Heilman, Raymond L.

AbstractBackgroundThe aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post‐transplant year with outcomes after kidney transplantation.MethodsWe conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post‐transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx‐all GEP results normal, 1 Not‐TX had one GEP result abnormal and >1 Not‐TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation.ResultsWe enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not‐TX n = 59 (25%) and >1 Not‐TX n = 64 (27%). Compared to the TX group, the >1 Not‐TX group had lower eGFR (p < .001) and more chronic changes on 1‐year surveillance biopsy (p = .007). Death censored graft survival showed inferior graft survival in the >1 Not‐TX group (p < .001) but not in the 1 Not‐TX group. All graft losses in the >1 Not‐TX group occurred after 1‐year post‐transplant.ConclusionsWe conclude that a pattern of persistently Not‐TX GEP assay correlates with inferior graft survival.

Abstract Introduction Significant center‐to‐center variation in attitudes and management of delayed graft function (DGF) remains common. Methods A survey to describe current DGF practices was developed by workgroup members sponsored by the National Kidney Foundation (NKF) and was distributed to both the NKF DGF workgroup members, kidney transplant program directors and the transplant community within the United States and Canada. Seventy‐one percent of NKF workgroup members completed the survey along with 70 unique the United States and three Canadian kidney transplant programs. All Organ Procurement and Transplantation Network (OPTN) regions were represented. Results DGF was reported to occur at rate of 20%–40% for most centers with 3.9% indicating their incidence to be >60%. Most centers reported longer hospital lengths of stay and more frequent outpatient visits. Despite the commonality of DGF, only half of centers reported having an established protocol to manage DGF. Kidney allograft biopsies were the only consistent DGF management strategy observed, although use of machine perfusion was also heavily favored. Other DGF management strategies voiced by a minority included having established outpatient practices to care for DGF patients and administering outpatient community‐based hemodialysis. Conclusion Although approximately a third of survey responders indicated that risk of DGF played a role in their willingness to accept organs, most did not feel that increased cost or clinical impact on outcomes was a deterrent. Future strategies, including broader sharing of best practices, redefining terminology specific to DGF, the establishment of DGF dialysis guidelines and improving access to machine perfusion across OPOs may help reduce discard and improve utilization of kidneys at risk for DGF.

Background. The objective of this study was to compare the long-term outcomes of older (50–65 y) type 1 diabetics with body mass index <35 kg/m2 and type 2 diabetics with body mass index <30 kg/m2 who received simultaneous pancreas kidney transplantation (SPKT) versus living donor kidney transplants (LDKTs). All subjects had insulin-dependent diabetes. Methods. This is a retrospective single-center study from July 2003 to March 2021 with a median follow-up of 7.5 y. Results. There were 104 recipients in the SPKT and 80 in the LDKT group. The mean age was 56 y in SPKT and 58 y in LDKT. There were 55% male recipients in the SPKT group versus 75% in LDKT. The duration of diabetes was 32 y in SPKT versus 25 y in LDKT. The number of preemptive transplants and length of dialysis were similar. However, the wait time was shorter for LDKT (269 versus 460 d). Forty-nine percent of the LDKT recipients received the organ within 6 mo of being waitlisted compared with 28% of SPKT recipients (P = 0.001). Donor age was lower in the SPKT group (27 versus 41 y). The estimated 5-y death censored kidney survival was 92% versus 98%, and 5-y patient survival was 86% versus 89% for SPKT versus LDKT. Death censored kidney and patient survival, acute kidney rejection by 1 y, and BK viremia were similar between the 2 groups. There were 17 pancreas graft losses within 1 y of transplant, the majority related to surgical complications, and it was not associated with increased mortality. Conclusions. SPKT in selected recipients aged 50 and above can have excellent outcomes similar to LDKT recipients.

