KEY POINTS:Pretransplant early acute rejection risk stratification offers a novel approach to personalized immunosuppression management in patients who received a kidney transplant. Stratifying immunologic risk independent of donor characteristics may help guide immunosuppression management in patients who received a kidney transplant. The pretransplant risk assessment gene set reflects metabolic and immune pathways involved in T-cell- and antibody-mediated mechanisms of transplant rejection. BACKGROUND:Although donor and recipient characteristics are used to estimate graft failure risk, they remain limited in predicting early acute rejection (EAR). We developed and validated a next-generation sequencing assay targeting the pretransplant immunologic profile to predict EAR following kidney transplantation. METHODS:This prospective, international study enrolled 321 kidney transplant participants across 13 sites, forming discovery and validation cohorts. Peripheral blood was collected before transplant and at 1, 3, 6, 12, and 24 months post-transplant, with protocol biopsies performed at 3 and 12 months, as well as any indication biopsies. Biopsies were assessed by a blinded central pathologist according to the 2019 Banff criteria. The pretransplant risk assessment (PTRA) test to evaluate RNA expression of a 29-gene signature algorithm designed to predict EAR risk was clinically validated using 122 deceased donor kidney transplant recipients. RESULTS:PTRA classified 31 of 122 participants (25%) as high risk and 91 (75%) as low risk. There were nine EAR events in the first 60 days post-transplant: 6/31 (19%) in the high-risk group and 3/91 (3%) in the low-risk group. PTRA discrimination for EAR at 60 days post-transplant yielded an area under the curve of 0.78 (95% confidence interval [CI], 64.4 to 91.5), P < 0.001. A cutoff of ≤45 was defined as low risk and >45 as high risk for EAR within 60 days post-transplant. Sensitivity was 0.67 (95% CI, 0.36 to 0.97), specificity 0.78 (95% CI, 0.70 to 0.86), positive predictive value 0.19 (95% CI, 0.05 to 0.33), and negative predictive value 0.97 (95% CI, 0.93 to 1.00). The odds ratio comparing patients identified as high versus low risk by PTRA was 7.04 (95% CI, 1.64 to 30.2), P = 0.009. CONCLUSIONS:This study validates the ability of PTRA to stratify kidney transplant recipients as high or low risk for EAR using a pretransplant transcriptomic profile, with implications for graft health and personalized treatment management.

Kidney transplantation (KT) is the treatment of choice for suitable candidates with advanced kidney disease, offering improved survival compared with chronic dialysis. However, KT recipients remain at high risk for cardiovascular mortality and complications. Cardiovascular-kidney-metabolic syndrome is commonly present, with high rates of obesity, diabetes, and dyslipidemia posttransplant. These risk factors are exacerbated by the metabolic effects of immunosuppression. Management includes utilizing standard pharmacologic therapy such as statins and antihypertensives, and newer agents such as glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter 2 inhibitors. Modification of the immunosuppressive regimen to reduce cardiometabolic effects should be weighed against other risks such as allograft rejection.

BACKGROUND:Over the last decade, the number of simultaneous heart-kidney transplants (SHKTs) has increased dramatically. There are few reports of renal allograft outcomes in these high acuity patients. The goal of the present study was to identify variables that were related to early adverse outcomes (EAOs), including delayed graft function (DGF), primary non-function (PNF), and renal allograft futility (RAF) after SHKTs. METHODS:We performed a single center retrospective review of all adults undergoing SHKTs from October 2011 to August 2021. Multivariable logistic regression models with backward elimination were used to test the relationships between recipient (pre-transplant dialysis, intra-aortic balloon pump, serum lactate, norepinephrine use, and re-do sternotomy) and operative (cold ischemia time [CIT]) variables and the likelihood of DGF, PNF, and RAF. RESULTS:Sixty-eight patients underwent SHKT during the study period. Overall, patient survival was 87%, 83%, and 80% at 6 months, 1 year, and 3 years, respectively. Twenty-four patients (35%) experienced DGF, whereas 4 patients (6%) had PNF, and 12 patients (18%) had RAF (Table 1). Pre-transplant dialysis, serum lactate, and CIT were significantly associated with an increased likelihood of DGF. Norepinephrine (NE) and CIT were associated with increased likelihood of RAF (Table 2). CONCLUSIONS:Pre-transplant dialysis is related to an increased likelihood of EAO following SHKT, with CIT and NE contributing to increased likelihood of RAF. Given that SHKT recipients are at risk of remaining on dialysis following SHKT, strategies that allow for expedited kidney transplantation after heart transplantation may mitigate the hemodynamic and ischemic constraints of SHKT that contribute to early adverse outcomes.

