Steroids & Fluid Balance

Intern report today was a thrill. The question arose about the effect of prednisone on total body fluid balance. Something potentially controversial: While we are classically instructed that prednisone causes weight gain and fluid retention, prednisone may actually potentiate diuresis in patients with heart failure and diuretic resistance.

1. How on earth would prednisone cause diuresis? 

See the figure above. (J Cardiac Fail 2014; 20: 625-629) Basically, glucocorticoids address a potential mechanism of diuretic resistance in heart failure, which is blunted response of the kidneys to natriuretic peptides. Glucocorticoids work at the level of DNA, to increase transcription of natriuretic peptide receptors in the kidney and brain to address this problem. Moreover, there is some evidence that glucocorticoids cause direct vasodilation of the renal vasculature, increasing GFR. Finally, it's possible the anti-inflammatory effect of steroids oppose the proinflammatory state of decompensated heart failure, reducing the maladaptive effect this has on RAAS activation. 

2. Is there any data to support this claim? 

Yes. Numbers are small, but there is at least one controlled trial (J Cardiovasc Pharmacy 2006; 48: 173-176) that suggests prednisone promotes natriuresis and increases UOP in diuretic refractory decompensated HF (see figure below). Another 2014 study looked at the use of prednisone 60mg/day for 7 days as an adjunct to loop diuretics vs. placebo + loop diuretic in ~100 patients with ADHFS and found not only an improvement in creatinine over a period of months compared with placebo, but also found a small mortality benefit (J Cardiovasc Pharmacy 2014; 63: 333-338). Granted, this second study was unblinded and did not record mean loop diuretic doses between each group, so considerable bias is likely.

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This is certainly not standard practice and should be only be used academically at this point, not clinically. Could also be a consideration when approaching the patient on prednisone (for COPD or otherwise) and also with decompensated CHF.