Natriuretic response to hypervolemia and injection of diuretics in patients with chronic heart failure

Dmitrij S. Frolov; Фролов Дмитрий Сергеевич; Sergej B. Shustov; Шустов Сергей Борисович; Tatyana S. Sveklina; Свеклина Татьяна Сергеевна; Ruslan T. Sardinov; Сардинов Руслан Тальгатович; Vladimir V. Saluhov; Салухов Владимир Владимирович

doi:10.17816/mechnikov202012239-44

Natriuretic response to hypervolemia and injection of diuretics in patients with chronic heart failure

Authors: Frolov D.S.¹, Shustov S.B.¹, Sveklina T.S.¹, Sardinov R.T.¹, Saluhov V.V.¹
Affiliations:
1. S.M. Kirov Military Medical Academy
Issue: Vol 12, No 2 (2020)
Pages: 39-44
Section: Original research
URL: https://journals.eco-vector.com/vszgmu/article/view/34089
DOI: https://doi.org/10.17816/mechnikov202012239-44
ID: 34089

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Abstract
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Abstract

Relevance. The article analyze the results of changes in the diuretic and natriuretic response to standard hypervolemic load and the injection of a diuretic in patients with chronic heart failure with preserved and reduced left ventricular ejection fraction.

Purpose. Evaluation of changes in the natriuretic response to hypervolemia and diuretic injection in patients with chronic heart failure.

Materials and methods. 25 men with chronic heart failure were examined; the average age was 68 y. o. (67; 73). Of these, 13 patients with chronic heart failure and a left ventricular ejection fraction (LVEF) of less than 50 % entered the first studied group and 12 patients with chronic heart failure with preserved LVEF (more than 50%), who entered the second studied group. In all the patients, hypervolemia was induced by Ringer’s solution, followed by the injection of furosemide and the registration of diuresis and natriuresis.

Results. When analyzing natriuresis in the studied patients, it was found that at the same concentration of serum sodium, there is a multidirectional reaction to the excretion of sodium in the urine in both groups. At the same time, the rates of diuresis in both groups did not differ significantly.

Conclusion. Thus, with chronic heart failure and reduced LVF less than 50% patients had a lower natriuresis compared to those studied with preserved LVF. In the patients with chronic heart failure fluid overload on the mixed response it is noted that if the urine sodium level is at the lower limit of normal in patients with reduced LVF less than 50%, then, against the background of stimulation of diuresis, sodium begins to be excreted more intensively. In the patients with chronic heart failure with preserved LVF, the urine sodium level is at the upper limit of the norm and when furosemide is stimulated, there is a decrease in its excretion.

Keywords

natriuresis, hypervolemia, chronic heart failure

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Background

Severe congestion in the systemic and pulmonary blood circulation is the main cause of unexpected hospitalization of patients with heart failure.

With age, renal function decreases in a substantial proportion of patients with chronic heart failure (CHF), despite therapy with β-blockers and angiotensin-converting enzyme inhibitors. In addition, these patients may develop resistance to diuretics following their long-term use, which is associated with increased mortality [1].

Sodium is the main regulator of water and acid–base balance. It is a component of all body fluids and has the highest concentration in the blood and extracellular fluid. The level of extracellular sodium is mainly influenced by kidney function. Healthy people have stable concentration of blood electrolytes, since their food intake is balanced by defecation and excretion with urine and sweat.

The sodium concentration in the extracellular fluid is regulated by hormones that increase or decrease the loss of sodium in the urine (natriuretic peptide and aldosterone), prevent fluid loss in the urine (antidiuretic hormone), and control thirst (antidiuretic hormone). The human body takes a portion of sodium intake for its own needs, and the remaining amount is excreted by the kidneys in the urine. As a result, the concentration of electrolytes in the blood is maintained within a very narrow range [2].

This study aimed to evaluate changes in the natriuretic response to hypervolemia and diuretic administration in patients with CHF.

