IDEXX Laboratories. Renal Disease Case Studies

Transcription

1 IDEXX Laboratories Renal Disease Case Studies

2 Authors Dennis DeNicola, DVM, PhD, DACVP Chief Veterinary Educator, Clinical Pathologist, IDEXX Laboratories Dr. DeNicola completed his DVM in 1978 and his PhD in 1981, both at Purdue University. For more than twenty years, he served as educator in clinical and surgical pathology. In addition, he directed the primary cytology and surgical pathology service at the veterinary school laboratory and ran a private pathology service for 15 years. A speaker at more than 100 national and international education symposia, Dr. DeNicola also has authored or co-authored more than 150 publications in various aspects of veterinary clinical pathology. Fred Metzger, DVM, DABVP Owner, Metzger Animal Hospital Dr. Metzger is a 1986 graduate of the Purdue School of Veterinary Medicine and a diplomate of the American Board of Veterinary Practitioners, with specialties in canine and feline medicine. He is an adjunct professor at Pennsylvania State University and serves on the practitioner advisory boards of Veterinary Economics and Veterinary Medicine magazines. He recently co-authored Guide to Hematology in Dogs and Cats with Dr. Alan Rebar. Dr. Metzger owns the Metzger Animal Hospital, a four-doctor practice in State College, Pennsylvania, that received the 1998 Veterinary Economics/Pfizer Practice of Excellence award. Pete Fernandes, DVM, DACVP Clinical Pathologist, IDEXX Laboratories Dr. Fernandes completed his DVM at the University of Wisconsin-Madison, followed by an internship in smallanimal medicine and surgery at South Shore Animal Hospital in Boston. Dr. Fernandes residency was in clinical pathology at Texas A&M University and the University of Florida. He is a diplomate of the American College of Veterinary Pathologists. Brian Poteet, DVM, DAVCR, DABSNM Director, Gulf Coast Veterinary Diagnostic Imaging Dr. Poteet received his DVM from Texas A&M University and completed his radiology residency at the University of Tennessee. In addition to being board-certified with the American College of Veterinary Radiology, Dr. Poteet is also a member of the American Board of Science in Nuclear Medicine. Dr. Poteet is a member of several local and national veterinary medical associations, Vice President of the Veterinary Cancer Associates, and holds two adjunct faculty positions at Texas A&M University. Richard Goldstein, DVM, DACVIM, DECVIM-CA Assistant Professor, Small-Animal Medicine, Cornell University Dr. Goldstein received his DVM from the Koret School of Veterinary Medicine, the Hebrew University of Jerusalem, Israel. He completed his residency in smallanimal internal medicine at the University of California, Davis. He is a diplomate of the American College of Veterinary Internal Medicine and the European College of Veterinary Internal Medicine Companion Animals. He joined the faculty at Cornell in Dr. Goldstein s clinical and research interests include nephrology and leptospirosis and Lyme nephritus in dogs. Roberta Relford, DVM, MS, PhD, DACVIM, DACVP Divisional Vice President of Worldwide Pathology Coagulation, Cytology, Internal Medicine, IDEXX Laboratories Dr. Relford received her DVM from Auburn University in 1982 and worked as a small-animal practitioner for four years before pursuing her advanced training. She started her residency training in clinical pathology and obtained an MS in pathology from Mississippi State University. She then transferred to Texas A&M, where she completed her pathology residency training and obtained a PhD in pathology. While completing her PhD, Dr. Relford pursued a residency in small-animal internal medicine. Dr. Relford is board-certified in internal medicine by the American College of Veterinary Internal Medicine and in clinical pathology by the American College of Veterinary Pathologists. She currently serves as Divisional Vice President of Worldwide Pathology for IDEXX Reference Laboratories. Dr. Relford has given numerous lectures on a wide variety of topics including clinical pathology, internal medicine, infectious diseases, cytology, platelet disorders, health maintenance programs and zoonotic diseases.