Introduction: Data on long-term outcomes following A2/A2B to B kidney transplants since the 2014 kidney allocation system (KAS) changes are few. The primary aim of this study is to report our 7-year experience with A2/A2B to B kidney transplants and to compare post-transplant outcomes of A2/A2B to a concurrent group of B to B kidney transplants. Additionally, the study evaluates the impact of pre-transplant anti-A1 titers on survival outcomes in A2/A2B transplants. Methods: This retrospective, single-center analysis included all adults who received A2/A2B to B deceased donor kidney transplants from December 2014 to June 2021 compared to B to B recipients. The effects of pre-transplant IgM/IgG titers, stratified as <= 1:8 and >= 1:16, on death-censored, rejection-free, and overall graft survival were tested. Results: Fifty-three A2/A2B and 114 B to B adults were included with a median follow-up time of 32 months. Overall graft survival, patient survival, and rejection-free graft survival did not differ between the two groups. There were no differences between the groups' overall kidney function values (p > .80) or their temporal trajectories (time by group interaction p > .11). Unadjusted death-censored graft survival was lower in A2/A2B to B compared to B recipients (p = .03), but the effect was not significant (p = .195) after adjusting for any readmissions (p = .96), rejection episodes (p < .001) or BK infection (p = .76). We did not detect an effect of pre-transplant titer group on death-censored (p = .59), rejection-free (p = .61), or overall graft survival (p = .26) Conclusions: A2/A2B to B kidney transplants have comparable overall patient and graft survival, rejection-free graft survival, and longitudinal renal function compared to B to B transplants at our center. Allograft survival outcomes were not significantly different between patients with low and high pre-transplant anti-A1 IgM/IgG titers.

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post–kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

1Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 2Section of Nephrology, University of Chicago, Chicago, Illinois Correspondence: Dr. Beatrice P. Concepcion, Section of Nephrology, University of Chicago, 5841 S. Maryland Avenue, MC 5100 Chicago, IL 60637. Email: [email protected]

Anwar, Amber; Abu Kar, Sarah; Binari, Laura; Wang, Yihan; Shawar, Saed Author Information

INTRODUCTION:Utilization of hepatitis C viremic (HCV+) deceased donor kidneys (DDKT) for aviremic recipients increases opportunities for transplantation with excellent short-term outcomes. Our primary aim was to understand longer-term outcomes, specifically assessing kidney and liver function in the first year posttransplant. METHODS:This was a retrospective single-center study of adult DDKT recipients of HCV+ kidneys (cases) matched 1:1 to recipients of HCV- kidneys (comparators). Between-group outcomes were analyzed using comparisons of means and proportions, survival analysis methods, and multivariable mixed effects models. RESULTS:Sixty-five cases and 65 comparators had statistically comparable demographic and clinical characteristics. There were no between-group differences in serum creatinine or estimated glomerular filtration rate at month 12 (p = .662) or in their trajectories over months 1-12 (p > .292). Within the first 60 days, rates of liver function values >3 times upper limit of normal among cases were comparable to comparators for aspartate aminotransferase (AST) (14% vs. 6%, p = .242) and higher for alanine transaminase (ALT) (23% vs. 6%, p = .011). AST declined during the first 8 weeks (p = .005) and stabilized for both groups (p = .406) during the following 10 months. ALT declined during the first 8 weeks (p < .001), continued to decline over months 3-12 (p = .016), and the trajectory was unrelated to antiviral therapy initiation among cases. CONCLUSIONS:Aviremic recipients of HCV+ kidneys had comparable kidney outcomes to matched recipients of HCV- kidneys. Despite more HCV+ recipients having an elevation in ALT within the first 60 days, ALT values normalized with no identified liver complications attributed to HCV.