Renal Negative Pressure Treatment as a Novel Therapy for Cardio-Renal Syndrome

Introduction Decongestion is the primary therapeutic objective in most acute decompensated heart failure (ADHF) hospitalizations. However, congestion itself commonly represents a barrier to successful diuresis. Renal congestion results in increased renal tubular pressures, reducing glomerular filtration and urine output. This is further aggravated by loop diuretics, which also increase tubular pressures. Because each nephron is a fluid filled column, renal negative pressure treatment (rNPT) applied to the urinary collecting system should reduce tubular pressure, potentially improving kidney function and diuresis. Hypothesis rNPT will improve diuresis, natriuresis, and renal function in a congestion predominate heart failure (CHF) model. Methods Ten ∼80 kg pigs underwent thoracotomy with implantation of a pericardial, Swan Ganz, & bilateral ureteral JuxtaFlow® catheters. High dose furosemide (400mg bolus, then 80mg/hr) was administered since HF clinical use of rNPT will be in conjunction with loop diuretics. Each animal served as its own control with randomization of L vs. R kidney to -30 mmHg rNPT or no rNPT. HF was induced via cardiac tamponade (∼200 ml of pericardial 6% hydroxyethyl starch) and IV normal saline. Pericardial pressure was maintained at 20-22.5 mmHg. Results Prior to HF induction, rNPT increased urine output (UOP) & creatinine clearance (CrCl) compared to the control kidney during furosemide diuresis (p lt 0.001 for all, Figure). HF induction achieved the target hemodynamic profile with stable cardiac output & elevated filling pressures (Figure). UOP, sodium excretion, and CrCl decreased during HF (p lt 0.001 for all, Figure), but were higher consistently in rNPT kidney vs. control (p lt 0.05 for all, Figure). UOP (p=0.38) was the same in rNPT during HF as control prior to HF (Figure). Conclusions rNPT with the JuxtaFlow® system resulted in significantly increased diuresis, natriuresis, and creatinine clearance, both in the presence and absence of experimental HF. Notably, rNPT rescued the congested cardio-renal phenotype with equivalent diuresis and natriuresis during HF with rNPT as was observed in the non-HF period without rNPT. Additional research into the efficacy of the JuxtaFlow® system in human ADHF is warranted.