Renal Disease Flashcards
Azotemia
increased urea nitrogen with/without increased creatinine
uremia
excessive urea in blood with clinical signs of renal failure
vomiting, diarrhea, ammoniacal breath odor
renal function
Produce hormones (EPO, Renin)
Activate vitamin D (Ca, Phos homeostasis)
Regulate blood pressure (RAAS)
Excretes waste products
Conserves important substrates (WATER!)
T/F kidneys have a large functional capacity if basement membrane is intact
true
with loss of nephrons:
‒ Lose the ability to concentrate urine (1st)
‒ Become azotemic (2nd)
serum chemistry
‒ Urea Nitrogen concentration (BUN, UN, SUN)
‒ Creatinine concentration (Crea, Cre, Ct)
‒ Symmetric dimethylarginine (SDMA-new IDEXX test)
Urine tests
‒ Urine Specific Gravity (SpGr, USG)
‒ Urine Protein Concentration
Specialized Testing
‒ Urine Protein: Creatinine Ratio (UPCR)
‒ Fractional excretion of protein
‒ Fractional excretion of electrolytes
Blood Urea Nitrogen (BUN)
Synthesized in the liver
Urea is measured as BUN
the majority of urea is excreted by
the kidney
T/F any analyte filtered by the glomerulus is an indicator of GFR
true
is BUN an indicator of GFR
yes, filtered by glomerulus but there are better ones
BUN concentration varies with the rate of:
1.Production by the liver
- Reabsorption by the:
• Kidney (all species)
• GI tract (ruminants) - Excretion by the kidney
what can cause increased protein in the upper GI
‒ High protein diet
‒ Upper GI bleed (stomach, proximal duodenum)
‒ Increased catabolism
how will increased protein in the upper GI effect BUN
↑ production of BUN → ↑ serum BUN
liver insufficiency effect on BUN
↓ production of BUN → ↓ serum BUN
renal resorption of BUN
Passively resorbed in the proximal tubules (~50%)
Actively resorbed in the collecting tubules (~10%)
T/F Resorption of BUN varies with rate of flow thru tubules.
true
Slow flow rate, more BUN resorbed → ↑ serum BUN
Fast flow rate, less BUN resorbed → ↓ serum BUN
T/F Ruminants & horses have unique microflora that allow for GI excretion of BUN
true
how do you predict renal disease in ruminants and horses
Correlate changes in BUN with changes in CREA and USG
where can decreases in BUN can happen
Pre-renal
Renal
Pre-Renal causes of decreased BUN
↓ urea production
Intestinal loss of proteins
causes of ↓ urea production
Decreased amino acid delivery to liver
− Decreased protein in diet
− Portosystemic shunt (PSS)
Hepatic insufficiency (>80% loss)
causes of intestinal loss of proteins
Monogastric species (protein-losing enteropathies)
Horses and Cattle
– Blood urea excrete into saliva & goes to the rumen
– Rumen microflora create amino acids
– Urea is lost in the creation of proteins
(Results in a net protein gain and BUN loss.)
renal causes of decreased BUN
Decreased water resorption in proximal convoluted tubules
‒ ↑ GFR (ie, IVF diuresis)
‒ ↑ tubular flow (ie, osmotic diuresis)
Osmotic Diuresis mechanism
↑ urine osmolality pulls H2O into urine: ↑ urine volume and ↑ tubular flow
With ↑ tubular flow, ↓ time to resorb BUN → ↓ [BUN]
in what condition is osmotic diuresis common
diabetes
concentration of BUN is dependent on
Dietary protein
Liver function
Glomerular filtrate rate
T/F creatinine has a constant rate of production
true: Produced by endogenous muscle catabolism, rate of production is proportional to muscle mass
T/F creatine is resorbed by the kidney
false
what releases CREA into plasma
muscle cells
why is CREA and excellent indicator of GFR
Filtered by the glomerulus
Not resorbed by the renal tubules
Excreted unchanged by kidneys
increased plasma levels of CREA implies…
a decrease in GFR
possibly altered nephron function
decreased CREA
not clinically significant
SDMA increases with…
~40% loss of renal tubular function
Symmetric dimethylarginine (SDMA)
Released into circulation by all nucleated cells
Filtered by the glomerulus
Excreted almost exclusively by the kidneys (≥90%)
Not impacted by extrarenal factors (esp. lean body mass)
interpreting SDMA
Increases in SDMA suggest renal tubular disease
Interpret alongside history, clinical signs, PE findings, other markers of renal injury
ALWAYS COME BACK TO YOUR PATIENT.
clinical use of SDMA
monitoring
management
if SDMA is increased and CREA is normal:
Does your history, C/S, and/or PE findings support renal disease?
