Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records

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, LCLaHRUCL) 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, 3.364.596.27). 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, 3.555.007.04). 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, 1.031.482.14, 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.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152001/1/ctr13696_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152001/2/ctr13696.pd

UNDERSTANDING POST-DONATION KIDNEY FUNCTION IN LIVING KIDNEY DONORS

Living donors provide a third of the kidney transplants each year in the United States. Because donor nephrectomy is truly elective, transplant providers must offer personalized risk estimates to people considering kidney donation, as well as individualized post-donation care. This dissertation focuses on post-donation kidney function and the association of early post-donation outcomes with recipient graft outcomes. First, since hypertension and diabetes are the predominant causes of end-stage renal disease (ESRD) in living kidney donors, we sought to clarify their early post-donation incidence rates (Chapter 2). Using national registry data, we estimated 310 per 10,000 donors developed hypertension within 2-years of donation, while only 15 per 10,000 donors developed diabetes. We then focused on hypertension and obesity and their association with post-donation renal function (Chapters 3 and 4). We compared a cohort of 1295 donors to a weighted cohort of 8233 healthy non-donors. We found that kidney donation was independently associated with a 19% higher risk of hypertension and that donors who developed hypertension had a plateau in the usual post-donation increase of estimated glomerular filtration rate (eGFR). We also found that donor eGFR trajectory varied by obesity. Non-obese donors had an increase in eGFR of +0.55 mL/min/year while obese donors had an attenuated increase of +0.30 mL/min/year. In comparison, obese and non-obese non-donors had a similar decrease in eGFR over time. Finally, we studied early post-donation markers of donor renal function and recipient graft outcomes using national registry data (Chapters 5 and 6). Given that donor ESRD is associated with recipient graft loss, we found that the risk of recipient graft loss increased with each decrement in 6-month post-donation eGFR. Last, although hypertension is a frequent causes of donor ESRD, we found iii that recipients whose donors developed incident hypertension within 2-years post-donation had no higher risk of graft loss. Our results will be used by nephrologists and transplant surgeons to better personalize counseling for people considering living kidney donation as well as better individualize post-donation care

Transplant waitlisting attenuates the association between hemodialysis access type and mortality

Prior studies have shown that beginning hemodialysis (HD) with a hemodialysis catheter (HC) is associated with worse mortality than with an arteriovenous fistula (AVF) or arteriovenous graft (AVG). We hypothesized that transplant waitlisting would modify the effect of HD access on mortality, given waitlist candidates' more robust health status. Using the US Renal Data System, we studied patients with incident ESRD who initiated HD between 2010 and 2015 with an AVF, AVG, or HC. We used Cox regression including an interaction term for HD access and waitlist status. There were 587,607 patients that initiated HD, of whom 82,379 (14.0%) were waitlisted for transplantation. Only 26,264 (4.5%) were transplanted. Among patients not listed, those with an AVF had a 34% lower mortality compared to HC [adjusted hazard ratio (aHR) 0.66, 95% confidence interval (CI) 0.65-0.67] while those with an AVG had a 21% lower mortality compared to HC (aHR 0.79, 95% CI 0.77-0.81). Transplant waitlisting attenuated the association between hemodialysis access type and mortality (interaction p < 0.001 for both AVF and AVG vs. HC). Among patients on the waitlist, those with an AVF had a 12% lower mortality compared to HC (aHR 0.88, 95% CI 0.84-0.93), while those with an AVG had no difference in mortality (aHR 0.95, 95% CI 0.84-1.08). While all patients benefit from AVF or AVG over HC, the benefit was attenuated in waitlisted patients. Efforts to improve health status and access to healthcare for non-waitlisted ESRD patients might decrease HD-associated mortality and improve rates of AVF and AVG placement

In-hospital and one-year outcomes are similar for women and men following transcarotid artery revascularization in symptomatic and asymptomatic patients

