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InFocus

Renal replacement therapy in companion animals

With increasing use in veterinary medicine, a good knowledge of renal replacement therapy is needed to fully understand the indications for, and complications of, these techniques

Renal replacement therapy (RRT) is increasingly used in veterinary medicine. These life-saving techniques allow extracorporeal circulation and treatment of blood. Due to the financial costs, technical difficulties and high level of care needs, a good knowledge of the indications for, and complications of, RRT is important.

Basic physical principles

RRT can be divided into three main techniques: intermittent haemodialysis (IHD), continuous renal replacement therapy (CRRT) and peritoneal dialysis (PD). Each of these techniques is based on the same physical principles of diffusion, convection and adsorption.

Diffusion

Diffusion allows the movement of small molecules (less than 500 Daltons) between two fluids across a semi-permeable membrane according to a concentration gradient. Molecules move from the more concentrated fluid to the less concentrated fluid to form an equilibrium. The efficiency of the diffusion process is determined by the membrane characteristics (including thickness and surface area) and the molecular weight (MW) of each molecule. As an example, urea has a MW of 60 Daltons and will diffuse easily.

Convection

Convection is the transfer of larger molecules according to a pressure gradient between two compartments separated by a semi-permeable membrane. Molecules containing water will move from the higher-pressure compartment to the lower-pressure compartment. The movement of molecules is determined mainly by the membrane characteristics (including permeability and surface area) and transmembrane hydrostatic pressure. Removal of water can be of interest in volume overload patients.

Adsorption

Adsorption is the binding of molecules present in a fluid, such as blood, by a specific surface. The transfer of molecules depends mainly on the chemical properties of the binding membrane. Usually, and when indicated, charcoal is added into the dialysis membrane in the extracorporeal circuit to enable this process. Adsorption is saturable and so plays a minor role in clearance.

Renal replacement therapy techniques

FIGURE (1) A 4kg Yorkshire Terrier hospitalised for an acute kidney injury treated with intermittent haemodialysis

For IHD and CRRT, the blood is drawn from a large-bore jugular catheter and circulates through an extracorporeal circuit. The blood then runs through an artificial kidney which is composed of semi-permeable membranes within a fluid dialysate. The dialysis machine contains a generator that controls blood rate, dialysate rate and a replacement fluid rate, if needed. The properties of the membrane, the dialysate composition and the pressure differential between the blood and the dialysate solution generate an exchange of molecules between the two fluids. This exchange allows the removal of uraemic toxins from the blood, with the purified blood returning to the patient through a circuit (Figure 1).

CRRT differs from IHD in that it mimics normal renal function, operating for 24 hours, allowing progressive equilibration until renal function returns or a transition to IHD is indicated. Sessions of IHD range from three to eight hours and can be performed daily according to the patient’s clinical and biological status. Further, toxin removal by CRRT is mostly performed by convection whereas diffusion is the major mechanism of IHD.

Continuous renal replacement therapy differs from intermittent haemodialysis in that it mimics normal renal function […] allowing progressive equilibration until renal function returns or a transition to IHD is indicated

On the other hand, PD is based on the exchange of molecules (ie toxins) between dialysate and peritoneal capillaries through the peritoneal membrane. This membrane is considered as semi-permeable with three different pore sizes allowing diffusion, convection and ultrafiltration mechanisms. The dialysate solution is injected into the peritoneal cavity through a catheter, left for several hours to allow exchange and then the solution is retrieved. This technique is associated with increased labour and has a high rate of complications (Cooper and Labato, 2011).

Indications

Currently, RRT is used for two major categories of disease: acute and chronic kidney failure, and severe intoxication such as metaldehyde poisoning.

Kidney failure

Acute kidney injury

Acute kidney injury (AKI) is defined as an abrupt decrease in renal function. The International Renal Interest Society (IRIS) published guidelines for the diagnosis and grading of AKI. The origin of this loss of kidney function can be pre-renal due to haemodynamic disturbances, post-renal due to obstruction or diversion of the urinary tract, or intrinsic.

Pre-renal AKI must be managed with adapted fluid therapy, while post-renal AKI must be managed by restoring urinary flow. Intrinsic AKI may be caused by infectious diseases, toxins or systemic diseases (Table 1). When identified, specific treatment of the parenchymal diseases must be given. Several processes can be involved; in particular, prolonged ischaemia can aggravate parenchymal injury.

