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Background: Chronic kidney disease (CKD) is prevalent and related to poor clinical outcomes in patients with heart failure (HF). The pathophysiology of CKD in HF with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF) is not well defined. In this study we compared clinical and proteomic profiles of CKD between patients with HFrEF and HFpEF., Methods: We included 478 patients of the Scottish BIOSTAT-CHF cohort, of which 246 had HFrEF and 232 had HFpEF. CKD was defined as an eGFR <60 mL/min/1.73m 2 . We compared HFrEF-patients with CKD to HFpEF-patients with CKD using logistic- and Cox-regression. We performed a differential expression analysis using 6376 proteins., Results: The prevalence of CKD was 36 % and 32 % in patients with HFpEF and HFrEF, respectively. CKD patients were on average 7 years older. BMI, higher NT-proBNP, ACE-inhibitors, HDL-cholesterol and Stroke were associated with CKD- patients with HFrEF. In HFpEF, CKD was associated with MRA-use and higher platelet count. CKD was associated with increased risk of death or heart failure hospitalization (HR 1.82, p < 0.001), with similar effect in HFrEF and HFpEF. The pattern of differentially expressed proteins between patients with and without CKD was similar in both HF-groups., Conclusion: Clinical profiles related to CKD- patients with HFrEF were different from CKD-patients with HFrEF. CKD was associated with an increased risk of death or heart failure hospitalization, which was not different between HFpEF and HFrEF. Patterns of circulating proteins were similar between CKD-patients with HFpEF and HFrEF, suggesting no major differences in CKD-pathophysiology., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Proteins are decorated with a diverse array of post-translational modifications (PTMs) that regulate their spatial and temporal functions. Recent mass spectrometry (MS)-based studies have identified hundreds of thousands of PTM sites in mammalian proteomes. However, the signaling cues and enzymes regulating individual sites are often not known and their functional roles remain uncharacterized. Quantification of PTM site stoichiometry can help in prioritizing sites for functional analyses and is important for constructing mechanistic models of PTM-dependent protein regulation. Here, we review the concept of PTM site stoichiometry, critically evaluate the merits and drawbacks of different MS-based methods used for quantifying PTM site stoichiometry, and discuss the usefulness and limitations of stoichiometry in informing on the biological function of modified sites. Protein PTM site stoichiometry is the fraction of proteins that contain a specific PTM at a given site. Thorough understanding of PTM site stoichiometry is valuable for revealing global properties of the different types of PTMs, and for understanding the mechanistic implications of PTMs in regulating protein function. Different MS-based approaches have been developed to quantify site-specific stoichiometry of PTMs. Quantitative accuracy varies among different methods; therefore, understanding the strengths and limitations of different methods is useful for selecting appropriate methods for quantifying and interpreting PTM site stoichiometry. Proteome-wide analyses reveal stoichiometry of thousands of phosphorylation and acetylation sites in diverse cells and organisms. [ABSTRACT FROM AUTHOR]