title: Proof of principle:  hydration by low-osmolar mannitol-glucose solution alleviates undesirable renal effects of an iso-osmolar contrast medium in rats.
abstract: OBJECTIVE
  Saline infusion is widely used to prevent contrast media (CM)-induced acute kidney injury, because it fosters diuresis. Osmodiuretics have a stronger diuretic effect than saline, yet previous trials indicate that osmodiuretic mannitol tends to promote rather than to prevent CM-induced acute kidney injury. However, these studies used hypertonic mannitol solutions that will result in rebound volume contraction. We hypothesize that combining the osmodiuretic effects of a nonhypertonic mannitol solution with sustained volume expansion alleviates undesirable renal effects of CM.
  
  
  METHODS
  Forty-four anesthetized rats were studied by 4 protocols. Urine flow rate, urine viscosity, and glomerular filtration rate (GFR) were measured. Intravenous infusions of hydration solutions were initiated 60 minutes before CM administration and continued throughout the observation period. Hydration by a 3.2% mannitol and 3.2% glucose solution infused at 12 mL/kg per hour (Mannit-Gluc regimen) was compared with a standard regimen of isotonic saline at 4 mL/kg per hour (NaCl regimen); greater infusion rates are required for the Mannit-Gluc regimen because of the profound diuretic effect of mannitol. Two CM were studied: iso-osmolar iodixanol (320 mg I/mL) and low-osmolar iopromide (370 mg I/mL), they were administered as 1.5-mL bolus injection into the thoracic aorta.
  
  
  RESULTS
  The Mannit-Gluc regimen resulted in higher urine flow rates than the standard NaCl regimen, yet maintained a good volume status. By virtue of its stronger diuretic effect, the Mannit-Gluc regimen greatly diminished the increase in urine viscosity and completely prevented the transient decrease in GFR caused by iodixanol with the NaCl regimen. After iopromide, the differences between the hydration regimens were much less, as iopromide increased urine flow rates much more than iodixanol, thus resulting in a much smaller increase in viscosity than iodixanol and no decrease in GFR even with the NaCl regimen.
  
  
  CONCLUSIONS
  This proof of principle study shows that a hydration regimen that combines the osmodiuretic effect of a low-osmolar mannitol-glucose solution with sustained volume expansion is effective in reducing high urine viscosity and preventing GFR reduction caused by iso-osmolar iodixanol. For low-osmolar CM, the beneficial effects seem negligible, because these compounds per se exert greater osmodiuretic action.
authors.affiliation: Institute of Physiology, Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, CCM, Berlin, Germany. erdmann.seeliger@charite.de
authors.forename: Erdmann
authors.initials: E
authors.lastname: Seeliger
authors.forename: Mechthild
authors.initials: M
authors.lastname: Ladwig
authors.forename: Lilit
authors.initials: L
authors.lastname: Sargsyan
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cantow
authors.forename: Pontus B
authors.initials: PB
authors.lastname: Persson
authors.forename: Bert
authors.initials: B
authors.lastname: Flemming
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D004232:Diuretics / Q000008:administration & dosage; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008353:Mannitol / Q000008:administration & dosage*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D004232:Diuretics; D012996:Solutions; D014867:Water; D008353:Mannitol; D005947:Glucose