OBJECTIVE: In randomized controlled trials and retrospective series, women have higher rates of periprocedural stroke and death following carotid endarterectomy and transfemoral carotid artery stenting compared with men. We sought to compare outcomes by sex following transcarotid artery revascularization (TCAR) among patients in the Vascular Quality Initiative (VQI). METHODS: We reviewed all patients in the VQI who underwent TCAR from 2017 to 2020. We stratified the analysis by symptom status. The primary outcome was in-hospital stroke/death, and secondary outcomes were in-hospital stroke and death and 1-year stroke/death, stroke, and death. We used multivariable logistic and Cox regression models to assess the association of sex with in-hospital and 1-year outcomes after adjusting for preoperative and intraoperative characteristics. RESULTS: We identified 15,851 patients who underwent TCAR, of whom 7391 (47%) were symptomatic (2708 or 37% female) and 8460 (53%) were asymptomatic (3097 or 37% female). Women were less frequently considered anatomic high risk than men in both groups (symptomatic: 43% vs 46%; P = .004; asymptomatic: 44% vs 48%; P = .004). Among symptomatic patients, women more often had severe ≥70% stenosis (89% vs 87%; P = .02). There were no differences in in-hospital death, stroke, or stroke/death for women vs men following TCAR among symptomatic or asymptomatic patients (all P \u3e .05). After adjusting for baseline differences between groups, female sex was not associated with in-hospital stroke/death in either symptomatic (odds ratio, 1.05; 95% confidence interval, 0.72-1.56) or asymptomatic (odds ratio, 0.93; 95% confidence interval, 0.53-1.63) patients undergoing TCAR. There were also no differences in 1-year stroke, death, or stroke/death risk for women compared with men with and without symptoms on unadjusted or adjusted analyses (P \u3e .05). CONCLUSIONS: We found no sex differences in in-hospital or 1-year stroke/death following TCAR, regardless of symptom status. TCAR appears to be as safe of a surgical procedure for women as for men in patients with both symptomatic and asymptomatic carotid artery disease

Temporal changes in the composition of a large multicenter kidney exchange clearinghouse: Do the hard-to-match accumulate?

One criticism of kidney paired donation (KPD) is that easy-to-match candidates leave the registry quickly, thus concentrating the pool with hard-to-match sensitized and blood type O candidates. We studied candidate/donor pairs who registered with the National Kidney Registry (NKR), the largest US KPD clearinghouse, from January 2012-June 2016. There were no changes in age, gender, BMI, race, ABO blood type, or panel-reactive antibody (PRA) of newly registering candidates over time, with consistent registration of hard-to-match candidates (59% type O and 38% PRA ≥97%). However, there was no accumulation of type O candidates over time, presumably due to increasing numbers of nondirected type O donors. Although there was an initial accumulation of candidates with PRA ≥97% (from 33% of the pool in 2012% to 43% in 2014, P = .03), the proportion decreased to 17% by June 2016 (P < .001). Some of this is explained by an increase in the proportion of candidates with PRA ≥97% who underwent a deceased donor kidney transplantation (DDKT) after the implementation of the Kidney Allocation System (KAS), from 8% of 2012 registrants to 17% of 2015 registrants (P = .02). In this large KPD clearinghouse, increasing participation of nondirected donors and the KAS have lessened the accumulation of hard-to-match candidates, but highly sensitized candidates remain hard-to-match

Temporal changes in the composition of a large multicenter kidney exchange clearinghouse: Do the hard-to-match accumulate?

One criticism of kidney paired donation (KPD) is that easy-to-match candidates leave the registry quickly, thus concentrating the pool with hard-to-match sensitized and blood type O candidates. We studied candidate/donor pairs who registered with the National Kidney Registry (NKR), the largest US KPD clearinghouse, from January 2012-June 2016. There were no changes in age, gender, BMI, race, ABO blood type, or panel-reactive antibody (PRA) of newly registering candidates over time, with consistent registration of hard-to-match candidates (59% type O and 38% PRA ≥97%). However, there was no accumulation of type O candidates over time, presumably due to increasing numbers of nondirected type O donors. Although there was an initial accumulation of candidates with PRA ≥97% (from 33% of the pool in 2012% to 43% in 2014, P = .03), the proportion decreased to 17% by June 2016 (P < .001). Some of this is explained by an increase in the proportion of candidates with PRA ≥97% who underwent a deceased donor kidney transplantation (DDKT) after the implementation of the Kidney Allocation System (KAS), from 8% of 2012 registrants to 17% of 2015 registrants (P = .02). In this large KPD clearinghouse, increasing participation of nondirected donors and the KAS have lessened the accumulation of hard-to-match candidates, but highly sensitized candidates remain hard-to-match