Rule out all other causes of ↓ GFR besides RF: Pre-renal, Renal, Post-renal
Urine Specific Gravity
an estimate of urinary concentrating capacity
Kidney’s Ability to Conserve Water!!!
run a USG when…
Suspected renal disease
Geriatric wellness
Hx of PU/PD
2 parts of the kidney are used to concentrate and/or dilute urine
The thick ascending Loop of Henle
The collecting tubule via ADH (Vasopressin)
kidneys ability to conserve water is dependent on
33% functional nephrons
Production & responsiveness to ADH
Concentration gradient
- Medullary hypertonicity
- Production of urea
- Production of aldosterone
urine dilution
Remove osmoles
Minimize H2O resorption
minimum concentrating capacity in dehydration for a dog
1.030
minimum concentrating capacity in dehydration for a cat
1.035
minimum concentrating capacity in dehydration for bovine/equine
1.025
range of minimal concentration (ROMC)
- 013-1.030 Dog
- 013-1.034 Cat
- 013-1.024 Equine, Ruminants, Porcine
urine specific gravity should always be interpreted with…
patients hydration status
why is creatinine is a better indicator of GFR than BUN
BUN is resorbed in the kidney
Creatinine is continually and consistently produced by muscle
Creatinine is not resorbed by the kidney
polyuria
Inability to concentrate urine
Implies loss of ~ 66% of functional renal mass
Low specific gravity (isosthenuric 1.007-1.013)
DDx for polyuria
Renal
- Renal failure
- pyelonephritis
Extra-renal
- Diuresis
- Medullary washout
- Endocrine (diabetes, hyperadrenocorticism)
- Pyometra
Azotemia is due to
retention of nitrogenous waste products in blood
implies 75% loss of renal function
3 categories of azotemia
pre-renal
renal
post-renal
what will you see with pre-renal azotemia
↑ BUN, +/- ↑ CREA, ↑ SpGr
DDx of pre-renal azotemia
Decreased renal blood flow leads to ↓ GFR (dehydration!! shock, ↓cardiac output)
Increased urea production (upper GI bleed, high protein diet, ↓ ruminal motility)
pre-renal azotemia: Decreased renal blood flow leads to ↓ GFR- analytes effected
2 renal analytes affected by ↓ GFR - BUN - CREA Other analytes affected by ↓ GFR - Phosphorus (increases) - Magnesium (increases)
what happens in a dehydrated animal with normal renal function
urine volume is decreased (less blood = less urine)
urine specific gravity is increased (concentrated urine)
T/F persistently decreased blood flow will cause renal damage
true
why is there increased urea production with pre-renal azotemia
Liver takes amino acids & makes urea
Urea moves into blood → measured as BUN
sources of amino acids
GI tract
- Upper GI bleed
- High protein diet
- Ruminants: ↓ ruminal motility
Endogenous protein catabolism (starvation, cachexia, neoplasia)
causes of increased CREA in pre-renal azotemia
Increased muscle mass
Neonatal foals
– Dams with dysfunctional placentas; prevents normal clearance of fetal CREA
– ↑ CREA resolves within a few days
renal azotemia
↑ BUN, ↑ CREA, ↓ SpGr
renal azotemias result in
↓ GFR
– Increased BUN
– Increased CREA
– Increased PHOS
Loss of the kidney’s concentrating ability
– Isosthenuria (1.008-1.012)
- Increased water loss, even in a de-H2O animal
- Implies polyuria
Causes of renal azotemia =renal damage! DDx:
infectious toxins hypoxia neoplasia congenital (hypoplasia or aplasia)
T/F An animal with azotemia and inappropriately low USG is always in renal failure
false
other causes of azotemia and inappropriately low USG (besides renal failure)
Imbalances in electrolyte metabolism, endocrine function, or drug effects:
- Calcium
- Diabetes insipidus
- Endocrine: cortisol, glucose
- Fanconi syndrome
- Diuresis
Post-renal Azotemia
↑ BUN, ↑ CREA, variable SpGr
causes of post-renal azotemia
Obstruction of urinary outflow
– Urolithiasis in castrated males
– Uroabdomen (urine leaks into peritoneal cavity): trauma, urolithiasis
T/F polyuria occurs before azotemia
True:
− Polyuria: ~66% nephron loss
− Azotemia: ~75% nephron loss
origin of azotemia is determined by…
SpGr
− Prerenal azotemia: ↑ SpGr
− Renal azotemia: ↓ SpGr
− Postrenal azotemia: Variable SpGr (use clinical signs)
differentiating azotemias: pre-renal
Are there other signs of dehydration?