Materials and methods

We examined 25 male patients with CHF, including 13 patients with left ventricular ejection fraction (LVEF) <50% (group 1) and 12 patients with LVEF >50% (group 2). The average patient age was 68 (67; 73; range, 61–78) years (Table 1). The study groups were comparable in terms of age, body mass index, and CHF duration. All patients were treated according to the clinical guidelines for the prevention, diagnosis, and treatment of CHF in the absence of contraindications to the drugs taken [3] (Table 1). In group 1, most patients received spironolactone, a mineralocorticoid receptor antagonist, at a dose of 25 mg/day, but it did not significantly affect natriuresis. The rest of the therapy was comparable. The level of the N-terminal fragment of the brain natriuretic peptide (NT-proBNP) was assessed. After evaluating the initial clinical and instrumental parameters for 9 h, the urine output volume and urine sodium level were determined every 3 h. After the 3-h period, hypervolemia was induced (10-min infusion of Ringer’s solution in a volume of 0.5 L [8.6 g/L sodium chloride, 0.33 g/L calcium chloride, and 0.3 g/L potassium chloride], followed by parenteral administration of 0.5 Ringer’s solution in a volume of 1 L for 1 h 50 min). Then, after 6 h of monitoring, 40 mg of furosemide was administered intravenously to the patients.

Table 1 / Таблица 1

Clinical characteristics of patients, Me (25; 75%)

Клиническая характеристика пациентов, Ме (25; 75 %)

Parameters	Group 1 (n = 13)	Group 2 (n = 12)
Age, years	70.5 (67.5; 75.5)	68 (61; 69)
Body mass index, kg/m²	34.3 (29.2; 39.4)	30.8 (29.2; 37.8)
Left ventricular ejection fraction, %	40.5 (38; 45)*	54 (50; 57)
Duration of chronic heart failure, years	14 (12.5; 17.5)	10 (9; 18)
Drugs used to treat chronic heart failure
ACE inhibitors/ARBs	13 (100%)	12 (100%)
β-blockers	12 (92%)	10 (83%)
MCRA	12 (92%)	3 (25%)
Thiazide diuretics	6 (46%)	5 (42%)
Loop diuretics	3 (23%)	2 (17%)

Note. ACE, angiotensin-converting enzyme; ARBs, angiotensin II receptor blockers; MCRA, mineralocorticoid receptor antagonist. * p < 0.05.

Statistical analysis of the results was performed using Statistica 10.0 Software Package (StatSoft, USA). Quantitative data were presented as Me (25%; 75%), where Me is the median and 25% and 75% are interquartile ranges in the form of the 25^th and 75^th percentiles. Quantitative indicators were compared using the Wilcoxon rank method (for dependent variables) and the Mann–Whitney U-test (for independent groups). To analyze the relations between the studied characteristics (correlations), the nonparametric Spearman method (r) was used.

Results and discussion

The examination revealed that the NT-pro-BNP level was 2000 (1200; 2250) pg/ml in group 1 and 181.7 (140.6; 222.6) pg/ml in group 2 (p < 0.05), which corresponds to a more pronounced CHF with LVEF <50%.

The renal function assessment revealed that the glomerular filtration rate was significantly lower in patients with LVEF <50% at 60 (51; 66) ml/min per 1.73 m² than in patients with preserved LVEF at 73 (73; 74) ml/min per 1.73 m² (p < 0.05), which is consistent with the findings of other studies [4–6].

At the same concentration of serum sodium, natriuretic analysis showed a multidirectional response to sodium excretion in the urine. There was a tendency (p = 0.051) to lower va lues of the initial baseline natriuresis (3 h) as well as natriuresis with intravenous administration of Ringer’s solution (6 h) in group 1 than in group 2. The absence of statistically significant differences is apparently due to the small sample size (Table 2).

