A major example of ongoing debate and controversy is the management of fluid therapy in acute kidney injury. Pre-renal azotemia, better defined as fluid responsive AKI, occurs when the kidneys are not being perfused adequately or there is increased urea production. If the kidneys are not being perfused adequately, the animal should be able to produce concentrated urine that is marked by the following urine specific gravities:

1.  Dog >1.030

2.  Cat >1.035

Of interest, normal dogs concentrated to 1.050–1.076 with 4–16% dehydration following water deprivation. With only 5% dehydration, 95% of dogs had a specific gravity of greater than 1.048. With 5% dehydration, cats could concentrate to greater than 1.052. So, the numbers above are the minimum urine specific gravity that a dehydrated animal should be able to attain. Identification of azotemia plus appropriately concentrated urine makes the suspect diagnosis of pre-renal azotemia in most situations. In most situations, pre-renal azotemia will disappear rapidly (within 12 hours) after correction of underlying cause (e.g., improved cardiovascular function, correction of hypovolemia, return to appropriate renal perfusion).

The severity of AKI is also now staged based on the increase in serum creatinine and reduction in urine output as follows:

Figure 1

Important aspects of fluid resuscitation of patients with suspect fluid responsive azotemia are:

• Treat aggressively hypotension and hypovolemia to restore renal perfusion.
• Clinical assessment of dehydration is largely subjective and unreliable (the reliability of clinical signs to define moderate dehydration (<8%) is equivalent to flipping a coin!).
• When dehydration is suspected as possible cause of azotemia, expect a resolution of the azotemia within 24 hours from initiation of fluid therapy.
• Weigh your patients at regular intervals: if azotemia does not resolve and weight gain occurs, the patient is retaining excess water and sodium! This is the first indication that the azotemia is not fluid responsive, and the patient is at risk of volume overload!
• Avoid IV fluid solution with high chloride content (such as 0.9% NaCl): excess chloride is responsible for further reduction in GFR by activation of the macula densa feed-back and also causes metabolic acidosis. Clinical trials in humans have demonstrated worse outcome and worsening of AKI in patients treated with high chloride solution as normal saline compared to balanced solution (i.e., LRS).
• Use of colloid solutions in fluid resuscitation have been recently proven to not have any advantage over crystalloid solutions in regard to intravascular volume expansion. In septic human patients has also been demonstrated a direct association between use of synthetic colloids and occurrence of AKI.
• Avoid liberal fluid therapy at all costs! Volume overload kills your patients!
• In polyuric AKI it is critical to replace ongoing losses of water and maintain electrolyte intake. Close serial monitoring of urine production, serum electrolytes and acid-base status are mandatory to optimize fluid therapy in these patients.
• In oligo/anuric AKI, limit fluid therapy to the metabolic needs and insensible losses of the patient. Accurate and serial monitoring of patient body weight is necessary to avoid volume overload.
• When available, ultrasonography is extremely useful in the early identification of cardiovascular volume overload: atrial chamber dilation, caudal vena cava distension, and presence of cavitary effusion are some of the attainable parameters suggestive of excessive intravascular fluid volume.
• Note: In the course of AKI, particularly in patients affected by glomerulonephritis, it is common to recognize systemic edematous conditions (systemic fluid overload) concurrently to intravascular volume deficit (low effective circulating volume). This occurs especially in the course of hypoalbuminemia and in the presence of severe inflammatory states and secondary capillary leakage.

What is the current evidence in regard to the type of intravenous fluid choices in the course of AKI?

• Use of 6% hydroxyethyl starch (HES) 130/0.4 for fluid resuscitation is associated with increased in-hospital mortality and an increased need for renal replacement therapy compared with Ringer’s acetate in patients with severe sepsis.
• Use of 6% HES 130/0.4 is associated with an increased need for renal replacement therapy in a general intensive care population.
• Liberal administration of chloride-rich solutions is associated with an increase in the incidence of acute kidney injury and an increase in the need for renal replacement therapy.
• In critically ill patients, normal saline is associated with a significant increase in the need for renal replacement therapy compared with use of Plasma-Lyte.
• Multiple studies have shown that 0.9% saline is associated with the development of metabolic acidosis and that its high chloride content affects kidney function. The administration of large quantities of chloride anion leads to a reduction in glomerular filtration rate via a tubuloglomerular feedback mechanism and afferent arteriolar vasoconstriction.
• One human trial examined the association between a chloride-liberal or a chloride-restrictive fluid administration strategy and acute kidney injury in critically ill patients. Any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution and 4% albumin in sodium chloride) was restricted to being used only after prescription by the attending specialist for specific conditions. The intervention resulted in an average decrease in the amount of chloride anion administered from 694 mmol to 496 mmol per patient. Patients in the chloride-restrictive group showed a lower incidence of severe acute kidney injury and less use of renal replacement therapy compared with those admitted in the chloride-liberal group.

Another trial analysed data from more than 30,000 patients who exclusively received either 0.9% saline or Plasma-Lyte on the day of a major general surgical procedure. Patients who received 0.9% saline required dialysis five times more often than those who received Plasma-Lyte®. In addition, saline-treated patients had a higher incidence of postoperative infections and interventions (buffer administration, fluids, and blood) than those who received Plasma-Lyte.

Fluid Choices in Hyperkalemia

Often the choice of using 0.9% NaCl in patients with AKI is based on the presence or possible risk of developing hyperkalemia. The choice of this type of crystalloid solution is often based upon the fact that normal saline does not contain any potassium, so it would “flush the kidneys” without adding any extra potassium to the body. Sadly, this explanation does not have any physiological nor physicochemical rationale.

First of all, the amount of potassium contained in any replacement balanced crystalloid solution (i.e., Normosol R, LRS, Plasmalyte148) is negligible compared to the amount of potassium present in the patient’s body. As a reminder 1 L of LRS contains a total of 3.9 mEq of potassium. The total body potassium of a mammalian is 150 mEq/kg of body weight, of which 98% is distributed intracellularly. The serum concentration of potassium is tightly regulated by the organism by maintaining a constant electrochemical gradient between intracellular and extracellular compartments. In presence of acidosis we assist to an alteration of the balance between intracellular and extracellular potassium, inducing hyperkalemia. Therefore, even a tiny shift of potassium out of the cellular compartment will have a major effect on extracellular potassium levels. Normal saline causes a non-anion gap metabolic acidosis, which shifts potassium out of cells, thereby increasing the risk of extracellular shift of potassium and increase in serum potassium level. On the other hand, LRS, despite containing potassium and being mildly acidifying (LRS has a lower strong ion difference compared to plasma), does not cause hyperchloremia and secondary acidosis. Potassium shifts have a much greater effect on the serum potassium than the actual concentration of potassium in the infused solution.

How Much Fluid Does Your AKI Patient Need?

Although fluid resuscitation and optimization of renal perfusion pressure are central to the prevention and treatment of AKI in presence of pre-renal conditions, excessive fluid administration is terribly harmful. Normal, healthy kidneys can easily handle excessive water and solute intakes by increasing GFR and decreasing water and salt reabsorption by the tubules. In the course of AKI, the ability of the kidneys to maintain such a tight homeostatic regulation is lost and any fluid or solutes administered in excesses will be retained in the organism with significant detrimental effect. The most obvious result of this is tissue edema, however, the consequences of volume and salt overload are far more severe than the simple accumulation of water in the tissues. Volume overload negatively affects the function of nearly every organ including GI tract, myocardium, lungs, and kidneys.

3% Increase in Mortality for Each 1% Increase in Degree of Fluid Overload

Effect of Renal Edema on GFR Renal Edema and GFR - Normal Conditions

Renal Edema and GFR Anuria Secondary to Renal Edema!

aintenance Fluid Therapy Needs

Daily water and electrolyte needs are determined by obligatory losses from the body. Sensible loss of both occur via urine and feces; insensible evaporative loss of water via the skin and respiratory tract is largely electrolyte-free in dogs and cats. Because most evidence suggests that the estimates of water needs for healthy, active laboratory animals are higher than the requirements for sedentary/sick dogs and cats, the authors’ intensive care unit employs an rational estimate of daily water requirement of 97*BW^0.655. This formula provides an excess of water that is sufficient to produce at least a mild diuresis. In this application, a sick 10 kg dog would receive 456 mL of water/day (19 mL/hour). Since a significant amount of water is derived from metabolism, estimates of water requirements in hospitalized animals should account for whether the animal is eating or not. Moreover, in oligo-anuric patients the maintenance fluid requirements are reduced to the insensible losses (15–20 mL/kg/day), unless pathologic GI losses are occurring in the form of vomiting and diarrhea.

Maintenance Therapy

• Hypotonic fluids (“Low” Na): 0.45% NaCl PlasmaLyte 56
• Minimum Na requirements in dogs: 1 mEq/kg/day
• Goal: fluid distribution to intra- and extracellular compartments
• Minimum water requirements: 1 mL/kcal of metabolic energy in dogs; 0.6 mL/kcal of metabolic energy in cats.
• 0.75
• ME = 70x (BW)
• Short-cut calculations:
• 20 mL/kg/day = insensible losses (breathing)
• 40 mL/kg/day = maintenance requirements in dogs (it includes required water
• losses in urine and feces and breathing)
• 30 mL/kg/day = maintenance requirements in cats (it includes required water losses in urine and feces and breathing)
• *use lean body weight

In addition to the reduction in water requirement associated with inactivity, several features of illness may reduce the need for both water and electrolytes. After addressing existing deficits and contemporaneous ongoing pathological losses in those patients, a modified maintenance fluid therapy plan may be required. Classic examples of common conditions altering water and salt balance in hospitalized patients are decreased renal water and sodium clearance. The mammalian response to severe illness is to conserve both sodium and water, and excessive medical administration of water (hypotonic fluid) or water and sodium (isotonic solutions) yields complications. Overzealous fluid administration will result in free water accumulation and secondary hyponatremia when using hypotonic solutions, whereas salt overload and hypervolemia without occurrence of hyponatremia will complicate excessive isotonic fluid administration. Both conditions represent a supra-physiologic increase of total body water, the first associated with altered osmoregulation and the second associated with salt and water retention in equal proportions, expanding the extracellular compartment. It is the responsibility of the clinician, therefore, to be attentive to early signs of fluid overload with or without associated alterations in water/solute balance, and promptly intervene with adjustments of fluid therapy.

Replacement Therapy

• Isotonic fluids (high Na): LRs, NS, PlasmaLyte, Vetivex
• Goal: Restore Extracell fluid compartment
• Estimate deficit in % (clinical estimate)
• mL to replace: deficit (%) x BW (kg)
• *use lean body weight
• Rate of replacement 12–48 hours based on preexisting condition and severity of deficit. Very severe deficit requires initial resuscitation to stabilize circulation and perfusion.
• TM
• Vetivex 11: similar to LRs
• Na in LRS 130 mEq/L, Vetivex 131 mEq/L
• Cl in LRS 109 mEq/L, Vetivex 111 mEq/L
• Ca in LRS 2.7 mEq/L, Vetivex 4 mEq/L
• K in LRs 4 mEq/L, Vetivex 5 mEq/L
• bicarb (as L-lactate) n LRS: 28 mEq/L, Vetivex 29 mEq/L

References

References are available upon request.