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Chronic kidney disease (CKD) is a risk factor for premature cardiovascular disease. As kidney function declines, the presence of left ventricular abnormalities increases such that by the time kidney replacement therapy is required with dialysis or kidney transplantation, more than two-thirds of patients have left ventricular hypertrophy. Historically, much research in nephrology has focussed on the structural and functional aspects of cardiac disease in CKD, particularly using echocardiography to describe these abnormalities. There is a need to translate knowledge around these imaging findings to clinical outcomes such as unplanned hospital admission with heart failure and premature cardiovascular death. Left ventricular hypertrophy and cardiac fibrosis, which are common in CKD, predispose to the clinical syndrome of heart failure with preserved left ventricular ejection fraction (HFpEF). There is a bidirectional relationship between CKD and HFpEF, whereby CKD is a risk factor for HFpEF and CKD impacts outcomes for patients with HFpEF. There have been major improvements in outcomes for patients with heart failure and reduced left ventricular ejection fraction as a result of several large randomized controlled trials. Finding therapy for HFpEF has been more elusive, although recent data suggest that sodium-glucose cotransporter 2 inhibition offers a novel evidence-based class of therapy that improves outcomes in HFpEF. These observations have emerged as this class of drugs has also become the standard of care for many patients with proteinuric CKD, suggesting that there is now hope for addressing the combination of HFpEF and CKD in parallel. In this review we summarize the epidemiology, pathophysiology, diagnostic strategies and treatment of HFpEF with a focus on patients with CKD.

Introduction:\ud \ud End stage renal disease (ESRD) is the irreversible deterioration of renal function requiring renal replacement therapy by dialysis or transplant. Human leucocyte antigens (HLA) have been well examined however research still is required into the non-HLA antibodies. Antibody mediated rejection (AMR) can be seen in the absence of HLA antibodies on biopsies of patients who have received identical transplants; anti-endothelial cell antibodies may explain this. Investigation into endothelial cell antigens on donor and recipient endothelium may elucidate and stratify the degree of risk of any given transplant and may guide towards the best matched donor.\ud \ud Methods:\ud \ud Protein array analysis was carried out on 8 patient pairs using nitro-cellulose membranes and biotinylated detection antibodies. The fluorescence emitted was captured by X-Ray film and results were recorded with ImageJ software. A fold increase of more than 2 was considered to be positive.\ud \ud Results:\ud \ud 11 proteins identified had a fold increase of increase ≥2 and were present in ≥2 patient pairs which may point to potential clinical utility. Nectin2/CD112 may be measured in order analyse graft survival time in transplant recipients. Prognosticating renal failure has clinical importance and potential markers that have been identified to aid which include MEPE, CRELD2, and TIMP-4. Novel pharmacological therapies for specific biomarkers identified in this study include JAM-A, E-Selectin, CD147, Galectin-3, JAM-C, PAR-1, and TNFR2.\ud \ud Conclusion:\ud \ud Protein analysis showed differences in expression of antigens between patients with and without Chronic Kidney Disease (CKD). This information could be used at the matching stage of renal transplantation and also in the treatment of rejection episodes. The results highlight biomarkers that potentially prognosticate and pharmacological therapies that may ameliorate kidney disease and rejection in ESRD and transplant recipients.

Background:\ud Patients with end-stage kidney disease (ESKD) are at increased risk premature death, with cardiovascular disease being the predominant mode of death. We hypothesized that left ventricular global longitudinal strain (LV-GLS) measured by feature tracking cardiovascular magnetic resonance imaging (CMR) would be associated with all-cause mortality in patients with ESKD.\ud \ud Methods:\ud A pooled analysis of CMR studies in patients with ESKD acquired within a single centre between 2002 and 2016 was carried out. CMR parameters including left ventricular ejection fraction (LVEF), LV mass index (LVMI), left atrial emptying fraction (LAEF) and LV-GLS were measured. We tested independent associations of CMR parameters with survival using a multivariable Cox model.\ud \ud Results:\ud Among 215 patients (mean age: 54 years, 62% male), mortality was 53% over 5.0 years median follow-up. The median LVEF was 64.7% (IQR 58.5, 70.0) and median LV-GLS was -15.3% (-17.24, -13.6). While 90% of patients had preserved LVEF (>50%), 58% of this group had abnormal LVGLS (>-16%). On multivariable Cox regression, age (HR: 1.04, 95%CI: 1.02-1.05), future-renal transplant (HR 0.29 95%CI: 0.17-0.47), LAEF (HR: 0.98, 95%CI: 0.96-1.00) and LV-GLS (HR: 1.08, 95%CI: 1.01-1.16) were independently associated with mortality.\ud \ud Conclusions:\ud In this cohort of patients with ESKD, LV-GLS on feature tracking CMR and LAEF were associated with all-cause mortality, independent of baseline clinical variables and future renal transplantation. This effect was present even when >90% of the cohort had normal left ventricular ejection fraction (LVEF). Using LV-GLS, instead of LVEF, to diagnose cardiac dysfunction in patients with ESKD could result in a major advance in our understanding of cardiovascular disease in ESKD.