Endocan is a water-soluble proteoglycan exclusively secreted by vascular endothelium. Endocan levels may be elevated in kidney transplant recipients experiencing antibody-mediated rejection (ABMR), which is characterized by vascular inflammation in transplanted kidney. We evaluated the clinical relevance of endocan as markers of microvascular inflammation in patients who underwent kidney transplantation. Plasma and urinary endocan levels were measured in 203 kidney transplant recipients and were compared across different etiologies of allograft dysfunction and various pathologic scores. Both plasma and urinary endocan levels were significantly higher in patients with acute ABMR than those in patients with normal pathology, acute tubular necrosis (ATN), acute pyelonephritis, BK virus associated nephropathy (BKVN), and T-cell mediated rejection (TCMR). Patients with chronic active ABMR also exhibited significantly higher plasma and urinary endocan levels than patients with long-term graft survival. Scores of glomerulitis and peritubular capillaritis, which are typical features of microvascular inflammation, were significantly elevated in patients with higher plasma and/or urinary endocan levels. Furthermore, plasma and urinary endocan levels could effectively discriminate ABMR from ATN, BKVN, and TCMR. Finally, patients exhibiting high urinary and plasma endocan levels in acute ABMR group showed significantly worse renal survival. Altogether, plasma and urinary endocan levels may serve as potential markers of microvascular inflammation in kidney transplant recipients.

We investigated the phenotype and molecular signatures of CD8 + T cell subsets in kidneytransplant recipients (KTRs) with biopsy-proven T cell-mediated rejection (TCMR). We included 121 KTRs and divided them into three groups according to the pathologic or clinical diagnosis: Normal biopsy control (NC)(n = 32), TCMR (n = 50), and long-term graft survival (LTGS)(n = 39). We used flowcytometry and microarray to analyze the phenotype and molecular signatures of CD8 + T cell subsets using peripheral blood from those patients and analyzed significant gene expressions according to CD8 + T cell subsets. We investigated whether the analysis of CD8 + T cell subsets is useful for predicting the development of TCMR. CCR7 + CD8 + T cells significantly decreased, but CD28 null CD57 + CD8 + T cells and CCR7-CD45RA + CD8 + T cells showed an increase in the TCMR group compared to other groups (p<0.05 for each); hence CCR7 + CD8 + T cells showed significant negative correlations to both effector CD8 + T cells. We identified genes significantly associated with the change of CCR7 + CD8 + T, CCR7-CD45RA + CD8 + T, and CD28 null CD57 + CD8 + T cells in an ex vivo study and found that most of them were included in the significant genes on in vitro CCR7 + CD8 + T cells. Finally, the decrease of CCR7 + CD8 + T cells relative to CD28 null CD57 + T or CCR7-CD45RA + CD8 + T cells can predict TCMR significantly in the whole clinical cohort. In conclusion, phenotype and molecular signature of CD8 + T subsets showed a significant relationship to the development of TCMR; hence monitoring of CD8 + T cell subsets may be a useful for predicting TCMR in KTRs.

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Background and Aims BK virus nephropathy (BKVN) is one of the significant contributors to allograft dysfunction in kidney transplantation. Because of the lack of effective anti-viral medication, early detection of BKV replication and preemptive management is vital to preserving allograft function. Herein, we investigated the predictive value of urinary exosomal BKV-microRNA for BKVN in the kidney transplantation cohort. Method ARTKT (assessment of immunologic risk and tolerance in kidney transplantation) is a prospective observational cohort in which a total of 420 kidney transplant recipients were enrolled from 7 teaching hospitals in South Korea since 2015. Urine samples were collected at 0.5, 3, 6, 12, and 24 months after kidney transplantation in this cohort. All enrolled patients were reviewed to identify the patients diagnosed with BKVN histologically (biopsy-proven BKVN) and those experienced BK viremia defined as plasma BKV DNA load &gt; 4 log10 copies per mL (presumptive BKVN). Urinary exosomal miR was quantified using real-time reverse transcription PCR. Results 10 patients and 14 patients developed biopsy-proven BKVN and presumptive BKVN, respectively. Because of unavailable urine samples, urinary exosomal BKV-microRNA was investigated in 8 patients with biopsy-proven BKVN and 13 patients with presumptive BKVN. 61 patients with no evidence of BKVN were selected as a negative control. Most of BKVN was developed in a median time of 3.4 months after transplantation. In line with this pattern, urinary exosomal BKV-microRNA peaked at 3 months after transplantation and decreased thereafter in biopsy-proven BKVN and presumptive BKVN, keeping higher value in biopsy-proven BKVN compared to presumptive BKVN after 3 months. At 2 weeks after transplantation, half of the patients with biopsy-proven BKVN showed an early rise of urinary exosomal BKV-microRNA, whereas patients with presumptive BKVN and no evidence of BKVN did not. However, plasma BK virus DNA was not detected in all groups at 2 weeks after transplantation. In multivariate cox proportional hazards model, urinary exosomal BKV-microRNA was significantly associated with biopsy-proven BKVN. Conclusion A urinary exosomal BKV-microRNA increase as early as 2 weeks after kidney transplantation predicts future BKVN development, enabling early intervention.