Glomerulonephritis in Dogs and Cats: Diagnosis and Treatment* KEY FACTS Virginia Tech I the Urine Protein:Creatinine Ratio David C

798 VV Vol. 23, No. 9 September 2001 Email comments/questions to [email protected] or fax 800-556-3288 CE Article #2 (1.5 contact hours) Refereed Peer Review Glomerulonephritis in Dogs and Cats: Diagnosis and Treatment* KEY FACTS Virginia Tech I The urine protein:creatinine ratio David C. Grant, DVM is a reliable indicator of renal S. Dru Forrester, DVM, MS, DACVIM protein loss when the urine sediment is inactive and UTI is not present. ABSTRACT: Initial suspicion of glomerulonephritis (GN) arises when proteinuria is documented without evidence of urogenital tract inflammation. Diagnosis involves thoroughly evaluating the I A renal biopsy and histologic patient for concurrent diseases known to be associated with GN and ruling out prerenal and evaluation are required for postrenal causes of proteinuria. Definitive diagnosis requires a renal biopsy. In the past, man- differentiating GN from agement has included elimination of the underlying cause, immunosuppression, and measures amyloidosis. to prevent complications of GN. Immunosuppressive therapy has been successful in managing certain forms of GN in humans but does not appear helpful in dogs and cats and may even be harmful. Recently, use of angiotensin-converting enzyme (ACE) inhibitors and thromboxane I ACE inhibitors decrease synthetase inhibitors has shown beneficial effects in the management of canine GN. proteinuria in dogs but may also exacerbate renal failure. lomerulonephritis is suspected when significant proteinuria exists with an inactive urinary sediment, especially in patients with a history of Glethargy, anorexia, or vomiting. Often, however, proteinuria is an incidental finding during routine urinalysis. This should prompt further investiga- tion of the origin of the protein being lost. DIAGNOSIS Causes of preglomerular and postglomerular proteinuria (Box 1) should be ruled out initially with a minimum database of a complete blood cell count (CBC), chemistry profile, complete urinalysis, and urine culture. If an extraglomerular cause of proteinuria is detected, treatment should be directed toward that cause and reevalua- tion of proteinuria conducted during treatment and/or after resolution of the disor- der. Diagnostic evaluation should continue if proteinuria persists after treatment or an extraglomerular source of proteinuria is not detected with the minimum database. *A companion article entitled “Glomerulonephritis in Dogs and Cats: Glomerular Func- tion, Pathophysiology, and Clinical Signs” appeared in the August 2001 (Vol. 23, No. 8) issue of Compendium. Compendium September 2001 Small Animal/Exotics 799

Urinalysis Box 1. Extraglomerular Sources of Proteinuria A complete analysis of urine obtained by cystocentesis should be Preglomerular Postglomerular done. The urine sediment is typically • Bence Jones proteins (myeloma) • Urogenital tract infection inactive in patients with GN, with the • Hemoglobin (hemolysis) • Urogenital tract neoplasia possible exception of hyaline or gran- • Myoglobin • Urinary tract calculi ular casts. If the sediment contains • Fever • Urogenital tract hemorrhage increased numbers of leukocytes, ery- • Seizures • Urogenital tract trauma throcytes, renal tubular cells, transi- • Extreme exercise • Fanconi syndrome tional cells, or bacteria, other urinary • Acute renal failure tract diseases (e.g., infection, calculi, neoplasia) should be considered. Isos- thenuria (urine specific gravity of 1.008 to 1.012) is to 1 in cats should be considered questionable for a present in some patients with GN. An aerobic culture protein-losing nephropathy.2,4,5 of urine obtained by cystocentesis should be performed to rule out urinary tract infection (UTI) as a cause of Complete Blood Cell Count proteinuria. If proteinuria persists after elimination of and Chemistry Profile UTI, additional evaluation is indicated. Laboratory abnormalities are often nonspecific and There are numerous tests for the detection of pro- are likely to reflect the underlying disease, if one exists: teinuria: • Anemia has been reported in more than 44% of • The initial test used by most practitioners is based dogs and 63% to 85% of cats with GN.6–9 on a color change of tetrabromophenol blue, which • Hypoalbuminemia is commonly present in dogs primarily detects albumin. The degree of color (61%) and cats (92% to 96%) with GN.6,8,9 change roughly corresponds to a concentration of • Hypercholesterolemia is noted in both dogs (79%) protein in mg/dl. and cats (73% to 90%) with GN.6,8,9 • Other commonly used tests, such as the sulfosali- • Azotemia is also a common finding in dogs (49% to cylic or nitric acid test, are based on precipitation of 53%) and cats (greater than 70%) with GN.6–9 proteins and subjective measurement of the turbidi- ty of the subsequent suspension. These precipitation If the UP:C is consistently greater than 1 and the min- tests detect more kinds of proteins (Tamm-Horsfall imum database has failed to identify the cause of pro- proteins, albumin, Bence Jones proteins) than the teinuria, additional tests should be done to identify dis- dipstick. eases that may predispose the dog or cat to GN (Box 2).

