Chronic kidney disease (CKD) represents a global health issue with a high socioeconomic impact. Beyond a progressive decline of kidney function, patients with CKD are at increased risk of cardiovascular diseases, including heart failure (HF) and sudden cardiac death. HF in CKD can manifest both as HF with reduced ejection fraction and HF with preserved ejection fraction, with the latter further increasing in relative importance in the more advanced stages of CKD. Typical cardiac remodeling characteristics in uremic cardiomyopathy include left ventricular hypertrophy, myocardial fibrosis, cardiac electrical dysregulation, capillary rarefaction, and microvascular dysfunction, which are triggered by increased cardiac preload, cardiac afterload, and preload and afterload-independent factors. The pathophysiological mechanisms underlying cardiac remodeling in CKD are multifactorial and include neurohormonal activation (with increased activation of the renin-angiotensin-aldosterone system, the sympathetic nervous system, and mineralocorticoid receptor signaling), cardiac steroid activation, mitochondrial dysfunction, inflammation, innate immune activation, and oxidative stress. Furthermore, disturbances in cardiac metabolism and calcium homeostasis, macrovascular and microvascular dysfunction, increased cellular profibrotic responses, the accumulation of uremic retention solutes, and mineral and bone disorders also contribute to cardiovascular disease and HF in CKD. Here, we review the current knowledge of HF in CKD, including the clinical characteristics and pathophysiological mechanisms revealed in animal studies. We also elaborate on the detrimental impact of comorbidities of CKD on HF using hypertension as an example and discuss the clinical characteristics of hypertensive heart disease and the genetic predisposition. Overall, this review aims to increase the understanding of HF in CKD to support future research and clinical translational approaches for improved diagnosis and therapy of this vulnerable patient population.

Background: Malignant hypertension, the most severe form of hypertension, is defined by high blood pressure and acute ischemic organ damage. It has a worse prognosis than other forms of hypertension, especially in black patients. New tools to assess organ damage, especially that of the heart and brain, are now available and may contribute to a better evaluation of these patients. This report improves knowledge of the characteristics of involved organs to facilitate diagnosis and to evaluate the effectiveness of our treatment protocol. Method: The Bordeaux registry, started in 1995, recruited 168 patients. In addition to evaluations of their eyes and kidneys, these patients had a systematic evaluation of their hearts with ECG and echocardiography and, since 2007, a systematic brain MRI. Blood pressure was lowered with a protocol based on blockers of the renin–angiotensin system started at a very low-dose with forced titration over 48 h. Only an oral route was used for antihypertensive medication. Results: Systematic MRIs found significant brain damage in 93% of patients. Heart involvement was highly prevalent: 82% had left ventricular mass more than 60 g/m^2.7, and 56% had systolic dysfunction (estimated by global longitudinal strain). Renal involvement and thrombotic microangiopathy were respectively present in 55 and 15% of patients. Median follow-up was 48 months. Renal survival at 5 years was 90.8%, similar to other studies. Conclusion: Malignant hypertension is a systemic disease causing severe damage to the brain, heart, kidneys and eyes, even in absence of symptoms. Renin–angiotensin system blockers seem to be the cornerstone of treatment.

Background: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. Methods: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. Results: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12–23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54–140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. Conclusion: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.

Background: While endothelial dysfunction is suggested to contribute to heart failure with preserved ejection fraction pathophysiology, understanding the importance of the endothelium alone, in the pathogenesis of diastolic abnormalities has not yet been fully elucidated. Here, we investigated the consequences of specific endothelial dysfunction on cardiac function, independently of any comorbidity or risk factor (diabetes or obesity) and their potential effect on cardiomyocyte. Methods: The ubiquitine ligase Pdzrn3 , expressed in endothelial cells (ECs), was shown to destabilize tight junction. A genetic mouse model in which Pdzrn3 is overexpressed in EC (iEC-Pdzrn3) in adults was developed. Results: EC-specific Pdzrn3 expression increased cardiac leakage of IgG and fibrinogen blood-born molecules. The induced edema demonstrated features of diastolic dysfunction, with increased end-diastolic pressure, alteration of dP/dt min, increased natriuretic peptides, in addition to limited exercise capacity, without major signs of cardiac fibrosis and inflammation. Electron microscopic images showed edema with disrupted EC-cardiomyocyte interactions. RNA sequencing analysis of gene expression in cardiac EC demonstrated a decrease in genes coding for endothelial extracellular matrix proteins, which could be related to the fragile blood vessel phenotype. Irregularly shaped capillaries with hemorrhages were found in heart sections of iEC- Pdzrn3 mice. We also found that a high-fat diet was not sufficient to provoke diastolic dysfunction; high-fat diet aggravated cardiac inflammation, associated with an altered cardiac metabolic signature in EC- Pdzrn3 mice, reminiscent of heart failure with preserved ejection fraction features. Conclusions: An increase of endothelial permeability is responsible for mediating diastolic dysfunction pathophysiology and for aggravating detrimental effects of a high-fat diet on cardiac inflammation and metabolism.

The risk of chronic kidney disease (CKD) following severe acute kidney injury (AKI) in critically ill patients is well documented, but not after less severe AKI. The main objective of this study was to evaluate the long-term incidence of CKD after non-severe AKI in critically ill patients. This prospective single-center observational three-years follow-up study was conducted in the medical intensive care unit in Bordeaux’s hospital (France). From 2013 to 2015, all patients with severe (kidney disease improving global outcomes (KDIGO) stage 3) and non-severe AKI (KDIGO stages 1, 2) were enrolled. Patients with prior eGFR < 90 mL/min/1.73 m² were excluded. Primary outcome was the three-year incidence of CKD stages 3 to 5 in the non-severe AKI group. We enrolled 232 patients. Non-severe AKI was observed in 112 and severe AKI in 120. In the non-severe AKI group, 71 (63%) were male, age was 62 ± 16 years. The reason for admission was sepsis for 56/112 (50%). Sixty-two (55%) patients died and nine (8%) were lost to follow-up. At the end of the follow-up the incidence of CKD was 22% (9/41); Confidence Interval (CI) _95% (9.3–33.60)% in the non-severe AKI group, tending to be significantly lower than in the severe AKI group (44% (14/30); CI _95% (28.8–64.5)%; p = 0.052). The development of CKD three years after non-severe AKI, despite it being lower than after severe AKI, appears to be a frequent event highlighting the need for prolonged follow-up.