Infectious causes of acute kidney injuryNephrotoxinsSystemic causes of acute kidney injury
– Leptospirosis

– Pyelonephritis

– Babesiosis
– Drugs (aminoglycosides, amphotericin B, carboplatin, cisplatin, non-steroidal anti-inflammatory drugs, diuretics)

– Organic compounds (ethylene glycol)
Miscellaneous agents (grapes, raisins, lilies, radiocontrast agents, venom, vitamin D-containing rodenticides)
– Systemic inflammation response syndrome (SIRS) and multiple organic dysfunction syndrome (MODS)

– Sepsis

– Acute pancreatitis

– Haemoglobinuria and myoglobinuria
TABLE (1) List of common intrinsic causes of acute kidney injury in veterinary medicine

For post-renal AKI, some practitioners use RRT techniques to stabilise the patient before surgical management of the obstruction. For intrinsic AKI, when appropriate medical management over a 24-hour period has been tried, RRT is indicated when at least one of the following criteria is present:

  • Oliguria or anuria
  • Fluid overload
  • Severe electrolyte disturbances
  • Azotaemia refractory to conventional medical management (24-hour period)

Small animals with AKI treated with RRT have a survival rate ranging from 40 to 80 percent depending on the cause of the AKI (Eatroff et al., 2012). Non-infectious aetiologies have a poorer prognosis (Legatti et al., 2018), while early recognition of indication criteria could increase the survival rate.

Chronic kidney failure

RRT can also be used to manage chronic kidney disease (CKD), where patients become dependent on extracorporeal treatments to control their clinical signs. However, due to complications associated with the placement of long-term venous access, the need for prolonged hospital stays and the financial involvement, long-term treatment of CKD with RRT is rare in veterinary medicine.

Intoxication

Toxins can be removed from the blood by RRT, with removal efficiency dependent on the volume of distribution, molecular weight and protein binding of the toxin (Monaghan and Acierno, 2011). IHD can easily remove small MW molecules (less than 500 Daltons) that have a low degree of protein binding (less than 80 percent) and a low volume of distribution (less than 1l/kg).

Recent case reports describe using RRT for the management of lethal doses of different toxins, from cannabinoids, metaldehyde, ethylene glycol, ethanol, phenobarbital and ibuprofen, to digoxin

Recent case reports describe using RRT for the management of lethal doses of different toxins, from cannabinoids, metaldehyde, ethylene glycol, ethanol, phenobarbital and ibuprofen, to digoxin. For metaldehyde poisoning, RRT was shown to decrease the period of hospitalisation, the volume of anaesthesia required and the occurrence of aspiration pneumonia (Teichmann-Knorrn et al., 2020). The survival rate is high, and is increased if RRT is offered before clinical signs of toxicity have started (Groover et al., 2022).

For toxins with high protein binding and a low volume of distribution, such as non-steroidal anti-inflammatory drugs, therapeutic plasma exchange is the preferred option. In this therapy, the blood is centrifuged, and the plasma is removed and replaced by an exogenous plasma.

Other indications

Iatrogenic or cardiogenic volume overload can be managed by RRT, primarily using the principle of convection to remove extra fluid. However, congestive heart failure is rarely managed by RRT as the conventional treatment can be efficient and RRT is associated with more risks (eg anaesthesia, bleeding, etc). Therefore, the balance of risks and benefits must be assessed.

Complications

RRT is associated with many complications linked to blood access and the therapy itself. The jugular catheter complication rate varies from 15 to 30 percent and can be limited by hygiene and RRT use. Complications include haemorrhage, local to systemic infection, thrombosis and embolism (Reminga et al., 2018).

As RRT removes molecules from the blood, it can remove not only uraemic toxins but also electrolytes, thus inducing severe disorders and acid-base derangements. To limit these complications, the dialysate composition must be adapted before each session. Further, as extracorporeal blood circulation can cause hypothermia, the patient must be kept warm during the treatment.

As renal replacement therapy removes molecules from the blood, it can remove not only uraemic toxins but also electrolytes, thus inducing severe disorders and acid-base derangements

Hypotension can also occur during RRT, particularly in patients below 5kg. For these patients, the size of the extracorporeal circuit must be adapted, and the circuit can be pre-filled with blood or colloid to limit the extracorporeal loss of fluid volume. To prevent clot formation during the treatment, an anti-coagulant should be administered, although haemorrhage or hypocalcaemia are risks if citrate is chosen.

Dialysis disequilibrium syndrome is another potential complication, which is an acute neurological deterioration during or immediately after the first RRT treatment. It is typically caused by a rapid drop of osmolarity in the brain and may be managed by stopping the RRT and administering mannitol.

Summary

RRT is increasingly used in veterinary medicine for the management of AKI and severe intoxications. Early intervention is critical to improve prognosis, necessitating recognition of indication criteria. However, with the potential for numerous complications, the client must be made aware of the risks (and benefits) of this treatment.

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