Diuretic resistance is not uncommon in severe congestive heart failure (CHF) patients. In most cases, diuretic resistance can be overcome by intravenous administration of a high dose of loop diuretics. The objective of the current communication is to present the evidence for the use of glucocorticoids to reverse refractory diuretic resistance in a CHF patient who failed with intravenous administration of a high dose of furosemide (1000 mg/day).
A 65-year-old man with a history of triple vessel disease and systolic ventricular dysfunction was transferred to our hospital because of refractory diuretic resistance. The echocardiogram revealed ischemic cardiomyopathy with left ventricular ejection fraction of 35%, global wall motion abnormalities, dilated left ventricle end-diastolic diameter (65 mm), and a moderate mitral regurgitation. An ECG showed sinus rhythm and QRS duration of 120 ms. A blood chemistry test revealed renal insufficiency that was probably caused by cardiorenal syndrome. Before admission, the patient was administered furosemide (1000 mg/day) intravenously for several days but failed to obtain enough diuresis and natriuresis. The last N-terminal pro-B-type natriuretic peptide was 7827 pg/ml. Chest radiography revealed an overt pulmonary congestion and bilateral pleural effusions (Fig. 1). Physical examination showed that the patient was in a severe edematous state with bilateral pleural effusions, pitting edema, and a notable edematous scrotum (Fig. 1). His weight was 105 kg, blood pressure was 115/77 mmHg, heart rate was 106 beats/min, and respiratory rate was 22 breaths/min. The patient refused to undergo ultrafiltration. Therefore, dexamethasone sodium phosphate (20 mg/day) was used intravenously for 3 days, followed by prednisone (60 mg/day, orally, daily) for 10 days. The glucocorticoids slowly but dramatically reversed diuretic resistance. After a 3-day glucocorticoid treatment, glucocorticoid administration induced a potent diuretic effect and renal function improvement in the patient (Supplementary Fig. 1, Supplemental digital content 1, http://links.lww.com/CAEN/A2). His maximum daily urine output was 8950 ml/day on day 8. His average daily output was 5636 ml/day. His N-terminal pro-B-type natriuretic peptide levels decreased markedly with diuresis induced by glucocorticoids over time (Supplementary Fig. 1, Supplemental digital content 1, http://links.lww.com/CAEN/A2). Finally, the patient lost 42 kg of his body weight. His edematous state disappeared, and his scrotum returned to normal after the 13-day treatment. Hematology and blood chemistry tests showed there was a notable increase in the concentration of serum total protein, albumin, and hematocrit after the 13-day treatment (Supplementary Table 1, Supplemental digital content 2, http://links.lww.com/CAEN/A3). His renal function also went back to normal (Supplementary Table 1, Supplemental digital content 2, http://links.lww.com/CAEN/A3). Finally, glucocorticoid treatment completely reversed refractory diuretic resistance in this patient. The patient was discharged from the hospital with furosemide (40 mg/day, orally) and prednisone (35 mg/day, orally). The patient was followed up once a week to monitor adverse effects of glucocorticoids and diuretics. Prednisone was gradually tapered off according to the patient’s clinical response in the following 2 months after discharge. The patient remained stable during the 1-year follow-up period.
Despite its frequency, the term ‘diuretic resistance’ is poorly defined. Traditionally, diuretic resistance in the edematous patient has been defined as the failure to lose weight and/or inappropriate urinary sodium excretion despite sufficient diuretic therapy, for example, furosemide administered orally or intravenously at a dose of 200–250 mg/day 1. The major causes of diuretic resistance are an activated renin–angiotensin–aldosterone system, altered diuretic pharmacokinetics, and the development of resistance to natriuretic peptides (NPs, including atrial NP and B-type NP) due to a decreased expression of their primary receptor, natriuretic peptide receptor A (NPR-A), in the kidney 2,3. Strategies to combat diuretic resistance include restriction of fluid and sodium intake, variation in the route of diuretic administration, and use of diuretic combinations 1,2. Newly emerging evidence also shows that hypertonic saline may improve renal responsiveness to the diuretics in refractory CHF as well 4–6. Here, we have reported that glucocorticoid therapy successfully reversed diuretic resistance in a heart failure patient when other conventional treatments failed. As early as 1950s, physicians found that prednisone could successfully reverse diuretic resistance using mercurial diuretics 7–9. With the advent of potent diuretics such as furosemide, intractable cardiac edema became less intractable and attempts to use glucocorticoids in the treatment of heart failure vanished. However, new evidence from randomized clinical trials showed that prednisone could produce remarkable diuretic effects when added to the standard diuretic therapy (e.g. furosemide, hydrochlorothiazide, and spironolactone) 10,11. The possible mechanism of using glucocorticoids in heart failure is that they could increase the density of NPR-A, the primary receptor of NPs’ diuretic action, in the inner medullary collecting duct cells 12,13. Therefore, glucocorticoids may overcome NPs’ resistance in heart failure and potentiate renal action to endogenous NPs in decompensated heart failure. An observed 3-day time lag for prednisone to take action in the present study is consistent with the previous clinical observations 10,11,14–16, and the evidence from an animal model with CHF that the effect of glucocorticoids on NPR-A expression is time-dependent 12,13. It is noteworthy that medium to large doses of glucocorticoids have adverse effects, especially when used long term. These adverse effects include disturbances in glucose tolerance, risk of suppression of the hypothalamo–pituitary–adrenal axis, susceptibility to infection, sleep disorder, hyperactivity, osteoporosis, and muscle wasting. Therefore, they should be used with caution. Moreover, one of the important limitations is the latent period that compromises their use in acute, rapid developing, and life-threatening heart failure.
Conflicts of interest
There are no conflicts of interest.
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