While these tests may confirm proteinuria, they are Renal Biopsy not quantitative and thus do not verify pathologic pro- If a potential cause of proteinuria has not been iden- teinuria.1 In addition, both tests must be interpreted in tified after performing the diagnostics listed in Box 2 or light of the urine concentration. A 2+ protein is proba- if proteinuria persists following appropriate treatment bly of much less importance in urine with a specific of an identified cause, a renal biopsy should be done. gravity greater than 1.030 than in urine with a lower Additionally, if proteinuria is severe (UP:C greater than specific gravity. 10), membranous GN and amyloidosis are most likely The urine protein:creatinine ratio (UP:C) is a simple and differentiation of the two via biopsy is impor- test that allows an approximation of urinary protein tant.3,10 There is much debate as to the need for a renal loss and negates urine concentration as a complicating biopsy once a thorough diagnostic evaluation has failed factor.2,3 While glomerular filtration rate and urine con- to reveal a cause of GN; however, there are several centration may change, the UP:C remains constant in situations in which renal biopsy does provide useful in- most instances. Urine samples should be collected by formation. The most obvious benefit of biopsy is differ- cystocentesis to decrease the likelihood of contamina- entiation of GN from amyloidosis. Patients with amy- tion from the urethra and genital tract. Prostatic reflux loidosis have a poor to grave prognosis and usually do into the urinary bladder could still affect urine collect- not respond to treatment. In contrast, some patients ed by cystocentesis. A UP:C greater than 1 is abnormal with GN respond favorably to correction or treatment and highly suggestive of a protein-losing nephropathy of the underlying disease and others with idiopathic in dogs and cats. A UP:C of 0.2 to 1 in dogs and 0.25 GN can be managed successfully for years.11–13 Another 800 Small Animal/Exotics Compendium September 2001

Box 2. Diagnostic Evaluation of Patients • Hematuria with Suspected Glomerulonephritis • Hydronephrosis • Renal ischemia or infarction Cats Dogs Improper technique is the cause in Urine culture Urine culture most cases. Patients should be assessed CBC, chemistry panel CBC, chemistry panel for coagulopathies by determining a prothrombin time, partial thrombo- Feline leukemia virus/feline Heartworm antigen ELISA immunodeficiency virus ELISA plastin time, and buccal mucosal Thoracic/abdominal radiography bleeding time; however, normal re- Thoracic/abdominal radiography Abdominal ultrasonography sults do not absolutely rule out a co- Abdominal ultrasonography agulopathy or eliminate the possibility and titers Heartworm antigen/antibody tests Rickettsia Borrelia of severe hemorrhage. Microscopic (in endemic areas) Adrenocorticotropin stimulation test hematuria is common for several days Blood pressure Blood pressure following biopsy. Hydronephrosis as a result of clot formation in the renal Antinuclear antibody titer Antinuclear antibody titer pelvis is uncommon, but perioperative intravenous fluid therapy may be used Renal biopsy (light, immunofluorescence, and electron microscopy)a in an attempt to decrease its likelihood. Unless hemorrhage is life a Consider if diagnostic evaluation fails to reveal a concurrent disease associated with threatening, conservative management GN, if treatment of concurrent disease fails to significantly reduce proteinuria, or if proteinuria is severe (UP:C > 10). (e.g., fluid replacement, blood trans- fusions) is typically indicated.14 Renal biopsies should be limited to reason to perform a biopsy is to obtain a histologic clas- cortical tissue to avoid structures in the renal hilus and sification of GN. Reports of long-term survival of cats medulla (Figure 1). The method chosen should be with membranous GN emphasize the usefulness of this based on the condition of the animal, experience of the classification system.8,9 While it is true that this repre- person performing the biopsy, and risks and benefits to sents a small number of cases in which histologic type the patient. may provide prognostic information, our ability to as- sign treatment and prognosis based on identified common factors will not improve without the