Principles and applications of hemodialysis (Proceedings)

Principles of Dialysis

Hemodialysis (HD) refers to the process of using an artificial kidney to clear urea, metabolic waste products, toxins, and excess fluid from the blood. The term dialysis refers to the net movement of solutes and water across a semipermeable membrane along a concentration gradient. Hemodialysis is the extracorporeal exchange of water and solutes between blood and an artificial solution termed dialysate, across manufactured semipermeable membranes. This exchange allows for the removal of metabolic waste products or toxins from the blood and correction of fluid, electrolyte and acid-base derangements. (Figure 1)

Figure 1: Schematic representation of solute transport across the semi-permeable dialysis membrane. The plasma concentration of urea and creatinine is high resulting in diffusive movement down concentration gradients into the dialysate. The reverse is true of bicarbonate resulting in net movement from the dialysate into the plasma.

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).

The techniques and equipment used to deliver hemodialysis to veterinary patients are the same as those used in human medicine. 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 for Hemodialysis

Acute Uremia

Acute uremia is the most common indication for hemodialysis in dogs and cats. Animals with severe acute renal failure generally die within days from complications of uremia. The majority of animals presented for HD are acutely uremic and nonresponsive to attempted diuresis with intravenous fluids and pharmacologic manipulation. Often these patients are volume overloaded from attempted diuresis in the face of oliguria, and many have life threatening hyperkalemia. Hemodialyisis rapidly mitigates hyperkalemia and can restore fluid balance, thus stabilizing the patient and allowing time for recovery of their own renal function. Hemodialysis should be initiated when the clinical consequences of the uremia cannot be managed effectively with medical therapy alone.

The prognosis for recovery from acute uremia in dogs and cats treated with hemodialyasis depends on the etiology, extent of renal damage, co-morbid diseases, and presence of multiple organ system involvement. Based on the published studies, global survival for dogs with severe acute uremia is approximately 50%. Survival from infectious (60%), hemodynamic and metabolic etiologies (40%) was greater than survival from toxic causes (20%). The outcome for dogs with acute leptospirosis is especially favorable with 85% survival with either severe (dialysis-dependent) or milder forms (medically manageable) of ARF. Global survival for cats requiring HD since 1996 is reported to be 56%. The increased survival rate is due largely to the dramatic increase in the number of cats presented for acute ureteral obstruction. In a report of 50 cats presented for dialytic management of acute ureteral obstruction, 70% survived to discharge. Overall, hemodialysis substantially increases the global survival for both dogs and cats with severe acute uremia beyond what would be expected with conventional management.

Chronic Kidney Disease and Renal Transplantation

Hemodialysis is also effective for the management of uremia in animals with end-stage kidney disease. Although routinely used to manage end stage kidney disease in human patients, hemodialysis is less commonly used in veterinary medicine due to its expense and limited availability. Conventional medical management of chronic kidney disease becomes less efficacious as the serum creatinine levels 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 end stage kidney disease. 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.

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.

Hemodialysis is also used frequently in the periopertive management of candidates for renal transplantation. Many animals requiring renal transplant have overt nutritional deficiencies, anemia, and metabolic disorders that would preclude successful transplantation. For these patients short courses of hemodialysis are necessary to manage the 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.

Acute Intoxications and Fluid Overloads

Dialytic techniques are uniquely suited to the management of specific acute toxicoses. Drugs and chemicals whose physical characteristics permit passage through dialyzer membrane pores and which are not bound to plasma proteins can be quickly and efficiently removed from the bloodstream, often with a single HD session. The benefits include the ability to remove toxins that are already absorbed from the gut lumen, removal of substances that do not adhere to enteric activated charcoal, and the ability to remove both the parent compound and the active toxic metabolites. 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.

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. For suspected cases, hemodialysis should be initiated without delay, regardless of any other therapy that has been instituted. For an acute poisoning (within 5-6 hours), it is possible to remove all of 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 in oliguric animals. 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.

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. Hemodialysis is an outstanding bridging mechanism that often permits life-saving repair of renal injury in patients when no other therapeutic options exist, but clients must understand that dialysis does not "fix" damaged kidneys. Usually it is impossible to determine at the outset how long therapy must continue. In general, with severe acute tubular necrosis, clients should financially and emotionally be prepared to undertake 2-4 weeks of dialytic therapy; though some patients can recover more quickly. Conversely, some patients have recovered renal function only after many months of dialysis dependency and some patients never recover renal function. Prognosis and duration of therapy vary tremendously from patient to patient and depend on the etiology and degree of renal insult, as well as patient condition and comorbidities.

Table 1: Indications for Hemodialysis.