Assessment of renal function

what to categories of substances can we measure to assess the kidneys?

• clearance of waste from plasma

• preservation of plasma resources

what products of clearance of waste from plasma can we measure

• amount of plasma being produced

• waste products being cleared

what 3 categories of substances can we measure for kidney function of preservation of plasma resources?

• water

• protein

• minerals

what waste products can we measure for kidney function in the blood? (6)

• urea

• creatinine

• phosphorus

• SDMA

• potassium

• FGF-23

what is GFR

• glomerular filtration rate is the volume of fluid filtered from glomerular capillaries into bowmans capsule per unit time

what is GFR related to?

• function of whole kidneys

How does renal damage affect GFR

• renal damage → nephron loss → GFR falls

why do we measure renal clearance and not GFR

• more feasible

what do we require a substance to be in order to measure it for renal clearance?

• filtered

• not reabsorbed

• not secreted

how do we calculate renal clearance

• urine conc of substance x urine volume per unit time / plasma conc of substance

what are the units of GFR

• volume per time (per kg BW)

why is urea not reliable to measure for renal clearance?

• produced in liver by NH3 but is reabsorbed in the kidney - also highyl influenced by external factors e.g. diet

why do we want to use other markers in concurrence with creatinine?

• creatinine only lowers in the case of very severe renal disease therefore whilst it’s a good marker it’s not a good for detecting early signs of disease

state 3 causes of why urea levels may change besides due to disease

• distal nephron resorption of urea for medullary conc grad

• post-prandial increase after protein meal

• GI bleeding causes it to increase

why is urea less reliable marker in horses and ruminants?

• microbial NH3 production

what is an:

1. ammoniotelic

2. ureotelic

3. uricotelic species?

1. excretes ammonium

2. excretes urea

3. excretes uric acid

what does this graph tell us?

• urea and creatinine concentrations only increase above the normal threshold when there’s significant nephron damage - around 70-75%

how does excretion of phosphate change with GFR change?

• phosphate excretion reduces with GFR reduction

if phosphate isn’t excreted in the kidney due to reduced GFR where does it build up?

• in the blood

are high levels of phosphate in the blood lead ot a good prognosis?

• no

how can we restrict phosphate with kidney disease?

• restrict intake - renal food

• phosphate binders

what is an issue iwth renal food, especially for outdoor cats?

• they don’t enjoy it - sometimes it’s better to ensure the animal is eating rather than be super picky on what they eat and make owners feel bad

why may plasma potassium change with renal disease?

• failure to excrete → due to acute renal failure and blockage/bladder rupture

what does SDMA stand for?

• symmetric dimethylarginine

is SDMA better than creatinine?

• not hugely, both only show up when the kidney has severe nephron loss

should we just take a measure of creatinine on its own and use this to determine the health of the kidneys?

• no, we should use other parameters in onjunction e.g. SDMA

what is FGF-23 used to detect?

• CKD-MBD (chronic kidney disease -metabolic bone disease) in early stages

why do we use FGF-23 over phosphorus?

• it increases before phosphorus levels increase

what does a USG of 1.010 compared to 1.020 tell us about osmolality of plasma?

• urine with 1.020 has a plasma of twice the solute concentration than the urine of 1.010

if we have a very concentrated sample with a USG off the scale, how do we determine the USG?

Dilute the urine sample e.g. 50:50, calculate USG and then multiply the USG (after the decimal point) - and that gives you the original

• USG of diluted sample is 1.040

• double this = 1.080

what are typical USG values for:

1. dogs

2. cats

3. horses

4. cattle

1. 1.015 - 1.045

2. 1.035 - 1.065

3. 1.020 - 1.050

4. 1.025 - 1.045

why may the USG of a healthy animal fall out of the given ‘reference intervals’

• depends on the animals’ water intake vs water loss

what may give us a false impression of osmolality in the urine?

• presence of non-typical solutes will change the SG

what assumption does USG rely on

• only things in urine are what’s supposed to be in healthy urine

why is isosthenuric urine a concern (in context of other things

• it means the kidneys aren’t secreting or reabsorbing in the renal tubule

what do we need to look at in addition to USG to determine if there’s a concentrating problem?

• hyddration status

• azotaemia

in an animal with healthy renal function, what is azotaemia an indication of?

• poor renal perfusion

in animals with typical renal perfusion, what is azotaemia an indicator of?

• insufficient nephrons

if there’s insufficient nephrons to filter the blood, what type of azotaemia will this cause?

• renal

if there’s insufficient renal blood supply - not enough to be filtered what type of azotaemia will this cause?

• pre-renal

what does it mean if an animal is dehydrated/azotaemic and the USG is;

• 1.008-1.012

• <1.008

• >1.025

1. no active change - renal failure

2. can dilute, kidneys aren’t failing but may be ADH issue

3. is appropriately concentrating - azotaemia is pre-renal

Why is hyposthenuria an ADH problem and not a renal failure problem?