information that would be acquired via renal biopsies. Useful de- scriptions of equipment and techniques used for renal biopsy can be found elsewhere.14 Generally accepted contraindications to renal biopsy include the following: • Bleeding disorders • A solitary kidney • Uncontrollable hypertension • Pyonephrosis • Renal abscess • Hydronephrosis • A suspected unilateral renal neoplasm • Moderate to severe uremia as it predisposes animals to bleeding • Small end-stage kidneys Figure 1—The biopsy needle should be directed into the renal cortex in such a manner as to avoid damage to structures of Potential complications of renal biopsy include the the renal hilus and medulla. (From Forrester SD: Diseases of following: the kidney and ureter, in Leib MS, Monroe WE [eds]: Prac- tical Small Animal Internal Medicine. Philadelphia, WB Saun- ders Co, 1997, pp 283–331; with permission.) • Hemorrhage Compendium September 2001 Small Animal/Exotics 801

• Surgical biopsy can be performed assuming the pa- Box 3. Treatment Regimen tient is an adequate anesthetic risk. In the authors’ for Glomerulonephritis opinion, benefits of this method are direct visualization of physical abnormalities, acquisition of a larger • Elimination or treatment of any concurrent disease section of tissue than is obtained with needle biopsy • Dietary protein restriction techniques, and ability to rapidly detect and treat —Dogs: 2 to 3 g/kg/day hemorrhage. A potential disadvantage of this method —Cats: 4 g/kg/day is that tissue healing may be impaired due to hy- • Aspirin (0.5 to 5 mg/kg q12–24h) poproteinemia. A previous study found no complica- • ACE inhibitors tions of intestinal biopsies in severely hypoalbumine- —Enalapril (0.5 mg/kg q12–24h) mic dogs; however, tissue healing in hypoproteinemic —Lisinopril (0.7 mg/kg/day)a 15 animals remains a controversial topic. —Benazepril (0.5 mg/kg q12–24h)a • Laparoscopy can be useful in obtaining renal biop- • Supportive therapy sies and is far less invasive than laparotomy; howev- —Furosemide as needed for ascites/edema er, equipment is not available in most practices and —Paracentesis for severe accumulations of body 14 general anesthesia is required. cavity effusions Blind or ultrasound-guided, percutaneous needle • a biopsies can also be obtained. General anesthesia of Among ACE inhibitors, enalapril is the only one with documented benefit in the management of idiopathic GN in dogs. short duration is typically required. Blind techniques Dosages for lisinopril and benazepril are extrapolated from ex- are most successful in cats because the kidneys can perimental reports. be immobilized.14 Ultrasound allows visualization of the needle and important structures (e.g., renal pelvis, renal vessels, cystic structures) that should be heartworm disease, chemotherapy for lymphoma). In avoided with the needle. In addition, it allows rapid many cases, however, the diagnosis is either idiopathic detection of hemorrhage.14 While percutaneous or the cause of secondary GN cannot be eliminated methods may be the most rapid and practical, sam- (e.g., some neoplasms, feline infectious peritonitis, sys- ples obtained in this manner are generally small. A temic lupus erythematosus). 16-gauge needle may provide a more reliably adequate sample than do smaller needles.16 Immunosuppressive Therapy In veterinary medicine there is only one relatively Laboratories should be contacted prior to renal biop- well-controlled study evaluating the efficacy of im- sy to obtain specific requirements for tissue submission. munosuppressive therapy in patients with this condi- Renal tissue specimens should be submitted for routine tion.13 The use of cyclosporine in dogs with naturally light microscopy, immunofluorescence studies, and if occurring GN was compared with standard care (as- possible, electron microscopy. In most cases, samples pirin and a moderately restricted protein diet). No dif- for light microscopy should be placed in 10% formalin ference in proteinuria was seen between the two and will be stained with hematoxylin and eosin for groups, and some patients receiving cyclosporine devel- morphologic examination and Congo red to evaluate oped side effects; thus cyclosporine cannot be advocat- for the presence of amyloid. In most cases, samples for ed for the treatment of canine GN. immunofluorescence