Faculty Bibliography

BACKGROUND:Despite providing survival benefit, increased risk for infectious disease (IRD) kidney offers are declined at 1.5 times the rate of non-IRD kidneys. Elucidating sources of variation in IRD kidney offer acceptance may highlight opportunities to expand use of these life-saving organs. METHODS:To explore center-level variation in offer acceptance, we studied 6765 transplanted IRD kidneys offered to 187 transplant centers between 2009 and 2017 using Scientific Registry of Transplant Recipients data. We used multilevel logistic regression to determine characteristics associated with offer acceptance and to calculate the median odds ratio (MOR) of acceptance (higher MOR indicates greater heterogeneity). RESULTS:Higher quality kidneys (per 10 units kidney donor profile index; adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.92-0.95), higher yearly volume (per 10 deceased donor kidney transplants; aOR, 1.08, 95% CI, 1.06-1.10), smaller waitlist size (per 100 candidates; aOR, 0.97; 95% CI, 0.95-0.98), and fewer transplant centers in the donor service area (per center; aOR, 0.88; 95% CI, 0.85-0.91) were associated with greater odds of IRD acceptance. Adjusting for donor and center characteristics, we found wide heterogeneity in IRD offer acceptance (MOR, 1.96). In other words, if listed at a center with more aggressive acceptance practices, a candidate could be 2 times more likely to have an IRD kidney offer accepted. CONCLUSIONS:Wide national variation in IRD kidney offer acceptance limits access to life-saving kidneys for many transplant candidates.

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007-2016) to examine associations (adjusted hazard ratio, _LCL aHR_UCL ) of post-donation fills of antidiabetic medications (ADM, insulin or non-insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, _3.36 4.59_6.27 ). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9-year incidence, 6.87% vs 1.85%, aHR, _3.55 5.00_7.04 ). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1-year post-donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m² by year 1 was associated with increased risk of subsequent ADM use (aHR, _1.03 1.48_2.14, P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.

BACKGROUND AND OBJECTIVES:The risk of hypertension attributable to living kidney donation remains unknown as does the effect of developing postdonation hypertension on subsequent eGFR. We sought to understand the association between living kidney donation, hypertension, and long-term eGFR by comparing donors with a cohort of healthy nondonors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We compared 1295 living kidney donors with median 6 years of follow-up with a weighted cohort of 8233 healthy nondonors. We quantified the risk of self-reported hypertension using a parametric survival model. We examined the association of hypertension with yearly change in eGFR using multilevel linear regression and clustering by participant, with an interaction term for race. RESULTS:=0.01, respectively, after hypertension). CONCLUSIONS:Kidney donors are at higher risk of hypertension than similar healthy nondonors, regardless of race. Donors who developed hypertension had a plateau in the usual postdonation increase of eGFR.

Background/UNASSIGNED:Limited data are available regarding clinical implications of lower renal function after living kidney donation. We examined a novel integrated database to study associations between postdonation estimated glomerular filtration rate (eGFR) and use of antihypertensive medication (AHM) treatment after living kidney donation. Methods/UNASSIGNED:) between AHM use and postdonation eGFR levels (random effect) with fixed effects for baseline donor factors. Results/UNASSIGNED:). Conclusions/UNASSIGNED:This novel linkage illustrates the ability to identify postdonation kidney function and associate it with clinically meaningful outcomes; lower eGFR after living kidney donation is a correlate of AHM treatment requirements. Further work should define relationships of postdonation renal function, hypertension, and other morbidity measures.

End-stage liver disease (ESLD) is associated with cognitive impairment ranging from subtle alterations in attention to overt hepatic encephalopathy that resolves after transplant. Natural language processing (NLP) may provide a useful method to assess cognitive status in this population. We identified 81 liver transplant recipients with ESLD (4/2013-2/2018) who sent at least one patient-to-provider electronic message pre-transplant and post-transplant, and matched them 1:1 to "healthy" controls-who had similar disease, but had not been evaluated for liver transplant-by age, gender, race/ethnicity, and liver disease. Messages written by patients pre-transplant and post-transplant and controls was compared across 19 NLP measures using paired Wilcoxon signed-rank tests. While there was no difference overall in word length, patients with Model for End-Stage Liver Disease Score (MELD) ≥ 30 (n = 31) had decreased word length in pre-transplant messages (3.95 [interquartile range (IQR) 3.79, 4.14]) compared to post-transplant (4.13 [3.96, 4.28], p = 0.01) and controls (4.2 [4.0, 4.4], p = 0.01); there was no difference between post-transplant and controls (p = 0.4). Patients with MELD ≥ 30 had fewer 6+ letter words in pre-transplant messages (19.5% [16.4, 25.9] compared to post-transplant (23.4% [20.0, 26.7] p = 0.02) and controls (25.0% [19.2, 29.4]; p = 0.01). Overall, patients had increased sentence length pre-transplant (12.0 [9.8, 13.7]) compared to post-transplant (11.0 [9.2, 13.3]; p = 0.046); the same was seen for MELD ≥ 30 (12.3 [9.8, 13.7] pre-transplant vs. 10.8 [9.6, 13.0] post-transplant; p = 0.050). Application of NLP to patient-generated messages identified language differences-longer sentences with shorter words-that resolved after transplant. NLP may provide opportunities to detect cognitive impairment in ESLD.

Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = _1.08 1.38_1.78 , P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.