3 Case Study 1 Jake Douglas Patient Three-year-old intact male Labrador retriever Presenting Complaints Rear leg lameness History Traveling hunting dog with recent trips to Texas and New Mexico four months ago Physical Exam Dehydration (~10%), fever, edema, generalized peripheral lymphadenopathy, uveitis, bilateral swollen hocks and right stifle

4 Case Study 1 Hematology Hct = 32.2 % LOW Hgb = 10.1 g/dl LOW RBC = 4.9 µl LOW MCV = 63.5 fl MCH = pg MCHC = 33.2 g/dl RDW = 17.3 % HIGH % RETIC = 0.6 % RETIC = 40,000 µl WBC = 18,237 µl HIGH 5,500 16,950 NEU = 14,200 µl HIGH 2,000 12,000 LYM = 900 µl LOW ,900 MONO = 2,900 µl HIGH 100 1,400 EOSIN = 223 µl 100 1,490 BASO = 14 µl PLT = 360 K/µL Biochemical profile Alk Phos = 899 U/L HIGH ALT (SGPT) = 201 U/L HIGH Albumin = 1.6 g/dl LOW Total Protein = 8.1 g/dl Globulin = 6.5 g/dl HIGH Total Bilirubin = 0.2 mg/dl BUN = 37 mg/dl HIGH 7 27 Creatinine = 2.2 mg/dl HIGH Glucose = 99 mg/dl Calcium = 10.3 mg/dl Phosphorus = 9.0 mg/dl HIGH Sodium = 150 meq/l Potassium = 5.1 meq/l Chloride = 111 meq/l Complete Urinalysis: Cystocentesis Dipstick Tests Urine Sediment Examination Color Yellow WBCs/hpf 0 Transparency Clear RBCs/hpf 0 Specific Gravity Epithelial cells/hpf 0 Protein 3+ Casts/hpf 5 to 7, granular Glucose Negative Crystals 0 Bilirubin Trace Bacteria 0 Blood Negative ph 6.5 UPC Ratio 5.1

5 Case Study 1 Serology Leptospirosis negative SNAP 3Dx Test Heartworm antigen negative E. canis antibody negative Lyme C 6 antibody positive Rocky Mountain spotted fever negative Lyme-positive SNAP 3Dx Test Cytology Arthrocentesis (hock and stifle): suppurative inflammatory joint fluid Lymph node FNA (inguinal & popliteal): lymphoid hyperplasia, consistent with reactive lymph nodes Cytology: fi ne-needle aspirate Renal biopsy 10x Renal biopsy 60x

6 Case Study 1 Interpretive Summary Hematology There is mild nonregenerative anemia. The most common cause of mild nonregenerative anemia is anemia of chronic disease. The modest leukocytosis composed of mature neutrophilia and monocytosis with concurrent lymphopenia is consistent with an established infl ammatory condition. The thrombon/platelets are within normal limits Biochemical profile Hypoalbuminemia and azotemia with an elevated UPC and the presence of granular casts support renal disease. The positive Lyme serology along with the hyperglobulinemia suggests Lyme nephritis. The specifi c gravity indicates some, yet inadequate, concentrating ability, and hypoalbuminemia may be masked somewhat by dehydration. Signifi cant hypoalbuminemia is caused by protein-losing glomerulopathy and worsened by systemic vasculitis, severe hepatic insuffi ciency and hyperglobulinemia related to antigenic stimulation. Azotemia is likely of mixed origins or primarily of renal origins with some degree of a prerenal component. Decreased urine concentrating ability in the face of dehydration is an indication of renal azotemia. Confounding renal azotemia, severe hypoalbuminemia can decrease colloidal osmotic pressure and essentially decrease vascular volume or renal perfusion. In the later stages of Lyme nephritis, lesions can include some combination of interstitial lymphoplasmacytic nephritis, tubular necrosis and diffuse glomerulonephritis, all of which can be a cause of proteinuria. The pathogenesis of the tubular changes in canine Lyme nephritis is questionable, but immune-mediated glomerular disease, decreased perfusion and hypoxia, and the toxic effects of severe proteinuria are all postulated as potential causes. Liver enzymes are increased by hepatocellular damage, systemic or intrahepatic vasculitis, and vacuolar hepatopathy associated with chronic infl ammation or infection and ischemia. Urinalysis Urine specifi c gravity shows inappropriate concentrating ability caused by glomerular and tubular dysfunction. Observation of granular casts can confi rm coexisting tubular damage, but the density of casts in urine cannot reliably measure severity, reversibility or duration of lesion. The pathogenesis of the tubular changes in canine Lyme nephritis is questionable, but immunemediated glomerular disease, decreased perfusion and hypoxia, and the toxic effects of severe proteinuria are most likely responsible. Additional testing Serology Follow-up with quantitative C 6 antibody test aids in determining when treatment is warranted, accurately tracking response to therapy and, eventually, as an indicator of when treatment has been effective. Lyme C 6 antibody to the C 6 antigen is a highly specifi c for Borrelia burgdorferi infection. Dogs with leptospirosis, Rocky Mountain spotted fever, babesiosis, ehrlichiosis and heartworm disease do not have antibodies to C 6, nor are antibodies to C 6 produced in response to immunization with currently available canine Lyme vaccines. Diagnosis The clinical diagnosis is Lyme nephritis. Treatment/Plan Blood was sent to a reference laboratory for quantitative C 6 antibody testing. The patient was treated with doxycycline, intravenous fl uid support and a renal diet. Recheck renal panel in 3 5 days. Renal biopsy Prevention Prevention of Lyme disease includes reducing tick exposure, utilizing tick repellant products and vaccinating at-risk patients. Zoonotic onotic Potential Since pets share our environment, they may incidentally become our sentinels; therefore, borreliosis in our canine ne companions should be a warning to increase vigilance and re-evaluate tick-prevention protocols. Lyme disease is not transmissible directly from the canine patient to the owner. However, the owners should be educated d that they are living in a tick-endemic area and the ticks may be infected with Lyme disease.

