Renal Function Disorders Flashcards
What are the two types of kidney disorders?
Acute and chronic
How can you tell acute kidney disease from chronic?
Acute - damage occurring over hours or days, high mortality, reversible
Chronic - damage occurring over months or years, not reversible, treatment to slow progression and management
Causes o acute kidney disease?
Hypoglycaemia, renal stones, medications, sepsis, tumours, infection, renal insults
Causes of CKD?
Diabetes, heart disease, hypertension, many others …
Having chronic kidney disease can put you at risk of developing?
Stroke mi
Are early stages of AKI and CKD asymptomatic?
Yes
Who would you monitor for kidney disease?
Vulnerable or at risk people - People on medications which are toxic to kidneys, those with diabetes
What are some non-biochemical tests that assess the renal/urinary system?
History,
Physical exam,
Urine for culture ad sensitivity (bacteria)
Imaging
Renal biopsy
Do biochemical tests provide definitive diagnosis?
No
What would you want for an ideal renal bio marker?
- Simple, rapid, widely available
- affordable
- Results comparable between hospital
- undetectable in healthy kidney and detectable in unhealthy
- level of marker correlates with degree of damage
- able to detect early stages of AKI and CKD.
- equally applicable to all populations (ages, genders, ethnicities)
What is the glomerular? What does it do?
Glomerular filters blood (cells and proteins not filtered), majority of filtrate is re absorbed and excess fluid and waste products lost via urine.
What is the glomerular filtration rate (GFR)?
The rate at which kidneys filter blood and is used as an indicator of kidney health.
The volume of plasma filtered by glomerular in unit time (mm/min)
What is the calculation for GFR?
GFR x P = U x V
In GFR equation what is P?, U? And V? And units
Plasma concentration (mmol/L)
Urine concentration (mmol/L)
Rate of formation of urine (ml/min)
In practice when using GFR what would you calculate?
Clearance
What is the clearance calculation?
Clearance = (U x V)/ P
What is clearance?
Volume of plasma by which a substance is removed by glomerular filtration e.g if clearance of a substance of 100ml then each minute 100ml of plasma clears substance X
When would GFR be lower than the expected values?
If substance is reassured into the blood
When would GFR be higher than expected?
If the substance is filtered at glomerulars and secrete into urine
When measuring clearance what is the ideal biomarker?
Freely filtered at glomerulus
Not have an affect of GFR itself
Not be generated or metabolised within the kidney itself
Not be excreted or reabsorbed within the kidney or body
Inulin clearance (THIS MIGHT AUTOCORRECT TO INSULIN THIS IS NOT CORRECT ITS INULIN, there should be no mention of insulin during these cue cards it’s INULIN)
Inulin clearance - what is Inulin?
Polymer of fructose found in plants which isn’t produced in the body and so administered intravenously where it is freely filtered, not reabsorbed, secreted or metabolised.
Inulin clearance equation?
( Concentration of Inulin in urine x rate of urine formation) / concentration of Inulin in plasma
What are some cons of Inulin clearance?
IV infusion isn’t convenient and therefore not used in clinical practice is however still gold standard and used in research.
What is creatinine?
Waste product of creating metabolism and produced constantly and removed by glomerular filtration.
How would you do a creatinine clearance?
Take urine at 24 hours
Why is creatinine used in clinical practice?
Easy and cheap
Equation for creatinine clearance?
(Concentration of creatinine in urine x rate of urine formation) / concentration of creatinine in plasma
What are the problems of creatinine clearance?
Timed urine collections are:
- major source of inaccuracy
- inconvenient
- not rapid
Based on four measurements which are all Ian accurate (urine, serum creatinine, time, volume)
GFR is overestimated as small amounts of creatinine is excreted by tubules
GFR is underestimated in advanced renal failure
How many measurements of creatinine is normal taken in clinics?
One
Do lower values of creatinine clearance suggest kidney damage?
Yes
Do higher values of creatinine in the blood suggest kidney damage?
Yes
Why is creatinine good at assessing renal function?
