Proteinuria Proteinuria is a condition in which there are increased amounts of protein in the urine. There are a number of different diseases which can result in proteinuria. In the early stages of the condition, the patient does not have any symptoms. Therefore, we often diagnosis this condition incidentally when we are performing a urinalysis and chemistry for other reasons. As the condition worsens, the patient may start showing symptoms (see below for complications). When proteinuria is present, it is due either to disease within the bladder or lower urinary tract or disease within the part of the kidney called the glomerulus. The glomerulus is the part of the kidney in which the blood is filtered to make urine. Causes: There are a variety of disease processes that can result in proteinuria. We normally break these up into 4 major categories: benign, non-urinary tract related, urinary tract but not kidney related, and kidney related. Benign: o Change in exercise level o Fever o Stress o Seizure activity Non Urinary Tract: o Congestive heart failure o Release of hemoglobin or myoglobin into the blood stream o Increased protein formed secondary to cancer o Infection anywhere in the body including: pneumonia, endocarditis, infection of the genital tracts, diseases spread by ticks (Lyme disease, Ehrlichia, Anaplasma), heartworm disease, leptospirosis, chronic bacterial infections, FeLV, FIP and mycoplasma. o Inflammation anywhere in the body including: pancreatitis, prostatitis, inflammatory bowel disease, immune mediated hemolytic anemia (attack of the red blood cells), immune mediated thrombocytopenia (attack of the platelets), and hepatitis (inflammation of the liver) Page 1 of 5
o Cushing s disease or the use of steroids can cause mild increases in the amount of protein in the urine. This increase in urine protein does not need to be specifically treated. When the Cushing s disease is under control or the steroid therapy is stopped, this proteinuria will resolve. Urinary Tract: o Bacterial infections within the bladder or the kidneys o Leptospirosis infections within the kidneys Disease within the glomerulus of the kidney: o Amyloidosis o Glomerulonephritis inflammation of the glomerulus Membranoproliferative form types I (mesangiocapillary) and II (dense deposit disease) Proliferative glomerulonephritis (mesangial and endocapillary) o IgA nephropathy o Glomerulosclerosis scarring of the glomerulus o Hereditary nephritis o Lupus nephritis o Membranous glomerulopathy o Minimal change glomerulopathy Diagnostics: Without obvious symptoms to help narrow down our search, numerous tests are performed to find the potential underlying cause of the proteinuria. We obtain a thorough history see if there have been any subtle symptoms of disease. From there we will start with the following tests: Complete Blood Count (CBC) / Chemistry Panel: These tests give us information on the presence of an infection or inflammation somewhere in the body, any possible organ damage, organ function, electrolyte changes, the level of protein in the blood and if the protein is decrease, which type of protein is decreased. Urinalysis: This examines the urine for increases in white blood cells, red blood cells, and other sediment that indicates disease of the urinary tract or of the kidneys. Urine culture with sensitivity: If a urinary tract infection is suspected, we spread a sample of the urine out on a Petri dish to see if any bacteria grow. If bacteria grow, we test those bacteria against different antibiotics to see which antibiotics are effective at killing the bacteria. Urine protein/ creatinine ratio: This test looks to see if protein is being excreted by the kidneys in quantities higher than creatinine, a metabolic product that is normally filtered and excreted by the kidneys. Changes may indicate kidney tubule or glomerulus disease. This is the best test to quantify the amount of protein in the urine. Page 2 of 5
Abdominal Radiographs (x-rays): To look for signs of neoplasia (cancer) in the abdomen and to look for signs of urinary tract disease such as kidney stones and bladder stone. Chest Radiographs (x-rays): To look for signs of infection or neoplasia (cancer) in the lungs, heart and other areas of the chest. Abdominal Ultrasound: To look for signs of cancer, infection or inflammation in the organs of the abdomen. We can also evaluate the kidney to see if any obvious abnormalities are present 4 DX Test: This blood test evaluates 4 different blood borne diseases that are spread by biting insects. The test includes Anaplasma spp infection, Ehrlichia spp infection, Lyme disease and heartworm disease. Leptospirosis: This is a blood test looks for antibodies produced again leptospira (a specific type of bacterial infection). This infection is spread through urine and can cause liver or kidney damage. The infection can be treated with doxycycline or amoxicillin. Other infectious disease testing: We may test for other infectious diseases based on the specifics of your pet. Biopsies for histopathology, electron microscopy, and immuno-fluorescence staining: If primary disease within the kidney is suspected, we can gain more information to help us best modify our treatment plan by obtaining a more specific diagnosis as to the type of glomerular damage. There are various ways to obtain kidney biopsies but all require general anesthesia. Treatment: Treatment is specific for the specific disease process that caused the proteinuria. Unfortunately, there is no way to include treatments for all associated diseases in one handout. This handout will concentrate on treatment for protein loss through the kidney that is not specific for a particular disease process: Change the diet to one with mild to moderate protein and salt restriction. There are many diets that are pre-formulated for animals with kidney disease and are available with a veterinary prescription. ACE inhibitors. ACE inhibitors are a class of drug that change the pressure within the blood vessels of the kidney had help prevent ongoing protein loss. Two commonly used ACE inhibitors in veterinary medicine are enalapril and benazepril. o Side effects of Enalapril can include GI distress (anorexia, vomiting and/or diarrhea). Less frequently, you can see weakness, decreased blood pressure and decreased renal function. o Side effects of Benazepril are not as well understood in dogs, but it has the potential to cause the same side GI side effects as Enalapril as well as decreased Page 3 of 5
