Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.

The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.

Fracture Risk Among Living Kidney Donors 25 Years After Donation.

Importance: Living kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone. Objective: To compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so. Design, Setting, and Participants: This survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023. Exposure: Living kidney donation. Main Outcomes and Measures: The rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs). Results: At the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83). Conclusions and Relevance: This survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.

Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation.

Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

Transportability of causal inference under random dynamic treatment regimes for kidney-pancreas transplantation.

A difficult decision for patients in need of kidney-pancreas transplant is whether to seek a living kidney donor or wait to receive both organs from one deceased donor. The framework of dynamic treatment regimes (DTRs) can inform this choice, but a patient-relevant strategy such as "wait for deceased-donor transplant" is ill-defined because there are multiple versions of treatment (i.e., wait times, organ qualities). Existing DTR methods average over the distribution of treatment versions in the data, estimating survival under a "representative intervention." This is undesirable if transporting inferences to a target population such as patients today, who experience shorter wait times thanks to evolutions in allocation policy. We, therefore, propose the concept of a generalized representative intervention (GRI): a random DTR that assigns treatment version by drawing from the distribution among strategy compliers in the target population (e.g., patients today). We describe an inverse-probability-weighted product-limit estimator of survival under a GRI that performs well in simulations and can be implemented in standard statistical software. For continuous treatments (e.g., organ quality), weights are reformulated to depend on probabilities only, not densities. We apply our method to a national database of kidney-pancreas transplant candidates from 2001-2020 to illustrate that variability in transplant rate across years and centers results in qualitative differences in the optimal strategy for patient survival.

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study.

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.

The Minnesota attributable risk of kidney donation (MARKD) study: a retrospective cohort study of long-term (> 50 year) outcomes after kidney donation compared to well-matched healthy controls.

BACKGROUND: There is uncertainty about the long-term risks of living kidney donation. Well-designed studies with controls well-matched on risk factors for kidney disease are needed to understand the attributable risks of kidney donation. METHODS: The goal of the Minnesota Attributable Risk of Kidney Donation (MARKD) study is to compare the long-term (> 50 years) outcomes of living donors (LDs) to contemporary and geographically similar controls that are well-matched on health status. University of Minnesota (n = 4022; 1st transplant: 1963) and Mayo Clinic LDs (n = 3035; 1st transplant: 1963) will be matched to Rochester Epidemiology Project (REP) controls (approximately 4 controls to 1 donor) on the basis of age, sex, and race/ethnicity. The REP controls are a well-defined population, with detailed medical record data linked between all providers in Olmsted and surrounding counties, that come from the same geographic region and era (early 1960s to present) as the donors. Controls will be carefully selected to have health status acceptable for donation on the index date (date their matched donor donated). Further refinement of the control group will include confirmed kidney health (e.g., normal serum creatinine and/or no proteinuria) and matching (on index date) of body mass index, smoking history, family history of chronic kidney disease, and blood pressure. Outcomes will be ascertained from national registries (National Death Index and United States Renal Data System) and a new survey administered to both donors and controls; the data will be supplemented by prior surveys and medical record review of donors and REP controls. The outcomes to be compared are all-cause mortality, end-stage kidney disease, cardiovascular disease and mortality, estimated glomerular filtration rate (eGFR) trajectory and chronic kidney disease, pregnancy risks, and development of diseases that frequently lead to chronic kidney disease (e.g. hypertension, diabetes, and obesity). We will additionally evaluate whether the risk of donation differs based on baseline characteristics. DISCUSSION: Our study will provide a comprehensive assessment of long-term living donor risk to inform candidate living donors, and to inform the follow-up and care of current living donors.

The Organ Shortage Continues to Be a Crisis for Patients With End-stage Kidney Disease.

This Viewpoint describes the organ shortage for patients with end-stage kidney disease despite increases in kidney donations between 2000 and 2021.

Long-term Outcomes Associated With Post-kidney Donation Pregnancy Complications.