Is there a reason for this patient to bleed? (GI ulcer, upper GI bleed, coagulopathy)
Is the patient on a ↑ protein diet?
T/F Azotemia + Isosthenuria = Renal disease until proven otherwise
true
what is the exception to isosthenuria + azotemia=renal disease
cats: can maintain some concentrating capacity with renal failure
differentiating azotemias: post-renal
Look to your signalment and PE findings: −Castrated males (more frequent) −Straining to urinate −Large turgid bladder −Distended abdomen (uroabdomen)
T/F healthy dogs may have a measurable protein concentration
true: mostly albumin
Urine protein concentration
Measurement by reagent strip
Measures albumin!
3 types of proteinuria
Prerenal (increased protein in blood)
Renal (glomerular & tubular)
Postrenal (hemorrhagic / inflammatory)
pre-renal proteinuria
Increase in a small protein in blood • Paraproteinuria (Bence-Jones) • Hemoglobinuria • Myoglobinuria • Post-colostral proteinuria
renal proteinuria
Glomerular proteinuria
– Hypoalbuminemia
– Disease damages filtration barrier
Tubular proteinuria
– Normal or increased serum ALB (e.g. no hypoalbuminemia)
– Usually associated with acute or congenital renal diseases
– Proximal tubules defective – filtered proteins not resorbed
post-renal proteinuria
Hemorrhagic / Inflammatory (will see pyuria)
when do we use UPCR
Don’t have hemorrhage or pyuria, not febrile, no history of seizure- nothing to points in the direction its going on before the kidney
Differentiates between leaking of glomerular proteins and leaking of tubular proteins: albumin is one way but can be more subtle than that
what does UPCR do
Estimate quantity of urinary protein excreted/ day
T/F glomerular proteinurias tend to be more severe
true
hypercalcemia in renal failure
Impairs urine concentrating ability causing primary PU
- affects ADH receptors
Commonly leads to mineralization of renal tubules → nephronal(kidney) dysfunction
T/F Most of the time, hypercalcemia causes kidney disease
true
calcium levels in renal failure
Dogs, cats & cattle: mild hypocalcemia
– ↓ 1,25-dihydroxy vitamin D
Horses: hypercalcemic (diet & excretion)
hyperphosphatemia in renal failure
GFR is
T/F hyperphosphatemia is not as common in cattle and horses
true:
- horses tend to lose from the gut
- cattle: Salivary Phos excretion > renal Phos excretion
T/F cattle with renal failure can be hypochloremic
true
why do you see a metabolic acidosis with severe renal disease
↑ urinary loss of HCO3
↓ tubular secretion of H+ ions
Normokalemia
– Potassium is often normal in CRF
– Increased tubular secretion prevents hyperkalemia
Hypokalemia
– Uremic animals often eat less → ↓K intake
– Hypokalemic nephropathy in cats
- Pathogenesis unknown, likely multifactorial
Hyperkalemia
– Associated with oliguria/ anuria
– Life-threatening in ARF and/or post-renal conditions
Uroabdomen and Electrolyte Imbalances: Dogs, cats & newborn foals
– ↑ K, PO4
– ↓ Na, Cl
An ↑K and ↓Na occurs with several diseases. Uroabdomen = one ddx
Uroabdomen and Electrolyte Imbalances: cattle
– Hyperkalemia does not occur
–Excess potassium excreted in saliva
when is peritoneal [CREA] diagnostic for uroperitoneum
Peritoneal [CREA] 2x serum [CREA]
why is [CREA] used as an indicator of uroperitoneum
CREA takes longer to move from peritoneal urine into blood (large molecule)
smaller molecules move more quickly
what are major diagnostic indicators of uroabdomen?
