Renal Replacement Therapy in Veterinary Medicine

By Shawn Kearns, DVM, DACVIM
internalmedicine@angell.org
angell.org/internalmedicine
617-541-5186

Renal replacement therapies (RRT) were first reported in companion animal veterinary medicine in the early 1990’s. Although initially limited to a few specialty centers, these therapies are becoming more available throughout the United States as well as other countries around the world.  Most often RRT is considered for acute kidney injury but other applications include treatment of chronic kidney disease, acute on chronic kidney disease and for treatment of exposure to various drugs and toxins.

RRT primarily relies on three basic principles for removal of uremic toxins. In all instances, a semipermeable membrane filled with thousands of small straws is used to separate patient blood from dialysate.  Blood typically passes through these straws while dialysate passes on the outside. With blood running countercurrent to dialysate, small molecular weight molecules, typically < 500 Daltons, will move from the higher concentration in the blood to the dialysate via diffusion.  Similarly, certain substances such as bicarbonate, can pass from dialysate to the blood.  By applying a pressure across the membrane, water can be pushed through the membrane pores (ultrafiltration) and with water, small and middle size molecules will follow through a process called solvent drag or convection.  Balanced electrolyte replacement fluids are administered in this instance to avoid volume depletion. Adsorption contributes the least to removal of molecules but is the process by which molecules will adhere to the membrane.

Traditional intermittent hemodialysis (IHD) therapies use large amounts of dialysate that are generated from a purified water system.  High blood and dialysate flows can be achieved with this, allowing diffusion to be the primary method of clearance.  Intermittent hemodialysis can achieve fairly large clearances of major uremic toxins in short periods of time due to the faster processing of blood and dialysate. Conventional continuous renal replacement therapy (CRRT) is based on convective therapies but CRRT machines, such as the Prismaflex®, also allow for diffusive clearance or a combination of both diffusive and convective clearance (hemodiafiltration).  In the past, machines used for IHD were used primarily for short (< 6 hours) and efficient treatments while continuous therapy provided a slower, more physiologic resolution to azotemia given for about 24 hours per day.  However, systems and/or treatment plans have been adapted in recent years so that slow treatments or treatments for smaller patients can be achieved on IHD machines.  Likewise, prolonged intermittent treatments (PIRRT) on CRRT machines closely resemble treatments on IHD machines. Additionally, there are a variety of dialyzer options available, depending on the machine type, that can alter treatment based on pore size, membrane surface area and ultrafiltration abilities.

Over-hydration has been shown to be an independent predictor of death in people (CRRT vet clinics) and the human literature documents the negative effect of aggressive fluid therapy on survival, length of hospital stays, and oxygenation status.  Clinical over-hydration is common in veterinary patients, especially in those presenting in oliguric or anuric renal failure. ^{1, 2} This is often due to attempts of converting patients to polyuria with aggressive fluid therapy.  Ultrafiltration, achieved through the convection principle, can be used to only remove excess plasma water in cases of volume overload as well as refractory congestive heart failure. The percentage of over-hydration is determined prior to therapy and machines are set to remove the indicated volume slowly over the course of treatment.  Care must be taken with fluid removal to monitor for hypovolemia as this amount of fluid is not being returned to the patient and rapid fluid removal may result in marked hemodynamic changes.  An in-line monitor (Critline®) is used to help monitor these volume changes.

Indications for dialytic intervention include significant or rising azotemia and oliguria or anuria in the face of appropriate medical management.  Significant electrolyte abnormalities along with metabolic acidosis will respond to dialysis but are rarely indications for therapy by themselves.  What constitutes significant azotemia and timing for intervention is still variable.  In the literature, the majority of patients undergoing hemodialysis were reported to have a creatinine > 10mg/dL ^{1, 2, 3, 4}, however with severe azotemia comes increased risk of extra-renal uremic complications that are not always reversible with treatment.  The decision for intervention should be considered on a case-by-case basis but it is speculated that earlier interventions than what is in past reports may improve the survival statistics over time.

There are several complications that can occur in the intra and inter-dialytic period.  Patients undergoing therapy must be anticoagulated during the treatment.⁵ If systemic heparinization is performed, patients may be at risk for hemorrhage even after the conclusion of therapy.  Regional anticoagulation can be performed using citrate, which forms complexes with calcium, an important cofactor in the coagulation cascade.  This form of anticoagulation can be associated with clinical hypo or hypercalcemia.⁶ With both forms of anticoagulation, clotting can occur during treatment which may necessitate stopping treatment prematurely and possible administration of blood products due to blood loss in the line.  Other common but often correctable complications include hypotension ^{1, 2, 3, 8, 9} and hypothermia⁷.  Dialysis disequilibrium syndrome (DDS) is one of the most serious complications of dialysis therapy. Though the exact pathogenesis is not fully understood, clinical signs are thought to be due to rapid, dialysis-induced changes in the composition of blood. An osmotic concentration gradient leads to intracellular swelling and subsequent cerebral edema.  Treatments over a longer period of time and/or smaller reductions in urea improvement for those that are significantly azotemia can reduce the risk of DDS.

The survival rates of dogs and cats undergoing hemodialysis are about 50%, which is similar to overall survival rates in patients with acute kidney injury. ^{4, 8, 9, 10, 11} A recent meta-analysis review looked at differences in survival between patients treated conservatively versus with hemodialysis and although the mortality rate was higher in the dialysis group, the difference was not significant between groups.⁴ In addition, the patients undergoing dialysis had more severe disease, including a higher rate of oliguria or anuria in comparison to the conservative group (88% versus 11.6%). Definition of survival across studies also makes it difficult to compare outcomes for patients but in one study looking at long-term survival (> 365 days), ~35% of patients were still alive.¹⁰  Besides severity of disease, etiology of the renal injury plays an important role in prognosis.  Infectious (leptospirosis, pyelonephritis) and obstructive (ureterolith; cats) etiologies consistently have a better prognosis (~70-80% survival) even in the face of low urine output, compared to toxic (ethylene glycol) or ischemic causes. ^{1, 2, 8, 9, 10, 11} Owners should be aware that even with treatment, some patients will have chronic kidney disease that may require medical management after the cessation of dialytic therapies.

At Angell Animal Medical Center, we are now pleased to be able to offer hemodialysis to our veterinary patients in addition to total plasma exchange.  For more information, please feel free to contact either Dr. Shawn Kearns (skearns@angell.org) or Dr. Courtney Peck (cpeck@angell.org) For after hour cases, please contact our Emergency department staff who will then be in touch with us.

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