odds ratio in 2005-2007:13.15 15.2817.74 ; 2008-2011:11.77 13.4115.29 ; 2012-2014:9.87 11.3713.10 ; 2015-2017:7.79 8.8910.15 , P < .001 for all). Conversely, posttransplant outcomes of recipients of SDLs improved over time: recipients of SDLs from 2012 to 2017 had 46% lower risk of mortality (adjusted hazard ratio [aHR]: 0.43 0.540.68 , P < .001) and 47% lower risk of graft loss (aHR: 0.42 0.530.67 , P < .001) compared to 2005 to 2011. In fact, in 2012 to 2017, recipients of SDLs had equivalent mortality (aHR: 0.90 1.041.21 , P = .6) and graft loss (aHR: 0.90 1.041.20 , P = .6) to recipients of non-SDLs. Increasing utilization of SDLs might be a reasonable strategy to expand the donor pool.

Early Developmental Exposure to Repetitive Long Duration of Midazolam Sedation Causes Behavioral and Synaptic Alterations in a Rodent Model of Neurodevelopment.

There is a large body of preclinical literature suggesting that exposure to general anesthetic agents during early life may have harmful effects on brain development. Patients in intensive care settings are often treated for prolonged periods with sedative medications, many of which have mechanisms of action that are similar to general anesthetics. Using in vivo studies of the mouse hippocampus and an in vitro rat cortical neuron model we asked whether there is evidence that repeated, long duration exposure to midazolam, a commonly used sedative in pediatric intensive care practice, has the potential to cause lasting harm to the developing brain. We found that mice that underwent midazolam sedation in early postnatal life exhibited deficits in the performance on Y-maze and fear-conditioning testing at young adult ages. Labeling with a nucleoside analog revealed a reduction in the rate of adult neurogenesis in the hippocampal dentate gyrus, a brain region that has been shown to be vulnerable to developmental anesthetic neurotoxicity. In addition, using immunohistochemistry for synaptic markers we found that the number of presynaptic terminals in the dentate gyrus was reduced, while the number of excitatory postsynaptic terminals was increased. These findings were replicated in a midazolam sedation exposure model in neurons in culture. We conclude that repeated, long duration exposure to midazolam during early development has the potential to result in persistent alterations in the structure and function of the brain.