blood pressure and decreased renal function. In cats it may increase food consumption and cause weight gain. Fatty Acid Supplementation to increase the omega 3 to omega 6 ratio. Fish oil and flax seed oils are good for supplementing omega 3 fatty acids and your veterinarian can advise you on how much of these oils to give your pet. There are products specifically made for pets such as 3V caps or you can buy products at stores such as GMC. Treat hypertension (high blood pressure) if it is present. Medications commonly used to treat hypertension in animals include hydralazine and amlodipine, often in combination with an ACE inhibitor. Amlodipine is a calcium channel blocker which, in cats, will rarely cause lethargy, changes in electrolytes, decreased heart rate, weight loss and renal dysfunction. Hydralazine is a vasodilator drug with possible side effects of overcorrection of the blood pressure (hypotension), sodium and water retention and GI distress (anorexia, vomiting, diarrhea). Anti-clotting therapy: Aspirin is commonly prescribed to animals to prevent clotting problems that can develop when the blood level of albumin decreases to a certain level. The most common side effect of aspirin is gastric and/or intestinal irritation with possible ulcer formation and bleeding into the GI tract, but this is extremely uncommon when given at the low doses that should be used for glomerular disease. Treatment specific to the underlying disease. Complications: Thromboembolism (blood clots): Patients with proteinuria can lose a protein cause antithrombin (or anti-thrombin III). This protein is about the same size as albumin so we can use the amount of albumin in the blood as a marker for whether anti-thrombin has been lost. Anti-thrombin prevents blood clots so when the body loses this protein, there is increased risk of developing a clot in the blood. Therefore, we place patients on low doses of aspirin. It is very important that you do not change the dose of this medication, as higher doses can cause ulcers. If a clot forms, it can go anywhere in the body. The most common location is that it goes to the lungs so please monitor for increased respiratory rate and effort, collapse, and weakness. Blood clots can also go to the brain, kidneys, heart, GI tract or legs. Decreased protein in the urine can lead to fluid leaking out of the vessels. This can lead to a condition called ascites, or free fluid in the abdomen, which can appear as sudden distention of the stomach, as if your pet has suddenly gained weight around his/her middle. It can also result in edema, or swelling of the soft tissues of the body as fluid leaks out into these tissues, which can be seen as swollen legs or face. If fluid leaks out around or into the lungs, increased respiratory rate or effort can develop. If you notice changes in your pet s breathing, please seek veterinary care. Page 4 of 5
As more and more protein is lost into the urine, the protein can cause damage to the other part of the kidney (tubules) as it goes through. This can result in kidney failure (elevated kidney values on the blood work and unconcentrated urine). High blood pressure. The kidney is critical in regulated blood pressure. Therefore, as damage to the glomerulus occurs, the patient s blood pressure can become elevated. Frequent checks of blood pressure is recommended. Some treatments for the disease have the unfortunate side effect of causing kidney dysfunction. Continuous monitoring of the kidneys is necessary to be sure that the kidneys are being protected throughout treatment. Despite best our best efforts, the disease itself may eventually lead to kidney failure as well. Complications associated with each specific disease process. Patients with either type of kidney disease kidney failure or glomerular disease are at increased risk of further damage to the kidney when certain medications are given. Therefore, medications such as non-steroidal anti-inflammatory medications (NSAIDS, such as Deramaxx, Rimadyl, Piroxicam, Previcox, high dose aspirin (low doses are good for this disease), and Metacam) should be avoided. Prognosis: The prognosis with glomerular disease varies depending on the underlying condition. If the condition is reversible, the prognosis is better. Literature sites that the median survival time (time at which half of the patients are still alive and half have died) is about 6 months. We feel that this does not really accurately represent what we see clinically and many patients can live much longer than that (up to years) with a good quality of life. Often, the disease will progress but it is difficult to predict how quickly that will occur in any specific patient until we are able to see the trends of the lab results. At times, the disease will hold steady for quite some time and then, once things worsen to a certain point, the patient may deteriorate very quickly with both proteinuria and kidney failure. Page 5 of 5