The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial

Aim The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). Methods In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. Results From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). Conclusion In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Randomized Trial

Aim:The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF).Methods: In a double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion.Results:From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p= 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53).ConclusionIn patients with SCR-1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results of renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 in June 2017 retrospectively registered.

Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function

SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose–dependent and –independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

LEVOSIMENDAN – A VALUABLE PLAYER IN THE TREATMENT OF A RIGHT-SIDED HEART FAILURE

A 66 year-old obese man, suffering from type 2 diabetes, high blood pressure, chronic nephropathy in stage 4, permanent atrial fibrillation accompanied by bradycardia was admitted to a cardiology ward with the signs and symptoms of acute right-sided heart failure. A standard therapy was used including combined diuretics therapy. In spite of the applied methods and pharmaceuticals, no significant reduction of the body weight neither improvement in cardiovascular capacity or renal parameters were observed. Due to the ineffectiveness of the standard combined pharmacotherapy applied in the case of the acute circulatory failure, the resistance to diuretics was recognized and as a result of the above, infusion of levosimendan was decided to be applied. This therapy resulted in rich diuresis, significant loss in body weight and considerable improvement in cardiovascular capacity which allowed to continue further diagnostics and appropriate invasive treatment. The article describes current knowledge on the place of levosimendan and its application in the treatment of an right-sided heart failure.

Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets

Despite the development of pharmacological inventions and new nonpharmacological techniques to prevent and treat heart failure (HF), the mortality rate in patients with symptomatic HF remains high. To conquer these difficulties, the pathophysiology of HF should be considered within a wide range of views. Given the diverse mechanisms of HF pathophysiology, renal and cardiac functions have close and complementary interconnections. Recent studies have suggested that communication between the kidney and heart through bidirectional pathways causes significant pathological changes. This review summarizes the pathophysiology of cardiorenal syndrome (CRS) from three different viewpoints, namely, underlying chronic kidney disease, worsening renal function during hospitalization due to HF, and resistance to diuretics. We also summarize the presently available data on the pathophysiology of CRS, identify the challenges associated with some clinical approaches, and explore the potential therapeutic target for CRS.