Interrelation between heart failure with preserved ejection fraction and renal impairment.

Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) are global diseases of increasing prevalence and are frequent co-diagnoses. The two conditions share common risk factors and CKD contributes to HFpEF development by a variety of mechanisms including systemic inflammation and myocardial fibrosis. HFpEF patients with CKD are generally older and have more advanced disease. CKD is a poor prognostic indicator in HFpEF, while the impact of HFpEF on CKD prognosis is not sufficiently investigated. Acute kidney injury (AKI) is common during admission with acute decompensated HFpEF, but short and long-term outcomes are not clear. Pharmacological treatment options for HFpEF are currently minimal, and even more so limited in the presence of CKD with hyperkalaemia being one of the main concerns encountered in clinical practice. Recent data on the role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of HFpEF are encouraging, especially in light of the abundance of evidence supporting improved renal outcomes. Herein, we review the pathophysiological links between HFpEF and CKD, the clinical picture of dual diagnosis, as well as concerns with regards to renal impairment in the context of HFpEF management.

The role of sodium-glucose co-transporter (SGLT)-2 inhibitors in heart failure management and implications for the kidneys.

Sodium-glucose co-transporter (SGLT)-2 inhibitors were initially developed for management of type 2 diabetes but have been shown to offer improved outcomes in heart failure, a condition in which concomitant chronic kidney disease (CKD) is common. Randomised controlled trials initially demonstrated prognostic cardiovascular and renal benefits of SGLT2 inhibitors in high cardiovascular risk individuals with type 2 diabetes particularly in relation to heart failure. Improved outcomes have been replicated in cohorts with established heart failure and/or CKD and appear to extend in those without diabetes. Several specific agents have been considered, with evidence of a class effect, and dapagliflozin and empagliflozin are now incorporated into major international cardiovascular guidelines for management of heart failure with reduced ejection fraction. Beyond glucose lowering effects the mechanisms mediating SGLT2 inhibitors favourable actions are not fully elucidated. Haemodynamic alterations, natriuresis, osmotic diuresis, and weight loss likely contribute to improved outcomes, along with an enhanced cardiometabolic profile. The functional drop in estimated glomerular filtration rate (eGFR) which accompanies SGLT2 inhibitor initiation, before eGFR stabilisation, is likely central in the observed renal benefits. In this review we discuss in detail the evidence for SGLT2 inhibitors in heart failure, particularly with regard to kidney health.

COVID-19-related acute kidney injury; incidence, risk factors and outcomes in a large UK cohort.

BACKGROUND: Acute kidney injury (AKI) is common among patients hospitalised with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in patients with COVID-19 in a large UK tertiary centre. METHODS: We analysed data of consecutive adults admitted with a laboratory-confirmed diagnosis of COVID-19 across two sites of a hospital in London, UK, from 1st January to 13th May 2020. RESULTS: Of the 1248 inpatients included, 487 (39%) experienced AKI (51% stage 1, 13% stage 2, and 36% stage 3). The weekly AKI incidence rate gradually increased to peak at week 5 (3.12 cases/100 patient-days), before reducing to its nadir (0.83 cases/100 patient-days) at the end the study period (week 10). Among AKI survivors, 84.0% had recovered renal function to pre-admission levels before discharge and none required on-going renal replacement therapy (RRT). Pre-existing renal impairment [odds ratio (OR) 3.05, 95%CI 2.24-4,18; p <  0.0001], and inpatient diuretic use (OR 1.79, 95%CI 1.27-2.53; p <  0.005) were independently associated with a higher risk for AKI. AKI was a strong predictor of 30-day mortality with an increasing risk across AKI stages [adjusted hazard ratio (HR) 1.59 (95%CI 1.19-2.13) for stage 1; p < 0.005, 2.71(95%CI 1.82-4.05); p < 0.001for stage 2 and 2.99 (95%CI 2.17-4.11); p < 0.001for stage 3]. One third of AKI3 survivors (30.7%), had newly established renal impairment at 3 to 6 months. CONCLUSIONS: This large UK cohort demonstrated a high AKI incidence and was associated with increased mortality even at stage 1. Inpatient diuretic use was linked to a higher AKI risk. One third of survivors with AKI3 exhibited newly established renal impairment already at 3-6 months.