should be snap frozen or fixed in Controlled studies evaluating the use of corticos- Michel’s medium, and tissue for electron microscopy teroids, azathioprine, or cyclophosphamide for GN should be placed in Trump’s fixative.16 Electron mi- in dogs or cats have not been conducted. Considering croscopy is often not done but should be considered to the potential for thromboembolism and hypertension increase our understanding of glomerular disease in vet- that exists with GN, the use of corticosteroids may be erinary patients. more detrimental than helpful. In addition, results of treatment with these medications have been disap- TREATMENT pointing. Currently, immunosuppressive therapy can- Management of patients with GN is based on de- not be advocated as a treatment for idiopathic GN. creasing immune stimulation, modifying the immune Immunosuppressive drugs do have a place in manag- response, and preventing or treating complicating dis- ing patients with GN when they are appropriate orders (Box 3). In patients with secondary GN, de- treatment for a concurrent disease (e.g., immune-me- creasing immune stimulation is achieved through treat- diated hemolytic anemia, neoplasia, systemic lupus ment of concurrent disease (e.g., melarsomine for erythematosus). 802 Small Animal/Exotics Compendium September 2001

Angiotensin-Converting Enzyme Inhibitors success in research models. However, enalapril should Reports of the use of ACE inhibitors for reduction of still be the initial ACE inhibitor of choice for treatment proteinuria in animals and humans have emerged.17–20 of dogs with GN because of its documented efficacy. The mechanism of beneficial effects provided by ACE inhibitors in proteinuric patients is uncertain. Evidence Thromboxane Synthetase Inhibitors exists for reduction in efferent arteriolar pressures, thus Another group of immune-response modulators that decreasing glomerular capillary hydrostatic pressure and has shown great promise are thromboxane synthetase proteinuria.17 ACE inhibition appears to reduce the ra- inhibitors.23–25 Thromboxane concentrations are in- dius of endothelial cell pores and improve glomerular creased in the urine of dogs with GN and are believed barrier size selectivity in human diabetic glomerulopa- to have a role in the pathologic process.23–26 Thrombox- thy.20 Other evidence exists suggesting angiotensin II has ane synthetase inhibitors have been shown to prevent inflammatory properties and that inhibition of its effects histologic lesions, decrease proteinuria, and decrease may be useful as an antiinflammatory mechanism.21 urinary thromboxane in experimentally induced and In a report by Brown and colleagues, lisinopril (0.7 naturally occurring GN in dogs.23–26 mg/kg/day) provided significant reduction in protein- Long-term treatment of one dog with naturally oc- uria in uninephrectomized dogs with experimentally in- curring membranous GN has been described.26 The duced diabetes mellitus.17 Samoyed dogs with X-linked patient presented with clinical signs of nephrotic hereditary nephritis given enalapril (2 mg/kg bid) had a syndrome that resolved during treatment with a throm- slower rate of increase in proteinuria and longer survival boxane synthetase inhibitor and recurred with its dis- times than untreated, affected dogs.19 Recently, Grauer continuation. and coworkers performed a prospective multicenter trial Unfortunately, these drugs are not currently available evaluating enalapril versus standard care (low-dose as- in the United States. They are marketed for throm- pirin and a moderately restricted protein diet) for the boembolic disease in humans in Japan (ozagrel) and treatment of naturally occurring canine idiopathic Italy (picotamide). GN.18 Dogs receiving enalapril (0.5 mg/kg PO q12–24h) had significant reductions in their UP:C over Aspirin 6 months of treatment, without significant increases in Because of the role of platelets in the pathogenesis of serum creatinine. Placebo-treated dogs did not improve, glomerular disease, aspirin has been recommended for whereas the majority of dogs in the enalapril group im- patients with GN. Through its inhibition of cyclooxy- proved (reduction in UP:C greater than 50% with a sta- genase, aspirin is also a nonspecific thromboxane syn- ble serum creatinine level); however, the only