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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.

Characterizing structural and tissue abnormalities of the kidney is fundamental to understanding kidney disease. Functional multi-parametric renal magnetic resonance imaging (MRI) is a noninvasive imaging strategy whereby several sequences are employed within a single session to quantify renal perfusion, tissue oxygenation, fibrosis, inflammation, and oedema without using ionizing radiation. In this review, we discuss evidence surrounding its use in several clinical settings including acute kidney injury, chronic kidney disease, hypertension, polycystic kidney disease and around renal transplantation. Kidney size on MRI is already a validated measure for making therapeutic decisions in the setting of polycystic kidney disease. Functional MRI sequences, T1 mapping and apparent diffusion coefficient, can non-invasively quantify interstitial fibrosis and so may have a near-future role in the nephrology clinic to stratify the risk of progressive chronic kidney disease or transplant dysfunction. Beyond this, multi-parametric MRI may be used diagnostically, for example differentiating inflammatory versus ischaemic causes of renal dysfunction, but this remains to be proven. Changes in MRI properties of kidney parenchyma may be useful surrogate markers to use as end points in clinical trials to assess if drugs prevent renal fibrosis or alter kidney perfusion. Large, multi-centre studies of functional renal MRI are ongoing which aim to provide definitive answers as to its role in the management of patients with renal dysfunction.

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.

Additional file 1. Supplementary material: S1. Baseline characteristics of participants. S2. Summary of clinically significant incidental findings. S3. Intra- and inter-observer reproducibility for cardiovascular MRI parameters. S4. Determinants of blood pool native T1. S5. Analyses exploring the potential influence of intravenous iron therapy on native T1.

Additional file 2. Sensitivity Analysis (with 3 outliers excluded) Results and Scatterplot.

Additional file 1. Flowchart of cardiovascular magnetic resonance (CMR) and computed tomography (CT) scans available for analysis.

Additional file 3. Sensitivity Analysis Bland-Altman plot.

Background:\ud The clinical significance of common histological parameters in acute interstitial nephritis (AIN) is uncertain. We aimed to evaluate the utility of histology in predicting clinical outcomes in patients with AIN.\ud \ud Methods and results:\ud Adult renal biopsies yielding a diagnosis of AIN between 2000 and 2015 were re‐examined. Patients were divided into groups based on: 1) the percentage of non‐fibrotic cortex containing inflammation (NFI‐score), (NFI‐1=0‐24%, NFI‐2=25‐74%, NFI‐3=75‐100%), and 2) the percentage of cortex containing tubular atrophy (TA score), (TA1=0‐9%, TA2=10‐24%, TA3=25‐100%). The primary outcome was a composite of ≥50% reduction in serum creatinine (sCr) or an eGFR >60 ml/min/1.73m2 1‐year post‐biopsy. From a total of 2817 native renal biopsies, there were 120 patients with AIN and adequate data for analysis. Of these, 66 (56%) achieved the primary outcome. On univariable logistic regression, NFI‐3 was associated with a 16 times increased likelihood of achieving the primary outcome compared to NFI‐1 (OR 16 (95% CI 5.2‐50)). In contrast, TA3 were associated with a 90% reduced likelihood of achieving the primary outcome compared to TA1 (OR=0.10 (95%CI 0.0‐0.3)). Maximal clinical utility was achieved by combining TA and NFI into a single prognostic ‘TANFI’ score, which had an independent predictive effect on the primary outcome in a multivariable regression model consisting of age, sex, baseline sCr and identified drug cause.\ud \ud Conclusions:\ud In patients with biopsy‐proven AIN, a lower percentage of cortical tubular atrophy and, paradoxically, a higher percentage of inflammation in non‐fibrosed cortex were associated with an increased likelihood of a positive clinical outcome.