The pathological diagnosis of borderline rejection (BL‐R) denotes possible T cell–mediated rejection (TCMR), but its clinical significance is uncertain. This single‐center, cross‐sectional cohort study compared the functional and histological outcomes of consecutive BL‐R diagnoses (n = 146) against normal controls (n = 826) and acute TCMR (n = 55) from 551 renal transplant recipients. BL‐R was associated with the following: contemporaneous renal dysfunction, acute tubular necrosis, and chronic tubular atrophy (P < .001); progressive tubular injury with fibrosis by longitudinal sequential histology (45.3% at 1 year); increased subsequent acute rejection (39.4%), allograft failure (P < .001), and patient mortality (P = .007). BL‐R detected by biopsy indicated for impaired function was followed by suboptimal functional recovery (46.3%), persistent inflammation (27.2%), and acute rejection episodes (50.0%) despite antirejection treatment in 83.3%. By 1 year after BL‐R, the incidence of new‐onset microvascular inflammation (9.3%), C4d staining (22.3%), transplant glomerulopathy (13.3%), and de novo donor‐specific antibodies (31.5%) exceeded normal controls (P < .05‐.001). BL‐R inflammation in protocol biopsy persisted in 28.0% and progressed to acute rejection in 32.6%; however, it resolved in 61.6% of the untreated cases. In summary, BL‐R is a heterogeneous diagnostic grouping, ranging from mild inconsequential inflammation to clinically significant TCMR, which is capable of immune‐mediated tubular injury resulting in inferior functional, immunological, and histological consequences.

word count: 246 16 Word count: 3110 Abstract 34 Background: Cardiovascular (CV) disease is the leading cause of death in kidney and 35 simultaneous pancreas-kidney (SPK) transplant recipients. Assessing abdominal aortic 36 calcification (AAC), using lateral spine x-rays and the Kaupilla 24-point AAC (0-24) score, 37 may identify transplant recipients at higher CV risk. 38 Methods: Between the years 2000-2015, 413 kidney and 213 SPK first transplant recipients 39 were scored for AAC at time of transplant and then followed for CV events (coronary heart, 40 cerebrovascular or peripheral vascular disease), graft-loss and all-cause mortality. 41 Results: The mean age was 44 ± 12 years (SD) with 275 (44%) having AAC (26% moderate: 42 1-7 and 18% high: ≥8). After a median of 65 months (IQR 29-107 months), 46 recipient's 43 experienced CV events, 59 died and 80 suffered graft loss. For each point increase in AAC, 44the unadjusted hazard ratios (HR) for CV events and mortality were 1.11 (95% CI 1.07-1.15) 45 and 1.11 (1.08-1.15). These were similar after adjusting for age, gender, smoking, transplant 46 type, dialysis vintage and diabetes: aHR 1.07 (95% CI 1.02-1.12) and 1.09 (1.04-1.13). For 47 recipients with high versus no AAC, the unadjusted and fully-adjusted HR for CV events 48 were 5.90 (2.90-12.02) and 3.51 (1.54-8.00), for deaths 5.39 (3.00-9.68) and 3.38 (1.71-6.70), 49 and for graft loss 1.30 (0.75-2.28) and 1.94 (1.04-3.27) in age and smoking history-adjusted 50 analyses. 51 Conclusion: Kidney and SPK transplant recipients with high AAC have 3-fold higher CV 52 and mortality risk and poorer graft outcomes than recipients without AAC. AAC scoring may 53 be useful in assessing and targeted risk-lowering strategies. 54 55 56 KEY WORDS; vascular calcification, cardiovascular disease, kidney transplant, 57 simultaneous pancreas-kidney transplant, mortality.

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Purpose of reviewEvolution of human leukocyte antigen (HLA) molecular typing techniques has progressively enabled more accurate determination of the three-dimensional building blocks that form the antibody accessibility and binding sites of each HLA allele. These immunogenic HLA regions known as epitopes are composed of polymorphic sequences of amino acid residues termed eplets. This review provides a critical appraisal of the current understanding of epitope compatibility in kidney transplantation. Recent findingsThere is a tendency to suggest that epitope matching is likely to be superior to broad antigen HLA matching such that the allocation of donor kidneys to patients with a more favorable epitope compatibility profile may lead to better allograft outcomes. A growing body of work has highlighted the association between a greater number of eplet mismatches and adverse allograft outcomes, and approaches using eplet matching have been successfully implemented in organ allocation programs. However, our understanding of epitope compatibility remains in its infancy, requiring further and more in-depth evaluation. Critically, it remains unclear how best to translate findings derived at the population level to the care of individual patients. Questions that need to be answered include a lack of consensus in the definition and interpretation of epitope compatibility, are class I and II compatibility of similar clinical importance, how best to define predetermined mismatch thresholds for utilization in organ allocation, and whether other properties such as differences in electrostatic potential between donor and recipient HLA alleles are also important in determining immunological compatibility. SummaryEpitope matching likely represents a valid progression in understanding donor-recipient HLA compatibility. However, more clinical data and a better understanding about differences in methods to determine epitope compatibility are required before the approach can be widely applied in clinical practice.