animals thetase inhibitor. A low dose of aspirin (0.5 to 5 mg/kg euthanized for renal failure were in the enalapril group. q12–24h) is recommended; however, there are no stud- An initial dose of 0.5 mg/kg PO bid appears reasonable ies documenting its efficacy in dogs or cats with but should be administered with caution, and patients GN.27,28 A short-term in vivo study of the effects of as- should be monitored carefully as enalapril may exacer- pirin on canine platelets may suggest that ultra-low bate azotemia. To detect azotemia, serum creatinine and dosing (0.5 mg/kg q12h) decreases platelet blood urea nitrogen should be evaluated before and 7 aggregation.29 Such low doses require reformulation in days after beginning treatment. The appropriate interval smaller patients. between UP:C reevaluations is unknown, but initially every 2 weeks may be reasonable. The dose should be Diet increased only if reduction in the UP:C is not seen on Reductions in dietary protein reduce proteinuria in three consecutive measurements. human nephrotic patients while increasing or main- If azotemia develops or is exacerbated during treat- taining serum albumin concentration.30 Additionally, ment, an alternative ACE inhibitor should be consid- protein restriction may help to alleviate clinical signs of ered or the dosage of enalapril should be reduced. In a concurrent renal failure. One recommendation is 2 to 3 recent study it was shown that there is increased expo- g/kg/day of protein for dogs and 4 g/kg/day for cats.31 sure to enalaprilat (the active metabolite of enalapril) in Albumin concentration and UP:C should be moni- dogs with mild renal insufficiency, whereas this did not tored. Increasing albumin concentrations, decreasing occur with benazeprilat (the active metabolite of be- UP:C, and weight gain would be reasons for continu- nazepril).22 One potential benefit of benazepril is the in- ing on a protein-restricted diet. creased biliary elimination of its active metabolite com- Omega-3 fatty acid supplementation in dogs with ex- pared with that of enalaprilat, which is primarily perimentally induced renal insufficiency may be reno- eliminated by the kidneys. Lisinopril has been used with protective.32,33 Omega-3 fatty acids may alter throm- Compendium September 2001 Small Animal/Exotics 803

boxane formation in complement-stimulated glomeru- 8. Arthur JE, Lucke VM, Newby TJ, et al: The long-term prog- lar epithelial cells in vitro.34 In humans with chronic nosis of feline idiopathic membranous glomerulonephritis. glomerular disease, supplementation has also decreased JAAHA 22:731–737, 1986. 35 9. Nash AS, Wright NG, Spencer AJ, et al: Membranous proteinuria. These results appear promising as adjunc- nephropathy in the cat: A clinical and pathological study. Vet tive therapy for GN, but placebo-controlled prospective Rec 105:71–77, 1979. clinical trials in naturally occurring GN are needed. 10. Biewenga WJ: Proteinuria in the dog: A clinicopathological study in 51 proteinuric dogs. Res Vet Sci 41:257–264, 1986. PROGNOSIS 11. Osborne CA, Stevens JB, McClean R, et al: Membranous lupus glomerulonephritis in a dog. JAAHA 9:295–303, 1973. The prognosis for GN is quite variable in dogs and 12. Willard MD, Krehbiel JD, Schmidt GM, et al: Serum and cats. Survival of several years beyond diagnosis and urine protein abnormalities associated with lymphocytic complete remissions have been reported in as many as leukemia and glomerulonephritis in a dog. JAAHA 17:381– half of cats with idiopathic membranous GN. Those 386, 1981. cats with evidence of renal failure died or were euth- 13. Vaden SL, Breitschwerdt EB, Armstrong PJ, et al: The effects of cyclosporine versus standard care in dogs with naturally anized within a short time due to severe clinical occurring glomerulonephritis. J Vet Intern Med 9:259– 8,9,36 signs. Dogs with a diagnosis of idiopathic GN that 266, 1995. were not euthanized after initial evaluation had a medi- 14. Bartges JW, Osborne CA: Canine and feline renal biopsy, in an survival time of 28 days (range, 5 to 1170 days).7 Osborne CA, Finco DR (eds): Canine and Feline Nephrology Another study reported a median survival time of 16 and Urology. Baltimore, Williams and Wilkins, 1995, pp 277–302. months for dogs with idiopathic GN of various histo- 15. Harvey HJ: Complications of