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1.
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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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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3.
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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4.
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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5.
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.
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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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Interventions to prevent hemodynamic instability during renal replacement therapy in critically ill patients: a systematic review.
Douvris, A, Malhi, G, Hiremath, S, McIntyre, L, Silver, SA, Bagshaw, SM, Wald, R, Ronco, C, Sikora, L, Weber, C, et al
Critical care (London, England). 2018;(1):41
Abstract
BACKGROUND Hemodynamic instability related to renal replacement therapy (HIRRT) may increase the risk of death and limit renal recovery. Studies in end-stage renal disease populations on maintenance hemodialysis suggest that some renal replacement therapy (RRT)-related interventions (e.g., cool dialysate) may reduce the occurrence of HIRRT, but less is known about interventions to prevent HIRRT in critically ill patients receiving RRT for acute kidney injury (AKI). We sought to evaluate the effectiveness of RRT-related interventions for reducing HIRRT in such patients across RRT modalities. METHODS A systematic review of publications was undertaken using MEDLINE, MEDLINE in Process, EMBASE, and Cochrane's Central Registry for Randomized Controlled Trials (RCTs). Studies that assessed any intervention's effect on HIRRT (the primary outcome) in critically ill patients with AKI were included. HIRRT was variably defined according to each study's definition. Two reviewers independently screened abstracts, identified articles for inclusion, extracted data, and evaluated study quality using validated assessment tools. RESULTS Five RCTs and four observational studies were included (n = 9; 623 patients in total). Studies were small, and the quality was mostly low. Interventions included dialysate sodium modeling (n = 3), ultrafiltration profiling (n = 2), blood volume (n = 2) and temperature control (n = 3), duration of RRT (n = 1), and slow blood flow rate at initiation (n = 1). Some studies applied more than one strategy simultaneously (n = 5). Interventions shown to reduce HIRRT from three studies (two RCTs and one observational study) included higher dialysate sodium concentration, lower dialysate temperature, variable ultrafiltration rates, or a combination of strategies. Interventions not found to have an effect included blood volume and temperature control, extended duration of intermittent RRT, and slower blood flow rates during continuous RRT initiation. How HIRRT was defined and its frequency of occurrence varied widely across studies, including those involving the same RRT modality. Pooled analysis was not possible due to study heterogeneity. CONCLUSIONS Small clinical studies suggest that higher dialysate sodium, lower temperature, individualized ultrafiltration rates, or a combination of these strategies may reduce the risk of HIRRT. Overall, for all RRT modalities, there is a paucity of high-quality data regarding interventions to reduce the occurrence of HIRRT in critically ill patients.
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Effect of perioperative goal-directed hemodynamic therapy on postoperative recovery following major abdominal surgery-a systematic review and meta-analysis of randomized controlled trials.
Sun, Y, Chai, F, Pan, C, Romeiser, JL, Gan, TJ
Critical care (London, England). 2017;(1):141
Abstract
BACKGROUND Goal-directed hemodynamic therapy (GDHT) has been used in the clinical setting for years. However, the evidence for the beneficial effect of GDHT on postoperative recovery remains inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effect of perioperative GDHT in comparison with conventional fluid therapy on postoperative recovery in adults undergoing major abdominal surgery. METHODS Randomized controlled trials (RCTs) in which researchers evaluated the effect of perioperative use of GDHT on postoperative recovery in comparison with conventional fluid therapy following abdominal surgery in adults (i.e., >16 years) were considered. The effect sizes with 95% CIs were calculated. RESULTS Forty-five eligible RCTs were included. Perioperative GDHT was associated with a significant reduction in short-term mortality (risk ratio [RR] 0.75, 95% CI 0.61-0.91, p = 0.004, I 2 = 0), long-term mortality (RR 0.80, 95% CI 0.64-0.99, p = 0.04, I 2 = 4%), and overall complication rates (RR 0.76, 95% CI 0.68-0.85, p < 0.0001, I 2 = 38%). GDHT also facilitated gastrointestinal function recovery, as demonstrated by shortening the time to first flatus by 0.4 days (95% CI -0.72 to -0.08, p = 0.01, I 2 = 74%) and the time to toleration of oral diet by 0.74 days (95% CI -1.44 to -0.03, p < 0.0001, I 2 = 92%). CONCLUSIONS This systematic review of available evidence suggests that the use of perioperative GDHT may facilitate recovery in patients undergoing major abdominal surgery.
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A perspective on diuretic resistance in chronic congestive heart failure.
Shah, N, Madanieh, R, Alkan, M, Dogar, MU, Kosmas, CE, Vittorio, TJ
Therapeutic advances in cardiovascular disease. 2017;(10):271-278
Abstract
Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy. In this review, we discuss the definition, prevalence, mechanism of development and management strategies of diuretic resistance in HF patients.
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10.
Therapy of acute kidney injury in the perioperative setting.
Romagnoli, S, Ricci, Z, Ronco, C
Current opinion in anaesthesiology. 2017;(1):92-99
Abstract
PURPOSE OF REVIEW The current review analyzes the current pharmacologic approaches in cardiac surgery-associated acute kidney injury and renal replacement/support therapies. RECENT FINDINGS Hemodynamic management and promising therapies, including atrial natriuretic peptide, calcium sensitizer inodilators, and mesenchymal stem cells have been discussed. Encouraging results from pre-emptive renal replacement therapies have been also addressed. SUMMARY Cardiac surgery is responsible for the highest risk of renal dysfunction with respect to other surgical settings. A number of different and coacting insults, including toxins, renal hypoperfusion, ischemia-reperfusion injury, and systemic inflammation, are leading causes of this frequent complication. Intense research is ongoing on the treatment of established cardiac surgery-associated acute kidney injury and, in this view, a holistic approach including preoperative data, risk stratification, prevention, timely diagnosis, and aggressive intervention can limit the burdening consequences of renal dysfunction in these patients. Although no specific pharmacologic and nonpharmacologic strategy can be currently recommended outside clinical research, the prompt identification of renal dysfunction and the application of multimodal treatments are fundamental aspects. Right ventricular dysfunction and increased central venous pressure, frequently affecting cardiac surgery patients, potentially lead to congestive renal dysfunction. Hemodynamic management covers a central role in these cases.