7 Case Study 2 Muriel Jones Patient Nine-year-old DSH female cat Presenting Complaints Mild PU/PD, intermittent vomiting sometimes containing hair, weight loss Physical Exam Moderate dental tartar, unkempt coat, evidence of diarrhea on tail, tachycardia, dehydration and palpable thyroid nodule

8 Case Study 2 Hematology Hct = 47 % HIGH Hgb = 10 g/dl RBC = µl HIGH MCV = 49 fl MCH = 15 pg MCHC = 33 g/dl RDW = 19 % % RETIC = 0.2 RETIC = 15.3 K/µL WBC = 18,025 µl 5,500 19,500 NEU = 16,680 µl HIGH 2,000 12,500 LYM = 1,000 µl 900 7,000 MONO = 230 µl EOSIN = 115 µl BASO = 0 µl PLT = 220 K/µL Biochemical profile Alk Phos = 86 IU/L HIGH 0 62 ALT (SGPT) = 80 IU/L HIGH Albumin = 2.6 g/dl Total Protein = 6.8 g/dl Globulin = 4.2 g/dl Total Bilirubin = 0.2 mg/dl BUN = 39 mg/dl HIGH Creatinine = 2.7 mg/dl HIGH Cholesterol = 145 mg/dl Glucose = 148 mg/dl Calcium = 9.3 mg/dl Phosphorus = 5.9 mg/dl Sodium = 152 meq/l Chloride = 116 meq/l Potassium = 3.8 meq/l LOW Total T 4 = 7.9 ug/dl HIGH Complete Urinalysis: Cystocentesis Dipstick Tests Urine Sediment Examination Color Yellow WBCs/hpf 0 Transparency Clear RBCs/hpf 0 Specific Gravity Epithelial cells/hpf 0 Protein Negative Casts/hpf 0 Glucose Negative Crystals 0 Bilirubin Negative Bacteria 0 Blood Negative ph 6.7 UPC Ratio 2.7