small intestinal biopsy in hy- 13 logic types. In the recent study by Grauer and col- poalbuminemic dogs. Vet Surg 19:289–292, 1990. leagues, all 14 of the untreated idiopathic GN patients 16. Vaden SL: Renal biopsy: How and why? 18th Annu Vet Med survived the 6-month trial.18 Azotemia or uremia at ini- Forum:675, 2000. tial evaluation may indicate a shorter survival time (3 17. Brown SA, Walton CL, Crawford P, et al: Long-term effects months or less) in dogs.6 Prognosis may be better for of antihypertensive regimens on renal hemodynamics and proteinuria. Kidney Int 43:1210–1218, 1993. secondary GN, assuming the causative disease is cur- 18. Grauer GF, Greco DS, Getzy DM, et al: Effects of enalapril able. These discordant survival times emphasize the versus placebo as a treatment for canine idiopathic glomeru- variability in prognosis and the importance of a thor- lonephritis. J Vet Intern Med 14:526–533, 2000. ough diagnostic evaluation and differentiation of GN 19. Grodecki KM, Gains MJ, Baumal R, et al: Treatment of x- from amyloidosis. linked hereditary nephritis in Samoyed dogs with angiotensin converting enzyme (ACE) inhibitor. J Comp Pathol 117:209–225, 1997. REFERENCES 20. Morelli E, Loon N, Meyer T, et al: Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopa- 1. Finco DR: Urinary protein loss, in Osborne CA, Finco DR thy. Diabetes 39:76–82, 1990. (eds): Canine and Feline Nephrology and Urology. Baltimore, 21. Nataraj C, Oliverio MI, Mannon RB, et al: Angiotensin II Williams and Wilkins, 1995, pp 211–215. regulates cellular immune responses through a calcineurin- 2. Grauer GF, Thomas CB, Eicker SW: Estimation of quantita- dependent pathway. J Clin Invest 104:1693–1701, 1999. tive proteinuria in the dog, using the urine protein-to-creati- 22. Lefebvre HP, Laroute V, Concordet D, et al: Effects of renal nine ratio from a random, voided sample. Am J Vet Res 46: impairment on the disposition of orally administered enala- 2116–2119, 1985. pril, benazepril, and their active metabolites. J Vet Intern 3. Center SA, Wilkinson E, Smith CA, et al: 24-Hour urine Med 13:21–27, 1999. protein/creatinine ratio in dogs with protein-losing 23. Grauer GF, Culham CA, Dubielzig RR, et al: Effects of a nephropathies. JAVMA 187:820–824, 1985. specific thromboxane synthetase inhibitor on development 4. Monroe WE, Davenport DJ, Saunders GK: Twenty-four of experimental Dirofilaria immitis immune complex hour urinary protein loss in healthy cats and the urinary pro- glomerulonephritis in the dog. J Vet Intern Med 2:192–200, tein–creatinine ratio as an estimate. Am J Vet Res 50:1906– 1988. 1909, 1989. 24. Grauer GF, Frisbie DD, Longhofer SL, et al: Effects of a 5. Adams LG, Polzin DJ, Osborne CA, et al: Correlation of thromboxane synthetase inhibitor on established immune urine protein/creatinine ratio and twenty-four-hour urinary complex glomerulonephritis in dogs. Am J Vet Res 53:808– protein excretion in normal cats and cats with surgically in- 813, 1992. duced chronic renal failure. J Vet Intern Med 6:36–40, 1992. 25. Longhofer SL, Frisbie DD, Johnson HC, et al: Effects of 6. Center SA, Smith CA, Wilkinson E, et al: Clinicopatholog- thromboxane synthetase inhibition on immune complex ic, renal immunofluorescent, and light microscopic features glomerulonephritis. Am J Vet Res 52:480–487, 1991. of glomerulonephritis in the dog: 41 cases (1975–1985). 26. Grauer GF, Frisbie DD, Snyder PS, et al: Treatment of mem- JAVMA 190:81–90, 1987. branoproliferative glomerulonephritis and nephrotic syn- 7. Cook AK, Cowgill LD: Clinical and pathological features of drome in a dog with a thromboxane synthetase inhibitor. J protein-losing glomerular disease in the dog: A review of 137 Vet Intern Med 6:77–81, 1992. cases (1985–1992). JAAHA 32:313–322, 1996. 27. Forrester SD: Diseases of the kidney and ureter, in Monroe 804 Small Animal/Exotics Compendium September 2001

