Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Practical Requirements for the Development of an Advanced Cardiorenal Unit.

BACKGROUND: Heart failure is frequently associated with kidney disease, and patients with kidney disease are at increased risk of heart failure. The co-occurrence of both entities not only significantly increases morbidity and mortality but also complicates therapy. SUMMARY: Cardiorenal syndrome often requires a broad, comprehensive, and multidisciplinary approach. As a result, a need has arisen to create specialized cardiorenal units that allow for rigorous and personalized management of this condition. Moreover, in some cases, cardiorenal syndrome is more complex, owing to an acute and critical situation that requires the concept of the cardiorenal unit to be extended toward advanced diagnostic and therapeutic positions, thus confirming the need for an advanced cardiorenal unit. The creation of these units constitutes a real challenge, necessitating a specific multilevel action plan, covering governance and management, type of patient, personnel requirements, service portfolio, care process, information systems, and other resources. Specific lines of action must be proposed for each of the relevant points in order to facilitate development of these units, together with continuous evaluation of unit activity through specific indicators, and to detect areas for improvement. KEY MESSAGES: This study addresses the conditions and organizational characteristics that enable the creation, development, and continuous improvement of advanced cardiorenal units.

The metabolomic differential plasma profile between dialysates. Pursuing to understand the mechanisms of citrate dialysate clinical benefits.

Background: Currently, bicarbonate-based dialysate needs a buffer to prevent precipitation of bicarbonate salts with the bivalent cations, and acetate at 3-4 mmol/L is the most used. However, citrate is being postulated as a preferred option because of its association with better clinical results by poorly understood mechanisms. In that sense, this hypothesis-generating study aims to identify potential metabolites that could biologically explain these improvements found in patients using citrate dialysate. Methods: A unicentric, cross-over, prospective untargeted metabolomics study was designed to analyze the differences between two dialysates only differing in their buffer, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Blood samples were collected in four moments (i.e., pre-, mid-, post-, and 30-min-post-dialysis) and analyzed in an untargeted metabolomics approach based on UPLC-Q-ToF mass spectrometry. Results: The 31 most discriminant metabolomic variables from the plasma samples of the 21 participants screened by their potential clinical implications show that, after dialysis with CD, some uremic toxins appear to be better cleared, the lysine degradation pathway is affected, and branched-chain amino acids post-dialysis levels are 9-10 times higher than with AD; and, on its part, dialysis with AD affects acylcarnitine clearance. Conclusion: Although most metabolic changes seen in this study could be attributable to the dialysis treatment itself, this study successfully identifies some metabolic variables that differ between CD and AD, which raise new hypotheses that may unveil the mechanisms involved in the clinical improvements observed with citrate in future research.

Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism-A Targeted Metabolomics Approach.

Acetate is widely used as a dialysate buffer to avoid the precipitation of bicarbonate salts. However, even at low concentrations that wouldn't surpass the metabolic capacity of the Krebs tricarboxylic acid (TCA) cycle, other metabolic routes are activated, leading to undesirable clinical consequences by poorly understood mechanisms. This study aims to add information that could biologically explain the clinical improvements found in patients using citrate dialysate. A unicentric, cross-over, prospective targeted metabolomics study was designed to analyze the differences between two dialysates, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Fifteen metabolites were studied to investigate changes induced in the TCA cycle, glycolysis, anaerobic metabolism, ketone bodies, and triglyceride and aminoacidic metabolism. Twenty-one patients completed the study. Citrate increased during the dialysis sessions when CD was used, without surpassing normal values. Other differences found in the next TCA cycle steps showed an increased substrate accumulation when using AD. While lactate decreased, pyruvate remained stable, and ketogenesis was boosted during dialysis. Acetylcarnitine and myo-inositol were reduced during dialysis, while glycerol remained constant. Lastly, glutamate and glutarate decreased due to the inhibition of amino acidic degradation. This study raises new hypotheses that need further investigation to understand better the biochemical processes that dialysis and the different dialysate buffers induce in the patient's metabolism.

Improvements in Inflammation and Calcium Balance of Citrate versus Acetate as Dialysate Buffer in Maintenance Hemodialysis: A Unicentric, Cross-Over, Prospective Study.

INTRODUCTION: The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate. METHODS: This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients' treatment remained unchanged during the study period. RESULTS: When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD. CONCLUSIONS: The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes.