Renal Disease Case Studies Guide

7/27/2019 Renal Disease Case Studies Guide

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Renal DiseaseCase Studies

IDEXX Laboratories


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Authors

Dennis DeNicola, DVM, PhD, DACVPChief Veterinary Educator, Clinical

Pathologist, IDEXX LaboratoriesDr. DeNicola completed his DVM in 1978 and his PhD in1981, both at Purdue University. For more than twenty

years, he served as educator in clinical and surgicalpathology. In addition, he directed the primary cytol-ogy and surgical pathology service at the veterinary

school laboratory and ran a private pathology servicefor 15 years. A speaker at more than 100 national and

international education symposia, Dr. DeNicola also hasauthored or co-authored more than 150 publications in

various aspects of veterinary clinical pathology.

Fred Metzger, DVM, DABVPOwner, Metzger Animal HospitalDr. Metzger is a 1986 graduate of the Purdue Schoolof Veterinary Medicine and a diplomate of the American

Board of Veterinary Practitioners, with specialties incanine and feline medicine. He is an adjunct

professor at Pennsylvania State University and serveson the practitioner advisory boards of Veterinary

Economics and Veterinary Medicine magazines. Herecently 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 StateCollege, Pennsylvania, that received the 1998 Veterinary

Economics/Pfizer Practice of Excellence award.

Pete Fernandes, DVM, DACVPClinical Pathologist, IDEXX LaboratoriesDr. Fernandes completed his DVM at the University ofWisconsin-Madison, followed by an internship in small-

animal medicine and surgery at South Shore AnimalHospital in Boston. Dr. Fernandes residency was in

clinical pathology at Texas A&M University and theUniversity of Florida. He is a diplomate of the American

College of Veterinary Pathologists.

Brian Poteet, DVM, DAVCR, DABSNMDirector, Gulf Coast Veterinary Diagnostic

ImagingDr. Poteet received his DVM from Texas A&M University

and completed his radiology residency at the Universityof 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 medicalassociations, Vice President of the Veterinary Cancer

Associates, and holds two adjunct faculty positions atTexas A&M University.

Richard Goldstein, DVM, DACVIM,DECVIM-CAAssistant Professor, Small-Animal Medicine,

Cornell UniversityDr. Goldstein received his DVM from the Koret School

of Veterinary Medicine, the Hebrew University ofJerusalem, Israel. He completed his residency in small-animal internal medicine at the University of California,

Davis. He is a diplomate of the American College ofVeterinary Internal Medicine and the European College

of Veterinary Internal MedicineCompanion Animals.He joined the faculty at Cornell in 2001. Dr. Goldsteins

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

PathologyCoagulation, Cytology, Internal

Medicine, IDEXX LaboratoriesDr. Relford received her DVM from Auburn University

in 1982 and worked as a small-animal practitioner forfour years before pursuing her advanced training. She

started her residency training in clinical pathology andobtained an MS in pathology from Mississippi State

University. She then transferred to Texas A&M, whereshe completed her pathology residency training and

obtained a PhD in pathology. While completing her

PhD, Dr. Relford pursued a residency in small-animalinternal medicine.

Dr. Relford is board-certified in internal medicine by theAmerican College of Veterinary Internal Medicine and inclinical pathology by the American College of Veterinary

Pathologists. She currently serves as Divisional VicePresident of Worldwide Pathology for IDEXX Reference

Laboratories. Dr. Relford has given numerous lectureson a wide variety of topics including clinical pathology,

internal medicine, infectious diseases, cytology, platelet

disorders, health maintenance programs and zoonoticdiseases.


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Case Study 1

Patient

Three-year-old intact male Labrador retriev

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, genera

peripheral lymphadenopathy, uveitis, bilate

swollen hocks and right stifle

Jake Douglas


4/20

HematologyHct = 32.2 % LOW 37 55

Hgb = 10.1 g/dL LOW 12.0 18.0

RBC = 4.9 L LOW 5.50 8.50

MCV = 63.5 fL 60.0 77.0MCH = 21.33 pg 19.50 24.50

MCHC = 33.2 g/dl 32.0 37.0

RDW = 17.3 % HIGH 12.0 16.0

% RETIC = 0.6 %

RETIC = 40,000 L

WBC = 18,237 L HIGH 5,500 16,950

NEU = 14,200 L HIGH 2,000 12,000

LYM = 900 L LOW 1000 4,900

MONO = 2,900 L HIGH 100 1,400

EOSIN = 223 L 100 1,490

BASO = 14 L 0 100

PLT = 360 K/L 175 500

Biochemical profileAlk Phos = 899 U/L HIGH 23 212

ALT (SGPT) = 201 U/L HIGH 10 100

Albumin = 1.6 g/dL LOW 2.2 3.9

Total Protein = 8.1 g/dL 5.2 8.2

Globulin = 6.5 g/dL HIGH 2.8 4.5

Total Bilirubin = 0.2 mg/dL 0.0 0.4

BUN = 37 mg/dL HIGH 7 27

Creatinine = 2.2 mg/dL HIGH 0.5 1.8

Glucose = 99 mg/dL 77 125

Calcium = 10.3 mg/dL 7.9 12.0

Phosphorus = 9.0 mg/dL HIGH 2.5 6.8

Sodium = 150 mEq/L 144 160

Potassium = 5.1 mEq/L 3.5 5.8

Chloride = 111 mEq/L 109 12

Complete Urinalysis: CystocentesisDipstick Tests Urine Sediment Examination

Color Yellow WBCs/hpf 0

Transparency Clear RBCs/hpf 0

Specific Gravity 1.013 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

Case Study 1


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Cytology Arthrocentesis (hock and stifle):

suppurative inflammatory joint fluid

Lymph node FNA (inguinal & popliteal):

lymphoid hyperplasia, consistent with reactive lymph nodes

SerologyLeptospirosis negative

SNAP 3Dx Test Heartworm antigen negative

E. canis antibody negative

Lyme C6 antibody positiveRocky Mountain spotted fever negative

Case Study 1

Lyme-positive SNAP 3Dx Te

Cytology: fine-needle aspirate Renal biopsy 10x

Renal biopsy 60x


6/20

DiagnosisThe clinical diagnosis is Lyme

nephritis.

Treatment/Plan

Blood was sent to a reference

laboratory for quantitative C6

antibody testing.

The patient was treated with

doxycycline, intravenous fluid

support and a renal diet.

Recheck renal panel in 35 days.

Renal biopsy

Prevention

Prevention of Lyme disease includes

reducing tick exposure, utilizing tick

repellant products and vaccinating

at-risk patients.

Zoonotic Potential

Since pets share our environment,

they may incidentally become our

sentinels; therefore, borreliosis inour canine 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 that they are living in a

tick-endemic area and the ticks may

be infected with Lyme disease.

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 inflammatory

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 specific gravity 1.013

indicates some, yet inadequate, concentrating ability, and hypoalbuminemia

may be masked somewhat by dehydration. Significant hypoalbuminemia

is caused by protein-losing glomerulopathy and worsened by systemic

vasculitis, severe hepatic insufficiency 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 inflammation or infection and ischemia.

Urinalysis

Urine specific gravity shows inappropriate concentrating ability caused

by glomerular and tubular dysfunction. Observation of granular casts can

confirm 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 immune-

mediated glomerular disease, decreased perfusion and hypoxia, and the

toxic effects of severe proteinuria are most likely responsible.

Additional testingSerology

Follow-up with quantitative C6

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 C6

antibody to the C6

antigen is a highly specific for Borrelia

burgdorferiinfection. Dogs with leptospirosis, Rocky Mountain spotted

fever, babesiosis, ehrlichiosis and heartworm disease do not have

antibodies to C6, nor are antibodies to C

6produced in response to

immunization with currently available canine Lyme vaccines.

Case Study 1


7/20

Case Study 2

Patient

Nine-year-old DSH female cat


Mild PU/PD, intermittent vomiting sometime

containing hair, weight loss

Physical Exam

Moderate dental tartar, unkempt coat,

evidence of diarrhea on tail, tachycardia,

dehydration and palpable thyroid nodule

Muriel Jones


8/20

Case Study 2

HematologyHct = 47 % HIGH 30 45

Hgb = 10 g/dL 0.0 15.1

RBC = 10.97 L HIGH 5.0 10.0MCV = 49 fL 41.0 58.0

MCH = 15 pg 12.50 17.60

MCHC = 33 g/dl 29.0 36.0

RDW = 19 % 17.3 22.0

% RETIC = 0.2

RETIC = 15.3 K/L 0.0 60

WBC = 18,025 L 5,500 19,500

NEU = 16,680 L HIGH 2,000 12,500

LYM = 1,000 L 900 7,000

MONO = 230 L 100 790

EOSIN = 115 L 100 790

BASO = 0 L 0 100

PLT = 220 K/L 175 600

Biochemical profileAlk Phos = 86 IU/L HIGH 0 62

ALT (SGPT) = 80 IU/L HIGH 28 76

Albumin = 2.6 g/dL 2.3 3.3

Total Protein = 6.8 g/dL 5.9 8.5

Globulin = 4.2 g/dL 3.6 5.2




Cholesterol = 145 mg/dL 82 218Glucose = 148 mg/dL 70 150

Calcium = 9.3 mg/dL 8.2 11.8

Phosphorus = 5.9 mg/dL 3.0 7.0

Sodium = 152 mEq/L 145 156


Potassium = 3.8 mEq/L LOW 3.9 5.8

Total T4 = 7.9 ug/dL HIGH 0.7 5.2



Transparency Clear RBCs/hpf 0

Specific Gravity 1.045 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


9/20

Case Study 2

Thoracic radiograph: lateral

Thoracic radiograph: DV

Nuclear scintigraphy

SNAP T4

Test


10/20


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 film) 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

difficult 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 renaldisease. Hypokalemia is present and can occur with many feline diseases

including CRF (chronic renal failure) and hyperthyroidism. Total T4

in

markedly elevated and hyperthyroidism is likely, especially considering the

associated polycythemia, azotemia and elevated liver enzymes.

Urinalysis

Urine specific gravity is concentrated and the urine protein ratio is

moderately elevated, especially for an azotemic patient.

Radiography

Mild cardiomegaly is present, characterized by biatrial enlargement. This is

recognized on the VD view (valentine heart).

Nuclear scintigraphy shows a right-sided, unilateral lesion, which is lesscommon than a bilateral lesion in feline hyperthyroidism.

Additional testing

Blood pressure

Systolic 180 mm/Hgif repeatable, consistent with mild hypertension

DiagnosisThe clinical diagnosis is

hyperthyroidism with likely concurrent

chronic renal disease.

Treatment/Plan

Hyperthyroidism can increase cardiac

output, decrease peripheral vascular

resistance, increase renal blood flow

and increase GFR. This chain of

events cannot only decrease BUN

and creatinine, but also perhapslead to glomerular hypertension and

hyperfiltration, thereby potentially

inducing or worsening concurrent

renal disease.

Systemic hypertension can be

associated with hyperthyroidism, and

supervision of some patient therapy

may benefit 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.

Case Study 2


11/20

Patient

One-year-old castrated male poodle-mix


Stumbling and vomiting

History12 hours of lethargy, vomiting, ataxia

Physical Exam

Dehydration, slow menace bilaterally

Spike James

Case Study 3


12/20

Case Study 3

HematologyHgb = 45.3 g/dL 37 55

Hgb = 13.6 g/dL 12.0 18.0

RBC = 5.92 L 5.5 8.5

MCV = 76.5 fL 60.0 77.0

MCH = 22.97 pg 19.5 24.5

MCHC = 30.02 g/dl LOW 32.0 37.0

RDW = 14.5 % 12.0 16.0

% RETIC = 0.3 %

RETIC = 17.8 K/L

WBC = 21,620 L HIGH 5,500 16,900

NEU = 16,830 L HIGH 2,000 12,000

LYM = 1,680 L 700 4,900

MONO = 1,790 L HIGH 100 1,400

EOSIN = 0 L 100 1,490

BASO = 0 L 0 .1

PLT = 280 K/L 175 500

MPV = 12.36 fL

PDW = 13.2 %

PCT = 0.3 %

Biochemical profileBUN = 33 mg/dL HIGH 7 27


Phosphorus = 8.4 mg/dL HIGH 2.5 6.8

Calcium = 10.2 mg/dL 7.9 12.0

Total Protein = 8.4 g/dL HIGH 5.2 8.2

Albumin = 2.3 g/dL 2.2 3.9

Globulin = 6.1 g/dL HIGH 2.5 4.5

ALT = 84 U/L 10 100

Alk Phos = 68 U/L 23 212Total Bilirubin = 0.1 mg/dL 0.0 0.9

Glucose = 85 mg/dL 77 125

Cholesterol = 289 mg/dL 110 320

Sodium = 158 mEq/L 144 160



Bicarbonate = 15 mEq/L 15 25

Anion Gap = 33 mEq/L HIGH 13 25

Complete UrinalysisDipstick Tests Urine Sediment Examination


Transparency Clear RBCs/hpf


13/20

Case Study 3

Blood film Renal ultrasound

Renal biopsy: H&E Renal biopsy: polarized

Urine sediment


14/20


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 film. Changes are most consistent with mild

inflammation. No significant 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 filtration (GFR). The finding of a nonconcentrated

urine specific gravity supports the presence of renal azotemia (renal

insufficiency). 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 finding 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 significant

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 TCO2

is due to the negating effects of the

typical increased TCO2

with metabolic alkalosis and the typical decreased

TCO2

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 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 inflammation.

Urinalysis

The finding 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 is warranted. Multiple significant

abnormalities are noted within the microscopic portion of the urinalysis. The

finding of monohydrate calcium oxalate crystals is strongly supportive of

ethylene glycol toxicity. The presence of granular casts suggests the presence

of significant tubular injury. The presence of white blood cells (WBC) in the

urine sediment indicates the presence of inflammation; however, localization

of the inflammation is not possible since the sample is a free-catch specimen.

A trace protein content is difficult to accurately assess in a urine sample that

has a fixed specific gravity (no concentration); however, the urine protein to

urine creatinine (UPC) ratio suggests that significant proteinuria is not present.

Even if there were a slight significant increase in the UPC ratio, accurate

interpretation would be difficult since the urine sediment is active (WBC and

granular casts present). Any slight protein present may be associated with

mild inflammation or tubular injury.

DiagnosisEthylene glycol toxicity

Treatment/Plan

Blood gas analysis

Osmolality and osmolar gap

evaluation

Abdominal ultrasound

Ethylene glycol assay

Initiate therapy for suspectedethylene glycol toxicity (fluids,

electrolytes, acid base therapy,

maintain adequate urine volumes)

4-methylpyrazole (4MP)

Consider dialysis if available

Case Study 3


15/20

Case Study 4

Patient

Eight-year old spayed female Shetland shee


Vomiting, diarrhea, lethargy, anorexia, edem

HistoryFive-day history of lethargy, anorexia, vomiti

and diarrhea

Physical Exam

Increased respiratory rate; bilateral facial, ve

and peripheral edema

Fezzie Smith


16/20

Case Study 4

HematologyHct = 36 g/dL LOW 37 55

Hgb = 11.1 g/dL LOW 12.0 18.0

RBC = 5.1 L LOW 5.5 8.5

MCV = 69 fL 60.0 77.0

MCH = 22 pg 19.5 24.5

MCHC = 31 g/dl LOW 32.0 37.0

RDW = 12.4 % 12.0 16.0

% RETIC = 1 %

RETIC = 51 K/L

WBC = 18,800 L HIGH 5,500 16,950

NEU = 16,300 L HIGH 2,000 12,000

LYM = 900 L LOW 1,000 4,900

MONO = 1,600 L HIGH 100 1,400

EOSIN = 0 L 100 1,490

BASO = 0 L 0 100

PLT = 468 K/L 175 500

Biochemical profileAlk Phos = 97 U/L 23 212

ALT (SGPT) = 4 U/L LOW 10 100

Albumin = 1.7 g/dL LOW 2.2 3.9

Globulin = 4.2 g/dL 3.0 4.3

Total Protein = 5.8 g/dL HIGH 5.2 8.2




Cholesterol = 443 mg/dL HIGH 110 320Glucose = 99 mg/dL 77 125

Calcium = 10.1 mg/dL 7.9 12.0

Sodium = 151 mEq/L 144 160



Bicarbonate = 14 mEq/L LOW 15 25

Anion Gap = 21 mEq/L 13 25


Color Yellow WBCs/hpf


17/20

Case Study 4

Blood film 10x Blood film 40x

Renal ultrasound Renal ultrasound

Renal biopsy


18/20


Hematology

Modest leukocytosis composed of mature neutrophilia and monocytosis with

concurrent lymphopenia is a stressed leukogram. This is typically consistentwith inflammation, 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 insufficiency), making liver insufficiency 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.

UrinalysisA very high UPC of 18.6 was identified 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, has all four criteria for nephrotic

syndrome: proteinuria, hypoalbuminemia, hypercholesterolemia 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 of the renal pelvices. No otherabnormalities are seen. The hyperechoic cortex is a nonspecific finding seen in

both acute and chronic renal disease. Amyloidosis can also cause hyperechoic

renal cortices. The mild pyelectasia is suggestive of recent fluid administration.

Additional testing

Renal Biopsy

Severe glomerulopathy with amorphous pink material consistent with amyloid.

Diagnosis

The clinical diagnosis isamyloidosis.

Treatment/Plan

Thoracic radiographs blood

gas analysis

Urine culture

Nonspecific therapy for

proteinuria and hypertension

Will not likely benefit from

immunosuppression.

Consider: DMSO, MSM

Case Study 4


19/20


20/20

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Many thanks to Bandit Bowker, a rescued stray.

One IDEXX DriveWestbrook, Maine 04092 USA

idexx.com

2005 IDEXX Laboratories Inc All rights reserved 09 65320 00 (5)

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