9 Case Study 2 SNAP T 4 Test Nuclear scintigraphy Thoracic radiograph: lateral Thoracic radiograph: DV

10 Case Study 2 Interpretive Summary Hematology Very mild polycythemia, which can be either relative or absolute. Relative polycythemia is associated with dehydration; absolute can be associated with polycythemia vera or causes of increased erythropeitin. Slight leukocytosis composed of mature neutrophilia (a lack of immature neutrophils on the blood fi lm) with lymphopenia suggests a stress leukogram. Biochemical profile Mild increases in alkaline phosphatase (ALKP) and alanine aminotransferase (ALT) are present. Azotemia is present (BUN, creatinine increased). Deciding if azotemia is prerenal, renal or postrenal can be diffi cult because cats can have renal azotemia with relatively concentrated urine. Moreover, the urine of hyperthyroid cats can be nonconcentrated as a direct result of the hyperthyroidism without any secondary renal disease. Hypokalemia is present and can occur with many feline diseases including CRF (chronic renal failure) and hyperthyroidism. hyroidism. Total T 4 in markedly elevated and hyperthyroidism is likely, especially considering the associated polycythemia, azotemia and elevated liver enzymes. Urinalysis Urine specifi c gravity is concentrated centrated and the urine protein ratio is moderately elevated, especially for an azotemic patient. Radiography Mild cardiomegaly is present, ent, characterized by biatrial enlargement. This is recognized on the VD view (valentine heart). Nuclear scintigraphy shows s a right-sided, unilateral lesion, which is less common than a bilateral lesion in feline hyperthyroidism. Additional testing Blood pressure Systolic 180 mm/hg if repeatable, e, consistent with mild hypertension Diagnosis The clinical diagnosis is hyperthyroidism with likely concurrent chronic renal disease. Treatment/Plan Hyperthyroidism can increase cardiac output, decrease peripheral vascular resistance, increase renal blood fl ow and increase GFR. This chain of events cannot only decrease BUN and creatinine, but also perhaps lead to glomerular hypertension and hyperfi ltration, thereby potentially inducing or worsening concurrent renal disease. Systemic hypertension can be associated with hyperthyroidism, and supervision of some patient therapy may benefi t from regular monitoring of UPC with a UPC less than 0.5 as a target for treatment. With successful Rx of hyperthyroidism (radioactive iodine, methimizole, thyroidectomy), the UPC may return to normal or may worsen if CRF is progressive. Careful monitoring of this patient is recommended.

11 Case Study 3 Spike James Patient One-year-old castrated male poodle-mix Presenting Complaints Stumbling and vomiting History 12 hours of lethargy, vomiting, ataxia Physical Exam Dehydration, slow menace bilaterally

12 Case Study 3 Hematology Hgb = 45.3 g/dl Hgb = 13.6 g/dl RBC = 5.92 µl MCV = 76.5 fl MCH = pg MCHC = g/dl LOW RDW = 14.5 % % RETIC = 0.3 % RETIC = 17.8 K/µL WBC = 21,620 µl HIGH 5,500 16,900 NEU = 16,830 µl HIGH 2,000 12,000 LYM = 1,680 µl 700 4,900 MONO = 1,790 µl HIGH 100 1,400 EOSIN = 0 µl 100 1,490 BASO = 0 µl 0.1 PLT = 280 K/µL MPV = fl PDW = 13.2 % PCT = 0.3 % Biochemical profile BUN = 33 mg/dl HIGH 7 27 Creatinine = 2.6 mg/dl HIGH Phosphorus = 8.4 mg/dl HIGH Calcium = 10.2 mg/dl Total Protein = 8.4 g/dl HIGH Albumin = 2.3 g/dl Globulin = 6.1 g/dl HIGH ALT = 84 U/L Alk Phos = 68 U/L Total Bilirubin = 0.1 mg/dl Glucose = 85 mg/dl Cholesterol = 289 mg/dl Sodium = 158 meq/l Potassium = 4.1 meq/l Chloride = 114 meq/l Bicarbonate = 15 meq/l Anion Gap = 33 meq/l HIGH Complete Urinalysis Dipstick Tests Urine Sediment Examination Color Yellow WBCs/hpf 5 20 Transparency Clear RBCs/hpf <5 Specific Gravity Epithelial cells/hpf None seen Protein Trace Casts/hpf Granular Glucose Trace Crystals Calcium oxalate Bilirubin Negative Bacteria None seen Blood Trace ph 5.0 UPC Ratio 0.4

