BACKGROUND A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear. METHODS In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study. RESULTS Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded. CONCLUSIONS This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)

Systematic review/guideline, level III.

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti‐HLA donor‐specific antibody (DSA). Program‐specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15–2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71–6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28–3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98–7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal‐quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19‐, 1.33‐ and 1.73‐fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22‐, 4.09‐ and 10.72‐fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life‐saving treatment in jeopardy of regulatory intervention.

WHAT'S KNOWN ON THIS SUBJECT: Kidney transplantation is the optimal treatment of children with end-stage renal disease. The field of pediatric kidney transplantation has changed over time with regard to immunosuppression, surgical technique, organ allocation policy, and rates of living donor transplantation. WHAT THIS STUDY ADDS:Outcomes after pediatric kidney transplantation in the United States have improved over time, independent of changes in recipient, donor, and transplant characteristics. These improvements were most dramatic within the first posttransplant year and among the most highly sensitized patients. abstract OBJECTIVE: To investigate changes in pediatric kidney transplant outcomes over time and potential variations in these changes between the early and late posttransplant periods and across subgroups based on recipient, donor, and transplant characteristics. METHODS:Using multiple logistic regression and multivariable Cox models, graft and patient outcomes were analyzed in 17 446 pediatric kidneyonly transplants performed in the United States between 1987 and 2012.RESULTS: Ten-year patient and graft survival rates were 90.5% and 60.2%, respectively, after transplantation in 2001, compared with 77.6% and 46.8% after transplantation in 1987. Primary nonfunction and delayed graft function occurred in 3.3% and 5.3%, respectively, of transplants performed in 2011, compared with 15.4% and 19.7% of those performed in 1987. Adjusted for recipient, donor, and transplant characteristics, these improvements corresponded to a 5% decreased hazard of graft loss, 5% decreased hazard of death, 10% decreased odds of primary nonfunction, and 5% decreased odds of delayed graft function with each more recent year of transplantation. Graft survival improvements were lower in adolescent and female recipients, those receiving pretransplant dialysis, and those with focal segmental glomerulosclerosis. Patient survival improvements were higher in those with elevated peak panel reactive antibody. Both patient and graft survival improvements were most pronounced in the first posttransplant year. CONCLUSIONS:Outcomes after pediatric kidney transplantation have improved dramatically over time for all recipient subgroups, especially for highly sensitized recipients. Most improvement in graft and patient survival has come in the first year after transplantation, highlighting the need for continued progress in long-term outcomes. The field of pediatric KT has evolved over the past 25 years, including changes in immunosuppression, surgical technique, organ allocation policy, and rates of living donor transplantation. 4 However, the relationship between these changes and post-KT outcomes remains unclear, both in terms of which patient phenotypes have been affected and when any changes in outcomes have occurred (ie, early versus late post-KT).The objective of this study was to examine changes in pediatric KToutcomes over the last 25 years. In particular, our work sought to assess trends in graft survival, rates of primary nonfunct...

The first cohort of surgical interns to train under the new regulations report decreased continuity with patients, coordination of patient care, and time spent in the operating room. Furthermore, suboptimal quality of life, burnout, and thoughts of giving up surgery were common, even under the new paradigm of reduced work hours.

SummaryBackground and objective The risk of graft loss after pediatric kidney transplantation increases during late adolescence and early adulthood, but the extent to which this phenomenon affects all recipients is unknown. This study explored interactions between recipient factors and this high-risk age window, searching for a recipient phenotype that may be less susceptible during this detrimental age interval.Design, setting, participants, & measurements With use of Scientific Registry of Transplant Recipients data from 1987 to 2010, risk of graft loss across recipient age was quantified using a multivariable piecewise-constant hazard rate model with time-varying coefficients for recipient risk factors.Results Among 16,266 recipients, graft loss during ages $17 and ,24 years was greater than that for both 3-17 years (adjusted hazard ratio [aHR], 1.61; P,0.001) and $24 years (aHR, 1.28; P,0.001). This finding was consistent across age at transplantation, sex, race, cause of renal disease, insurance type, pretransplant dialysis history, previous transplant, peak panel-reactive antibody (PRA), and type of induction immunosuppression. The high-risk window was seen in both living-donor and deceased-donor transplant recipients, at all levels of HLA mismatch, regardless of centers' pediatric transplant volume, and consistently over time. The relationship between graft loss risk and donor type, PRA, transplant history, insurance type, and cause of renal disease was diminished upon entry into the high-risk window.Conclusions No recipient subgroups are exempt from the dramatic increase in graft loss during late adolescence and early adulthood, a high-risk window that modifies the relationship between typical recipient risk factors and graft loss.

These data suggest that for patients manifesting early severe AMR, splenectomy plus eculizumab may provide an effective intervention for rescuing and preserving allograft function.

BackgroundThe emergence of multi-drug resistant Gram-negatives (MDRGNs) coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion.MethodsRelevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models.ResultsFourteen randomized controlled trials (RCTs) were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37) or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06) compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws.ConclusionsNo clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed.