Faculty Bibliography

RATIONALE AND OBJECTIVE/OBJECTIVE:Compared to recipients of ABO-compatible (ABOc) living donor kidney transplants (LDKT), recipients of ABO-incompatible (ABOi) LDKT have a higher risk of graft loss, particularly in the first few weeks after transplantation. However, the decision to proceed with ABOi LDKT should be based on a comparison of the alternative: waiting for future ABOc LDKT (e.g, through kidney paired exchange) or for a deceased donor kidney transplant (DDKT). We sought to evaluate the patient survival difference between ABOi LDKT and waiting for an ABOc LDKT or an ABOc DDKT. STUDY DESIGN/METHODS:Retrospective cohort study of adults in the Scientific Registry of Transplant Recipients (SRTR) SETTING AND PARTICIPANTS: 808 ABOi LDKT recipients and 2423 matched controls from among 245,158 adult, first-time kidney-only waitlist registrants who did not receive an ABOi LDKT and who remained on the waitlist or received either an ABOc LDKT or an ABOc DDKT, 2002-2017 EXPOSURE: Receipt of ABOi LDKT OUTCOME: Death ANALYTICAL APPROACH: We compared mortality among ABOi LDKT recipients versus a weighted matched comparison population using Cox proportional hazards regression as well as Cox models that accommodated for changing hazards ratios over time. RESULTS:Compared to matched controls, ABOi LDKT was associated with lower survival risk in the first 30 days post-transplant (99.0% vs 99.6%, respectively), but higher survival risk beyond 180 days post-transplant. Patients who received ABOi LDKT had higher survival at 5 and 10 years (90.0% and 75.4% respectively) than similar patients who remained on the waitlist or received ABOc LDKT or ABOc DDKT (81.9% and 68.4% respectively). LIMITATIONS/CONCLUSIONS:No measurement of ABO antibody titers in recipients; eligibility of participants for kidney paired donation is unknown. CONCLUSIONS:Transplant candidates who receive an ABOi LDKT and survive more than 180 days post-transplant experience a long-term survival benefit compared to remaining on the waitlist to potentially receive an ABO compatible kidney transplant.

BACKGROUND:Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. METHODS:We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. RESULTS:Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. CONCLUSIONS:In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

In March 2020, COVID-19 infections began to rise exponentially in the United States, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the United States compared to the same time the previous year. We saw an initial decrease in DDKT and LDKT by 47% and 82% compared to expected events and then a continual increase, with numbers reaching expected pre-pandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR _0.49 0.65 _0.85 ) and LDKT (IRR _0.17 0.38 _0.84 ) _{in states with high vs low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar cPRA, waitlist time and cause of ESRD as before the pandemic. The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the United States, but has not had a sustained effect.}

BACKGROUND:HIV-infected (HIV+) donor to HIV+ recipient (HIV D+/R+) transplantation might improve access to transplantation for people living with HIV. However, it remains unknown whether transplant candidates living with HIV will accept the currently unknown risks of HIV D+/R+ transplantation. METHODS:We surveyed transplant candidates living with HIV from 9 US transplant centers regarding willingness to accept HIV+ donor organs. RESULTS:Among 116 participants, the median age was 55 years, 68% were men, and 78% were African American. Most were willing to accept HIV+ living donor organs (87%), HIV+ deceased donor organs (84%), and increased infectious risk donor organs (70%). Some (30%) were concerned about HIV superinfection; even among these respondents, 71% were willing to accept an HIV D+ organ. Respondents from centers that had already performed a transplant under an HIV D+/R+ transplantation research protocol were more willing to accept HIV+ deceased donor organs (89% vs. 71%, P = 0.04). Respondents who chose not to enroll in an HIV D+/R+ transplantation research protocol were less likely to believe that HIV D+/R+ transplantation was safe (45% vs. 77%, P = 0.02), and that HIV D+ organs would work similar to HIV D- organs (55% vs. 77%, P = 0.04), but more likely to believe they would receive an infection other than HIV from an HIV D+ organ (64% vs. 13%, P < 0.01). CONCLUSIONS:Willingness to accept HIV D+ organs among transplant candidates living with HIV does not seem to be a major barrier to HIV D+/R+ transplantation and may increase with growing HIV D+/R+ transplantation experience.

Simple (Bosniak I) renal cysts are considered acceptable in living kidney donor selection in terms of cancer risk. However, they tend to increase in number and size over time and might compromise renal function in donors. To clarify their implications for long-term renal function, we characterized the prevalence of renal cysts in 454 individuals who donated at our center from 2000 to 2007. We estimated the association between the presence of cysts in the kidney remaining after nephrectomy (ie, retained cysts) and postdonation eGFR trajectory using mixed-effects linear regression. Donors with retained cysts (N = 86) were older (P < .001) and had slightly lower predonation eGFR (median 94 vs 98 mL/min/1.73 m² , P < .01) than those without cysts. Over a median 7.8 years, donors with retained cysts had lower baseline eGFR (_-8.7 -5.6 _-2.3  mL/min/1.73 m² , P < .01) but similar yearly change in eGFR (_-0.4 0.02 _0.4  mL/min/1.73 m² , P = .2) compared to those without retained cysts. Adjusting for predonation characteristics, there was no difference in baseline eGFR (P = .6) or yearly change in eGFR (P > .9). There continued to be no evidence of an association when we considered retained cyst(s) ≥10 mm or multiple retained cysts (all P > .05). These findings reaffirm current practices of accepting candidates with simple renal cysts for donor nephrectomy.

The outcomes of benzodiazepine and opioid co-prescription are not well-defined in transplant populations. We examined linked national transplant registry and pharmaceutical records to characterize benzodiazepine and opioid use in the years before and after transplant in large US cohort of kidney transplant recipients (2007-2016; N = 98 620), and associations (adjusted hazard ratio, _LCL aHR_UCL ) with death and graft failure. Among the cohort, 15.6% filled benzodiazepine prescriptions in the year before transplant, and 14.0% filled benzodiazepine prescriptions in the year after transplant (short-acting, 9.5%; long-acting, 3.3%; both 1.1%). Use of short-acting benzodiazepines in the year before transplant was associated with a 22% increased risk of death in the year after transplant (aHR, _1.08 1.22_1.38 ), while use of all classes in the year after transplant was associated with increased risk of death from >1 to 5 years (aHR: short-acting _1.29 1.39_1.48 ; long-acting _1.12 1.25_1.40 ; both _1.46 1.74_2.07 ). Recipients who used benzodiazepines were also more likely to fill opioid prescriptions. Recipients who filled both classes of benzodiazepine and the highest level of opioids had a 2.9-fold increased risk of death compared to recipients who did not use either. Co-prescription of benzodiazepines and opioids in kidney transplant recipients is associated with increased mortality. Ongoing research is needed to understand mechanisms of risk relationships.

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.

Prioritization of highly sensitized (HS) candidates under the kidney allocation system (KAS) and growth of large, multicenter kidney-paired donation (KPD) clearinghouses have broadened the transplant modalities available to HS candidates. To quantify temporal trends in utilization of these modalities, we used SRTR data from 2009 to 2017 to study 39 907 adult HS (cPRA ≥ 80%) waitlisted candidates and 19 003 recipients. We used competing risks regression to quantify temporal trends in likelihood of DDKT, KPD, and non-KPD LDKT for HS candidates (Era 1: January 1, 2009-December 31, 2011; Era 2: January 1, 2012-December 3, 2014; Era 3: December 4, 2014-December 31, 2017). Although the likelihood of DDKT and KPD increased over time for all HS candidates (adjusted subhazard ratio [aSHR] Era 3 vs 1 for DDKT: _1.74 1.85_1.97 , P < .001 and for KPD: _1.70 2.20_2.84 , P < .001), the likelihood of non-KPD LDKT decreased (aSHR: _0.69 0.82_0.97 , P = .02). However, these changes affected HS recipients differently based on cPRA. Among recipients, more cPRA 98%-99.9% and 99.9%+ recipients underwent DDKT (96.2% in Era 3% vs 59.1% in Era 1 for cPRA 99.9%+), whereas fewer underwent non-KPD LDKT (1.9% vs 30.9%) or KPD (2.0% vs 10.0%). Although KAS increased DDKT likelihood for the most HS candidates, it also decreased the use of non-KPD LDKT to transplant cPRA 98%+ candidates.

Stakeholders have expressed concerns regarding decreased deceased donor kidney transplant (DDKT) rates for pediatric candidates under the Kidney Allocation System (KAS). To better understand what might be driving this, we studied Scientific Registry of Transplant Recipients kidney offer data for 3642 pediatric (age <18 years) kidney-only transplant candidates between December 31, 2012 to December 3, 2014 (pre-KAS) and December 4, 2014 to January 6, 2017 (post-KAS). We used negative binomial regression and multilevel logistic regression to compare offer and acceptance rates pre- and post-KAS. We stratified by donor age (<18, 18-34, and 35+ years) and KDPI (<35% and ≥35%) to reflect differing allocation prioritization pre-KAS and post-KAS. As might be expected from prioritization changes, post-KAS candidates were less likely to receive offers for donors 18-34 years old with KDPI ≥ 35% (adjusted incidence rate ratio [aIRR]: _0.18 0.21_0.25 , P < .001), and more likely to receive offers for donors 18-34 years old and KDPI < 35% (aIRR: _1.12 1.20_1.29 , P < .001). However, offer acceptance practices also changed post-KAS: kidneys from donors 18-34 years old and KDPI < 35% were 23% less likely to be accepted post-KAS (adjusted odds ratio: _0.61 0.77_0.98 , P = .03). Using kidneys from donors 18-34 years old with KDPI < 35% post-KAS to the same extent they were used pre-KAS might be an effective strategy to mitigate any decrease in DDKT rates for pediatric candidates.

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.