Cross-talk between heart and kidney

Cardiorenal syndromes (CRS) encompass a spectrum of clinical entities that affect both the heart and the kidneys and in which acute or chronic organ dysfunction of one of the two organs leads to organ dysfunction of the other. In addition to treating the underlying cardiac disease, effective diuretic therapy with the aim of effective decongestion is at the forefront of treatment and is of decisive importance for the prognosis.

Patients who are hospitalized due to acute heart failure often experience a parallel deterioration in kidney function. Cardiorenal syndromes (CRS) encompass a spectrum of clinical entities that affect both the heart and the kidneys and in which acute or chronic organ dysfunction of one of the two organs leads to organ dysfunction of the other. The pathogenesis of KRS in the context of acute heart failure (AHI) is characterized by hemodynamic and neurohumoral changes. In particular, venous congestion plays a leading role in the development of impaired renal function. A careful combination of clinical, laboratory and sonographic parameters is essential for the diagnosis. Therapeutically, the treatment of the underlying cardiac disease and effective and complete decongestion are paramount. In addition to tried-and-tested diuretics, SGLT2 inhibitors also play a role, as their diuretic potential makes them useful combination partners for diuretic therapy. A frequently observed phenomenon is a deterioration in kidney function during diuretic therapy. This impairment of renal function, known as “worsening of renal function”, is not associated with a poorer prognosis if effective decongestion is achieved.

The cardiorenal axis plays a decisive role both under physiological conditions and in the context of chronic diseases such as heart disease and chronic kidney disease. It is not uncommon for both diseases to occur together, share identical risk factors for their development and worsen each other’s prognosis [1]. Underlying chronic kidney disease is one of the strongest predictors of adverse outcome in patients with chronic heart failure [2,3].

If an acute or chronic deterioration in the function of the heart or kidney leads to organ dysfunction of the other organ system, this is defined as cardiorenal syndrome (CRS). According to a consensus of the “Acute Dialysis Quality Initiative” from 2008, a subdivision into two groups – cardiorenal and renocardial syndromes – was made based on the triggering moment of the disease process [4,5] (Fig. 1). In clinical practice, a clear distinction between the two manifestations of cardiorenal pathophysiology, in particular a strict identification of the triggering “insult”, is often challenging. The following overview focuses mainly on the acute cardiorenal presentation (type 1 KRS), which is primarily associated with AHI and occurs in about 30-50% of patients who are hospitalized due to AHI [6–8]. Pre-existing chronic kidney disease is often found in this patient population and increases the risk of developing acute kidney injury (AKI). Acute kidney injury in the context of AHI is an independent risk factor for mortality [6,8].

Pathophysiology

In the context of acute heart failure, two basic pathophysiological mechanisms can contribute to renal dysfunction. Both prerenal hypoperfusion in the context of acute systolic heart failure and central venous congestion play a role and lead to the activation of multiple maladaptive counterregulatory mechanisms [1,9–11]. Traditionally, hypoperfusion in the context of a reduction in cardiac output has been considered a driving factor in the deterioration of renal function. However, deterioration of renal function during hospitalization is more common in patients with heart failure with preserved ejection fraction (HFpEF) than in patients with severely impaired ejection fraction (HFrEF) [12]. Renal venous congestion with resulting renal venous hypertension, increased resistance and ultimately reduced intrarenal blood flow therefore plays the central role in renal functional impairment in the context of KRS in AHI [1,13,14]. Renal microcirculation and the local lymphatic system are also significantly impaired by venous congestion [15]. As the kidney can only counteract these hydraulic effects to a limited extent due to the lack of capacity for spatial expansion of the renal tissue, a phenomenon known as renal “tamponade” occurs. The rigid renal capsule, peri-renal fatty tissue and also the increased intra-abdominal pressure caused by the congestion play a role here [16]. Ultimately, these hemodynamic effects result in activation of the renin-angiotensin-aldosterone system (RAAS), the sympathoadrenergic system and the release of vasopressin, which in turn leads to increased absorption of sodium and water in the proximal tubule [1,10,15] (Fig. 2).