BACKGROUND: Kidney donors have increased risk of postdonation gestational hypertension (gHTN) and preeclampsia. In the general population, pregnancy complications are associated with long-term maternal risk. However, little data exist on whether donors with postdonation pregnancy-related complications have similar increased long-term risks. We studied whether postdonation gHTN, preeclampsia/eclampsia, or gestational diabetes (gDM) was associated with increased risk of developing hypertension, DM, cardiovascular disease, or estimated glomerular filtration rate <45 mL/min/1.73 m 2 . METHODS: Postdonation pregnancies with complications were matched to pregnancies without complications based on time from donation. Incidence of outcomes was compared using sequential Cox regression with robust standard errors. Donors with predonation pregnancy complications were excluded. Models were adjusted for age at pregnancy, gravidity, year of donation, and family history of hypertension, DM, and heart disease. RESULTS: Of the 384 donors with postdonation pregnancies (median [quartiles] follow-up of 27.0 [14.2-36.2] y after donation), 39 experienced preeclampsia/eclampsia, 29 gHTN without preeclampsia, and 17 gDM. Median interval from donation to first pregnancy with preeclampsia was 5.1 (2.9-8.6) y; for gHTN, 3.7 (1.9-7.8) y; and for gDM, 7.3 (3.7-10.3) y. Preeclampsia/eclampsia (hazard ratio [HR] 2.70; 95% confidence interval [CI], 1.53-4.77) and gHTN (HR 2.39; 95% CI, 1.24-4.60) were associated with development of hypertension. Preeclampsia/eclampsia (HR 2.15; 95% CI, 1.11-4.16) and gDM (HR 5.60; 95% CI, 1.41-22.15) were associated with development of DM. Pregnancy-related complications were not associated with increased risk of cardiovascular disease or estimated glomerular filtration rate <45 mL/min/1.73 m 2 . CONCLUSIONS: In our single-center study, postdonation preeclampsia, gHTN, or gDM was associated with long-term risk of hypertension or DM.

Development and Validation of a Hypertension Risk Calculator for Living Kidney Donors.

BACKGROUND: Ideally, when deciding whether to donate, kidney donor candidates would understand their long-term risks. Using single-center data (N = 4055; median [quartiles] follow-up: 18 [9-28] y), we developed a calculator for postdonation hypertension and validated it using long-term data from an external single-center cohort (N = 1189, median [quartiles] follow-up: 9 [5-17] y). METHODS: Risk factors considered were routinely obtained at evaluation from donor candidates. Two modeling approaches were evaluated: Cox proportional hazards and random survival forest models. Cross-validation prediction error and Harrell's concordance-index were used to compare accuracy for model development. Top-performing models were assessed in the validation cohort using the concordance-index and net reclassification improvement. RESULTS: In the development cohort, 34% reported hypertension at a median (quartiles) of 16 (8-24) y postdonation; and in the validation cohort, 29% reported hypertension after 17 (10-22) y postdonation. The most accurate model was a Cox proportional hazards model with age, sex, race, estimated glomerular filtration rate, systolic and diastolic blood pressure, body mass index, glucose, smoking history, family history of hypertension, relationship with recipient, and hyperlipidemia (concordance-index, 0.72 in the development cohort and 0.82 in the validation cohort). CONCLUSIONS: A postdonation hypertension calculator was developed and validated; it provides kidney donor candidates, their family, and care team a long-term projection of hypertension risk that can be incorporated into the informed consent process.

The John S. Najarian symposium: The past, present, and future of surgery and transplantation, May 20, 2022, Minneapolis, MN.

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

Higher number of tacrolimus dose adjustments in kidney transplant recipients who are extensive and intermediate CYP3A5 metabolizers.

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.

Long-term Medical Outcomes of Living Kidney Donors.

Historically, to minimize risks, living kidney donors have been highly selected and healthy. Operative risks are well-defined, yet concern remains about long-term risks. In the general population, even a mild reduction in glomerular filtration rate (GFR) is associated with cardiovascular disease, chronic kidney disease, and end-stage kidney disease (ESKD). However, reduction in GFR in the general population is due to kidney or systemic disease. Retrospective studies comparing donors with matched general population controls have found no increased donor risk. Prospective studies comparing donors with controls (maximum follow-up, 9 years) have reported that donor GFR is stable or increases slightly, whereas GFR decreases in controls. However, these same studies identified metabolic and vascular donor abnormalities. There are a few retrospective studies comparing donors with controls. Each has limitations in selection of the control group, statistical analyses, and/or length of follow-up. One such study reported increased donor mortality; 2 reported a small increase in absolute risk of ESKD. Risk factors for donor ESKD are similar to those in the general population. Postdonation pregnancies are also associated with increased risk of hypertension and preeclampsia. There is a critical need for long-term follow-up studies comparing donors with controls from the same era, geographic area, and socioeconomic status who are healthy, with normal renal function on the date matching the date of donation, and are matched on demographic characteristics with the donors. These data are needed to optimize donor candidate counseling and informed consent.