13 Case Study 3 Blood fi lm Renal ultrasound Renal biopsy: H&E Renal biopsy: polarized Urine sediment

14 Case Study 3 Interpretive Summary Hematology There is a mild leukocytosis characterized by a mild neutrophilia, a minimal left shift, a mild monocytosis and eosinopenia observed on microscopic examination of the blood fi lm. Changes are most consistent with mild infl ammation. No signifi cant abnormalities are observed in the erythron, and platelet numbers are adequate. Biochemical profile There is a mild azotemia (increased BUN and creatinine) supporting decreased glomerular fi ltration (GFR). The fi nding of a nonconcentrated urine specifi c gravity supports the presence of renal azotemia (renal insuffi ciency). There is a mild hypernatremia, which correlates with the clinically noted dehydration and decreased water balance; however, the chloride is relatively low compared to the sodium, suggesting loss or sequestration of chloride. The clinical fi nding of vomiting suggests loss of HCl-rich gastric contents is most likely and a metabolic alkalosis is present. The moderately increased anion gap indicates the presence of signifi cant amounts of unmeasured anions, such as phosphates and sulfates due to the decreased GFR. This is supportive of the presence of a titrational metabolic acidosis; however, the degree of azotemia and increased anion gap appear discordant, and the presence of other unmeasured anions, such as ethylene glycol, must be considered. The within-reference-range TCO 2 is due to the negating effects of the typical increased TCO 2 with metabolic alkalosis and the typical decreased TCO 2 with titrational acidosis. Blood gas analysis to determine the degree of acidemia or alkalemia is warranted. The hyperphosphatemia is most likely due to the decreased ed GFR and retention of phosphorus. The slight hypokalemia may be due to decreased intake. There is a slight hyperproteinemia characterized by a low-normal albumin and a mild hyperglobulinemia. This protein pattern is most supportive of infl ammation. Urinalysis The fi nding of an acidic urine in the face of a metabolic alkalosis and acidosis suggests the acidosis condition is more severe and acidemia may be present. Evaluation of the blood gas data to determine if there is acidemia or alkalemia and the severity of the disorder r is warranted. Multiple signifi cant abnormalities are noted within the microscopic portion of the urinalysis. The fi nding of monohydrate calcium oxalate crystals is strongly supportive of ethylene glycol toxicity. The presence of granular casts suggests the presence of signifi cant tubular injury. The presence of white blood cells (WBC) in the urine sediment indicates the presence ence of infl ammation; however, localization of the infl ammation is not possible since the sample is a free-catch specimen. A trace protein content is diffi cult to accurately assess in a urine sample that has a fi xed specifi c gravity (no concentration); however, the urine protein to urine creatinine (UPC) ratio suggests that signifi cant proteinuria is not present. Even if there were a slight signifi cant increase in the UPC ratio, accurate interpretation would be diffi cult since the urine sediment is active (WBC and granular casts present). Any slight protein present may be associated with mild infl ammation or tubular injury. Diagnosis Ethylene glycol toxicity Treatment/Plan Blood gas analysis Osmolality and osmolar gap evaluation Abdominal ultrasound ± Ethylene glycol assay Initiate therapy for suspected ethylene glycol toxicity (fl uids, electrolytes, acid base therapy, maintain adequate urine volumes) 4-methylpyrazole (4MP) Consider dialysis if available

15 Case Study 4 Fezzie Smith Patient Eight-year old spayed female Shetland sheepdog Presenting Complaints Vomiting, diarrhea, lethargy, anorexia, edema History Five-day history of lethargy, anorexia, vomiting and diarrhea Physical Exam Increased respiratory rate; bilateral facial, ventral and peripheral edema

