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Renal haemodynamic and protective effects of renoactive drugs in type 2 diabetes: Interaction with SGLT2 inhibitors.
Scholtes, RA, van Baar, MJB, Kok, MD, Bjornstad, P, Cherney, DZI, Joles, JA, van Raalte, DH
Nephrology (Carlton, Vic.). 2021;(5):377-390
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Abstract
Diabetic kidney disease remains the leading cause of end-stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and dedicated kidney trials have shown that sodium-glucose cotransporter (SGLT)2 inhibitors reduce cardiovascular morbidity and mortality and attenuate hard renal outcomes in patients with type 2 diabetes (T2D). Underlying mechanisms explaining these renal benefits may be mediated by decreased glomerular hypertension, possibly by vasodilation of the post-glomerular arteriole. People with T2D often receive several different drugs, some of which could also impact the renal vasculature, and could therefore modify both renal efficacy and safety of SGLT2 inhibition. The most commonly prescribed drugs that could interact with SGLT2 inhibitors on renal haemodynamic function include renin-angiotensin system inhibitors, calcium channel blockers and diuretics. Herein, we review the effects of these drugs on renal haemodynamic function in people with T2D and focus on studies that measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) with gold-standard techniques. In addition, we posit, based on these observations, potential interactions with SGLT2 inhibitors with an emphasis on efficacy and safety.
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The Cardiorenal Syndrome in Heart Failure.
Costanzo, MR
Heart failure clinics. 2020;(1):81-97
Abstract
Abnormal fluid handling leads to physiologic abnormalities in multiple organ systems. Deranged hemodynamics, neurohormonal activation, excessive tubular sodium reabsorption, inflammation, oxidative stress, and nephrotoxic medications are important drivers of harmful cardiorenal interactions in patients with heart failure. Accurate quantitative measurement of fluid volume is vital to individualizing therapy for such patients. Blood volume analysis and pulmonary artery pressure monitoring seem the most reliable methods for assessing fluid volume and guiding decongestive therapies. Still the cornerstone of decongestive therapy, diuretics' effectiveness decreases with progression of heart failure. Extracorporeal ultrafiltration, an alternative to diuretics, has been shown to reduce heart-failure events.
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Eating during the Hemodialysis Session: A Practice Improving Nutritional Status or a Risk Factor for Intradialytic Hypotension and Reduced Dialysis Adequacy?
Fotiadou, E, Georgianos, PI, Chourdakis, M, Zebekakis, PE, Liakopoulos, V
Nutrients. 2020;(6)
Abstract
Historically, eating during the hemodialysis treatment has been associated with increased risk for adverse intradialytic symptoms and events, risks that have resulted in the implementation of restrictive in-center nutrition policies. Recent studies, however, have recorded a shift in clinical practice with a higher proportion of physicians following the view that administration of intradialytic meals and supplements represents a simple and effective approach to enhance caloric intake and improve nutritional status among patients on hemodialysis. This shift towards less restrictive in-center nutrition practices is mainly supported by evidence from observational studies associating intradialytic nutritional supplementation with improvements in protein-energy wasting, inflammatory state, and health-related quality of life. In sharp contrast, earlier and recent interventional studies have documented that feeding during the hemodialysis treatment provokes a rapid postprandial decline in blood pressure and raises the incidence of symptomatic intradialytic hypotension. Furthermore, other studies have shown that postprandial redistribution in intravascular volume and enhanced blood supply to the gastrointestinal circulation may interfere with the adequacy of the delivered hemodialysis. Those who defend the position that intradialytic nutritional support is beneficial do not dispute the physiology of postprandial hemodynamic response, but they argue against its clinical significance. In this article, we provide an overview of studies that explored the effect of eating during the hemodialysis treatment on intradialytic hemodynamic stability and adequacy of the delivered hemodialysis. We reason that these risks have important clinical implications that are not counteracted by anticipated benefits of this strategy on caloric intake and nutritional status.
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Cardiorenal Syndrome and Heart Failure-Challenges and Opportunities.
Yogasundaram, H, Chappell, MC, Braam, B, Oudit, GY
The Canadian journal of cardiology. 2019;(9):1208-1219
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Abstract
Cardiorenal syndromes (CRS) describe concomitant bidirectional dysfunction of the heart and kidneys in which 1 organ initiates, perpetuates, and/or accelerates decline of the other. CRS are common in heart failure and universally portend worsened prognosis. Despite this heavy disease burden, the appropriate diagnosis and classification of CRS remains problematic. In addition to the hemodynamic drivers of decreased renal perfusion and increased renal vein pressure, induction of the renin-angiotensin-aldosterone system, stimulation of the sympathetic nervous system, disruption of balance between nitric oxide and reactive oxygen species, and inflammation are implicated in the pathogenesis of CRS. Medical therapy of heart failure including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade can blunt these deleterious processes. Renovascular disease can accelerate the progression of CRS. Volume overload and diuretic resistance are common and complicate the management of CRS. In heart failure and CRS being treated with diuretics, worsening creatinine is not associated with worsened outcome if clinical decongestion is achieved. Adjunctive therapy is often required in the management of volume overload in CRS, but evidence for these therapies is limited. Anemia and iron deficiency are importantly associated with CRS and might amplify decline of cardiac and renal function. End-stage cardiac and/or renal disease represents an especially poor prognosis with limited therapeutic options. Overall, worsening renal function is associated with significantly increased mortality. Despite progress in the area of CRS, there are still multiple pathophysiological and clinical aspects of CRS that need further research to eventually develop effective therapeutic options.
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A review of the mechanism of action, metabolic profile and haemodynamic effects of sodium-glucose co-transporter-2 inhibitors.
Brown, E, Rajeev, SP, Cuthbertson, DJ, Wilding, JPH
Diabetes, obesity & metabolism. 2019;:9-18
Abstract
Inhibition of glucose transport in the kidney, to produce glucosuria and thus directly lower blood glucose seems a remarkably simple way to treat diabetes (type 1 or type 2). The development of sodium-glucose co-transporter-2 (SGLT2) inhibitors and their subsequent clinical development has on one hand shown this to be true, but at another level has helped reveal a complex web of interacting effects starting in the kidney and modulating multiple metabolic pathways in a variety of other organs. These underlie the now clear benefits of this class of drugs in the management of type 2 diabetes from glucose lowering, weight loss and blood pressure reduction through to the reductions in cardiovascular and renal complications observed in long-term outcomes trials. They also explain some of the adverse effects that have emerged, including the risk of diabetic ketoacidosis. This review describes the effects of SGLT2 inhibition in relation to this complex physiology, and shows how this can favourably alter the pathophysiology of type 2 diabetes.
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Risk Factor Variability and Cardiovascular Outcome: JACC Review Topic of the Week.
Messerli, FH, Hofstetter, L, Rimoldi, SF, Rexhaj, E, Bangalore, S
Journal of the American College of Cardiology. 2019;(20):2596-2603
Abstract
Until recently, intraindividual visit-to-visit variability of cardiovascular risk factors has been dismissed as random fluctuation. This simplistic concept was challenged by demonstrating that visit-to-visit blood pressure variability, independent of average blood pressure, was a powerful risk factor for stroke. Subsequently, variability of other cardiovascular risk factors such as cholesterol, glycemia, and body weight was documented to increase risk independent of their absolute values. Variability of these risk factors has been demonstrated to be a powerful predictor for all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia. With the notable exception of heart rate, cardiovascular risk factors must now be defined by 2 components: the magnitude and duration of sustained risk factor elevation and, equally important, the variability of the same risk factor over time.