Fluid therapy and acute kidney injury: a question of balance?

Fluid therapy remains one of the fundamental treatment options available for patients with acute kidney injury. However, there remains debate over several aspects of this treatment with many questions unanswered. Firstly, how do we prescribe fluid in this group of patients? Secondly, what is the role of fluid therapy in patients with or at risk of developing acute kidney injury and thirdly, what role does fluid balance play, if any, in the development of acute kidney injury. The following narrative review will attempt to tie some of the aspects of the treatment of this devastating syndrome together and formulate an overall hypothesis for fluid management in acute kidney injury.


INTRODUCTION
Since the introduction of the concept of acute kidney injury (AKI) over a decade ago much has been written about this syndrome that has numerous causes ranging from idiosyncratic drug reactions to the complications of septic shock.AKI is a common observation on the intensive care unit (ICU) with a recent international study reporting an incidence of 57.3% (95% confidence interval (CI) 55.0-59.6).
(1) Despite the varied causes of AKI, both observed mortality and morbidity is high and with increasing AKI severity an increase in hospital mortality is observed even when adjusted for other variables.For example, the mortality from stage 1 AKI the odds ratio observed = 1.679 (95% CI 0.890-3.169),increasing to 2.945 (95% CI 1.382-6.276)for stage 2 and for stage 3 = 6.884 (95% CI 3.876-12.228)compared to case mix adjusted patients without AKI.Patients developing AKI also have worse kidney function at hospital discharge with an observed estimated glomerular filtration rate (GFR) of less than 60 mL/ min/1.73m2 in 47.7% (95% CI 43.6-51.7)versus 14.8% (95% CI 11.9-18.2) in those without AKI (p < 0.001).
Few interventions have been shown to influence the outcomes from AKI. (2) However, fluid administration is often considered the mainstay of supportive therapy particularly in the face of oliguria and hypotension presumably in order to augment cardiac output.(3) However, there is now increasing evidence that volume overload is associated with impaired organ function particularly when associated with oedema (Table 1).( 4) It is this balance that is fundamental to managing patients with AKI appropriately where, under certain circumstances no fluid prescription may be the correct approach!.This has been best demonstrated in mechanically ventilated patients with acute lung injury where restrictive fluid management strategies have been associated with reduced period of mechanical ventilation and improved oxygenation.(5,6) Similarly, volume overload per se has been postulated as a potential cause of morbidity and mortality.

FLUID PRESCRIPTION IN AKI
Little evidence base exists for the prescribing of fluids in patients at risk of or with AKI although appropriate fluid management does play a vital role in the treatment of the critically ill.(7) This is particularly relevant in hypovolaemia and sepsis both conditions associated with AKI.(1) Although much has been published regarding the choice of intravenous fluid, little guidance is given as to the prescription.Indeed, a study from the UK suggested that as many as 1 in 5 patients may suffer harm through injudicious fluid use.( 8) For this reason it has been recommended that the use of fluid therapy should be accorded similar status as drug prescribing with care taken as to the adverse effects of fluids, dependent not only on the type of fluid but also the dose administered as well as the clinical context.(9,10) This has been addressed in part by the 12th Acute Dialysis Quality Initiative (ADQI) where a conceptual framework for fluid therapy was proposed rather than a "one size fits all" philosophy.(11) This includes individual assessment of the patient's fluid requirements, the timely administration of that fluid, and then the frequent re-assessment of response and ongoing needs and was conceptualized as having four distinct phases: In terms of the primary endpoint there was no difference with 9.6% of patients receiving buffered solutions developing AKI compared to 9.2% with saline (p =0.77).There was also no significant difference observed in any of the secondary outcomes between the groups.However, these results have not been met with universal acceptance.One could argue that these patients were not truly representative of many ICU patients given the relatively low APACHE II scores, low mortality and low RRT rates.Secondly, the volume administered was low averaging 1.5 litres on the day of inclusion and roughly 700 ml on the second day.Overall total fluid administration over 3 days was around 2500 ml and roughly 50% of the patients received their total amount of intravenous fluids on the first day.Consequently, the pro-balanced solution camp may argue this study adds little outside routine postoperative care and is not applicable to the septic patient in multi-organ failure: This, of course, remains to be seen.Importantly, it must not be forgotten that the so called 'balanced' solutions are neither balanced nor physiological in nature.
For example, Plasma-Lyte® 148 contains 27 mmol/l of acetate and some 23 mmol/l of gluconate both of which are not benign.Indeed, acetate once used as the main buffering agent in intermittent haemodialysis has been implicated in direct myocardial toxicity and as such is rarely used and the metabolism of gluconate has been even less well studied although evidence suggest that its metabolism may feed through anapleurotic pathways into the hexose monophosphate shunt.(19,20) The use of synthetic colloids, particularly the older higher molecular weight hyperoncotic hydroxyethyl starches (HES) are associated with an increased incidence of AKI and should not be used.This association has been observed in several multicenter randomized controlled trials with the effect of renal function being dose dependent and persistent.( 21) Moreover, there is recent evidence that gelatins may also increase the risk of AKI. ( 22) As a consequence the clinical use of HES solutions has been subject to considerable regulatory restriction and this is reflected in the results of the FENICE trial which confirms that buffered crystalloid solutions have become the most commonly used fluids by intensivists worldwide.( 23)

THE ROLE OF FLUID BALANCE IN THE DEVELOPMENT OF ACUTE KIDNEY INJURY
The association between fluid overload and mortality was first observed over 10 years ago in critically ill children with AKI requiring renal replacement therapy (RRT).(24,25) Subsequently a secondary analysis of the SOAP study by Payen and colleagues suggested that fluid overload was an independent risk factor for death in critically ill patients with AKI and sepsis.( 26

Table 1 .
Although the exact mechanisms of the pathophysiology remain to be fully elucidated there is now considerable data demonstrating that volume overload is associated with worse outcomes in AKI.Therefore treatment of patients at risk of, or with established, AKI must focus specifically on accurate volume assessment and fluid prescription in order to limit the potential catastrophic outcome from this devastating syndrome.Diverse Consequences Of Volume Overload: