What are the 3 steps in renal insufficiency at what percentage loss of function occur and what occurs at each stage
1) Regulatory failure
- Loss of ≥66% of nephron function
- Failure to concentrate urine→ polyuria
- Metabolic acidosis and electrolyte abnormalities
2) Excretory failure
- Loss of ≥75% of nephron function
- Nitrogen wastes accumulate
3) Biosynthetic failure : Erythropoietin
Non-regenerative Anaemia
List 3 causes of primary renal damage and 4 causes of secondary renal damage (decreased tubular function)
Primary
1) Toxic insult – ethylene glycol, grapes, lillies
2) Parenchymal damage and fibrosis - inflammation and infectious process
3) Nephritis - inflammation of the kidneys
Secondary
1) Primary diabetes insipidus - failure to excrete ADH
2) Secondary diabetes insipidus
3) Hypercalcemia, Hyperadrenocorticism, Pyometra
4) Loss of medullary concentration gradient – depletion of NaCl and urea
○reversible
List the 4 ways renal function is assessed and what is tested within each test
1) Excretion of waste products
- Urea and Creatinine in mammals
- Uric acid in birds and reptiles
- SDMA
2) Fluid and electrolyte balance - dehydration
- Urine concentration
- Serum and urine electrolytes
3) Acid-base regulation - Acidosis, alkalosis
- Serum bicarbonate
- Urine pH
- Blood pH and blood gases
4) Production of erythropoietin
- RBC count/PCV/Haemoglobin or measure EPO
How do you measure GFR in urinalysis
Measurement of Glomerular Filtration Rate (GFR) - don’t measure directly but indirectly through the 4 methods of assessing renal function
List 6 uraemias
1) Mucosal ulceration
2) Halitosis - bad breath
3) Vomiting
4) Depression
5) Weakness
6) Anorexia
Describe the 3 broad causes of azotaemia and examples within
Prerenal
Decrease Renal blood flow - something upstream
- Dehydration - reduced blood volume
- Severe haemorrhage
Renal
- decrease in functional nephrons, decrease GFR
Postrenal
Decrease urine output- get leakage of urine into abdomen and contents reabsorbed into circulation
- Tumour, inflammation - nephrosis
- Urinary tract disease
- Obstruction - kidney stones
urea filtration, reabsorption where occur and what are the 2 sources of urea
- Sources
1) Liver protein catabolism → ammonia → urea
2) Large intestine (small amount) - Freely filtered by glomerulus
- Some tubular reabsorption - especially with slower urine flow
What are the two main reasons serum urea increases and give examples within
1) ↓ glomerular filtration rate
- Decreased renal perfusion = prerenal
- Loss of nephron function = renal
- Obstruction of urine flow = postrenal
2) ↑ increased protein breakdown - prerenal
- High protein diet
- GI bleeding into the gut - increase protein breakdown in the gut, increase microbe convert to ammonia and liver convert to urea and excret into circulation on its way to the kidney
- Protein losing enterophathy
Which is more specific for pre-renal azotaemia urea or creatinine
Urea increases more with pre-renal azotaemia than creatinine increases - less specific
What are the 3 main downfalls of using urea as a measurement of azotaemia and why
1) Less useful in assessing renal function in ruminants and horses - use creatinine mainly
- Ruminants excrete urea via rumen
- horses excrete urea via large intestine
- Excretion depends on nitrogen intake
2) Not useful in birds and reptiles
- Protein catabolism →ammonia → uric acid
3) Increases can reflect dehydration
creatine filtration, excretion and reabsorption and why more specific then urea but what animal not used in
- Freely filtered by the glomerulus
- Small amount excreted in GIT
- No tubular reabsorption - more specific → better indicator of decreased GFR than urea
- Concentration not affected by diet
not used in birds as only see once advanced renal disease
List the 3 main reasons see increase serum creatinine and 1 decrease and examples within
1) ↑ muscle mass → ↑ creatinine
- Greyhounds are higher than labrador
2) ↑ muscle breakdown → ↑ creatinine
- Training or rhabdomyolysis
- When stable with weight and muscle turnover most effective
3) ↓GFR
- Decreased renal perfusion = prerenal
- Loss of nephron function = renal
- Obstruction of urine flow = postrenal
4) Decreases with generalized muscle wasting
- Could mask kidney disease as if occurring at same time one make go up either decrease so overall no change
What is the downside with creatinine
- Little change in creatinine until advanced renal failure
- normal creatinine doesn’t mean don’t have renal dysfunction
- need to explore early onset markers
uric acid in birds and reptile list 4 things that increase uric acid and why difficult to use
1) Renal disease (low sensitivity) - only really see increase in advanced renal disease
2) Profound dehydration - prerenal
3) Ovulation - very hard to know
4) Diet (high protein)
difficult
- Higher levels are seen in carnivorous species
- Hard to get good reference intervals
SDMA what does it stand for, when released, when increased levels seen and what causes increase levels
- Symmetrical dimethylarginine
- Released with proteolysis and excreted through the kidneys
- Increased levels are seen with ≥ 40% loss of renal function
- Slightly higher levels are seen in Greyhounds
- Increases with any cause of decreased GFR
e. g. dehydration, hypovolaemia (pre-renal)
List 3 clinical signs of renal azotaemia and pre-renal azotaemia
renal azotaemia
1) Polyuria and polydipsia
2) Anuria or oliguria
3) Inadequately concentrated urine
Pre-renal azotaemia
1) Concentrated urine - actively resorbing water
2) Evidence of dehydration
○ Vomiting, decrease skin turgor, dry tacky membranes, increase in urea and creatinine
3) Evidence of increase protein breakdown in GIT
○ Melena - blood in faeces
○ Increase in urea only, creatinine will be normal
Urine Specific gravity what measure with, what is it, what does it indicate and what does it reflect
- Refractometry
○ If above 1.000 greater than water (always the case with urine)
○ USG is ratio of refractive index of urine compared to water
○ Indication of tubular function = ability of tubules to absorb or excrete water
○ Reflects urine osmolality - High USG = more concentrated urine
- Low USG = less concentrated urine
What are the 3 ways to measure fluid and electrolyte balance
1) Urine specific gravity
2) Dipstick reagent pad
3) urine osmolality
1) If have azotaemia + concentrated urine =
2) Azotaemia + inadequate urine concentration =
1) = dehydration - prerenal
2) = renal
List 5 factors that influence urine concentration
1) Number of functional nephrons
2) Renal medullary hypertonicity
○ Resorption of NaCl & Urea
○ Renal medullary blood flow
3) ADH secretion and action - RAAS mechanism
- Extra-renal factors
○ Hydration status
○ Serum electrolytes
○ Concurrent diseases - inhibiting ADH function - diabetes insipidus
○ Drug therapy e.g. diuretics
4) renal insufficiency as unable to conserve water and electrolytes and unable to excrete N wastes
what are the 3 things that urine concentration does not distinguish
1) reversible from irreversible
2) acute from chronic renal disease
3) primary from secondary renal insufficiency
Progression of renal insufficiency what do you see:
1) ≥ 40% loss of function →
2) ≥ 66% loss of function →
3) ≥ 75% loss of function →
1) ↑ SDMA
2) polyuria
3) azotaemia
postrenal azotaemia findings of examination, history and histology
- History – stranguria or dysuria
- Examination/imaging findings:
○ Decreased urine output - leaking into abdomen or banking into the bladder
○ Distended bladder - pressure can build back to the kidney causing kidney disease
○ Uroabdomen
Hyperkalaemia - increase in potassium
What are the 2 main causes of postrenal azotaemia and examples within
1) Obstruction of urine flow
○ Urinary calculi - urinary stones could be suck in urethra
○ Urethral plug
2) Internal urine leakage/uroabdomen
○ Ruptured bladder - can be seen with contrast leaking into abdomen in radiograph
○ Torn ureter / urethra
○ Patent urachus
List the other 8 changes with renal insufficiency
- Potassium
- Phosphate
- Sodium
- Chloride
- Bicarbonate
- Albumin
- Anaemia
- Amylase and Lipase
potassium what causes increase and decrease
- Hyperkalaemia - Anuric (acute kidney injury), oliguric or obstructive disease (post-renal) ○ Decreased GFR ○ Decreased secretion ○ Associated acidemia - Hypokalaemia - Polyuric renal disease ○ Increased urine flow rate ○ Reduced tubular function - chronic kidney disease → decreased potassium absorption
phosphate what causes with increase and decrease
- Hyperphosphataemia
○ Decreased GFR - renal (generally more severe)
○ Bone activity (young animals) - also get high ALT
○ Sample haemolysis - pre-renal - Hypophosphataemia common in horses with chronic kidney disease uncommon in other species
calcium what occurs with chronic kidney and acute kidney disease
Chronic Kidney Disease
→ Hypocalcaemia in dogs and cats, rarely hypercalcaemia
- secondary to hyperphosphatemia and decreased Vitamin D production
→ Hypercalcaemia in horses and rabbits
- High calcium diet
- Renal excretion controls excess and when get disease hard to keep up with the calcium absorbed from the gut
Acute Kidney Injury
→ Hypercalcaemia or Hypocalcaemia
magnesium what occurs with decreases GFR
Decreased GFR - Hypermagnesaemia
- Don’t have on a routine biochemistry
sodium and cholide when elevated
- Elevated with dehydration
- Variable level with renal insufficiency
○ Depends on water loss vs electrolyte loss
○ Changes masked by dehydration
○ Selective Cl loss with vomiting
bicarbonate what does renal insufficiency cause and what are the two types
- Renal insufficiency causes a metabolic acidosis
1) Titrational acidosis - ureamic acids +/- Lactic acid
2) Secretory acidosis – renal loss of bicarb → Hypobicarbonataemia
amylase and lipase what are they
- Pancreatic enzymes
- Excreted by the kidneys
- Decreased GFR → ↑ amylase and lipase
What are the features of acute kidney injury and chronic kidney disease
Acute Kidney Injury (AKI) = abrupt decline in renal function (hours to weeks)
- (acute renal insufficiency)
- Have dysfunction but often reversible to the extent that the animal can live a healthy life
- Toxins, infection, drugs
Chronic Kidney Disease (CKD) = progressive decline in renal function over months to years
- (chronic renal insufficiency)
- Tends to be non-reversible
List two secondary renal insufficiency causes
1) Hyperadrenocorticism - cushings disease dogs
→ impaired tubular response to ADH
2) Diabetes insipidus
→ impaired ADH secretion (central DI)
→ ↓ tubular response to ADH (nephrogenic DI)
List 5 causes of urinary protein
1) Renal
- Glomerular loss - ↑ filtered protein
- Tubular dysfunction - ↓reabsorbtion
2) Inflammation of urinary tract
- Cystitis
- Pyelonephritis
3) Haemorrhage
4) Genital tract
- Prostatic disease
- Uterine or vaginal disease
5) Prerenal
- Physiologic e.g. dehydration, fever
- Hyperglobulinaemia, haemolysis, myopathy (a disease of muscle tissue)
What are the two sources of protein leakage within the kidney and which is more severe
1) Glomerular - excess filtration due to leaky glomerulus
○ Often higher level of proteinuria
○ Primarily Albumin
2) Tubular - less severe than glomerular
○ Milder proteinuria
○ Albumin and other proteins eg aminoacids
○ May see other evidence of tubular dysfunction eg renal glycosuria
List the 4 ways proteinuria is assessed and what do you need to rule out first before do any of these assessments
1) urine dipstick
2) urine sediment examination
3) urine protein:creatinine ratio
4) microallbuminuria
Need to rule out inflammation as a source of the increase in protein first
urine dipstick what most sensitive to, what effected by and when use urine sediment examination
- Urine dipstick
○ Most sensitive to albumin
○ Affected by urine temp, colour, pH, storage, contaminants - Urine sediment examination
○ Cytology evaluation for haematuria, pyuria (WBC), bacteriuria and casts
microallbuminuria when detects, what useful for, why not usually used
○ Early detection of renal disease before there is overt proteinuria (i.e. dipstick protein is negative)
○ Useful for screening predisposed breeds
○ Positive with high levels of exercise and so not normally done
How to differentiate between acute kidney injury vs chronic kidney disease
- Magnitude of azotaemia does not differentiate
- Need knowledge of:
•Duration of clinical signs
•Urine output
•Calcium and Potassium levels
•Other clues eg anaemia (RBC have long half-life so take awhile to see decrease in RBC when erythropoietin has been decrease), weight loss
what see in blood and clinical signs of chronic kidney disease
- Hypocalcaemia in dogs and cats (only 5-10% hypercalcaemic)
- Hypercalcaemia in horses
- Hypokalaemia common in cats
- Anaemia occurs with chronic renal failure
○ ↓erythropoietin - Chronic polyuria and polydipsia
- May see weight loss
what see in blood and clinical sings, history acute kidney injury
- May see hypercalcaemia or hypocalcaemia in dogs and cats
- Hyperkalaemia if anuric or oliguric
- Usually not anaemic
- Acute history of illness
What are the 4 routine urinalysis and what are the 2 additional testing
Routine urinalysis 1) Direct observation 2) Urine specific gravity (USG) 3) Urine dipstick 4) Urine sediment examination Additional testing 1) Urine protein:creatinine ratio (UPC) 2) Urine culture
what does the following colours of urine indicate
red, brown, dark yellow
- Red = haemoglobin or haemorrhage - can be common in rabbits
- Brown = Myoglobin, haemorrhage, bilirubin
- Dark yellow = concentrated or bilirubin
what does the clarity of urine indicate and what species has very cloudy urine and why
varies with species
Cloudiness can reflect - for