A regulated system of incentives for living kidney donation: Clearing the way for an informed assessment.

The kidney shortage continues to be a crisis for our patients. Despite numerous attempts to increase living and deceased donation, annually in the United States, thousands of candidates are removed from the kidney transplant waiting list because of either death or becoming too sick to transplant. To increase living donation, trials of a regulated system of incentives for living donation have been proposed. Such trials may show: (1) a significant increase in donation, and (2) that informed, incentivized donors, making an autonomous decision to donate, have the same medical and psychosocial outcomes as our conventional donors. Given the stakes, the proposal warrants careful consideration. However, to date, much discussion of the proposal has been unproductive. Objections commonly leveled against it: fail to engage with it; conflate it with underground, unregulated markets; speculate without evidence; and reason fallaciously, favoring rhetorical impact over logic. The present paper is a corrective. It identifies these common errors so they are not repeated, thus allowing space for an assessment of the proposal on its merits.

Pre-kidney Donation Pregnancy Complications and Long-term Outcomes.

BACKGROUND: Hypertension and diabetes are contraindications for living kidney donation in young candidates. However, little is known about the long-term outcomes of women who had these pregnancy-related complications and subsequently became donors. In the general population, gestational hypertension (GHtn), preeclampsia/eclampsia, and gestational diabetes (GDM) are associated with long-term risks. METHODS: Donors with the specified predonation complication were matched to contemporary control donors with pregnancies without the complication using nearest neighbor propensity score matching. Propensity scores were estimated using logistic regression with covariates for gravidity, blood pressure, glucose, body mass index, age, and creatinine at donation, donation year, race, relationship with recipient, and family history of disease. Long-term incidence of hypertension, diabetes, cardiovascular disease, and reduced renal function (estimated glomerular filtration rate [eGFR] <30, eGFR <45 mL/min/1.73 m 2 ) were compared between groups using proportional hazards models. RESULTS: Of 1862 donors with predonation pregnancies, 48 had preeclampsia/eclampsia, 49 had GHtn without preeclampsia, and 43 had GDM. Donors had a long interval between first pregnancy and donation (median, 18.5 y; interquartile range, 10.6-27.5) and a long postdonation follow-up time (median, 18.0; interquartile range, 9.2-27.7 y). GHtn was associated with the development of hypertension (hazard ratio, 1.89; 95% confidence interval, 1.26-2.83); GDM was associated with diabetes (hazard ratio, 3.04; 95% confidence interval, 1.33-6.99). Pregnancy complications were not associated with eGFR <30 or eGFR <45 mL/min/1.73 m 2 . CONCLUSIONS: Our data suggest that women with predonation pregnancy-related complications have long-term risks even with a normal donor evaluation. Donor candidates with a history of pregnancy-related complications should be counseled about these risks.

Outcomes of Kidney Donors With Impaired Fasting Glucose.

BACKGROUND: Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney. METHODS: We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG): <100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250). RESULTS: Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG <126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04). CONCLUSIONS: Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

Risk Prediction for Delayed Allograft Function: Analysis of the Deterioration of Kidney Allograft Function (DeKAF) Study Data.

BACKGROUND: Delayed graft function (DGF) of a kidney transplant results in increased cost and complexity of management. For clinical care or a DGF trial, it would be ideal to accurately predict individual DGF risk and provide preemptive treatment. A calculator developed by Irish et al has been useful for predicting population but not individual risk. METHODS: We analyzed the Irish calculator (IC) in the DeKAF prospective cohort (incidence of DGF = 20.4%) and investigated potential improvements. RESULTS: We found that the predictive performance of the calculator in those meeting Irish inclusion criteria was comparable with that reported by Irish et al. For cohorts excluded by Irish: (a) in pump-perfused kidneys, the IC overestimated DGF risk; (b) in simultaneous pancreas kidney transplants, the DGF risk was exceptionally low. For all 3 cohorts, there was considerable overlap in IC scores between those with and those without DGF. Using a modified definition of DGF-excluding those with single dialysis in the first 24 h posttransplant-we found that the calculator had similar performance as with the traditional DGF definition. Studying whether DGF prediction could be improved, we found that recipient cardiovascular disease was strongly associated with DGF even after accounting for IC-predicted risk. CONCLUSIONS: The IC can be a useful population guide for predicting DGF in the population for which it was intended but has limited scope in expanded populations (SPK, pump) and for individual risk prediction. DGF risk prediction can be improved by inclusion of recipient cardiovascular disease.

Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors.

BACKGROUND: Obesity is associated with the two archetypal kidney disease risk factors: hypertension and diabetes. Concerns that the effects of diabetes and hypertension in obese kidney donors might be magnified in their remaining kidney have led to the exclusion of many obese candidates from kidney donation. METHODS: We compared mortality, diabetes, hypertension, proteinuria, reduced eGFR and its trajectory, and the development of kidney failure in 8583 kidney donors, according to body mass index (BMI). The study included 6822 individuals with a BMI of <30 kg/m2, 1338 with a BMI of 30-34.9 kg/m2, and 423 with a BMI of ≥35 kg/m2. We used Cox regression models, adjusting for baseline covariates only, and models adjusting for postdonation diabetes, hypertension, and kidney failure as time-varying covariates. RESULTS: Obese donors were more likely than nonobese donors to develop diabetes, hypertension, and proteinuria. The increase in eGFR in obese versus nonobese donors was significantly higher in the first 10 years (3.5 ml/min per 1.73m2 per year versus 2.4 ml/min per 1.73m2 per year; P<0.001), but comparable thereafter. At a mean±SD follow-up of 19.3±10.3 years after donation, 31 (0.5%) nonobese and 12 (0.7%) obese donors developed ESKD. Of the 12 patients with ESKD in obese donors, 10 occurred in 1445 White donors who were related to the recipient (0.9%). Risk of death in obese donors was not significantly increased compared with nonobese donors. CONCLUSIONS: Obesity in kidney donors, as in nondonors, is associated with increased risk of developing diabetes and hypertension. The absolute risk of ESKD is small and the risk of death is comparable to that of nonobese donors.

Outcomes of Kidney Allograft and Recipient Survival After Liver Transplantation by Induction Type in the United States.

There are several choices for induction immunosuppression in kidney-after-liver transplantation. We used the Scientific Registry of Transplant Recipients database. We assessed all kidney-after-liver transplant recipients in the United States between 1/1/2000 and 7/31/2017 to study kidney graft and patient outcomes by induction type. We only included patients discharged on tacrolimus and mycophenolate with or without steroids and had a negative crossmatch before kidney engraftment. We grouped recipients by kidney induction type into the following 3 groups: depletional (n = 550), nondepletional (n = 434), and no antibody induction (n = 144). We studied patient and kidney allograft survival using Cox proportional hazard regression, with transplant center included as a random effect. Models were adjusted for liver induction regimen, recipient and donor age, sex, human leukocyte antigen mismatches, payor type, living donor kidney transplantation, dialysis status, time from liver engraftment, hepatitis C virus status, and the presence of diabetes mellitus at time of kidney transplantation and transplantation year. The 6-month and 1-year rejection rates did not differ between groups. Compared with no induction, neither depletional nor nondepletional induction was associated with an improved recipient or graft survival in the multivariable models. Depletional induction at the time of liver transplantation was associated with worse patient survival after kidney transplantation (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.09-2.67; P = 0.02). Living donor kidney transplantation was associated with a 48.1% improved graft survival (HR, 0.52; 95% CI, 0.33-0.82; P = 0.00). In conclusion, in the settings of a negative cross-match and maintenance with tacrolimus and mycophenolate, induction use was not associated with a patient or graft survival benefit in kidney-after-liver transplantations.