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The wide overlap between the syndromes of chronic kidney disease (CKD) and chronic heart failure (HF) means that familiarity with the 2021 European Society of Cardiology guidelines is of importance to nephrologists. The common risk factors for the two syndromes together with the adverse cardiac structural remodelling associated with CKD means that many kidney disease patients experience breathlessness and fall within the HF phenotypes categorized in the guidelines. The management of HF is evolving rapidly leading to significant changes in the latest guideline iteration. The 2021 guidelines have changed from the 2016 version firstly by an increased focus on identifying the three phenotypes of HF to guide appropriate evidence-based management. Secondly, a new and simplified treatment algorithm for HF with reduced ejection fraction involving the rapid sequential initiation and up-titration of four ‘pillars’ of drug treatment—angiotensin-converting enzyme inhibitors or angiotensin-neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists and now, thanks to convincing trial data, sodium-glucose co-transporter 2 inhibitors. Thirdly, guidelines for device therapy have been changed with down-graded advice on indications for primary prevention implantable cardioverter defibrillator therapy for patients with non-ischaemic HF and for cardiac resynchronization therapy with left bundle branch block (LBBB) and a QRS duration

Background and Aims Uraemic cardiomyopathy is characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis. Diffuse interstitial fibrosis of the myocardium, assessed using cardiac magnetic resonance imaging (CMR) techniques of native T1-mapping and extracellular volume (ECV), has been demonstrated in end stage chronic kidney disease (CKD) and in patients with stage 3 CKD and normal left ventricular mass. In living kidney donors estimated glomerular filtration rate (eGFR) declines by a third after donation, with 60% having a resultant eGFR comparable with stage 3 CKD. Recent studies have demonstrated small increases in LV mass at 12 months after donation as well as functional sequelae of reduced global circumferential strain and apical torsion. We sought to establish whether living kidney donors had CMR evidence of diffuse interstitial cardiac fibrosis which might contribute to observed functional correlates. Method A cross sectional blinded study of living kidney donors (n=50) and healthy controls (n=45) who underwent 3 Tesla CMR and blood samples for biomarkers of fibrosis. A modified look-locker inversion recovery (MOLLI) 5(3)3 sampling scheme was used for T1 mapping followed by T2 mapping sequences at the mid LV slice. Five minutes after the administration of gadolinium (Gadovist®) contrast (0.15mmol/kg), standard T1-weighted gradient echo inversion recovery images were repeated for the assessment of late gadolinium enhancement (assessment for focal fibrosis). Post contrast MOLLI images were acquired using identical slice positions as native images using a 4(1)3(1)2 sampling scheme 15 minutes after the administration of gadolinium. Native and post contrast T1 time was used to calculate ECV. Results There were no differences in demographics between groups; age (donors 54 ± 12yrs vs. healthy controls 50 ± 13yrs, p=0.128), ethnicity (89% Caucasian) or male gender (37%). LV mass and volumes were not significantly different. Forty four donors and 34 controls consented to receive gadolinium contrast. Native T1 in the septal mid LV slice was not significantly different between groups (donors 1223 ± 35ms vs. controls 1210 ± 36ms, p=0.102). There was also no difference in T2 time of the septal mid LV slice (donors 40 ± 2ms vs. controls 40 ± 4ms vs. p=0.455). Late gadolinium enhancement was seen in five living kidney donors in a right ventricular insertion point pattern but there was no mid wall or ischaemic pattern enhancement. There was no difference in septal ECV at the mid LV slice (donors 25 ± 2% vs. controls 25 ± 2%, p=0.896). There was also no corresponding difference in fibroblast growth factor-23 (RU/ml) in donors 74 [58-105] vs. controls 59 [47-75], p=0.081 or soluble α-klotho (pg/ml) in donors 610 [503-810] vs. controls 703 [550-955], p=0.061. Conclusion Septal T1 times and ECV in living kidney donors at 5 years from donation are no different from healthy controls. Biomarkers of cardiac fibrosis are also comparable to healthy controls in this small cohort. We found no CMR evidence of the ultrastructural changes reported in uraemic cardiomyopathy in the hearts of living kidney donors at 5 years from donation.