- Mucus
- Cells (pyuria) – leukocytes or epithelial, casts
- Crystals – especially horses and rabbits
- Bacteria
- Storage
horse and rabbit it is crystals and mucus
Urine sample storage and handling how long until perform testing, how to store and what to do before testing
- Collection should precede treatment
- Perform urinalysis within 30 minutes so best in clinic
- Can refrigerate up to 12 hours
○ May introduce crystals and alter pH
○ Bring to room temperature before testing
List the 4 methods of urine collection and what useful for
1) cystocentesis - least likely for contamination useful for dogs and cats
2) catheterisation - must use sterile technique
3) voided (free catch) - not sterile, midstream best, mainly dogs and cats good for USG
4) off the floor/litter tray - useful for USG
List the 7 things urine dipsticks assess
- Urobilinogen
- Protein
- pH
- Blood
- Ketones
- Bilirubin
- Glucose
Protein on the dipstick when get false positives and when positive results more significant and why
- False positives with alkaline urine (pH > 8.0) - so need to confirm with another test
- Positive results more significant in dilute urine
○ As if detect trace amount of protein means more protein is being lost as large amount of urine
What are the 2 other ways of assessing proteinuria if suspect false positive with alkaline urine
1) Sulfosalicylic acid precipitation test - detects all proteins - use with alkaline proteinuria
2) UPC
causes of glucosuria
○ Hyperglycaemia
1) exceeding renal threshold
2) Tubular disease (renal glucosuria)
ketones when see in urine, which ketone more sensitive, what one is major in the blood and which first ketonuria or ketonaemia
- Only really see in if catabolic state or ketosis (cattle, horses) and diabetes mellitus (dog and cat)
- Detects: acetone (most sensitive) and acetoacetic acid
- Dipstick does not measure β-hydroxybutyrate - measured in the blood
○ (Major intermediate in ketosis) - Ketonuria often precedes ketonaemia
bilirubin is it significant to find in a cat or a dog
- Dogs lower renal threshold - conjugate bilirubin in tubules - not really significant finding
- Bilirubinuria in cats is always significant
blood in the urine what are the 3 possible sources and the 3 ways to differentiate between them
- Reacts with haemoglobin (infection, RBC lysis), myoglobin (muscle breakdown), and intact erythrocytes
- Differentiation of cause
1. Sediment exam - is there intact RBCs
2. Plasma colour & CBC results - myoglobin has brown tinge
3. CK levels – increased with myopathy
urine pH what increases and decreases with normally and what does it affect
- Acidic pH (7.0) vegetable diet
- Post-prandial “alkaline tide” in dogs and cats
○ Straight after eating generally get pH increasing before normalising - Affects type of crystals and uroliths
urobilinogen how formed, what does presence in urine indicate, is there variation
- Formed in intestine by bacterial breakdown of conjugated bilirubin
- Presence indicates patent bile duct
- Correlation of increase and hepatobiliary disease is poor in animals
- Does vary quite a lot so don’t always use
What are the 3 things to ignore on a dipstick
1) nitrite
2) leukocytes
3) USG
what stain used in urine sediment evaluation
Can use Sedi-stain to stain the cells and bacteria however should make one stained and one unstained
What are the 6 things you can find within a urine sediment
1) cells
2) fat globules
3) casts
4) crystals
5) fungal hyphae
6) parasite eggs
what are the 3 types of cells found in urine and types within
- Erythrocytes
- Leukocytes
- Epithelial cells
○ Urothelial
○ Squamous
○ Caudate (tubular)
○ Sperm
○ Prostatic
What are the 4 type of casts and types within
1) Hyaline cast
2) granular cast
3) waxy cast
4) cellular cast
- epithelial
- erythrocyte
- leukocyte
Urinary tract neoplasia name some main ones
- Urothelial (transitional) cell carcinoma - most common and often aggressive
- Prostatic carcinoma
- Squamous cell carcinoma - of the bladder or urethra
- Leiomyoma - arise from bladder
- Leiomyosarcoma - arise from bladder
What occurs to globulin concentration in a dog with hepatic insufficiency, why and when else does this occur and what other changes would you see on biochemistry
Decreased serum concentration of globulins
○ Inflammation increase globulins like fibrinogen due to increased risk of infection without liver and kupffer cells removing microbes form the gut
- also see with PSS
Other changes
- decreased albumin, glucose, cholesterol in serum
- increase in bile acid concentration in serum