Evaluation of novel coagulation and platelet function assays in patients with chronic kidney disease.

BACKGROUND: Hemostasis evaluation in chronic kidney disease (CKD) is critical for optimal management of thrombotic and bleeding events. Standard coagulation screens are inadequate for predicting coagulopathy in CKD. OBJECTIVE: To evaluate hemostasis parameters in patients with different stages of CKD using novel coagulation assays. PATIENTS/METHODS: Cross-sectional study of 30 healthy controls (HC) and 120 CKD patients (10 Stage 2, 20 Stage 3, 20 Stage 4, 20 Stage 5 not requiring renal replacement therapy, 20 transplant, 10 newly started on hemodialysis [HD], 20 established on HD). Standard laboratory tests were performed in addition to rotational thromboelastometry (ROTEM), multiple electrode aggregometry (MEA), thrombin generation assays, D-dimer, and markers of thrombogenesis (thrombin-antithrombin [TAT]), fibrinolysis, and endothelial activation (intercellular adhesion molecule-1 [ICAM-1]). RESULTS: D-dimer, TAT, and ICAM-1 concentrations were significantly higher in patients with CKD than HC (P < .01). ROTEM maximum clot firmness was significantly higher in patients than in HC (P < .01). In CKD Stage 5 patients (pre-HD and started HD) adenosine diphosphate and thrombin receptor activating peptide MEA tests were significantly lower than HC indicating platelet aggregation defect (P < .05). Multivariate analysis confirmed the direct effect of estimated glomerular filtration rate (eGFR) in the variance of ROTEM and MEA tests. Endogenous thrombin potential and peak thrombin were not statistically different between groups, but Stage 5 CKD patients had prolonged lag time (7.91 vs. 6.33, P < .001) and time to thrombin peak (10.8 vs. 9.5, P < .05) compared to HC. CONCLUSIONS: Patients with CKD exhibit features of concomitant hypercoagulability measured by ROTEM and platelet dysfunction measured with MEA. eGFR was an independent determinant of platelet dysfunction and hypercoagulability.

Critically Ill COVID-19 Patients With Acute Kidney Injury Have Reduced Renal Blood Flow and Perfusion Despite Preserved Cardiac Function: A Case-Control Study Using Contrast-Enhanced Ultrasound.

BACKGROUND: Acute kidney injury (AKI) is a common complication of COVID-19 critical illness but the pathophysiology is uncertain. Some evidence has indicated that a vascular aetiology may be implicated. We used contrast-enhanced ultrasound (CEUS) and echocardiography to study renal perfusion and global blood flow and compared our findings with measurements taken in a group of septic shock patients and healthy volunteers. METHODS: Prospective case-control study. Renal perfusion variables were assessed with CEUS; macrovascular blood flow was assessed using Doppler analysis of large renal vessels; echocardiography was used to assess right and left heart function and cardiac output. RESULTS: CEUS-derived parameters were reduced in COVID-19 associated AKI compared with healthy controls (perfusion index 3,415 vs. 548 a.u., P = 0·001; renal blood volume 7,794 vs. 3,338 a.u., P = 0·04). Renal arterial flow quantified using time averaged peak velocity was also reduced compared with healthy controls (36·6 cm/s vs. 20·9 cm/s, P = 0.004) despite cardiac index being similar between groups (2.8 L/min/m2 vs. 3.7 L/min/m2, P = 0.07). There were no differences in CEUS-derived or cardiac parameters between COVID-19 and septic shock patients but patients with septic shock had more heterogeneous perfusion variables. CONCLUSION: Both large and small vessel blood flow is reduced in patients with COVID-19 associated AKI compared with healthy controls, which does not appear to be a consequence of right or left heart dysfunction. A reno-vascular pathogenesis of COVID-19 AKI seems likely.

