HEMODIALYSIS TECHNIQUES FOR DOGS AND CATS

Hemodialysis is a therapeutic procedure that integrates the physical principles of diffusion, convection, and ultrafiltration to correct the disorders of body fluid volume, electrolytes, and acid-base, and the toxicities associated with uremia. The composition of the uremic blood is normalized by exposure to a contrived solution, the dialysate, across a semipermeable membrane in a device called a hemodialyzer. During hemodialysis water and small molecular weight solutes and uremia toxins pass readily through the membrane pores (diffusion channels) along diffusive and hydrostatic gradients, but the movement of larger solutes, plasma proteins, and the cellular components of blood are limited by the size of the pores. Excessive body water and additional solute can forced through the membrane by ultrafiltration produced by hydrostatic or osmotic forces imposed across the dialysis membrane. Net removal of uremic solutes is influenced by: (1) the concentration gradient for diffusion, (2) the diffusivity of the solute, (3) permeability characteristics and surface area of the membrane, (4) blood and dialysate flow within the dialyzer, (5) the duration of dialysis, (6) the distribution volume of the solutes, and (7) amount of ultrafiltration (convective transfer).

Hemodialysis procedures used in animals are the same conceptually as those used for dialysis in humans. The delivery of hemodialysis is technically demanding and requires: (1) access to the patient=s vasculature, (2) a hemodialyzer, (3) an extracorporeal blood circuit, (4) a dialysis delivery system to formulate and deliver the dialysate, control blood flow in the extracorporeal circuit, deliver anticoagulant, and monitor the integrity and safety of the entire dialysis process, (5) physiologic monitoring equipment, (6) a source of purified water, and (7) a specifically trained and dedicated nursing and professional staff.

INDICATIONS AND CLINICAL APPLICATIONS OF HEMODIALYSIS

The major clinical application of hemodialysis in veterinary therapeutics is for the supportive management of acute and chronic uremia when conventional therapies are not effective. For severe or refractory uremia, no other therapy can match the efficacy, efficiency, and clinical benefits of hemodialysis. Hemodialysis should be instituted when the morbidity or pending mortality from severe uremia cannot be alleviated by conventional therapeutic means.

Acute Uremia

Acute uremia is the most common indication for hemodialysis in dogs and cats. Without dialysis, animals with severe acute renal failure generally die within 4 to 6 days from complications of uremia before there is opportunity for renal regeneration or repair of the injury to alleviate the uremia. Hemodialysis alleviates most of the clinical consequences of acute uremia and extends the life expectancy of these animals to permit their potential for recovery. Hemodialysis should be initiated when the clinical consequences of the uremia cannot be managed effectively with medical therapy alone. Animals with severe oliguria or anuria in which an effective diuresis cannot be maintained with replacement fluids, osmotic or chemical diuretics, and renal vasodilators should be transferred immediately to a referral center where hemodialysis can be performed. Delays imposed by continued conservative therapies result in deterioration of the animal=s condition and predisposition to life-threatening azotemia, hypervolemia, hyperkalemia, and metabolic acidosis. With dialytic support, the temporal definition of reversible versus irreversible renal failure may extend to 4 to 6 months rather than the conventional benchmark of 1 to 4 weeks.

Chronic Uremia

Hemodialysis is also indicated and effective for the management of uremia in animals with end-stage renal disease (ESRD) as in human patients but is used less commonly due to its expense and limited availability. The efficacy of medical treatment for chronic uremia become limited as the serum creatinine exceeds 7 mg/dl, and the clinical manifestations of uremia become overt as the BUN exceeds 90 to 100 mg/dl. At this stage of renal insufficiency, hemodialysis can ameliorate the azotemia, electrolyte, mineral and acid base disorders, nutritional deficiencies, and systemic hypertension complicating ESRD. Hemodialysis is required indefinitely for these animals; however, many pet owners desire short periods of dialytic support to adjust emotionally to the inevitability of the animal's disease. An intensive hemodialysis prescription provided every 2 to 4 days can supplement the residual excretory function to promote a predialysis BUN less than 90 mg/dl, a post-dialysis BUN less than 10 mg/dl, a time-averaged BUN less than 60 mg/dl over the dialysis interval, and promote good quality of life. Although medically justified, the decision to initiate chronic dialysis therapy in an animal whose serum creatinine is less than 5 mg/dl is generally outweighed by the effectiveness of conventional management and cost of indefinite dialysis. Animals supported with maintenance hemodialysis still require comprehensive medical therapy to manage the nutritional deficiencies, anemia, mineral disturbances, acidosis, and hypertension associated with severe renal failure. The prolonged survival afforded with hemodialysis will often promote manifestations of chronic renal failure (hyperkalemia, fluid retention, renal osteodystrophy, and refractory hypertension) rarely identified in animal patients managed solely with medical therapy.

A Bridge to (and from) Renal Transplantation

Finite periods of hemodialysis are frequently indicated for the preoperative management of animals awaiting renal transplantation. Many candidates for renal transplantation with ESRD have overt nutritional deficiencies, anemia, and metabolic disorders that would preclude successful transplantation. Hemodialysis facilitates the conditioning of these animals otherwise unsuitable or at attendant risk for the surgery. For animals with acute uremia secondary to etiologies where the expectations for renal regeneration are minimal (ethylene glycolin toxication, lily toxicity) or definitive therapy is fraught with complications (ureteral obstruction) renal transplantation may be the most appropriate and cost-effective therapeutic approach. For these patients short courses of hemodialysis are necessary to manage the acute uremia and stabilize the recipient for surgery while an appropriate donor animal is sought. Following transplantation, hemodialysis is used as required to support the recipient during periods of delayed graft function, revision of technical or surgical complications, acute rejection, or pyelonephritis until the graft is functioning adequately and complicating conditions have been resolved. Hemodialysis is a complimentary and essential adjunct to renal transplantation.

Acute Intoxications and Fluid Overloads

Hemodialysis should be considered for the management of acute poisoning or drug overdose when the toxin is readily dialyzable, when antidotal therapy has been delayed, or when there is no specific antidote to the intoxication. Dialysis hastens elimination of the toxin (or drug) or its metabolites according to its diffusibility, molecular size, concentration in extracellular fluid, distribution pool, and degree of protein binding. Hemodialysis is indicated for the treatment of common poisonings including: ethylene glycol, methanol, salicylate, lithium, ethanol, phenobarbital, acetaminophen, theophylline, aminoglycosides, tricyclic antidepressants, and possibly metaldehyde. Hemodialysis will secondarily correct acid-base or electrolyte abnormalities which may accompany the intoxication (ethylene glycol and salicylate. Hemodialysis should be initiated once conventional treatments are deemed to be ineffective and continued until the concentration of the toxin has decreased to an acceptable level and the clinical manifestations of the toxicity have disappeared. Dialysis treatments may need to be continued for prolonged periods to remove toxins with delayed toxicity (Paraquat) and low blood concentrations due to slow absorption or compartmentalization within tissues with poor diffusion. Ethylene glycol (antifreeze poisoning) is the most common intoxications encountered in companion animals. Clinical signs develop within minutes and progress variably in 12 to 24 hours to acute oliguric or anuric renal failure. The goals for hemodialysis are to eliminate the antifreeze and its metabolites from the animal as quickly as possible and to support the accompanying fluid, electrolyte, and acid-base disorders and attending uremia. Intoxicated animals that have developed oliguric acute renal failure have an impaired ability to excrete ethylene glycol or its metabolites and may have persistent toxic concentrations as late as 7 days following exposure despite appropriate administration of either alcohol or 4methylpyrazole. Institution of hemodialysis at these delayed times will eliminate the residual toxins and preclude ongoing renal injury. For suspected cases, hemodialysis should be initiated without delay to insure elimination of the toxin from the animal regardless of previous antidotal therapy or the absence of clinical signs. For an acute poisoning (within 5-6 hours), it is possible to remove all the toxin with a single dialysis treatment. If the treatment is delayed beyond this window, renal injury may have already resulted and a variable series of dialysis treatments must be provided to support the uremia and renal repair. Ethylene glycol poisoning causes severe renal damage which may require many months of dialytic care. After such extended periods of dialytic management, some animals recover normal or nearly normal renal function, some remain renal insufficient but not dialysis dependant, and some never regain renal function.

Overhydration associated with systemic hypertension, ascites, peripheral and pulmonary edema, plural effusion, and congestive heart failure is a common complication of aggressive fluid therapy in animals with acute uremia. Circulatory overload may be life threatening and fail to resolve with conventional therapy. Overhydration is a consistent feature of end-stage renal disease when animals have insufficient excretory ability to eliminate intravenous or subcutaneous fluid treatments, oral fluid supplements, or dietary water. These excessive fluid loads can be removed readily by the ultrafiltration capability of hemodialysis. Ultrafiltration is essential for the management of iatrogenic overhydration, life-threatening pulmonary edema, congestive heart failure, or therapies (like parenteral nutrition) requiring delivery of large volumes of fluid in animals with limited excretory capacity. Ultrafiltration without dialysis also can be used to treat noniatrogenic conditions associated with circulatory overload including cardiomyopathy and congestive heart failure.

CONCLUSIONS

With modern technology and techniques, hemodialysis is technically feasible, safe, efficacious, and indispensable for the management of both dogs and cats with life-threatening uremia. The very nature of its complexity, costs, and narrowly targeted applications will restrict widespread application of hemodialysis in veterinary practice. However, there is no alternative therapy as efficacious for animals with severe uremia, refractory oliguria, life-threatening hypervolemia, or acute poisoning. The increased awareness and acceptance of dialysis by primary care veterinarians, the increased sophistication of specialty veterinary practice and academic centers, increased training of veterinary internists with interest and knowledge in nephrology, and the increased demand by pet owners for this service promises its further expansion and availability on a regional basis worldwide.

REFERENCE

1.  Cowgill LD, Elliott DA: Hemodialysis. In DiBartola SP (ed):Fluid Therapy in Small Animal Practice. 2^nd Edition, WB Saunders Company, Philadelphia, PA, 2000.