Yuzhi Zhen

Potent diuretic effects of prednisone in heart failure patients with refractory diuretic resistance

BACKGROUND Refractory congestive heart failure (CHF) with diuretic resistance is life-threatening and predicts a short life expectancy. Glucocorticoids have been proven to have potent diuretic effects in animal studies; however, their efficacy in CHF patients with diuretic resistance is not known. METHODS Thirteen CHF patients with significant volume overload and diuretic resistance who failed to respond to a conventional sequential nephron blockade therapeutic strategy; that is, the coadministration of a thiazide (hydrochlorothiazide) and spironolactone, in combination with loop diuretics, were studied. Prednisone (1 mg/kg daily) was then added to standard care, with other medications unchanged, to determine diuretic efficacy in these CHF patients. Variables included body weight, urine volume, serum electrolytes and renal function. RESULTS Adding prednisone resulted in striking diuresis with a mean (+/- SD) body weight reduction of 9.39+/-3.09 kg. Prednisone significantly decreased serum creatinine by 52.21+/-48.68 mumol/L and increased glomerular filtration rate by 33.63+/-15.87 mL/min/1.73 m(2) compared with baseline. All patients were discharged from hospital with improved clinical status and renal function, and 11 patients remained alive in the long term. The main side effect of prednisone appeared to be hyperglycemia in diabetic patients. CONCLUSIONS The present study demonstrated that prednisone can rapidly eliminate volume overload and improve clinical status and renal function in CHF patients with diuretic resistance. Further prospective randomized clinical studies are warranted to confirm its clinical efficacy.

Serum uric acid as an index of impaired renal function in congestive heart failure

Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001). Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

Prednisone in Uric Acid Lowering in Symptomatic Heart Failure Patients With Hyperuricemia (PUSH-PATH) Study

BACKGROUND Chronic drug interactions that exist between symptomatic congestive heart failure (CHF) therapy and pharmacologic agents used for hyperuricemia and gout are a challenging problem in clinical practice. Recent observational studies showed that prednisone can induce a potent diuresis and lower serum uric acid concentration (SUA) in CHF. We therefore designed a randomized study to compare the effect of prednisone with allopurinol on SUA in symptomatic CHF patients with hyperuricemia. METHODS Thirty-four symptomatic CHF participants with hyperuricemia (≥ 565 μmol/L) were randomized to receive prednisone (1 mg/kg/d, orally) or allopurinol (100 mg, thrice daily, orally) for 4 weeks. The primary outcome measure was change from baseline in SUA. The secondary outcome measures were change from baseline in serum creatinine levels, estimated glomerular filtration rate, daily urine output, body weight, N-terminal pro-B-type natriuretic peptide levels, physician-assessed global clinical status, and New York Heart Association functional class. RESULTS Both prednisone and allopurinol greatly lowered SUA rapidly. The overall SUA-lowering effect did not differ between treatment groups during the study period (P = 0.48, 2-way repeated measures analysis of variance). However, prednisone increased estimated glomerular filtration rate and daily urine output, and lowered body weights and N-terminal pro-B-type natriuretic peptide. Consequently, participants treated with prednisone had an improvement in clinical status. CONCLUSIONS The study showed that the SUA-lowering effect of prednisone and allopurinol is similar in symptomatic CHF patients. Prednisone might be useful for short-term SUA-lowering in CHF patients with hyperuricemia.

Prednisone in Uric Acid Lowering in Symptomatic Heart Failure Patients with Hyperuricemia — The PUSH-PATH3 Study

Objective. To determine the safety and efficacy of prednisone in patients with symptomatic heart failure (HF) and hyperuricemia. Methods. Prednisone therapy was administered for a short time to 191 symptomatic HF patients with hyperuricemia (serum uric acid > 7 mg/dl). Results. Prednisone significantly reduced serum uric acid by 2.99 mg/dl (p < 0.01) and serum creatinine by 0.17 mg/dl (p < 0.01). These favorable effects were associated with a remarkable increase in urine output, improvement in renal function, and improvement in clinical status. Conclusion. Prednisone can be used safely in symptomatic HF patients with hyperuricemia.

Effect of Corticosteroid on Renal Water and Sodium Excretion in Symptomatic Heart Failure: Prednisone for Renal Function Improvement Evaluation Study.

Background: Recent evidence indicates that prednisone can potentiate renal responsiveness to diuretics in heart failure (HF). However, the optimal dose of prednisone is not known. Method: Thirty-eight patients with symptomatic HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/d, n = 8), medium-dose (30 mg/d, n = 10), or high-dose prednisone (60 mg/d, n = 10), for 10 days. During this time, we recorded the 24-hour urinary output and the 24-hour urinary sodium excretion, at baseline, on day 5 and day 10. We also monitored the change in the concentration of serum creatinine, angiotensin II, aldosterone, high-sensitive C-reactive protein, tumor necrosis factor-&agr;, interleukin 1&bgr;, and interleukin 6. Results: Low-dose prednisone significantly enhanced urine output. However, the effects of medium- and high-dose prednisone on urine output were less obvious. As for renal sodium excretion, high-dose prednisone induced a more potent natriuresis than low-dose prednisone. Despite the potent diuresis and natriuresis induced by prednisone, serum creatinine, angiotensin II, and aldosterone levels were not elevated. These favorable effects were not associated with an inflammatory suppression by glucocorticoids. Conclusions: Only low-dose prednisone significantly enhanced urine output. However, high-dose prednisone induced a more potent renal sodium excretion than low-dose prednisone.

Relationship between lipids levels and right ventricular volume overload in congestive heart failure

Background The relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechanisms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels. Methods We collected data of clinical characteristics, echocardiograph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels [including total cholesterol (TCL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area. Results There was a significantly inverse correlation between TCL levels and RVEDD (r = −0.34, P < 0.001) and RA (r = −0.36, P < 0.001). Other lipids such as LDL-C, HDL-C, and TG had a similar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use. Conclusions Lipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as well as identify a causal relationship, if any.

Depression is associated with increased C-reactive protein levels in patients with heart failure and hyperuricemia

Psychological depression is considered a major determinant of health status in patients with heart failure (HF). The incidence of depression in HF is four to five times higher than that in the general population. HF and depression share common pathophysiological features, which include stimulation of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic activity, and elevated levels of pro-inflammatory cytokines. Over the past decades, growing evidence implicates inflammation activation, as an important pathway, is involved in disease progression in chronic HF. High sensitivity C-reactive protein (hs-CRP), an inflammation cytokine, exerts a detrimental effect on the cardiovascular systems, such as cardiac fibroblasts, myocytes, and vascular cells, by amplifying the inflammatory responsible for adverse ventricular remodeling. Similarly, the link between inflammation and depression also has been well documented over the past two decades. A large amount of evidence shows that subjects with depression have increased level of hs-CRP compared with those without depression. In patients with HF and hyperuricemia, an elevation in uric acid (UA) is associated with impaired renal function and increased increases oxidative stress, resulting in bigger inflammatory burden. However, whether the link between hs-CRP and depression still exists in such population remains unclear. Therefore, we conducted this cross-sectional study to assess the association between hs-CRP and depression patients with HF and hyperuricemia.  The protocol of this cross-sectional study was approved by the institutional ethics committee. This study complied with the Declaration of Helsinki. Inclusion criteria were adult HF patients with New York Heart Association (NYHA) function Class II-IV and systolic dysfunction (left ventricular ejection fraction  45%) and serum uric acid > 7 mg/dL

Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance

Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

MECHANISM OF PREDNISONE IN LOWERING URIC ACID IN PATIENTS WITH DECOMPENSATED HEART FAILURE

Recently, several randomized clinical trials (RCTs) demonstrated that corticosteroids could potentiate patients’ renal responsiveness to diuretic without impairing renal function in heart failure (HF). One RCT showed prednisone could lower serum uric acid (SUA) in HF patients with hyperuricemia,