WE, Leib MS (eds): Practical Small Animal Internal Medicine. d. plasma globulins are normal, urine sediment is in- Philadelphia, WB Saunders Co, 1997, pp 283–331. active, and urine culture is negative. 28. Grauer GF, DiBartola SP: Glomerular disease, in Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine: 3. Enalapril maleate Diseases of the Dog and Cat. Philadelphia, WB Saunders Co, 2000, pp 1662–1678. a. has recently been shown to reduce proteinuria asso- 29. Rackear D, Feldman B, Farver T, et al: The effect of three ciated with canine idiopathic GN. different dosages of acetylsalicylic acid on canine platelet ag- b. has recently been labeled for use as a treatment for gregation. JAAHA 24:23–26, 1988. canine idiopathic GN. 30. Kaysen GA, Gambertoglio J, Jimenez I, et al: Effect of di- c. is safe for use in patients that have concurrent GN etary protein intake on albumin homeostasis in nephrotic patients. Kidney Int 29:572–577, 1986. and chronic renal failure. 31. Brown SA: Primary diseases of glomeruli, in Osborne CA, d. all of the above Finco DR (eds): Canine and Feline Nephrology and Urology. Baltimore, Williams and Wilkins, 1995, pp 368–385. 4. Which of the following statements regarding the use of 32. Brown SA, Brown CA, Crowell WA, et al: Beneficial effects corticosteroids in the management of GN is true? of chronic administration of dietary omega-3 polyunsaturat- a. Corticosteroids are contraindicated under any cir- ed fatty acids in dogs with renal insufficiency. J Lab Clin Med 131:447–455, 1998. cumstance. 33. Brown SA, Brown CA, Crowell WA, et al: Effects of dietary b. Corticosteroids cause lymphocyte lysis and inhibit polyunsaturated fatty acid supplementation in early renal in- phagocytosis, thus tempering the destructive im- sufficiency in dogs. J Lab Clin Med 135:275–286, 2000. mune-mediated process and slowing the progres- 34. Goldstein DJ, Wheeler DC, Salant DJ: Effects of omega-3 sion of idiopathic GN. fatty acids on complement-mediated glomerular epithelial c. Corticosteroids are used in patients with GN when cell injury. Kidney Int 50:1863–1871, 1996. 35. De Caterina R, Caprioli R, Giannessi D, et al: N-3 fatty they are part of an accepted therapeutic regimen for acids reduce proteinuria in patients with chronic glomerular the treatment of a concurrent disease. disease. Kidney Int 44:843–850, 1993. d. Corticosteroids are recommended for most forms 36. Lucke VM: Glomerulonephritis in the cat. Vet Annu 22: of GN. 270–278, 1982. 5. The most commonly employed urine dipstick test for ARTICLE #2 CE TEST proteinuria predominantly detects The article you have read qualifies for 1.5 con- a. Bence Jones proteins. tact hours of Continuing Education Credit from b. hemoglobin. the Auburn UniversityCE College of Veterinary Med- c. albumin. icine. Choose the best answer to each of the follow- d. thromboxanes. ing questions; then mark your answers on the postage-paid envelope inserted in Compendium. 6. ACE inhibitors a. have been shown to decrease proteinuria in naturally occurring, idiopathic canine GN. 1. Which of the following statements regarding prognosis b. may decrease proteinuria by decreasing glomerular for dogs and cats with GN is true? efferent arteriolar pressures. a. GN consistently carries a grave prognosis for sur- c. may decrease proteinuria by decreasing endothelial vival beyond 1 month. pore size. b. GN consistently carries a grave prognosis for sur- d. all of the above vival beyond 1 year. c. GN is an incidental finding and carries no prognos- 7. Renal biopsy samples should be obtained from tic significance. a. the medulla only. d. GN has a variable prognosis. b. the cortex only. 2. An increased UP:C is likely to indicate glomerular c. the cortex and medulla. protein loss if d. grossly abnormal tissue only. a. plasma globulins are normal, urine sediment is inactive, and urine culture is positive. 8. When added as a dietary supplement, ______may b. plasma globulins are normal, urine sediment reveals be renoprotective and decrease proteinuria in patients numerous transitional cells, and urine culture is with chronic glomerular disease. negative. a. omega-6 fatty acids c. plasma globulins are elevated, urine sediment is in- b. omega-3 fatty acids active, and urine culture is positive for Escherichia c. medium-chain triglyceride oil coli. d. fiber Compendium September 2001 Small Animal/Exotics 805

9. UP:C ratios of ______and ______are considered abnormal in dogs and cats, respectively. a. greater than 2; greater than 2 b. greater than 1; greater than 1 c. greater than 0.65; greater than 0.2 d. greater than 5; greater than 2

10. Renal biopsy samples are best evaluated for the presence of amyloid with which stain? a. toluidine blue b. periodic acid–Schiff c. Congo red d. trichrome