Urinary M

True or false

Lab work on dogs shows he is azotemic. this confirms he has glomerular disease

• False

• protienuria with inactive sediment is the hallmark of glomerular disease

What does an inactive sediment mean

• a urine sample that is <5 white blood cells / high powr filed (hpf) and <10 red blood cells /hpf were observed

How can you specifically diagnose what type of glomerular disease a animal has (the only way)

• Only biopsy which is not commonly done though expensive and have to send it off

Most common cause of proteinuria

• Lower urinary tract disease (bacterial cystitis)

• No need to run UPC ratio if active sediment present (because it will go away once infection clears)

Four cirteria that define nephrotic syndrome and must have all four

• proteinuria

• hypoalbuminamia

• hypercholesterolamia

• ascites/edema

How does leaking protein cause damage?

• Protein escapes into the mesangium triggering inflammation

• body response and you get formation of scar tissue

• this pretty much kills the glomerulas when you have excessive scar tissue

• the reamining gloemrulus have to pick up the load which also increases the pressure progressing the disease (snowball effect)

What is the most common undelrying cause of glomerulonephritis?

• Immunologic injury

• this could be due to circulating antigen antibody complex depositing into the kidney or in situ

• Note: many diseases can cause proteinuria so rule out any underlyig causes such as cancer or infectious diseases (most cases are idopathic)

Glomerular disease is more common in cats or dogs?

• Dogs

Familial glomerular disease of soft coated wheaton terriers, Bernese moutain dogs, brittany spaniels

• Membranoproliferative GN

Familial glomerular disease of English cocker spaniels, Samoyed, Doberman pinchers and bull terriers

• Basement membrane disorders

Amyloidosis is a diverse group of diseases characterized by extracellular deposition of protein, subunits that form Beta pleated sheets

Amyloidosis can be classified by what two categories

• Distribution of deposits

  • systemic (most common**)

  • Localized (pancreatic islet cells in cats)

• nature of responsible protein

  • reactive (AA) most common

Most common nature of amyloidosis is reactive systemic amyloidosis

can be associated with chronic infectious and non-infectious inflammatory disease and neoplasia

What is the most common cases in dogs and cats?

• Idiopathic or familial

Three dogs most commonly get familiar reactive systemic amyloidosis

• Sharpie

• Beagle

• English foxhound

Three common cats that get familiar reactive systeic amyloidosis

• Abyssinian

• Siamese

• Oriental short hair

Tissue distribution of amyloid deposits in dogs and cats widespread HOWEVER clinical signs are due to what organ involvement

• Kidney involvement, causing chornic kidney disease

• Amyloids like to deposit in the kidney

What is the exception to amyloid deposits concerning tissue tropism of amyloid proteins

• In sharpie dog, Siamese and oriental shorthair cats, you can also get severe liver involvement causing liver rupture and hemoabdomen

With reactive systemic amyloidosis they commonly have tropism for kidneys

Which animal does the distribution of deposits within the kidney involve the glomerulus more so than medullary (exam)

• Dogs

• Note: including human and horses

• important = you will get deposition in both, however with dogs you will see them more so in the gloemrular (important concept to understand)

What exception of dogs has more medullary involvement compaired to glomerular

• Sharpei dog

With reactive systemic amyloidosis which animal has more medullary involvement rather than glomerular

• Cats (including Abyssinian) and Sharpei

• note: cow

Dogs with amyloid deposition present with increased UPC because gloemrular is damaged

How do cats present if they get mainly medullary amyloidosis

• Chronic kidney disease (tubules are affected) - present with isosthenuria

which will give you a negative biopsy result for amyloid distribution

Glomerular or medullary

• Medullary

• you cant go in that deep to get biopsy

Mean age for Shar-Pei dog that gets amyloidosis

• Four years old (young dog)

• more commonly black and fawn breed

Shar-Pei dog presents with isosthenuria and self limiting fever with tibial joint swelling

What should be on your Ddx?

• Amyloidosis with kidney involvement

• this is known as Shar-Pei fever

• they will have signs consistent with CKD and have history of recurrent acute self-limiting fever adn tibial joint swelling

• Remember, they may also have severe liver involvement causing icterus, or Hemo abdomen due to liver rupture

How much loss of function of teh kidney before an animal can become azotemic (excludign dehydration)

• ¾

• so if the animal is isothenuric with azotemia this means that they have lost a significant function of the nephron

true or false

Glomerular disease is often a disease of middle aged to older animals

• True

There is no gender predilection for glomerular disease, however which gender of cats usually has GN

• Males

Six possible presentations of animals where you can also find glomerular disease

• CKD (most common)

• underlying infections, inflammatory or neoplastic disorder (glomerular disease due to antigen antibody complex)

• proteinuria as a incidential finding

• nephrotic syndrome

• thromboembolism (loss of antithrombin 3, liver making more clotting factors)

• sudden blindness (hypertension, causing retinal detachment)

What is the best way to determine significance of proteinuria

• Running a UPC

Three differentials for hypoalbuminaemia

• protein loosing neuropathy

• liver disease

• Protein loosing endocrine (cushings, hypothyroid)

Normal UPC

• <0.3-0.4

on average, the highest UPC ratios are seen in patient with what type of liver disorder

• Amyloidosis

• specifically glomerular amyloidosis

• Note: GN can range from normal to over 30 it is variable

Where do you see the lowest UPC ratios

• Interstitial renal disease

Magnitude of urinary protein/urinary creatine correlates with severity of glomerular disease in only what type of patient

• Non-azotemic patient

• once they are azotemic, there is no correlation

When is UPC unreliable? exam

• In the presence of pyuria or severe hematuria

If you have a azotemic patient and you see a decrease in their UPC does this mean they are improving?

• No

  • cannot assess because there are azotemic

Conventional dipstick tests can detect protein that is between 10-30 MG/DL

What test can you detect protein levels greater than one but below 10-30 mg/dl

• Microabluminuria test

True or false

Microalbuminuria can be an early indicator of vascular endothelial damage however, prognostic values in dogs and cats are uncertain.

• True

Two commonly used drugs to decrease protienuria

• Angiotensin converting enzyme inhibitor (ACE) (eg. Enalapril, Benazepril)

• Angiotensin recptor blocker (Telmisartan)

• The goal is to reduce hypertension

ACE inhibitors and ARB inhibitors preferentially act where in the kidney (exam)

• Efferent arteriole (this will promote vasodilation)

• Decrease glomerular capillary hydrostatic pressure (and proteinuria) by decreasing post-glomerular arteriolar resistance (efferent arteriole)

• Note: have the potential to make patient azotemic

• During rechecks, you measure, creatinine, potassium, blood pressure and UPC

What do you want to change in the diet with an animal that has glomerular disease?

• Lower protein intake

If the animal has a very high amount of hypertenison, what can you also use in addition to your ACE inhibitors and angiotensin receptor blockers?

• Amlodipine

Why are patients with glomerular disease high risk for thromboembolism?

• They lose antithrombin in urine

• this makes them hypercoagulable

Most common drug used to day to prevent thromboembolism

• Clopidogrel (platelet inhibitor)

if you rule out infectious, neoplastic diseases, and a biopsy supports glomerulonephritis how do you empirically treat?

• Immunosuppressive inflammatory therapy

• If owner does not want to do biopsy you can still treat with immunosuppressive therapy

What is the drug of choice for rapidly progressive glomerular disease of an apparent immune-mediated pathogenesis?

• Mycophenolate

What is the specific treatment for amyloidosis?

• No specific therapy shown to be beneficial

True or false

Hypertension occurs in 50 to 80% of dogs with glomerular disease.

• True

True or false

Control of blood pressure can slow progression of renal disease

• True

• Blood pressure should be measured in all dogs and cats with glomerular disease*** before you do anything else.

Prognosis for amyloidosis and glomerular nephritis

• Amyloidosis = poor

• Glomerular nephritis = variable (spontaneous remission, stable for months to years, progresses to CKD)

How can acute renal failure be defined?

• Abrupt decline in renal function with a recent onset of azotemia

• unable to regulate volume and composition of body fluids

Is acute renal failure reversible

• Potentially is

Three categories of acute renal failure

• Acute pre-renal

• Acute intrinsic renal (primary)

• acute post renal

Three common causes of acute intrinsic renal failure

• Nephrotoxic nephrosis

• Nephritis

• Ischemic nephrosis

True or false

Systemic arterial hypertension is not required to cause ischemic nephrosis

• True

Lepto affects what two organs

• kidney and liver

What is a universal feature of all leptospirosis pathogenic serovars

• They have the ability to colonize proximal renal tubules

• (results in prolonged renal carrier state, and urine shedding)

If a animla recovers from leptospirosis does it still shed?

• Yes, they can shed it in their urine for months to years after infection

• Note: wild animals are the reservoirs

How are animals usually exposed to lepto

• Through Mucocutaneous contact

• Can also penetrate mucosa or abraded skin

Leptospiremia occurs 4 to 12 days post-infection

it can affect the kidney liver or both

Why may you see thrombocytopenia with leptospiremia

• causes vasculitis and DIC from widespread acute endothelial injury

Most common cause of acute renal failure/nephritis

• Leptospirosis

Exposure to Neuro toxins/ischemia causes ___ injury

• Tubular

• Ranges from degeneration (nephrosis) to acute tubular necrosis (ATN)

three pathophysiologies of acute intrinsic renal failure (nephrosis)

• Afferent arteriolar constriction (vasomotor nephropathy hypertension)

• Obstruction (intraluminal or extraluminal)

• Tubular backleak (due to inflammation)

How can NSAIDs cause ischemic AIRF

• They block Reno prostaglandin synthesis, which is responsible for renal vasodilation

• so if you have an animal that is dehydrated or hypovolemic this can cause ischemia (give it only to the healthy dog)

• Not directly toxic

Mechanism of injury with nephrotoxic AIRF

• Cause direct cell injury rather than ischemia

• bind tubular cell membranes, and decrease energy production causing cell death

• some also cause renal vasoconstriction

Describe the latent (induction) phase of AIRF

• Often not detected

• clinical signs are minimal or absent

• if the agent is removed normal kidney function returns

How can you define the maintenance phase of AIRF

• Suddenly increased serum creatinine that persists despite correction of all pre-renal factors (hydrated)

• note: do not know how long this phase can persist

• characterized by severe drop in RBF and GFR

• even if RBF returns to normal, GFR remains low

true or false

when an animal is in the maintenance phase they become oliguric

• False

• they can have normal urine output, be oliguric, or polyuric

• note: the older definition of AIRF required oliguria for diagnosis but not the new one)

If you remove the insulitng agent that caused the AIRF during the maintenance phase will the kidney return to normal funciton

• No

• patient experiences a 1-3 week course before restoration of renal function can occur

If a patient is oliguic in the maintenance phase why is it important to still put on a catheter?

• Because they can go from oliguric to polyuric during the maintenance phase (better)

During the recovery phase, what two outcomes can occur

• You can have complete recovery

• partial improvement

• return of normal BUN and creatinine = POSSIBLE

• partial improvement = CKD

There is no single test to definitively diagnose AIRF

so how do you diagnose it?

• History (should be recent and possibly an exposure to something nephrotoxic or ischemic)

• physical exam (should have a normal BCS - not a chronic condition)

• renal size (should be normal or big not small)

• important = get your lab samples before you start treatment (such as fluids)

History:

• absence of longstanding PU/PD, potential for renal ischemia or nephrotoxin exposure, oliguria, polyuria, non-specific signs

CBC:

• especially PCV at outset

on physical exam with acute renal failure what symptoms would you see?

• Uremic symptoms (oral ulcers, uremic breath)

• May exhibit back pain (renal pain)

• Dehydration

• Bradycardia if markedly hyperkalemic

• normal to large kidneys

• no evidence of lower urinary tract obstruction

• Note: absence of pallor to mucous membranes

Do you see anemia with acute renal failure?

• No, not early on

• this is more common with CKD

How would your total proteins look with acute renal failure?

• Normal to elevated (relative to dehydration)

If animal with acute renal failure, also has thrombocytopenia, what should be on top of Ddx:

• Lepto

What do you see with urine concentration and glucose in AIRF pateint

• Dilute urine (tubules arent working)

  • USG often 1.007-1.017

  • Does NOT differentiate AIRF from CKD (both have lwo USG)

• Glucosuria (lack of function of glucose transporters in tubules)

What might you see on urine sediment with AIRF

• Casts

• Oxalate crystals if Etheline glycol poisoning

• Increased WBC, RBC tubular epithelial cells (reaction to tubular injury)

• Note: if bacteria also present suspect pyelonephritis (ascending infection)

• may be very active (cylindruria) but absence of casts does not exclude AIRF

• increased numbers of oxalate crystals supports ad diagnosis of ethylene glycol poisoning in an oliguric AIRF patient

What do you see on serum biochemistry in AIRF

• BUN creatinine phosphorous increase severe (azotemia)

• Note: cannot use the magnitude of azotemia to determine if it is AIRF versus CKD ***

• OR differentiate between pre-renal, renal, and post-renal

When would you see increase in serum potassium with AIRF

• Severely impaired renal excretory function and olguria (decreased urine production will cause the increase in potassium causing the bradycardia)

• Note: greater than 5.5

Metabolic acidosis more severe in acute renal failure or chronic kidney disease

• Acute renal failure

• Note: specifically during maintenance phase

Renal size with AIRF

• Three times the length of L2 on ventral dorsal view

• Note: normal or increased

Additional finding on ultrasound with AIRF to support diagnosis

• Increased echogenicity of the cortex (loss of corticomedullary distinction)

• Note: normal ultrasound does not exclude AIRF

What is the only cause of acute renal failure that can be inferred from ultrasound

• Ethylene glycol intoxication

• severe hyperechogenicity on ultrasound suggests possibility of ethylene glycol intoxication

Which animals will have an enlarged parathyroid gland CKD or AIRF

• CKD

• secondary renal hyper renal parathyroidism

Possible cause if nephritis versus glomerulonephritis

• nephritis = Leptospirosis

• glomerular nephritis = Lyme disease (Borrelia)

Leptospirosis prognosis

• Good with adequate supportive fluid and penicillin started early

True or false

AIRF patient with SEVERE baseline azotemia during the maintenance phase often are successfully managed without dailysis

• True (dialysis increases prognosis

• over 80% of patience with AIRF and high level azotemia either die or be euthanized

Main reasons animals with AIRF die or are euthanized

• Hyperkalemia (animal is oliguric - potassium level increases substantively)

• metabolic acidosis (owner elects euthanasia)

• severe azotemia

• overhydration and pulmonary edema due to vigorous fluid therapy

How to measure volume of IV fluid fluids when treating AIRF

• Separate 24 hours into four-hour blocks

• account for insensible losses 20 mg/kg

• add the measured urine output for the proceeding for hours

• (20 ml/kg/6 + measured urine output preceding four hours

• No “quick fix” (may require several weeks)

How can you treat the hyperkalaemic aspect?

• Insulin plus glucose (must include glucose)

• Calcium gluconate

What do you need to do if hyperkalemia persist even after attempting to treat it

• Must proceed to dialysis

What medication decreases shedding of leptospirosis and what can you give to treat carrier state?

• Decreased shedding = penicillin

• eliminate carrier state = doxycycline

What enzyme converts Etheline glycol to glycolate

• Alcohol dehydrogenase ( so this is where you intervene)

Stages of Etheline glycol poisoning (exam)

• Neurologic (30 minutes - 12 hours)

  • ataxia, stupor, seizures, coma

• cardio pulmonary (12 hours - 24 hours)

  • Tachycardia, tachypnea

• renal (24 hours - 72 hours)

  • initial PD/PU

  • progresses to profound oligo-anuric AIRF (almost always fatal once established

What metabolite of ethylene glycol poisoning causes tubular damage

• Calcium oxalate crystals (tubular back leak, obstruction, edema compromising RBF)

Why can you get false negatives and false positives with ethylene glycol measurement tests

• False negatives = test done too early or too late

• false positives = other items such as propylene glycol, glycerol and metaldehyde can trigger it to be positive

Clinical signs that are resumptive diagnosis for eg. poisoning

• Alcohol like intoxication

• PU/PD to oliguria

• renal pain

• progression to coma

What findings will you see that can help you diagnose eg. poisoning on lab work

• Dilute urine

• oxalate crystalluria

• anion gap metabolic

• acidosis

• progressive azotemia

• hypocalcemia

For best outcome of treating eg poisoning treat within how many hours of ingestion

• Four hours

• Do not wait for definitive test results start and induce vomiting and gastric lavage with activated charcoal

• Attempt to stimulate urine production with furosemide

What is the definitive treatment for eg poisoning to prevent metabolism of ethylene glycol

• Fomepizole (4-methylpyrazole)

• compeititve inhibitor