Hyperkalemia, hyponatremia (↑K, ↓Na)
Peritoneal creatinine greater than 2x higher than serum creatinine
which electrolytes move into plasma quickly?
Urea and K+ move into plasma quickly, plasma [ ] increases
which electrolytes move into urine quickly?
Na+ and Cl- move into urine quickly, plasma [ ] decreases
presentation of ARF
Patient: Any signalment
History: Acute onset of clinical signs (e.g. GET SICK FAST.)
physical exam AFR
Patients usually have a good BCS (vs. CRF patients)
GI - anorexia, vomiting, diarrhea, halitosis (NH3)
Renal - oliguric to anuric
Neuro - depressed → obtunded → nonresponsive → seizures
causes of ARF
Many!!
Commonly associated w/ toxicants, renal ischemia, or infection
– i.e., things that damage the kidneys swiftly! (antifreeze poisoning)
features of ARF
Marked decrease in GFR leading to azotemia
May be reversible or irreversible
Bloodwork findings ARF
Azotemia (fast increase with ARF)
+/- Hyperkalemia & Acidemia
- Impaired excretion of K+ and H+ leads to metabolic acidosis
- Failure to recapture HCO3
Urinalysis: ARF
‒ Oliguria or anuria (abrupt ↓GFR)
‒ Urine SpGr is variable
‒ +/- proteinuria
‒ +/- cellular casts
CRF presentation
Patient: Usually geriatric (but not always), frequently cats
History: Slow onset of clinical signs
CRF physical exam
Patients usually have a poor BCS (thin, cachexic)
GI - anorexia, vomiting, diarrhea, halitosis (NH3)
Renal - polyuric
Neuro - depressed
CV - hypertension
features of CRF
Irreversible kidney injury
Renal function is inadequate to maintain patient health
Decreased GFR
Azotemia
Isosthenuria
CRF Bloodwork and Urinalysis: GFR 20-25% normal
Nonregenerative anemia (no EPO production)
Dehydration
- kidneys cannot regulate body H2O
Azotemia
+/- Hyperphosphatemia (85%)
Metabolic acidosis
- kidneys cannot regulate electrolyte and A/B
Normokalemia to Hypokalemia
Polyuria, isosthenuria
CRF Bloodwork & Urinalysis: GFR less than 5% normal=end stage renal failure
Nonregenerative anemia
Marked dehydration
Marked azotemia (patients are uremic)
Hyperphosphatemia
Metabolic acidosis
Hyperkalemia
Isosthenuria
Oliguria to anuria
Glomerular Nephropathy
Renal glomerular damage:
1) Immune complex deposition
2) Amyloid deposition
GN causes:
Retraction of podocytes
Loss of selective permeability of the glomerular basement membrane
GN allows filtration of larger negatively charged proteins causing
proteinuria
hypoproteinemia
GN laboratory findings
Mild to marked hypoproteinemia
‒ Hypoalbuminemia
‒ Normoglobulinemia
Moderate to marked proteinuria (albuminuria)
+/- evidence of renal insufficiency (azotemia, isosthenuria)
albumin decreases on its own with…
Albumin decreases on it own with protein losing nephritis (glomerular nephropathies), vasculitis, liver failure, and INFLAMMATION!!!!
Nephrotic Syndrome:
Protein-losing nephropathy leading to abdominal transudation
what 5 things need to be present to Dx nephrotic syndrome
- Glomerular disease
- Hypoalbuminemia - Leaky glomeruli (PLN)
- Hypercholesterolemia - Poorly understood
- Edema/ abdominal effusion - Loss of plasma oncotic pressure
- Hypercoagulable state- Loss of antithrombin