• In the loop of Henle the tubular filtrate has water pumped out down the descending limb and salts pumped out in the ascending limb

• at the DCt therefore the tubular fluid is very dilute

• int he collecting duct and DCT ADH should be acting to alter the dilution of the urine based on the body’s needs

• if ADH isn’t working/not being produced then the urine won’t be concentrated, staying dilute

what does isosthenuria mean

• same strength urine - osmolarity equivalent to plasma osmolarity

what does hyposthenuric mean?

• lower strength urine - urine osmolarity less than isosthenuric

what does eusthenuria mean?

• expected strength urine - given normal renal function and hydration status

what is hypersthenuria?

• high strength urine - highly concentrated urine

in a dehydrated animal where the kidneys are tryingt o preserve water, what should the USG be around?

• >1.030 (depends on species)

ina dehydrated animal where the kidneys are unable to preserve water, what does this mean that’s been lost and what do we expect the USG to be?

• nephron loss

  • <1.030

for an azotaemic, pre-renal animal, what do we expect the urine concentration to be?

• >1.030 - concentrated - due to low GFR and low blood volume

for a renal azotaemic animal what do we expect the USG to be?

• <1.030 (but >1.007) or

• 1.008-1.012

for a hyposthenuric animal, when we restrict water/water intake is normalised what do we expect if:

1. hyposthenuric due to more water than required to offset losses

2. compromised ADH production or action

1. concentrated urine >1.030

2. <1.030

what should we measure to assess proteinuria?

• urine protein: creatinine = UPC

why do we measure urine protein: creatinine to determine if there’s proteinuria?

• it assumes constant creatinine clearance

cause of pre-renal proteinuria?

• overload like glucosuria

cause of renal (glomerular) proteinuria

• damaged glomeruli

cause of renal (tubular) proteinuria?

• unable to resorb normal amounts of filtered protein

cause of post renal proteinuria?

• urinary tract inflammation

what does the presence of casts indicate?

• tubule disease/damage

what are 4 types of casts

1. hyaline

2. cellular

3. granular - fine/coarse

4. waxy

what are hyaline casts

• mucoprotein

what are cellular casts

• rbc

• wbc

  • epithelial cells

are granular casts

• degenerate cellular casts - imply longer stasis

what are waxy casts, what do they imply?

• end-product of degeneration

• implies long period of stasis

what is renal clearance?

• indication of kidney’s ability to remove compounds

what are 3 things renal clearance depend on?-

• GFR

• tubular reabsorption

• tubular secretion

experimentally how could we measure GFR by clearance?

• timed urine collections and blood samples

  • inulin and exogenous creatinine infusion

• clearance from plasma e.g. radioisotopes

what can we measure clinically to determine GFR by clearance?

• timed urine collections and blood samples for endogenous creatinine

• plasma clearance - iohexol, exogenous creatinine

• scintigraphy

what do we need to measure creatinine clearance, is this feasible?

• accurate urine collection over time

• not practical clinically

why is blood creatinine not 100% reliable?

• there’s tubular secretion some Gi clearance at high concentrations too

how do we calculate creatinine clearance?

• urine creatinine x urine volume / serum creatinine x time x bodyweight

State how much of the following are absorbed into the PCT:

1. sodium and water

2. organic solutes

3. potassium

4. urea

5. phosphate

1. 2/3

2. 100%

3. 65%

4. 50%

5. 80%

what does a <1 fractional clearance indicate?

• net conservation(resorption) of the electrolyte

what does a fractional clearance >1 indicate?

• electrolyte is lost and not resorbed indicating tubular disease

what is the electrolyte fractional clearance compared to?

• creatinine

why may metabolic acidosis arise with renal disease?

• limitation on NH4+ production and excretion

• initial compensatory increase in remaining nephrons

• compensation fails at 10-20% normal GFR

• serum HCO3- decreases

• loss of buffer means pH change (small initially)

• until anions accumulate → larger pH gap

why may we see non-regenerative anaemia with kidney disease?

• reduced EPO from damaged kidneys

when we have clinical pathology of the kidneys, state 4 clinical changes we may see/measure

1. non-regenerative anaemia

2. increased plasma ‘‘waste’’

3. urine USG

4. urinalysis - pathology evidence and proteinuria

when we see the following, what does it tell us about nephron loss:

1. isosthenuria

2. azotaemia

3. hyperphosphataemia

4. hyperkalaemia

1. 67% loss

2. 75% loss

3. 85% loss

4. 95% loss

Is dog 1, pre-renal, post-renal or renal?

• urea and creatinine are high = azotaemia

• USG is high - but above 1.025 therefore not renal damage

• total protein is high → could be dehydrated

• therefore likely pre-renal and dehydration

For dog 2, are they pre-renal, renal or post-renal?

• high urea and creatinine high = azotaemic

• isosthenuric = indication of kidney damage

• protein is in range

• therefore likely renal

for dog 3, is it pre-renal, renal or post renal?

• urea is high but creatinine in range

• USG 1.025

• protein in range

Two options: wait and re-test to see if anything has changed or recognise that urea can be impacted by gastric disease therefore investigate there

So likely pre-renal

For dog 4 is it pre-renal, renal or post-renal?

• urea is high and creatinine = azotaemic

• isosthenuric

• high calcium levels

• calcium blocks ADH action therefore likely secondary diabetes insipidus - need to work out underlying primary disease