Renal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction

Am J Physiol Regul Integr Comp Physiol. 2021 Oct 1;321(4):R588-R594. doi: 10.1152/ajpregu.00115.2021. Epub 2021 Aug 18.

Abstract

Congestion is the primary pathophysiological lesion in most heart failure (HF) hospitalizations. Renal congestion increases renal tubular pressure, reducing glomerular filtration rate (GFR) and diuresis. Because each nephron is a fluid-filled column, renal negative pressure therapy (rNPT) applied to the urinary collecting system should reduce tubular pressure, potentially improving kidney function. We evaluated the renal response to rNPT in congestive HF. Ten anesthetized ∼80-kg pigs underwent instrumentation with bilateral renal pelvic JuxtaFlow catheters. GFR was determined by iothalamate clearance (mGFR) and renal plasma flow (RPF) by para-aminohippurate clearance. Each animal served as its own control with randomization of left versus right kidney to -30 mmHg rNPT or no rNPT. mGFR and RPF were measured simultaneously from the rNPT and no rNPT kidney. Congestive HF was induced via cardiac tamponade maintaining central venous pressure at 20-22.5 mmHg throughout the experiment. Before HF induction, rNPT increased natriuresis, diuresis, and mGFR compared with the control kidney (P < 0.001 for all). Natriuresis, diuresis, and mGFR decreased following HF (P < 0.001 for all) but were higher in rNPT kidney versus control (P < 0.001 for all). RPF decreased during HF (P < 0.001) without significant differences between rNPT treatments. During HF, the rNPT kidney had similar diuresis and natriuresis (P > 0.5 for both) and higher fractional excretion of sodium (P = 0.001) compared with the non-rNPT kidney in the no HF period. In conclusion, rNPT resulted in significantly increased diuresis, natriuresis, and mGFR, with or without experimental HF. rNPT improved key renal parameters of the congested cardiorenal phenotype.

Keywords: cardiorenal syndrome; diuretic; heart failure; renal negative pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardio-Renal Syndrome / diagnosis
  • Cardio-Renal Syndrome / physiopathology
  • Cardio-Renal Syndrome / therapy*
  • Disease Models, Animal
  • Diuresis* / drug effects
  • Female
  • Fluid Therapy*
  • Furosemide / administration & dosage
  • Glomerular Filtration Rate* / drug effects
  • Heart Failure / diagnosis
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Hemodynamics
  • Infusions, Intravenous
  • Kidney / drug effects
  • Kidney / physiopathology*
  • Natriuresis
  • Renal Plasma Flow
  • Sodium Potassium Chloride Symporter Inhibitors / administration & dosage
  • Sus scrofa

Substances

  • Sodium Potassium Chloride Symporter Inhibitors
  • Furosemide

Associated data

  • figshare/10.6084/m9.figshare.14503062.v1