Extracorporeal Therapies - Hemodialysis and Hemoperfusion
Hemodialysis
Hemodialysis (HD) is a therapy in which the patient's blood is cycled through a filter, or dialyzer, outside the body in order to remove dissolved wastes, toxins, and/or excess fluids. The dialyzer is connected to a dialysis delivery system which controls the waste removal process and regulates blood flow to and from the pet. Performance of HD requires placement of a large-gauge catheter in the jugular vein that stays in place for the duration of HD treatments. Some HD catheters have been maintained in pets for many months, even up to two years. HD frequently stabilizes critically ill patients to the point that they can leave the hospital and return for outpatient HD sessions while the kidney repair process occurs. Most outpatient HD patients feel quite well between sessions and are normally active and interactive.
Acute hemodialysis
When an animal's previously well-functioning kidneys fail suddenly, we say that that animal is in "acute kidney failure." Inherent in acute failure is the potential for recovery of kidney function, and HD is one tool used to sustain severely ill pets in acute kidney failure until their kidneys recover enough function to support them again. HD does not heal kidneys directly; rather it takes over kidney functions by correcting multiple (sometimes life-threatening) metabolic abnormalities, restoring fluid balance, and eliminating dissolved waste products from the patient's blood. Patients requiring acute HD often have severe azotemia, volume overload, hyperkalemia, or poisoning with ethylene glycol or other toxins. Many of these patients are not producing sufficient amounts of urine. HD frequently permits a patient who would otherwise die to survive long enough that recovery of kidney function and return to good-quality of life is possible. Most animals requiring acute HD recover within 2-4 weeks if recovery is possible. Some take less time and others take many months for sufficient kidney function to return.
Chronic hemodialysis
When kidney damage has occurred gradually, or when sudden injury is so severe that full recovery does not occur, we say that that animal is in "chronic kidney failure." In this form of kidney failure, permanent structural changes have taken place in the kidney tissue that preclude return to normal function. Many of these patients survive years with conservative medical therapies such as special diets, subcutaneous fluids, and certain medications. When these treatments can no longer maintain good-quality life, chronic HD may be a consideration. Just as with acute HD, chronic HD restores metabolic balance and helps to clear dissolved wastes from the bloodstream. Pets that require chronic HD will need treatment 2-3 times per week for life. This type of therapy is financially very intensive, and requires a tremendous commitment on the part of the owner. It's not for every owner and pet, but has the potential to provide excellent quality of life for additional months to years.
Hemoperfusion
Hemoperfusion (HP) is an extracorporeal therapy used to remove non-dialyzable toxins from the bloodstream. In HP, a catheter in the pet's jugular vein is connected to a circuit, just as is done for HD. The machine draws blood from the pet, into the circuit and passes the blood over substances designed to adhere certain types of molecules. The blood then passes back into the pet, and this cleansing cycle is repeated for several hours, until the clinician determines that the maximum amount of toxin possible has been removed from the pet. Hemoperfusion is useful for removal of exogenous toxins such as many kinds of drugs, as well as endogenous toxins such as those that accumulate in liver failure.
Therapeutic Apheresis
Separation of blood into is components in the apheresis machine prior to harvesting the pathologic plasma for removal.
Therapeutic apheresis is an extension of the extracorporeal (outside the body) therapies provided at the UCVMC-SD that extend the spectrum of pathologic substances that can be removed from the body. Many pathologic substances (e.g., autoantibodies and poisons) are too large to be eliminated by hemodialysis or are attached to blood proteins establishing them as large molecules. For these circumstances, we use therapeutic apheresis (which means, “to take away”) to remove these large substances creating the disease from the body. For therapeutic apheresis, the blood first is separated into its component fractions (red blood cells, white blood cells, and plasma), and the pathogenic fraction is removed. Therapeutic plasma exchange (TPE) is an apheresis modality in which plasma (containing pathologic antibodies, toxins, or proteins) is removed from the patient’s flowing blood and replaced with donor plasma prior to being returned to the patient to relieve the animal from further injury. Therapeutic plasma exchange also can be used to remove toxins or endogenous substances (i.e., bilirubin) which are sequestered in the plasma compartment by binding to plasma proteins.
