No abstract

The conference agenda, discussion questions, and plenary session presentations are available on the KDIGO website: https://kdigo.org/ conferences/controversies-conference-on-coronary-artery-valvulardisease/. 18 THM and MJS are primary co-authors.

Cellular senescence has been suggested to play a role in the deterioration of renal graft function and has been linked to telomere shortening. We have investigated markers of cellular senescence in the F344 to LEW rat model of chronic renal transplant rejection. Syngeneic and LEW to F344 transplants were used as controls. Substantial telomere shortening was observed in all transplants, including allogeneic and syngeneic grafts from day 7 post-transplant onwards. Ischemia of native F344 kidneys was already sufficient to induce telomere shortening. It is known that shortened telomeres can activate cell cycle regulators, such as p21 and p16. Accordingly, all cases showed a transient p21 increase, with a maximum at day 7 and a sustained expression of p16. Importantly, senescence-associated ␤-galactosidase staining, a cytological marker for senescence, was only observed in tubular epithelial cells of chronically rejecting F344 allografts from day 30 post-transplantation onwards. Long-term surviving LEW allografts or syngeneic F344 grafts were negative for senescence-associated ␤-galactosidase. In conclusion, ischemia during transplantation results in telomere shortening and subsequent activation of p21 and p16, whereas senescence-associated ␤-galactosidase staining is only present in chronically rejecting kidney grafts.

BackgroundLeft ventricular hypertrophy (LVH) is common in patients with end-stage renal disease (ESRD) and an independent risk factor for premature cardiovascular death. Left atrial volume (LAV), measured using echocardiography, predicts death in patients with ESRD. Cardiovascular magnetic resonance (CMR) imaging is a volume-independent method of accurately assessing cardiac structure and function in patients with ESRD.Study DesignSingle-center prospective observational study to assess the determinants of all-cause mortality, particularly LAV, in a cohort of ESRD patients with LVH, defined using CMR imaging.Setting & Participants201 consecutive ESRD patients with LVH (72.1% men; mean age, 51.6 ± 11.7 years) who had undergone pretransplant cardiovascular assessment were identified using CMR imaging between 2002-2008. LVH was defined as left ventricular mass index >84.1 g/m2 (men) or >74.6 g/m2 (women) based on published normal left ventricle dimensions for CMR imaging. Maximal LAV was calculated using the biplane area-length method at the end of left ventricle systole and corrected for body surface area.PredictorsCMR abnormalities, including LAV.OutcomeAll-cause mortality.Results54 patients died (11 after transplant) during a median follow-up of 3.62 years. Median LAV was 30.4 mL/m2 (interquartile range, 26.2-58.1). Patients were grouped into high (median or higher) or low (less than median) LAV. There were no significant differences in heart rate and mitral valve Doppler early to late atrial peak velocity ratio. Increased LAV was associated with higher mortality. Kaplan-Meier survival analysis showed poorer survival in patients with higher LAV (log rank P = 0.01). High LAV and left ventricular systolic dysfunction conferred similar risk and were independent predictors of death using multivariate analysis.LimitationsOnly patients undergoing pretransplant cardiac assessment are included. Limited assessment of left ventricular diastolic function.ConclusionsHigher LAV and left ventricular systolic dysfunction are independent predictors of death in ESRD patients with LVH.