Fluid Therapy for Acute Kidney Disease

Philip R Judge BVSc MVS PG Cert Vet Stud MACVSc (Vet Emergency and Critical Care; Medicine of Dogs)

Introduction

Acute kidney injury (AKI) is defined as a potentially reversible syndrome, having diverse aetiology, characterised by an abrupt and sustained decline in kidney function – including glomerular filtration, tubular reabsorption and excretion, that produces impaired excretion of metabolic wastes, and impaired ability to maintain fluid, electrolyte and acid-base balance.

Fluid therapy is among the most common interventions for patients with acute kidney injury. Principle goals for fluid therapy in acute kidney injury are to provide for restoration of cardiac output, systemic blood pressure and kidney perfusion in the first instance, and thereafter to provide for maintenance of homeostasis of kidney perfusion and function.

Causes of Acute Kidney Injury

Acute kidney disease represents a spectrum of disease associated with a sudden decrease in kidney function due to renal parenchymal injury.

Renal parenchyma injury leading to AKI has many possible causes, including:

• Glomerular and vascular disease (vasculitis, glomerulonephritis etc.)
• Coagulation abnormalities (DIC, thrombosis)
• Nephrotoxins
• Kidney ischaemia (intravascular volume depletion; cardiac insufficiency; hypotension; sepsis etc.)
• Obstructive uropathy
• Trauma 

Whilst hypovolaemia is a major risk factor for the development of AKI, and fluid therapy early in the diagnosis may be beneficial in managing hypovolaemia, and establishing kidney perfusion, the list above highlights that many conditions associated with AKI may not be amenable to intravenous fluid administration. Indeed, once oliguria and anuria become established, intravenous fluid therapy beyond managing hypovolaemia may become harmful. 

Additionally, intravenous fluid replacement in AKI may be of benefit only in early disease – with excess intravenous fluid potentially associated with worse outcome. Indeed, fluid administration causes increased workload to kidneys because of increased filtration of sodium chloride leading to increased resorptive activity, and increased consumption of O₂ and ATP in tubular cells.

Goals of Fluid Resuscitation in AKI

As stated above, the rationale for intravenous fluid administration in AKI is to achieve:

1. Optimise circulating blood volume
2. Optimise cardiac output
3. Optimise kidney blood flow and oxygen supply, as well as glomerular filtration rate
4. Optimise renal tubular luminal flow

It is important that the clinician be aware that that, depending on the stage of AKI present, the physiological response to fluid therapy may change. Whilst correction of hypotension with intravenous fluid therapy is beneficial early in AKI, fluid resuscitation beyond correction of hypovolaemia does not increase chances of kidney recovery.

The Problems of Excess Fluid Administration Rates

Excess fluid administration in human patients has been associated with the development of AKI secondary to intra-renal compartment syndrome. Intra-renal compartment syndrome occurs due to excess fluid accumulation within the kidneys, which, because the kidneys are encapsulated, causes a number of inter-related events that can both cause kidney damage, or exacerbate existing kidney damage:

1. Increased fluid administration leads to increased kidney interstitial fluid accumulation, which causes
   1. Increased kidney size relative to the renal capsule, resulting in increased intra-renal pressure and compression of capillary and venous vascular beds within the kidney parenchyma
   2. Decreased oxygen delivery to intra-renal tissues, secondary to increased kidney interstitial fluid accumulation
2. Increased renal venous pressure reduces the trans-renal pressure gradient for renal blood flow
3. Increased interstitial and renal tubular pressure reduce glomerular pressure gradients
4. Reduced chloride excretion produces afferent renal vasoconstriction
5. Tubular injury increases resistance to glomerular fluid transit, which further reduces renal blood flow.

Regarding fluid administration in the patient with AKI, it is important to remember that AKI is a dynamic disease process, and that fluid responsiveness is also dynamic – necessitating repeated assessment of the patient – including biomarkers for kidney disease, urine output, blood pressure and others.

Fluid Types in the Management of AKI

Different fluid types are known to have different effects on the kidney, with some fluids implicated in either causing acute kidney injury, or increasing risk of development of AKI. 

Synthetic Colloids

Synthetic colloids have been shown to be associated with increased incidence of AKI in patients with septic shock and other critically ill patients, and increased mortality in patients with sepsis. Regarding the kidney, synthetic colloids are associated with osmotic nephrosis, in which kidney tubular cells swell following colloid uptake during excretion, causing tubular obstruction.

Synthetic colloids are not recommended as a fluid choice in patients with AKI, or in patients at risk of AKI.

