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Background Developing a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells' proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection. Methods Using 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets. Results An exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature's negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell-mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature's negative predictive value was 90.6% and its positive predictive value was 77.8%. Conclusions Our findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.

BACKGROUND Sacrificing the superior petrosal vein (SPV) is controversial during a microvascular decompression (MVD). There have been multiple reports of complications including life-threatening brainstem infarction and cerebellar edema. OBJECTIVE To analyze the potential for vascular complications when the SPV is sacrificed during an MVD. METHODS Retrospective chart review was performed to identify all MVDs for trigeminal neuralgia and hemifacial spasm from 2007 to 2018 at 1 institution. Cases with ≥1 mo of follow-up were included and SPV sacrifice was noted. The primary outcome was complications related to SPV sacrifice including sinus thrombosis, cerebellar edema, and midbrain or pontine infarction. Imaging was used to confirm all potential vascular complications noted in medical records. Fisher's exact test and unpaired t-tests were used to compare between groups. RESULTS A total of 732 MVD cases were identified and 592 met inclusion criteria with an average follow-up of 11.8 ± 16.4 mo and a male-to-female ratio of 1:2.2. The SPV was sacrificed in 217 cases and retained in 375 cases. No SPV-related vascular complications were found in this study. Two unrelated cases of vascular complications were identified and both were in the nonsacrificed group. One case involved cerebellar bleeding while the other was an ipsilateral transverse sinus thrombosis that was present preoperatively. CONCLUSION In MVDs, there is no difference in the rate of vascular complications when the SPV is sacrificed compared to preserved. To best visualize a cranial nerve and optimize safe decompression, surgeons should feel free to sacrifice the SPV.