The veterinary indications for TPE are growing rapidly and include a variety of acute inflammatory or immune-mediated hematologic, neurologic, neuromuscular, kidney, rheumatic diseases, as well as metabolic disorders and snake envenomation. (see Table) The benefits of TPE are associated with very rapid control of the disease process within days while establishing time for conventional medical therapy to provide more sustained control. In a recent case review, TPE improved survival of dogs presented for immune-mediated hemolytic anemia (IMHA) from 48% to 92% compared to medical management alone. The responses from diseases like myasthenia gravis, refractory immune-mediated thrombocytopenia, and polyarthritis are typically very dramatic and life-saving. Diseases with current veterinary experience using therapeutic plasma exchangePatient undergoing Therapeutic Plasma Exchange for IMHA
TPE affords a rapid and effective means to eliminate toxicants associated with accidental poisoning or drug overdosages (especially chemotherapeutic drugs) by efficiently removing both the free and protein-bound toxicant from the blood. Essentially all the toxin can be eliminated within a few hours with a single TPE treatment. Occasionally a second treatment is required for complete toxin elimination if the toxicant has a large distribution in the body or has ongoing generation. This therapeutic approach is well suited for the treatment of massive NSAIDS exposure, chemotherapy overdosage, and other toxicants highly bound to plasma proteins.&
Therapeutic apheresis including TPE and plasma adsorption have become the advanced-standard-of-care for a variety of immune-mediated diseases and life-threatening intoxications for which there may be no effective alternative therapies. TPE is relatively new and novel to veterinary therapeutics. It is a technically complex procedures with limited regional availability for animals. However, for animals with acute, life-threatening immune-mediated diseases or intoxications, therapeutic apheresis provides effective immediate cure or control of the condition until long-term controls or solutions can be established. We are fortunate to have been early pioneers in the application of these therapies for animals which are readily available for your pet at the UCVMC-SD.
Medical Management of Chronic Kidney Diseases
Chronic interstitial nephritis
Chronic interstitial nephritis (CIN) is of the most common kidney diseases we see in companion animals, particularly in older cats, and is what most people mean when they say "chronic kidney/renal failure." CIN develops over time, usually years, and results in progressive, irreversible loss of kidney function. Loss of kidney function may lead to clinical signs like decreased energy, decreased appetite, weight loss, vomiting, hypertension, and anemia. Many medical therapies are available to manage the signs of advancing CIN and help animals with this condition maintain good quality of life for months to many years following diagnosis. Dietary therapy, gastroprotectants, antiemetics, fluid therapy, erythropoietin therapy, esophagostomy tubes and blood pressure medications are some of the tools clinicians may use to help a pet with CIN feel well. When medical therapies are no longer sufficient to keep a pet feeling well, chronic hemodialysis or kidney transplantation may be suitable options.
Glomerulonephritis
Glomerulonephritis (GN) is a disease resulting from damage to the glomerulus portion of the nephron. The glomerulus is responsible for initial filtration of blood in the process of urine formation; the normally functioning glomerulus retains proteins in the bloodstream. GN is usually suspected when excess protein is present in otherwise normal urine. Sometimes the first abnormality detected is a low serum albumin level. Many pets have hypertension as a result of their GN, and discovery of hypertension may lead a clinician to evaluate protein content of the urine. Definitive diagnosis of GN is made by histopathological analysis of kidney tissue biopsy. Animals with GN may be azotemic or non-azotemic. The presence of azotemia in an animal with GN often represents a more advanced stage of the disease. Animals with GN and azotemia may require some of the same therapies as animals with CIN.