Isotonic Crystalloids

Isotonic crystalloids are widely accepted as the fluid of choice in AKI risk patients. However, high chloride concentrations in 0.9% NaCl are associated with renal vasoconstriction and decreased glomerular filtration rates, as well as prolonged fluid retention when compared to lower-chloride buffered solutions such as lactated Ringer’s solution. For this reason, buffered isotonic crystalloid solutions such as lactated Ringer’s solution are preferred in the treatment of AKI and AKI-risk patients.

Plasma/Albumin

At present, there is little evidence that albumin produces survival benefit in AKI patients. However, plasma may have indications in patients at risk of bleeding, and in those with sepsis in which a lower-volume fluid may be preferable to isotonic crystalloids in patients at risk of volume overload.

Fluid Dose in AKI

Classic treatment goals associated with volume replacement in the critically ill patient is the establishment of urine output in the physiological range.

Absolute hypovolaemia causes oliguria, which has led to the thought that low urine output is due to decreased kidney perfusion in critically ill and that fluid administration will correct this abnormality. In many patients – particularly those with critical illness, this is likely to be oversimplification. 

Additionally, a potential harmful effect of increased positive fluid balance (fluid overload) has been suggested in several studies, with more recent approaches to fluid therapy based on correction of volume deficits, followed by stabilisation and de-escalation of administered fluid volumes within the first 3 days of hospitalisation in order to reduce the risk of AKI and other volume-associated organ dysfunction disorders.

Interestingly, several recent human trials have indicated that once hypovolaemia has been corrected, that increasing rates of intravenous fluid is not associated with increasing urine output. Furthermore, although urine output is cited as a frequent indication for fluid administration, there is limited data to support this practice. A recent clinical trial in humans with septic shock found that fluid-restricted patients had a lower incidence of AKI than liberal fluid resuscitation patients.

Practical application of available research data involves the following:

1. Restore intravascular deficits to achieve improvements in haemodynamic parameters
2. Once hypovolaemia has been treated (and dehydration corrected), it is unlikely that sustained supra-normal fluid rates will be of benefit in improving urine output. Additionally, it is likely that supra-normal fluid rates may exacerbate kidney injury
3. Isotonic, buffered fluid solutions are the fluid of choice. Plasma may be of benefit in patients with coagulopathy, or in sepsis, where lower-volume resuscitation may be preferrable to large volume isotonic crystalloid solutions
4. In anuric AKI, administration of intravenous fluids could rapidly lead to hypervolaemia/fluid overload. Intravenous fluids should be temporarily stopped in such cases, until dialysis is established.
5. Increasing fluid rates in patients with AKI to increase diuresis is an outdated concept that is not supported by current literature, and should be avoided
6. Failure to respond to administration of intravenous fluids for hypovolaemia should prompt further patient evaluation and, if appropriate, administration of medications to support the cardiovascular system, such as positive inotropes (dobutamine) +/- vasopressors – with the therapeutic aim to improve cardiac output and renal perfusion. Intravenous fluid rates should be reduced to maintenance rates if such an approach it employed

Even when fluid resuscitation is carefully administered and early inotropic and vasopressor support is employed, initial treatment of acute hypovolaemia/intravascular volume deficit almost always results in a positive fluid balance. This is particularly serious in patients with AKI, where fluid overload can rapidly develop. Therefore, following initial fluid resuscitation, the treatment focus should shift towards the prevention of further fluid overload, combined with active removal of accumulated excess salt and water. Adopting this approach to fluid management involves monitoring fluid balance (ins and outs) as well as monitoring for signs of fluid overload.

Removal of excess fluid requires minimising ongoing fluid administration, as well as enhancing fluid removal using diuretics (or extracorporeal ultrafiltration)  

Conclusion

Optimal fluid management has great beneficial potential in critically ill patients at risk of AKI and those with established AKI. Conversely, there is considerable risk to these patients if inappropriate fluid choices are made during treatment. Appropriate choices of fluid type and rate, along with intensive monitoring will allow fluid plan adjustment, which may have significant positive impact on patient survival.

References:

Perner, A., Prowle, J., Joannidis, M. et al. Fluid management in acute kidney injury. Intensive Care Med 43, 807–815 (2017).

Vaara, S.T., Ostermann, M., Bitker, L. et al. Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial. Intensive Care Med 47, 665–673 (2021).

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Ostermann M, Liu K, Kashani K. Fluid management in acute kidney injury. Chest. 2019 Sep 1;156(3):594-603.

Chuang CL. Fluid management in acute kidney injury. Acute Kidney Injury-From Diagnosis to Care. 2016;187:84-93.

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