Potent Potentiating Diuretic Effects Of Prednisone In Congestive Heart Failure

Objective:Chronic heart failure is a cluster of complicated clinical symptomatic syndrome. It is the severe end stage of all kinds of heart diseases. The basis of treating for heart failure in modern time is diuretic.But the forthcoming diuretic implement diuresis by more lesion of renal function.Forthermore,at the end of heart failure,as the application of diuretic for long time usually result in antidiuretic,the treatment of heart hailure become more difficult.So it's urgent to find a drug which can not only improve renal function,but also play a important role for powerful diuresis. Glucocorticoids are known to have pronounced physiological effects in kidney. Conventional teaching dictates that it should be used with caution in congestive heart failure(CHF)patients, due to its fluid and sodium retention effects. Surprisingly, despite the widespread prevalence of this belief within the medical community, there are few data to support it. In fact, animal studies showed glucocorticoids could specifically dilate renal vasculature, regulate synthesis and release of natriuretic peptide (ANP), upregulate ANP receptors on vascular endothelial cells thus have potent potentiating diuresis and natriuresis effects in animal studies, their diuretic efficacy in human yet to be known. Thus, we designed this randomized, double blind, placebo controlled, clinical study to determine the diuretic efficacy of prednisone, a glucocorticoid, in patients with CHF.Methods:Twenty clinically stable CHF patients without overt fluid retention (11 men and 9 women,age from 30 to 72,mean age 57.6±10.2 years) who had New York Heart Association (NYHA) classⅡ~Ⅲ( with normal cortical function, on diuretic therapy, and being clinically stable and whose body weight maintained the same for at least 3 days without overt signs of fluid retention )were randomized to prednisone group(in all 10 patients,7 male and 3 female,with mean age of 45±14.4 years) or placebo group(in all 10 patients,4 male and 6 female,with mean age of 51±10.7 years)between November 2005 and April 2006. Exclusion Criteria were patient refusal and having signs of infection, diabetes mellitus, acute coronary syndrome,uncontrolled hypertension,reactiveness peptic ulcer, recent gastrointestinal anastomosis,repairing in trauma, adrenocortical hyperfunction, worrying cacopathia and epilepsy ,malignant tumor, pregnancy or breastfeeding women,and life-threaten disease. Prednisone (1 mg/kg/day with maximum dose of 60 mg/day) was added to standard care for 7 days, leaving other medications unchanged,especially the diuretic. Variables included urine volume and electrolytes, serum electrolytes, and change from baseline in serum creatinine.All statistical tests were performed with two-sided alternatives and a typeⅠerror of 0.05 and with the use of SPSS software(version13.0).Initially the homogeneity of variance among all the groups was analyzed. All the measurement data was expressed as mean±standard deviation(mean±SD) unless otherwise stated. Mann-Whitney U test and student t test was used to analyze differences of parameters between two treatment groups. Chi-square test was used for analysis of categorical data.The other used compared two samples wilcoxon rank sum test.Results:The two groups of patients were well matched with regard to baseline characteristics of age, sex,weight,heart rate,blood pressure,etiology of heart failure, severity of left ventricle dysfunction, medical therapy, electrolyte status, and renal function (P>0.05)(table 1).Adding prednisone resulted in striking diuresis and natriuresis with time. As compared with placebo group, the maximum of mean daily urine volume was 810.5 ml larger than those in placebo group (95% confidence intervals [CI] 276.25 to 1344.86, P< 0.05). The maximum mean daily sodium excretion was 123.8 mmol higher than those patients given placebo (95% CI 11.4 to 236.2, P< 0.05). The placebo-corrected effect on change from baseline in serum creatinine was -19.5μmol/L (95% CI–7.4 to -31.6, P<0.01), favoring prednisone.It appeared that prednisone can improve renal function,comparing with the placobo,the patients of prednisone lost weight a little.But there were no significant differences between two groups. Conclusion:This pilot study showed that prednisone can increase urine volume,promote diuresis and natriuresis, had potent potentiating diuretic effects,but had no effects on urine potassium in patients with heart failure, promote the excretion of urine creatinine and might improve renal function in the same time,had no effects on serum electrolytes,and there were no serious adverse effect. Due to the sample size is small,we need multicenter,random,large scale clinical test to confirm nextly.Further prospective randomized clinical studies are warranted to determine the preferable dose and its efficacy in decompensated congestive heart failure.