Hyperchloremia is an electrolyte disturbance in which there is an elevated level of chloride ions in the blood. The normal serum range for chloride is 96 to 106 mEq/L, therefore chloride levels at or above 110 mEq/L usually indicate kidney dysfunction as it is a regulator of chloride concentration. Instead those with hyperchloremic metabolic acidosis are usually predisposed to hyperchloremia.

Hyperchloremia prevalence in hospital settings has been researched in the medical field since one of the major sources of treatment at hospitals is administering saline solution. Previously, animal models with elevated chloride have displayed more inflammation markers, changes in blood pressure, increased renal vasoconstriction, and less renal blood flow as well at glomerulus filtration, all of which are prompting researchers to investigate if these changes or others may exist in patients. Some studies have reported a possible relationship between increased chloride levels and death or acute kidney injury in severely ill patients that may frequent the hospital or have prolonged visits. There are other studies that have found no relationship. The amount of chloride to be released in the urine is due to the receptors lining the nephrons and the glomerulus filtration.

Normally, chloride reabsorption begins in the proximal tubule and nearly 60% of chloride is filtered here. In a person with hyperchloremia, the absorption of chloride into the interstitial fluid and subsequently into the blood capillaries is increased. This means the concentration of chloride in the filtrate is decreased, therefore, a decreased amount of chloride is being excreted as waste in the urine.

One suggested mechanism leading to hyperchloremia, there is a decrease in chloride transporter proteins along the nephron. These proteins may include sodium-potassium-2 chloride co-transporter, chloride anion exchangers, and chloride channels. Another suggested mechanism is a depletion in concentration gradient as a result of the reduced activity in these transporters. Such concentration gradient depletion would allow for the passive diffusion of chloride in and out the tubule. For the test to occur a healthcare provider must draw a sample of blood from the patient. The sample will then be sent to a laboratory and results will be provided to the patient's physician. As mentioned earlier a normal serum chloride range is from 96 to 106 mEq/L, and hyperchloremic patients will have levels above this range.

  • If the condition is caused or exacerbated by medications or treatments, these may be altered or discontinued, if deemed prudent.

In a separate study investigating the relation of critically ill patients and hyperchloremia, researchers found that there seems to be an independent association between ill patients with hyperchloremia and mortality. This study was conducted with septic patients admitted to ICUs for 72 hours. Chloride levels were assessed at baseline and 72 hours, and confounding variables were accounted for. This study is important because this continues to suggest there is increased risk associated with elevated chloride levels in vulnerable populations. Their article also states there needs to be avoidance of using solutions with chloride in specific patient subgroups

Several trials have been done comparing balanced fluid (chloride restricted) solution with saline (chloride liberal) with the hypothesis that it may reduce the risk of AKI and mortality. Initial randomized trials in septic shock comparing Plasma-Lyte and 0.9% saline (SPLIT and SALT trials) did not show any risk reduction in AKI. However, the later trials with larger sample size in critically and non critically ill adults (SMART and SALT-ED trials) showed reduction in major adverse kidney events. Extrapolating from the findings of septic shock, a recent trial comparing plasmalyte with 0.9% saline in DKA also did not show any significant difference in AKI. Hence, the causal link between hyperchloremia and AKI is yet to be conclusively established.

As studies continue, it is important to include a large patient sample size, a diverse patient population, and a diverse range of hospitals involved in these studies.