A molecular signature for delayed graft function.

Chronic kidney disease and associated comorbidities (diabetes, cardiovascular diseases) manifest with an accelerated ageing phenotype, leading ultimately to organ failure and renal replacement therapy. This process can be modulated by epigenetic and environmental factors which promote loss of physiological function and resilience to stress earlier, linking biological age with adverse outcomes post-transplantation including delayed graft function (DGF). The molecular features underpinning this have yet to be fully elucidated. We have determined a molecular signature for loss of resilience and impaired physiological function, via a synchronous genome, transcriptome and proteome snapshot, using human renal allografts as a source of healthy tissue as an in vivo model of ageing in humans. This comprises 42 specific transcripts, related through IFNγ signalling, which in allografts displaying clinically impaired physiological function (DGF) exhibited a greater magnitude of change in transcriptional amplitude and elevated expression of noncoding RNAs and pseudogenes, consistent with increased allostatic load. This was accompanied by increased DNA methylation within the promoter and intragenic regions of the DGF panel in preperfusion allografts with immediate graft function. Pathway analysis indicated that an inability to sufficiently resolve inflammatory responses was enabled by decreased resilience to stress and resulted in impaired physiological function in biologically older allografts. Cross-comparison with publically available data sets for renal pathologies identified significant transcriptional commonality for over 20 DGF transcripts. Our data are clinically relevant and important, as they provide a clear molecular signature for the burden of "wear and tear" within the kidney and thus age-related physiological capability and resilience.

Repair of radial tears and posterior horn detachments of the lateral meniscus: minimum 2-year follow-up.

PURPOSE: The aim of this study was to show that repair of posterior radial tears and horn detachments of the lateral meniscus is possible and to assess the outcomes. METHODS: A retrospective review of 24 patients who had repair of a posterior defunctioning tear of the lateral meniscus combined with anterior cruciate ligament reconstruction was undertaken. Patients completed a follow-up postal questionnaire that included Lysholm, subjective International Knee Documentation Committee (IKDC), and Tegner scoring systems. RESULTS: Eight patients had suture repair of a lateral meniscal radial tear. The mean Lysholm, IKDC, and Tegner scores were 86.9 (SD, 11.6), 81.6 (SD, 13.9), and 5.8 (SD, 2.7), respectively, at a mean follow-up of 70.5 months (range, 29.0 to 168.0 months). Subsequent arthroscopy in 2 patients confirmed meniscal healing. Sixteen patients underwent a posterior horn reattachment. The mean Lysholm, subjective IKDC, and Tegner scores were 86.1 (SD, 13.3), 84.3 (SD, 17.0), and 6.5 (SD, 2.1), respectively, at a mean follow-up of 53.6 months (range, 26.0 to 116.0 months). Three patients had subsequent magnetic resonance imaging and/or arthroscopy that indicated meniscal healing. Two further patients had reinjury, and magnetic resonance imaging and/or arthroscopy showed that their repairs had failed. CONCLUSIONS: Posterior radial tears that extend to the capsule and posterior horn detachments of the lateral meniscus are frequently amenable to repair. In this study 22 of 24 repairs functioned successfully over a mean follow-up of 58.6 months (range, 26.0 to 168.0 months). LEVEL OF EVIDENCE: Level IV, therapeutic case series.