AbstractIntroductionInfections are known complications of solid‐organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection.MethodsThis is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment.ResultsWe identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver‐kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients.ConclusionsInfections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver‐kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow‐up in kidney transplant patients. image

Background. The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome. Methods. A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded. Results. We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [P < 0.001]‚ respectively; year 2, 17.2% versus 4.3% [P < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody. Conclusion. Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies.

AbstractBackgroundThe pleiotropic effects of statin therapy on inflammation and coagulation may reduce the risk of venous thromboembolism. This study evaluated whether statin therapy is associated with decreased venous thromboembolic (VTE) events following kidney transplantation.MethodsWe performed a retrospective analysis of all primary kidney transplants performed between January 2014 and December 2019 at Mayo Clinic Arizona. Patients were divided into two groups depending on sustained statin therapy during the first year following transplantation. Recipient and donor clinical and demographic data were collected. The primary outcome was admission for symptomatic VTE events (deep vein thrombosis [DVT] or pulmonary embolism [PE]).ResultsSustained statin therapy in the first year following transplant was observed in 16.1% (n = 223) of 1384 kidney transplants. The overall incidence of VTE events in the year following kidney transplant was 3.8%. VTE occurred in 4.1% of recipients treated with statins and 3.8% of the controls – (hazard ratio [HR] .92, 95% confidence interval [95% CI] .39, 2.21, p = .86). However, there were significant differences between the groups in terms of age, sex, race/ethnicity, body mass index, indication for transplant, diagnosis of diabetes and discharge antiplatelet or anticoagulant therapy. Following sensitivity analysis in which cohort matching was performed to account for these differences, there was no difference in VTE event‐free survival (HR .89, 95% CI .41, 1.96, p = .78) or overall survival (HR .54, 95% CI .15, 1.94, p = .35) between patients treated with statins compared to controls.ConclusionStatin therapy in the year following successful kidney transplant was not associated with a reduction in risk of VTE.

AbstractDual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien‐Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1‐year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1‐ (P = .004) and 2‐years post‐transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5‐3.3, P = .58) or graft (HR 1.1, 95% CI .5‐2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard.

Abstract Donation after circulatory death (DCD) liver transplantation (LT) outcomes have been attributed to multiple variables, including procurement surgeon recovery techniques. Outcomes of 196 DCD LTs at Mayo Clinic Arizona were analyzed based on graft recovery by a surgeon from our center (transplant procurement team [TPT]) versus a local procurement surgeon (non‐TPT [NTPT]). A standard recovery technique was used for all TPT livers. The recovery technique used by the NTPT was left to the discretion of that surgeon. A total of 129 (65.8%) grafts were recovered by our TPT, 67 (34.2%) by the NTPT. Recipient age (p = 0.43), Model for End‐Stage Liver Disease score (median 17 vs. 18; p = 0.22), and donor warm ischemia time (median 21.0 vs. 21.5; p = 0.86) were similar between the TPT and NTPT groups. NTPT livers had longer cold ischemia times (6.5 vs. 5.0 median hours; p < 0.001). Early allograft dysfunction (80.6% vs. 76.1%; p = 0.42) and primary nonfunction (0.8% vs. 0.0%; p = 0.47) were similar. Ischemic cholangiopathy (IC) treated with endoscopy occurred in 18.6% and 11.9% of TPT and NTPT grafts (p = 0.23). At last follow‐up, approximately half of those requiring endoscopy were undergoing a stent‐free trial (58.3% TPT; 50.0% NTPT; p = 0.68). IC requiring re‐LT in the first year occurred in 0.8% (n = 1) of TPT and 3.0% (n = 2) of NTPT grafts (p = 0.23). There were no differences in patient (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.76–5.03; p = 0.23) or graft (HR, 1.99; 95% CI, 0.98–4.09; p = 0.10) survival rates. Graft survival at 1 year was 91.5% for TPT grafts and 95.5% for NTPT grafts. Excellent outcomes can be achieved using NTPT for the recovery of DCD livers. There may be an opportunity to expand the use of DCD livers in the United States by increasing the use of NTPT.