Acute Peritoneal Dialysis With Percutaneous Catheter Insertion for COVID-19-Associated Acute Kidney Injury in Intensive Care: Experience From a UK Tertiary Center.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic in 2020, high rates of acute kidney injury (AKI) in critically unwell patients are being reported, leading to an increased demand for renal replacement therapy (RRT). Providing RRT for this large number of patients is proving challenging, and so alternatives to continuous renal replacement therapies (CRRT) in the intensive care unit (ICU) are needed. Peritoneal dialysis (PD) can be initiated immediately after percutaneous insertion of the catheter, but there are concerns about impact on ventilation and RRT efficacy. We sought to describe our recent experience with percutaneous catheter insertion and peritoneal dialysis in patients in the ICU with COVID-19 infection. METHOD: Patients were selected according to local protocol, and catheters were inserted percutaneously by experienced operators using a Seldinger technique. Sequential Organ Failure Assessment (SOFA) score and ventilation requirements were recorded at the time of insertion and 24 hours later. Procedural complications, proportion of RRT provided by PD, renal recovery, and RRT parameters (serum potassium and maximum base excess) during PD were assessed. RESULTS: Percutaneous PD catheters were successfully inserted in 37 of 44 patients (84.1%) after a median of 13.5 days (interquartile range [IQR] = 10.0, 20.3 days) in the ICU. No adverse events were reported; SOFA scores and ventilation requirements were comparable before and after insertion; and adequate RRT parameters were achieved. The median proportion of RRT provided by PD following catheter insertion was 94.6% (IQR = 75.0, 100%). CONCLUSION: Peritoneal dialysis provides a safe and effective alternative to CRRT in selected patients with AKI and COVID-19 infection requiring ventilation on intensive care.

Predisposition to superimposed preeclampsia in women with chronic hypertension: endothelial, renal, cardiac, and placental factors in a prospective longitudinal cohort.

OBJECTIVE: To assess the contribution of maternal and placental factors to the development of superimposed preeclampsia in women with chronic hypertension. METHODS: Endothelial and renal function markers were serially assessed in 90 pregnant women with chronic hypertension and controls. RESULTS: Syndecan-1 concentrations were lower at 26-27+6 weeks in women with chronic hypertension who subsequently developed superimposed preeclampsia compared with those who did not. Decreased PlGF and raised urine albumin:creatinine ratio were also associated with development of superimposed preeclampsia. CONCLUSION: Decreased syndecan-1 and PlGF concentrations implicate endothelial glycocalyx disturbance and reduced placental angiogenic capacity, respectively, in the pathophysiology of superimposed preeclampsia.

Recognition and management of acute kidney injury in hospitalised patients can be partially improved with the use of a care bundle.

Acute kidney injury (AKI) is common in hospitalised patients but is known be suboptimally managed; the National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) report in 2009 identified significant failings in AKI care. An audit, using standards suggested by the NCEPOD report, of all adult inpatients with AKI in a large central-London NHS hospital in a 7-day period in 2011 showed poor recognition and management of AKI. In response, an AKI 'care bundle' was developed and deployed throughout the hospital along with a programme of enhanced education. Re-audit in 2013 showed that AKI was significantly more likely to have been recognised by the clinical team than in 2011, and patients with AKI were significantly more likely to have had fluid status clinically assessed and nephrotoxic medication stopped in 2013 than in 2011. There was no significant improvement in fluid administration if assessed as hypovolaemic and compliance with the guideline for prevention of contrast nephropathy. In 2011, all audit measures were met in 3.7% of patient-days versus 8.4% in 2013. More in-depth work is necessary to better understand the factors which limit optimal care.

Care of the critically ill emergency department patient with acute kidney injury.

Introduction. Acute Kidney Injury (AKI) is common and associated with significant mortality and complications. Exact data on the epidemiology of AKI in the Emergency Department (ED) are sparse. This review aims to summarise the key principles for managing AKI patients in the ED. Principal Findings. Timely resuscitation, goal-directed correction of fluid depletion and hypotension, and appropriate management of the underlying illness are essential in preventing or limiting AKI. There is no specific curative therapy for AKI. Key principles of secondary prevention are identification of patients with early AKI, discontinuation of nephrotoxic medication where possible, attention to fluid resuscitation, and awareness of the risks of contrast-induced nephropathy. In patients with advanced AKI, arrangements for renal replacement therapy need to be made before the onset of life-threatening uraemic complications. Conclusions. Research and guidelines regarding AKI in the ED are lacking and AKI practice from critical care departments should be adopted.