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      A comprehensive review of acute cardio-renal syndrome: need for novel biomarkers

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          Abstract

          Cardiorenal syndrome represents a wide-spectrum disorder involving the heart and kidneys as the primary affected organs. India has an increasingly high burden of acute CRS, coinciding with the rise in global statistics. Up to 2022, approximately 46.1% of all cardiorenal patients have been diagnosed with acute CRS in India. Acute CRS involves a sudden deterioration of kidney functionalities, referred to as acute kidney injury (AKI) in acute heart failure patients. The pathophysiology of CRS involves hyperactivation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) following acute myocardial stress. The pathological phenotype of acute CRS is associated with perturbed inflammatory, cellular, and neurohormonal markers in circulation. These complications increase the risk of mortality in clinically diagnosed acute CRS patients, making it a worldwide healthcare burden. Hence, effective diagnosis and early prevention are crucial to prevent the progression of CRS in AHF patients. Present biomarkers, such as serum creatinine (sCr), cystatin C (CysC), glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum and/or urine neutrophil gelatinase-associated lipocalin (NGAL), B-type natriuretic peptide (BNP), and NT-proBNP, are clinically used to diagnose AKI stages in CRS patients but are limitedly sensitive to the early detection of the pathology. Therefore, the need for protein biomarkers is emerging for early intervention in CRS progression. Here, we summarized the cardio-renal nexus in acute CRS, with an emphasis on the present clinicopathological biomarkers and their limitations. The objective of this review is to highlight the need for novel proteomic biomarkers that will curb the burgeoning concern and direct future research trials.

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          Cardiorenal syndrome.

          The term cardiorenal syndrome (CRS) increasingly has been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of heart-kidney interactions, we present a new classification of the CRS with 5 subtypes that reflect the pathophysiology, the time-frame, and the nature of concomitant cardiac and renal dysfunction. CRS can be generally defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of 1 organ may induce acute or chronic dysfunction of the other. Type 1 CRS reflects an abrupt worsening of cardiac function (e.g., acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS comprises chronic abnormalities in cardiac function (e.g., chronic congestive heart failure) causing progressive chronic kidney disease. Type 3 CRS consists of an abrupt worsening of renal function (e.g., acute kidney ischemia or glomerulonephritis) causing acute cardiac dysfunction (e.g., heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g., chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g., sepsis) causing both cardiac and renal dysfunction. Biomarkers can contribute to an early diagnosis of CRS and to a timely therapeutic intervention. The use of this classification can help physicians characterize groups of patients, provides the rationale for specific management strategies, and allows the design of future clinical trials with more accurate selection and stratification of the population under investigation.
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            Importance of venous congestion for worsening of renal function in advanced decompensated heart failure.

            To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced decompensated heart failure (ADHF). Reduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF. A total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine >/=0.3 mg/dl during hospitalization. In the study cohort (age 57 +/- 14 years, cardiac index 1.9 +/- 0.6 l/min/m(2), left ventricular ejection fraction 20 +/- 8%, serum creatinine 1.7 +/- 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 +/- 7 mm Hg vs. 12 +/- 6 mm Hg, p < 0.001) and after intensive medical therapy (11 +/- 8 mm Hg vs. 8 +/- 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP <8 mm Hg (p = 0.01). Furthermore, the ability of CVP to stratify risk for development of WRF was apparent across the spectrum of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated glomerular filtration rates. Venous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure.
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              Global epidemiology and outcomes of acute kidney injury

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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                23 May 2023
                2023
                : 14
                : 1152055
                Affiliations
                [1] 1 School of Biosciences and Bioengineering , Indian Institute of Technology (IIT)-Mandi , Mandi, Himachal Pradesh, India
                [2] 2 BioX Center , Indian Institute of Technology (IIT)-Mandi , Mandi, Himachal Pradesh, India
                [3] 3 Department of Cardiology , Postgraduate Institute of Medical Education and Research , Chandigarh, India
                [4] 4 Department of Translational and Regenerative Medicine , Postgraduate Institute of Medical Education and Research , Chandigarh, India
                Author notes

                Edited by: Yogesh A. Kulkarni, SVKM’s Narsee Monjee Institute of Management Studies, India

                Reviewed by: Anil Bhanudas Gaikwad, Birla Institute of Technology and Science, India

                Avijit Hazra, Institute of Postgraduate Medical Education and Research, India

                *Correspondence: Trayambak Basak, trayambak@ 123456iitmandi.ac.in ; Anupam Mittal, mittal.anupam@ 123456pgimer.edu.in
                Article
                1152055
                10.3389/fphar.2023.1152055
                10242013
                37288107
                409fdd51-6571-405a-a842-e1b965640e01
                Copyright © 2023 Dutta, Saha, Bahl, Mittal and Basak.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 January 2023
                : 03 May 2023
                Funding
                Funded by: Indian Council of Medical Research , doi 10.13039/501100001411;
                Funded by: Indian Institute of Technology Mandi , doi 10.13039/501100011067;
                This study on cardiorenal syndrome was funded by an ICMR ad hoc project (RFC No. NCD/Adhoc/207/2022-2023 dated March 11, 2023).
                Categories
                Pharmacology
                Review
                Custom metadata
                Renal Pharmacology

                Pharmacology & Pharmaceutical medicine
                cardiorenal syndrome,heart failure,fibrosis,proteomics,biomarkers,kidney failure

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