Table 2 / Таблица 2

The level of sodium in serum and urine, Me (25; 75%)

Уровень натрия в сыворотке крови и моче, Ме (25; 75 %)

Parameters	Group 1 (n = 13)	Group 2 (n = 12)
Serum sodium, mmol/l	142.5 (139.5; 143.5)	144 (143; 145)
Urine sodium after 3 h, mmol/l (normal 40–220 mmol/l)	62 (49.5; 71.5)	203 (196; 204)
Urine sodium after 6 h, mmol/l	63 (57.5; 70)	126 (90; 204)
Urine sodium after 9 h, mmol/l	112.5 (104.5; 120.5)	105 (76; 145)

Lower values of urine sodium in group 1 were possibly due to secondary hyperaldosteronism in the presence of CHF with LVEF <50%. A higher concentration of aldosterone leads to increased sodium reabsorption and a decrease in its excretion in the urine [6]. If the urine sodium level was at the lower limit of the normal in patients with CHF with LVEF <50%, sodium was excre ted more intensively when diuresis was induced. In patients with CHF with preserved LVEF, the urine sodium level was at the upper limit of the normal, and when stimulated with furosemide, its excretion decreased (Fig. 1). The decrease in sodium excretion was probably due to the activation of the renin–angiotensin–aldosterone system and resulted in a decrease in sodium excretion in the urine. The syndrome of paradoxical sodium retention is also possible, which is accompanied by a decrease in sodium excretion in the urine, water retention, and an increase in body weight due to latent edema. The syndrome is associated with a paradoxical reaction to vasopressin; in response to hyperhydration with Ringer’s solution, the release of vasopressin increases. Sodium remains in the body and retains water, but the diuresis vo lume does not decrease since sodium is exchanged for water in the collecting tubules [7].

Fig. 1. Dynamics of urinary sodium levels

Рис. 1. Динамика уровня натрия в моче

The characteristics of diuresis in patients are presented in Table 3 and Fig. 2.

Table 3 / Таблица 3

Characterization of diuresis, Me (25; 75%)

Характеристика диуреза, Ме (25; 75 %)

Parameters	Group 1 (n = 13)	Group 2 (n = 12)
Diuresis volume after 3 h, ml	125 (90; 375)	200 (150; 400)
Diuresis volume after 6 h, ml	275 (125; 575)	200 (150; 300)
Diuresis volume after 9 h, ml	1350 (1250; 1450)	1400 (1100; 2200)

Fig. 2. Dynamics of diuresis

Рис. 2. Динамика диуреза

The rate of diuresis in both groups was quite comparable and increased significantly with the introduction of loop diuretics.

Diuresis and sodium excretion correlated positively (r = 0.99; p < 0.05) in group 1 and negatively (r = –0.76; p < 0.05) in group 2, which confirms the theory of the activation of the renin–angiotensin–aldosterone system and the paradoxical reaction of vasopressin to sodium administration. Under physiological conditions, excess sodium blocks the release of vasopressin and is excreted in the urine. In a paradoxical response, an increase in the urine excretion of sodium with its excess in the blood still stimulates the release of vasopressin. As a result, sodium is exchanged for water in the collecting tubules and released into the blood, and the water is removed, but not completely. A portion of the water is retained due to the presence of excess sodium levels in the blood; the sodium particle enters the cells and pulls water with it, causing latent intracellular edemas [7, 8] which can be detected using modern bioimpedance body composition analyzers.

Conclusion

Patients with CHF and LVEF <50% are cha racterized by a lower natriuresis than patients with preserved LVEF. Patients with CHF have a multidirectional response to hypervolemia. In patients with LVEF <50%, sodium is excreted more intensively when diuresis is stimulated, provided that the urine sodium level is at the lower limit of the normal. In patients with CHF and preserved LVEF, the urine sodium level is at the upper limit of the normal, and when stimulated with furosemide, its excretion decreases. Further research is required to clarify the causes of these changes.

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