Diagnostics

The main focus of the diagnosis is on narrowing down the cardiac pathology or the trigger of cardiac decompensation and on determining the extent of the acute kidney damage. It is also important to distinguish between renal function impairment already present on admission due to cardiac congestion (possibly due to pre-existing chronic kidney disease) and additional renal function impairment aggravated during the course of treatment by drug therapy (diuretics, RAAS blockers), contrast agent exposure or other triggers [17].

Alternative causes of AKI other than KRS (drug-induced nephrotoxins, hemorrhages, hypovolemia, sepsis, shock) must be ruled out on admission. In addition to routine clinical examinations, the volume status, clinical signs of congestion and perfusion must be determined by physical examination, laboratory analysis (natriuretic peptides), echocardiographic/sonographic and, if necessary, invasive hemodynamic work-up. The aim of focused sonographic diagnostics (thoracic sonography, echocardiography) is to determine the volume status, the sonographic parameters of pulmonary venous congestion and the pulmonary fluid content [1,18]. A dedicated echocardiographic work-up forms the basis for further diagnostics. In particular, the phenotype of the underlying form of heart failure can be narrowed down in this way. In addition to the systolic ejection fraction, particular attention is paid to parameters such as the left atrial pressure or the non-invasively estimated left ventricular filling pressure (E/E’), the central venous pressure, the filling status of the vena cava and the systolic pressure of the pulmonary artery. Laboratory chemical analyses of the retention parameters and a urinalysis (urine albumin creatinine ratio, UACR, microscopy if necessary) as well as sonography of the kidneys are required. Duplex sonography of the kidneys provides information on organ size and surface area, arterial perfusion (resistance indices), diameter of the renal cortex and the ratio of the renal medulla to the renal cortex [1]. Renal venous congestion can also be detected by determining the intrarenal venous flow profile using duplex ultrasonography [19].

To date, there is no consensus on which classification should be used to categorize the deterioration in renal function in the context of a KRS. In addition to the established classification of the “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria, the term “Worsening Renal Function” (WRF) is described primarily in the cardiology literature [17,20,21]. This is mainly due to methodological differences in the characterization of renal function in the context of clinical studies on heart failure. The common consensus in both classifications is an increase in creatinine of 0.3 mg/dl, which defines a deterioration in renal function. In principle, the glomerular filtration rate (eGFR) should be estimated using the CKD-Epi formula, which is the most accurate method in the context of chronic heart failure [17].

Therapy

The main goals of KRS therapy are effective and complete decongestion, treatment of the underlying cardiac disease or the cardiac trigger of decompensation and the establishment or supplementation of guideline-compliant drug therapy for the underlying heart failure [22]. Residual congestion at the time of hospital discharge leads to an increased re-hospitalization rate and fundamentally worsens the prognosis of patients hospitalized due to a decompensation event [23].

Diuretics

Fluid retention and cardiopulmonary congestion are the main clinical features of patients with AHI and KRS. Diuretic treatment with effective natriuresis and effective fluid loss is therefore the essential basis of treatment. The aim is to achieve symptomatic clinical improvement by eliminating pulmonary congestion and renovenous congestion [18].

Loop diuretics: Loop diuretics (furosemide, torasemide) are primarily used. These inhibit the Na+-K+-2Cl–Co transporter in the ascending part of the Henle loop, induce natriuresis and thus increase NaCl excretion by up to 30% (24). Loop diuretics have high protein binding and must be secreted into the proximal tubule lumen, which requires adequate dosing [25]. Torasemide has a longer half-life and higher oral bioavailability than furosemide. A direct comparison of both active substances in use after inpatient treatment due to cardiac decompensation was carried out in the recently published TRANSFORM-HF study [26]. Torasemide was not superior to furosemide with regard to the primary endpoint (all-cause mortality) and also with regard to rehospitalizations in the first 12 months. Re. In the application of loop diuretics, both a bolus-based procedure and continuous, e.g. perfusor-controlled administration are used in clinical routine. Data from the DOSE-AHF study showed no advantage of a bolus concept compared with continuous diuretic administration. However, a high-dose loop diuretic dose (2.5 times higher than the existing home medication or at least 80 mg furosemide/day) was superior to a lower dose in terms of improving clinical parameters such as dyspnea, weight loss and net weight loss [27].

Sequential nephron blockade: A concept routinely established in everyday clinical practice to increase the diuretic effect is the combination of a loop diuretic with a thiazide diuretic or a thiazide analog, which leads to an inhibition of the sodium-chloride co-transporter in the distal tubule. In particular, a combination can achieve a significant increase in natriuresis (and potassiuresis!), which seems particularly useful in the case of resistance to loop diuretics [25]. The recently published CHLOROTIC study investigated the effects of sequential nephron blockade in patients with AHI (65% HFpEF, 48% women). The combination of hydrochlorothiazide with furosemide led to a more significant weight loss at the expense of a deterioration in renal function (creatinine increase >0.3 mg/dl) [28].

Assessment of the diuretic effect: An assessment of the diuretic effect is essential and can only be made by looking at various parameters such as the amount of urine (target >100-150 mL/h during the first 6 h), the reduction in body weight, clinical signs of congestion and the NT-pro-BNP value over the course of the treatment. Recent work also suggests an evaluation of sodium concentration in spot urine in the first hours after administration of i.v. diuretics as a direct measure of the sodium resorption achieved [29,30]. The current heart failure guideline of the ESC recommends measuring urine sodium two hours after administration of an intravenous loop diuretic [22]. A sufficient diuretic effect is defined by a urine sodium concentration of >50-70 mmol/L (in spot urine) (box).

Newer concepts for decongestion

Acetazolamide: The carbonic anhydrase inhibitor acetazolamide inhibits sodium bicarbonate absorption in the proximal tubule, the site of highest renal sodium reabsorption both under physiological conditions and in the context of heart failure. This long-known diuretic concept has been given a new scientific basis by the ADVOR study [31]. The addition of 500 mg i.v. acetazolamide to an i.v. loop diuretic resulted in more effective decongestion three days after randomization (primary endpoint) and at the time of hospital discharge compared to placebo treatment in patients with AHI. Adverse events, in particular negative effects on renal function, electrolyte imbalances or hypotensive episodes, did not occur relevantly more frequently in the treatment group than in the placebo arm. At the time of publication of this review, acetazolamide is approved for the treatment of heart failure in Switzerland and Austria, but not in Germany.

SGLT2 inhibitors: The SGLT2 inhibitors dapagliflozin and empagliflozin improve the prognosis of patients with chronic heart failure across the entire spectrum of left ventricular ejection fraction [32] as well as of patients with chronic kidney disease [33]. They also act in the proximal tubule and, by increasing the intratubular concentration of glucose and sodium, lead to consecutive glucosuria and a partially osmotically induced diuresis [34]. The positive effects of this substance group on intravascular and interstitial volume are discussed as potentially relevant mechanisms of action in the context of heart failure and form the rationale for recent clinical studies on its use in patients with acute heart failure.

In the placebo-controlled EMPULSE study, patients who were hospitalized due to AHI were treated with 10 mg empagliflozin in addition to standard therapy for a total of 90 days in the early hospital phase of recompensation. The primary endpoint (death from any cause, number of heart failure-related events/time to first event, quality of life) was significantly reduced by empagliflozin [35]. Notably, empagliflozin was associated with significantly greater weight loss and a more pronounced decrease in NT-pro-BNP. These effects were accompanied by a higher hemoconcentration and an improvement in a predefined clinical congestion score (dyspnea, orthopnea, fatigue) [36]. With regard to safety-related endpoints such as renal function, ketoacidosis or genital infections, the verum group did not differ from the control group.

The mechanisms underlying these effects, i.e. a more precise characterization of the diuretic effect, cannot be derived from the study data. Smaller placebo-controlled intervention studies in patients with acute and chronic heart failure show contrasting effects with regard to the mechanism of the diuretic effect of SGLT2 inhibitors. While 10 mg empagliflozin had no relevant effect on natriuresis in patients with AHI in the EMPA-RESPONSE AHF study [37] and in the EMPAG-HF study [38], patients with stable chronic HF showed a relevant increase in natriuresis with 25 mg (!) empagliflozin [39]. An increase in natriuresis was also demonstrated in the DICTATE-AHF study presented at the 2023 Congress of the European Society of Cardiology (ESC), which investigated the effect of early treatment of patients with acute heart failure with the SGLT2 inhibitor dapagliflozin. Interestingly, the study narrowly missed the primary endpoint (“diuretic efficacy” = weight loss (kg)/cumulative loop diuretic dose) and dapagliflozin did not lead to an increase in weight loss (as yet unpublished data). Ultimately, both effects, an osmotic effect in the course of increased glucosuria and an increase in natriuresis, are relevant for the diuretic effect of SGLT2 inhibitors. The results of the ongoing DAPA ACT HF-TIMI 68 trial (ClinicalTrials.gov ID NCT04363697), which is investigating the effects of dapagliflozin in patients with acute heart failure, are expected to be published in 2024.

“Worsening of renal function” under diuretic therapy

An increase in renal retention parameters is frequently observed during intensive i.v. diuretic therapy. Concomitant initiation of RAAS blockers or SGLT2 inhibitors can also contribute to a decrease in eGFR [17]. These are often fluctuating and cannot be definitively categorized using the usual classifications in the context of acute cardiac decompensation. In order to classify the phenomenon of a deterioration in renal function in the context of recompensation, a distinction must be made between “true” intrinsic renal damage (tubular, glomerular), such as can occur in the context of sepsis or drug-induced mechanisms, and a so-called “pseudo-worsening of renal function” [17]. A clear separation is not easy, as both can be based on parallel [40]. However, classification is crucial for the success of therapy and the resulting prognosis for the patient, as misinterpretation can lead to a reduction or termination of diuretic therapy too early. A distinction between tubular damage and pseudo-WRF cannot be made on the basis of retention values alone, but only on the basis of the overall clinical context. In particular, the extent of the congestion and the diuretic effect achieved (urine volume, sodium in spot urine) should be recorded by means of clinical and sonographic examinations. The determination of natriuretic peptides such as NT-pro-BNP during the clinical course of treatment also provides information on the extent of the decongestion achieved. In principle, any increase in creatinine should be assessed in the clinical context and a nephrological presentation should be made if there are indications of a serious deterioration in renal function (doubling of serum creatinine or increase >3.5 mg/dl, oligo-/anuria with diuresis <0.5 ml/kgKG/h in 12 h, relevant proteinuria or evidence of active urine sediment) [17].

Various studies show that forced diuretic therapy for the treatment of AHI does not lead to tubular damage. An analysis of the ROSE-AHF study shows no correlation between WRF (drop in eGFR by >20% within 72h) and the expression of tubular biomarkers such as N-acetyl-b-d-glucosaminidase, NGAL, or KIM-1 under forced diuretic therapy. The deterioration in kidney function had no influence on 6-month survival [41]. Further analyses of large clinical trials such as EVEREST and ESCAPE show that a deterioration in renal function has a particularly negative impact on prognosis if no effective recompensation, i.e. no complete decongestion, can be achieved [23,42]. To put it simply, an increase in creatinine under diuretic therapy can be classified as “pseudo-WRF” and thus as “benign” if it is accompanied by sufficient decongestion and recompensation [17].

Diuretic resistance: If the use of high-dose diuretics does not lead to clinically effective decongestion, this is referred to as diuretic resistance (1,25). This phenomenon, which is common in patients with AHI, often leads to prolonged hospitalization, increases the risk of rehospitalization, increases the risk of mortality and is often associated with a pronounced deterioration in renal function [43]. Risk factors for diuretic resistance are pre-existing kidney disease and long-term diuretic therapy [1]. The underlying mechanisms are diverse and range from insufficient (oral) resorption, reduced tubular excretion, the so-called “braking phenomenon” (reduced natriuresis under repetitive doses of diuretics) and tubular remodeling [24].

To break through diuretic resistance or if initial diuresis is insufficient (urine sodium concentration <50-70 mmol/L, urine volume <100-150 mL/h), the dose of the intravenous loop diuretic should first be gradually doubled as part of a structured approach. If this does not lead to sufficient diuresis, a thiazide diuretic can be combined to achieve sequential nephron blockade [18]. This staged approach is based on data from the CARESS-HF study, which showed that escalation of the loop diuretic dose was effective, safe and non-inferior to a filtration procedure [44].

Renal replacement procedure: If sufficient diuresis cannot be achieved even with high-dose diuretics, ultrafiltration or a renal replacement procedure must be considered as a last resort [45]. Two prospective studies are available on the use of ultrafiltration in patients with acute heart failure, but the results were heterogeneous and do not suggest a general recommendation for this procedure [44,46]. In clinical practice, extracorporeal renal replacement procedures are mainly used as part of intensive medical care. Randomized studies on the dedicated use of renal replacement procedures in acute heart failure are not yet available.

Take-Home-Messages

• The central role for renal functional impairment in the context of
  of the KRS in acute heart failure is renal venous congestion.
• In addition to treating the underlying cardiac disease, effective diuretic therapy with the aim of effective decongestion is at the forefront of treatment and is of decisive importance for the prognosis.
• A sufficient diuretic effect is defined by a urine sodium concentration of >50-70 mmol/L or by hourly urine portions of >100-150 ml during the first 6 h after diuretic administration.
• If effective decongestion can be achieved, a deterioration in renal function under diuretic therapy can generally be classified as prognostically favorable.
• The combination of loop diuretics with SGLT2 inhibitors can potentiate the diuretic effect and therefore represents a sensible treatment concept.

Literature:

1. Rangaswami J, et al.: Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies. A Scientific Statement From the American Heart Association Circulation 2019 16; 139(16): e840–e878.
2. Go AS, et al.: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–1305.
3. Damman K, et al.: Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J 2014 Feb; 35(7): 455–469.
4. Ronco C, et al.: Cardiorenal syndrome. J Am Coll Cardiol 2008; 52: 1527–1539.
5. Ronco C, et al.: Cardio-renal syndromes: report from the Consensus Conference of the Acute Dialysis Quality Initiative. Eur Heart J 2010; 31: 703–711.
6. Ronco C, et al.: Cardiorenal syndrome in Western countries: epidemiology, diagnosis and management approaches. Kidney Dis (Basel), 2017; 2: 151–163.
7. Damman K, et al.: Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail 2007; 13: 599–608.
8. Dar O, et al.: Acute heart failure in the intensive care unit: epidemiology. Crit Care Med 2008; 36: S3–S8.
9. Forman DE, et al.: Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol 2004 Jan 7;43(1): 61–67.
10. Lo, et al.: Mechanistic Insights in Cardiorenal Syndrome. NEJM Evid 2022; 1(9).
11. Arrigo M, et al.: Acute Heart Failure. Nat Rev Dis Primers 2020 Mar 5;6(1):16.
12. Sweitzer NK, et al.: Comparison of clinical features and outcomes of patients hospitalized with heart failure and normal ejection fraction (> or =55%) versus those with mildly reduced (40% to 55%) and moderately to severely reduced (<40%) fractions Am J Cardiol. 2008 Apr 15;101(8): 1151–1156.
13. Mullens, et al.: Importance of venous congestion for worsening of renal function in advanced decompensated heart failure J Am Coll Cardiol 2009 Feb 17; 53(7): 589–596.
14. Damman K, et al.: Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease. J Am Coll Cardiol 2009; 53: 582–588.
15. Mullens W, et al.: Renal sodium avidity in heart failure: from pathophysiology to treatment strategies European Heart Journal (2017) 38, 1872–1882.
16. Boorsma EM, et al.: Renal Compression in Heart Failure. JACC Heart Fail 2022 Mar; 10(3): 175–183.
17. Mullens W, et al.: Evaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2020 22(4):584-603.
18. Mullens W, et al.: The use of diuretics in heart failure with congestion – a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2019 Feb; 21(2): 137–155.
19. Husain-Syed: Congestive nephropathy: a neglected entity? Proposal for diagnostic criteria and future perspectives. ESC Heart Failure 2021; 8: 183–203.
20. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2012; suppl 4: 1–138.
21. Damman K, et al.: Terminology and definition of changes renal function in heart failure. European Heart Journal (2014) 35, 3413–3416.
22. McDonagh T, et al.: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure Eur Heart J 2021 Sep 21; 42(36): 3599–3726.
23. Ambrosy AP, et al.: Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial Eur Heart J 2013; 34(11): 835–843.
24. Felker, et al.: Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol 2020, Mar 17; 75(10): 1178–1195.
25. Ellison DH, et al.: Diuretic Treatment in Heart Failure N Engl J Med 2017; 377: 1964–1975.
26. Mentz, et al.: Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. JAMA 2023 Jan 17; 329(3): 214–223.
27. Felker GM, et. al.: Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 2011; 364: 797–805.
28. Trullas JC, et al.: Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial. European Heart Journal (2023) 44, 411–421.
29. Meekers, et al.: Spot Urinary Sodium Measurements: the Future Direction of the Treatment and Follow‑up of Patients with Heart Failure Current Heart Failure Reports (2023) 20: 88–100.
30. Ter Maaten, et al.: Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial Nat Med 2023 Oct; 29(10): 2625–2632.
31. Mullens W, et al.: Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med 2022 Sep 29; 387(13): 1185–1195.
32. Vaduganathan M, et al.: SGLT2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet 2022; 400(10354): 757–767.
33. Baigent, et al.: Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet 2022; 400(10365): 1788–1801.
34. Mullens, et al.: Empagliflozin and renal sodium handling: an intriguing smart osmotic diuretic. Eur J Heart Fail 2021 Jan; 23(1): 79–82.
35. Voors, et al.: The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 2022 Mar; 28(3): 568–574.
36. Biegus, et al.: Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial. European Heart Journal (2023) 44: 41–50.
37. Damman, et al.: Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). European Journal of Heart Failure (2020) 22: 713–722.
38. Schulze, et al.: Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF) Circulation 2022; 146: 289–298.
39. Griffin, et al.: Empagliflozin in Heart Failure. Diuretic and Cardiorenal Effects. Circulation 2020;142: 1028–1039.
40. Belcher JM, et al.: Is it time to evolve past the prerenal azotemia versus acute tubular necrosis classification? Clin J Am Soc Nephrol 2011; 6: 2332–2334.
41. Ahmad, et al.: Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury Circulation 2018 May 8;137(19): 2016–2028.
42. Nohria A, et al.: Cardiorenal interactions: insights from the ESCAPE trial J Am Coll Cardiol. 2008 1;51(13): 1268–1274.
43. Valente, et al.: Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 2014 May 14; 35(19): 1284–1293.
44. Bart BA, et al.: Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med 2012; 367: 2296–2304.
45. Schwenger, et al.: Dialyse- und Ultrafiltrationsverfahren bei kardiorenalem Syndrom. Empfehlung der Arbeitsgemeinschaft «Herz Niere» der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e.V. und der Deutschen Gesellschaft für Nephrologie e.V. Kardiologe 2014, 8: 26–35.
46. Costanzo MR, et al: Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 2007;49: 675–683.

HAUSARZT PRAXIS 2024; 19(7): 10–15