16 Case Study 4 Hematology Hct = 36 g/dl LOW Hgb = 11.1 g/dl LOW RBC = 5.1 µl LOW MCV = 69 fl MCH = 22 pg MCHC = 31 g/dl LOW RDW = 12.4 % % RETIC = 1 % RETIC = 51 K/µL WBC = 18,800 µl HIGH 5,500 16,950 NEU = 16,300 µl HIGH 2,000 12,000 LYM = 900 µl LOW 1,000 4,900 MONO = 1,600 µl HIGH 100 1,400 EOSIN = 0 µl 100 1,490 BASO = 0 µl PLT = 468 K/µL Biochemical profile Alk Phos = 97 U/L ALT (SGPT) = 4 U/L LOW Albumin = 1.7 g/dl LOW Globulin = 4.2 g/dl Total Protein = 5.8 g/dl HIGH Total Bilirubin = 0.2 mg/dl BUN = 96 mg/dl HIGH 7 27 Creatinine = 5.5 mg/dl HIGH Cholesterol = 443 mg/dl HIGH Glucose = 99 mg/dl Calcium = 10.1 mg/dl Sodium = 151 meq/l Potassium = 4.8 meq/l Chloride = 121 meq/l Bicarbonate = 14 meq/l LOW Anion Gap = 21 meq/l Complete Urinalysis: Cystocentesis Dipstick Tests Urine Sediment Examination Color Yellow WBCs/hpf <5 Transparency Clear RBCs/hpf <5 Specific Gravity Epithelial cells/hpf None seen Protein 3+ Casts/hpf 0 Glucose Negative Crystals 0 Bilirubin Negative Bacteria 0 Blood Negative Culture Pending ph 6.5 UPC Ratio 18.6

17 Case Study 4 Blood fi lm 10x Blood fi lm 40x Renal ultrasound Renal ultrasound Renal biopsy

18 Case Study 4 Interpretive Summary Hematology Modest leukocytosis composed of mature neutrophilia and monocytosis with concurrent lymphopenia is a stressed leukogram. This is typically consistent with infl ammation, infection or increased cortisol concentrations from exogenous use or hyperadrenocorticism. Biochemical profile This dog is suffering from severe hypoalbuminemia. Because the serum globulin concentration is high-normal, this is likely a result of liver disease, renal loss or vasculitis. All other parameters assessing liver function (cholesterol, glucose, and bilirubin) are within normal limits (the cholesterol is actually high and not low as in liver insuffi ciency), making liver insuffi ciency much less likely. Therefore, renal loss and vasculitis become the two likely possibilities. The facial edema evident on presentation may be a result of the hypoalbuminemia, with or without a degree of vasculitis. Urinalysis A very high UPC of 18.6 was identifi ed in this dog. This degree of proteinuria is very likely to be glomerular in origin and is enough to explain the severe hypoalbuminemia. This dog, therefore, re, has all four criteria for nephrotic syndrome: proteinuria, hypoalbuminemia, hypercholesterolemia rolemia and edema. Aggressive diagnostic and therapy are necessary in cases of nephrotic syndrome in an attempt to reverse the cause. Likely causes include glomerulonephritis and amyloidosis. Radiology Abdominal ultrasound report The renal cortices appear to be mildly hyperechoic being isoechoic with the adjacent spleen. There is mild dilatation tion of the renal pelvices. No other abnormalities are seen. The hyperechoic hoic cortex is a nonspecifi c fi nding seen in both acute and chronic renal disease. e. Amyloidosis can also cause hyperechoic renal cortices. The mild pyelectasia is suggestive gestive of recent fl uid administration. Additional testing Renal Biopsy Severe glomerulopathy with amorphous ous pink material consistent with amyloid. Diagnosis The clinical diagnosis is amyloidosis. Treatment/Plan Thoracic radiographs ± blood gas analysis Urine culture Nonspecifi c therapy for proteinuria and hypertension Will not likely benefi t from immunosuppression. Consider: DMSO, MSM

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20 NEW for the VetTest Detect urine protein loss, diagnose early renal disease IDEXX Urine P:C Ratio and alter your patient s prognosis by possibly adding months or even years to her life. The first in-house fully quantitative measure of proteinuria helps you detect renal disease long before irreversible damage occurs, giving you time to alter the outcome and improve the prognosis. Our new urine protein:creatinine (UPC) ratio allows you to confidently monitor the course of renal disease, and evaluate therapeutic response and disease progression. To learn more about using the UPC ratio to diagnose early renal disease, visit idexx.com/upc. Many thanks to Bandit Bowker, a rescued stray. One IDEXX Drive Westbrook, Maine USA idexx.com 2005 IDEXX Laboratories, Inc. All rights reserved (5)