Assessment and management of urolithiasis
Uroliths are mineral aggregations that occur very commonly in the urinary tracts of both dogs and cats. They can be found anywhere in the urinary tract from the kidney to the urethra, and can be a benign, incidental finding or the cause of life-threatening illness. Management of urolithiasis depends on the mineral type of urolith present and the location of the urolith(s) within the urinary tract. Mineral type can only be definitively determined by retrieving stone material and submitting it for analysis, but sometimes a "best guess" can be made by considering the species/breed, sex and age of an animal. Radiography and ultrasound imaging are two of the most commonly used tools to define the location of uroliths and to assess the animal's entire urinary tract. Sometimes more advanced studies such as the antegrade pyelogram or computed tomography (CT scan) are used for precise localization, especially prior to surgery.
Management of hypertension
Hypertension, or high blood pressure, is a common finding in pets (and people) with both acute and chronic kidney diseases; additionally, persistent hypertension can worsen existing kidney disease. Blood pressure is most often assessed in pets either oscillometrically or with a Doppler unit. Oscillometric assessment permits measurement of both systolic and diastolic pressures, while the Doppler method best measures systolic pressures. Both methods require placement of an inflatable cuff on a limb or tail. Repeated measurements on a calm pet provide the most accurate assessment of pressures. The clinician or nurse may wait until your pet has calmed and acclimated to the exam room prior to measuring pressures, or may even place the cuff, leave the room and have you start the measurements when you believe your pet is relaxed. Repeated measurements of blood pressure over time are critical to management of hypertension, particularly when blood pressure medications are prescribed.
Lower Urinary Tract Disease Management
Assessment and Management of Incontinences
Proper urine storage and release depends on normal structure and function of the urinary tract, as well as normal function of the central nervous system. Incontinence refers to abnormal leakage of urine from the bladder out the urethra. This problem is most often seen in spayed female dogs, but can occur in any species and in either sex, whether spayed/castrated or not. There are many different causes of incontinence, and appropriate management depends first on determination of the cause. Investigation of incontinence may require laboratory tests, radiography, ultrasound, computed tomography, uroendoscopy, and/or urethral pressure profilometry. Management of incontinence may include medical therapies, surgical therapies, or both.
Chronic Urinary Tract Infections
Urinary tract infections (UTI) are usually bacterial in origin and can affect either the lower urinary tract or both the upper and lower tracts. Bacteria from the intestinal tract and the external genital region ascend through the urethra into the bladder on a regular basis; the balance between bacterial virulence factors and host immune defenses determines whether the bacteria can colonize the bladder and cause UTI. Some concomitant patient factors such as kidney failure, diabetes mellitus, Cushing's syndrome, urolithiasis, hyperthyroidism, the presence of a urinary catheter, incontinence and spinal cord disease, among others, can increase the likelihood of UTI. Sometimes medical situations such as the ones listed above render the infection more difficult to clear and may make a pet more likely to become reinfected. Medications that suppress the immune system can also increase the likelihood of developing UTI and/or complicate UTI treatment. When patients develop sequential UTIs, have difficulty clearing a UTI despite appropriate management, systematic evaluation of patient anatomy and physiology may help to identify complicating factors and appropriate methods for clearing/controlling UTI.
Assessment and Management of Urolithiasis
Uroliths are mineral aggregations that occur very commonly in the urinary tracts of both dogs and cats. They can be found anywhere in the urinary tract from the kidney to the urethra, and can be a benign, incidental finding or the cause of life-threatening illness. Management of urolithiasis depends on the mineral type of urolith present and the location of the urolith(s) within the urinary tract. Mineral type can only be definitively determined by retrieving stone material and submitting it for analysis, but sometimes a "best guess" can be made by considering the species/breed, sex and age of an animal. Radiography and ultrasound imaging are two of the most commonly used tools to define the location of uroliths and to assess the animal's entire urinary tract. Sometimes more advanced studies such as the antegrade pyelogram or computed tomography (CT scan) are used for precise localization, especially prior to surgery.
Uroendoscopy
For assessment of some urinary problems, your clinician may recommend uroendoscopy. In this procedure, a flexible or rigid endoscope is introduced through the urethra into the bladder. This procedure permits direct visual assessment of the lower urinary tract structures and may also permit biopsy of these structures if necessary. Uroendoscopy is often recommended for problems such as incontinence, chronic urinary tract infection, and bladder or urethral masses.
