Madness Of DEF6

In canine experiments, the renal infusion of solutions containing chloride, such as 0.9% saline or NH4Cl, led to reductions in the total RBF and GFR in both denervated and in situ kidneys[34]. In an animal model of sepsis, unbalanced solutions worsened sepsis-induced AKI[36]. Other experiments confirmed that extracellular chloride is essential for contraction in renal afferent arterioles[37,38]. In humans, an infusion of 2 L of 0.9% saline over 1 h was associated with a reduction in the RBF velocity and renal cortical tissue perfusion measured by magnetic resonance imaging (MRI); these changes were not observed after a similar infusion of a balanced crystalloid[39]. Moreover, studies in healthy volunteers have shown a delayed urine output with saline compared to a balanced DEF6 solution[40]. An infusion of hypertonic solutions containing chloride into the renal artery causes a biphasic response in renal vascular resistance[34]. Hyperosmolality leads to an abrupt renal vasodilatation and consequent increase in RBF. After 1-5 min, vasodilation is PD0325901 in vitro reversed, and RBF and GFR decrease below pre-infusion levels. The second phase is absent in hypertonic solutions that do not contain chloride. In vitro, the entry of chloride from elevated tubular chloride concentrations into epithelial renal cells causes the depolarization of the basolateral membrane[41]. Increased NaCl concentrations in the macula densa stimulate ATP release, resulting in the extracellular formation of adenosine, which is involved in the signal transmission of the tubule-glomerular feedback response, increasing afferent arteriolar resistance and reducing GFR[35,42]. Clinically, Yunos et al[43] translated this experimental knowledge to a large population of critically ill patients in a prospective open-label sequential period pilot study. After a control period and a wash-out phase, the use of chloride-rich intravenous fluids was restricted; this resulted in decreased chloride administration (694 to 496 mmol/patient) and led to better renal outcomes even after adjustment for covariates, including less high-severity AKI [OR = 0.52 (95%CI: 0.37-0.75); selleckchem P