Background and Aims Chronic kidney disease (CKD) is a highly prevalent risk factor for cardiovascular disease with an inverse relationship between estimated glomerular filtration rate (eGFR) and increases in all-cause and cardiovascular mortality. Living kidney donation provides a model to study the cardiovascular effects of a reduced kidney function in previously healthy subjects without comorbidities. We report follow up results in a group of kidney donors and healthy controls who underwent cardiovascular assessment at baseline, 12 months and 5 years after nephrectomy in the CRIB-DONOR studies (NCT01028703, NCT02973607). Method A longitudinal blinded end point study of kidney donors (n=50) and healthy controls (n=45) followed up between May 2017 to May 2019. Participants underwent a cardiac MRI (3.0 Tesla) for assessment of left ventricular (LV) size, mass, systolic function (ejection fraction and 3-dimensional feature tracking) and aortic distensibility. Clinical assessment included; office and 24-hr ambulatory blood pressure measures, measurement of arterial stiffness (SphygmoCor) and blood and urine analysis. Results Mean follow up time was 5.7 ± 0.7 yrs. Mean eGFR in donors was 95 ± 15 ml/min/1.73m2 prior to donation, 65 ±13ml/min/1.73m2 at 12 months and 67 ± 14 ml/min/1.73m2 at 5 years. This compared with an annual decline in eGFR of -1ml/min/1.73m2 in healthy controls. Despite a rise in LV mass at 12 months in the original study, by 5 years, LV mass in donors was no different to controls (113 ± 31g vs. 115 ± 30g, p=0.707). There was also no significant difference in LV volumes or LV geometry. At 5 years, 3D global longitudinal strain (donors -16.2 ± 2.5% vs. controls -14.9 ± 2.1%, p=0.007) and 3D global circumferential strain (donors -19.0 ± 2.5% vs. controls -17.7 ± 2.2%, p=0.004) were marginally greater in donors than controls. Markers of vascular stiffness (pulse wave velocity and augmentation index) were increased in donors compared to controls at 12 months but at 5 years they were not significantly different. No changes in office or ambulatory blood pressure were observed at any time point in donors or controls. At 5 years, uric acid was significantly greater in donors than controls (335 ± 83 µmol/L vs. 276 ± 7, p= Conclusion The reduction in eGFR associated with nephrectomy in living kidney donors in the absence of intrinsic renal disease or comorbidity does not lead to adverse changes in cardiovascular structure and function at 5 years. This study offers reassurance to living kidney donors and the transplant community but should prompt further work into the causes of cardiovascular disease in CKD as we have found no medium term deleterious cardiovascular effects of an isolated reduction in eGFR.

Background. The rate of decline in kidney function is a powerful predictor of cardiovascular risk in patients with chronic kidney disease (CKD). Serum phosphate and increased arterial stiffness are associated with elevated cardiovascular risk in CKD and the general population. We sought to determine whether serum phosphate and markers of arterial stiffness predict progression of renal dysfunction in patients with early CKD. Methods. Two hundred and twenty-five patients with Stage II–IV CKD were prospectively followed up at University Hospital Birmingham. Serum phosphate was measured at baseline and arterial stiffness was determined through measurement of aortic pulse wave velocity (PWV) and augmentation index (AIx). Progression of renal dysfunction was defined as the slope of estimated glomerular filtration rate (eGFR) against time. We determined the associations between possible predictors and rate of progression and also examined a combined end point of start of dialysis or � 25% decline in eGFR. Results. Mean baseline eGFR was 43 6 19 mL/min/1.73 m 2 and serum phosphate 1.22 6 0.27 mmol/L. Median followup was 924 days. Serum phosphate independently predicted a greater decline in eGFR; a 1 mmol/L increment in serum phosphate was associated with a 0.34 mL/min/month steeper decline (P ¼ 0.02). Brachial and aortic systolic pressure independently predicted the rate of renal function decline but aortic PWV and AIx had no significant influence. Forty-one patients (18%) reached the combined end point; serum phosphate was significantly higher in this group (1.32 6 0.36 versus 1.19 6 0.24 mmol/L, P ¼ 0.04) and was an independent predictor for the combined end point. Conclusions. Serum phosphate independently predicts decline in renal function in early CKD. Further studies are required to determine the mechanisms involved and to investigate the potential benefits of phosphate lowering on preserving kidney function.