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      Emerging Treatments of Cardiorenal Syndrome: An Update on Pathophysiology and Management

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          Abstract

          Cardiorenal syndrome refers to combined cardiac and renal dysfunction that adversely impacts both organs and is also associated with severe clinical outcomes. The pathophysiology is believed to be multifactorial and complex. Increased central venous pressure and intra-abdominal pressure, overactivation of the Renin-Angiotensin-Aldosterone System (RAAS), systemic illnesses like sepsis, amyloidosis, diabetes are important factors in developing the cardiorenal syndrome. Our review article attempts to review the pathophysiology and treatment aspect of cardiorenal syndrome and explores potential therapeutic strategies that can be adopted for the management.

          We searched PubMed, EMBASE, Google Scholar for relevant articles using different keywords and Medical Subject Headings, and finalized 38 articles to be included in our study. Cardiorenal syndrome management aims to eliminate venous congestion and fluid retention, which leads to improved cardiorenal status. This is usually achieved using pharmacologic agents like diuretics, vasodilators, inotropes, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), neprilysin inhibitors, and extracorporeal methods like ultrafiltration. The use of therapeutic agents such as sodium-glucose co-transporter 2 inhibitors and tolvaptan (a vasopressin V2 receptor antagonist), and cardiac resynchronization therapy has also been shown to have potential benefits in managing the disease. These agents can be instrumental in the management and require large-scale clinical trials specifically aimed at improving cardiorenal outcomes based on severity and type of cardiorenal syndrome.

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          Most cited references38

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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            Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

            Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).
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              Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

              The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                17 August 2021
                August 2021
                : 13
                : 8
                : e17240
                Affiliations
                [1 ] Internal Medicine/Family Medicine, Janaki Medical College, Janakpurdham, NPL
                [2 ] Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
                [3 ] Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
                [4 ] Internal Medicine, Andhra Medical College, Visakhapatnam, IND
                [5 ] Internal Medicine, King George Hospital, Visakhapatnam, IND
                [6 ] Internal Medicine, Royal Lancaster Infirmary/Health Education England/ North West, Lancaster, GBR
                [7 ] Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
                [8 ] Internal Medicine, KIST Medical College, Lalitpur, NPL
                [9 ] Internal Medicine, B.P. Koirala Institute of Health Sciences, Dharan, NPL
                [10 ] Internal Medicine, Janaki Medical College, Janakpurdham, NPL
                [11 ] Gynaecology, Bhaktapur Cancer Hospital, Kathmandu, NPL
                Author notes
                Article
                10.7759/cureus.17240
                8448169
                34540466
                347654b6-2c17-4ad6-bccc-2b616987abfa
                Copyright © 2021, Verma et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 July 2021
                : 16 August 2021
                Categories
                Cardiology
                Internal Medicine
                Nephrology

                cardiorenal syndrome,pathophysiology,management,sglt2 inhibitors,tolvaptan,cardiac resynchronization therapy

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