Convenient and rapid
Creatinine levels tend to remain stable throughout adulthood
Do creatinine levels rise with declining renal function?
Yes
What are some issues with plasma creatinine concentration being used to assess renal function?
- Creatinine produced by muscles so plasma levels reflects both renal function and muscle mass
- Muscle mass varies with age, ethnicity, gender so the reference range needs to reflect this.
- There is normally no baseline level for each patient which would be ideal.
How do you overcome using a restrictive reference range? And what are some key things to remember about this?
Use modified equations depending on age and gender
This gives you the eGFR (estimated GFR)
Valid for CKD not AKI
How do you normalise GFR?
Divide by 1.73 as some people will be larger and have bigger kidneys than other people.
Cockcroft-Gault - what does this equation take into account when calculating creatinine eGFR?
- Age
- Gender
- Weight
- creatinine concentration
What does the Cockcroft-Gault equation estimate (over estimate or under estimate)
Overestimated
The modification of dilate in Renal Disease study - MDRD - what is this validated against?
Inulin
MDRD - what does this take into account?
Creatinine concentration
Age
Gender
ethnicity
Does MDRD overestimate GFR at higher levels?
No it underestimates it
Is MDRD standardised?
Yes
What does CKD-EPI equation account for?
Age
Gender
Ethnicity
Creatinine Concentration
Why is creatinine not a great biomarker?
Doesn’t take into account gender, age, ethnicity
Why isn’t GFR good for measuring renal disease?
Nephrons will compensate for failing nephrons and therefore GFR levels wont decrease to begin with
Other biochemical markers - Urea - what is urea?
Ammonia is converted into the less toxic urea and is excreted via urine
When GFR is reduced what is urea doing?
Increasing levels in the body
Why is urea not a good biochemical marker and GFR?
Can be excreted in gut and sweat,
Some is reabsorbed (which increases as GFR decreases)
Urea increases as volume depletion occurs independent of GFR reduction
Reference range in adults levels reflect dietary protein intake muscle mass.
What does increased urine and creatinine indicate?
AKI or CKD
What does urea being increased proportionally higher than creatinine mean?
High protein turnover or increased re absorption at kidneys due to reduced blood flow to the kidneys or outflow obstruction.
Could mean bleeding into the gut, dehydration or hypovelimic
Other biomarker - radio labelled substance
Inject a radiolabelled substance and monitor the drop in the concentration - this could be Cr-labelled EDTA, I-iodothalamate etc.
Should be excreted completely fro glomerular and you can therefore work out GFR from this.
It isn’t convenient though but used in children or during chemotherapy
Other biochemical markers - cystatin C
Synthesised by all cells and is a cysteine protease inhibitor. It is produced consistently and unaffected by muscle mass, gender, diet or age
Filtered at glomerulus and is reabsrobed By proximal renal tubule
What happens to cystatin C levels when GFR decreases?
Increased
Is cystatin C more sensitive than creatinine in mild disease and rises fast in AKI?
Yes
Why isn’t cystine C used?
Expensive and nt as available
Not standardised
Is there equations developed to use Cystatin C to work out eGFR?
Yes
Other biomarker - NGAL - where is this tested?
Urine or blood
In healthy people is NGAL high?
No
When is NGAL released?
Inflammation or tissue injury also infection
What would an increased NGAL and decreased GFR mean?
Damaged kidney
Why don’t we use NGAL?
Expensive although simple
Not much current evidence to support its use
Other biomarker - urine dipstick - what do you do?
Dip into urine and compare coloured strip to guide - do follow up tests if anything looks unusual. This is a good place to start.
What are downsides of urine dipstick?
The person needs to be good,
Interpretation subjective
Care is required
What are some tests tested for in a urine dipstick?
Glucose - diabetes
Specific gravity - concentration of urine
PH - acid base disturbances
ketones - starvation, anorexia, diabetic ketoacidosis
Protein - presence suggests damage to the kidney/ infection/abnormal protein
bilirubin, urobilinogen - liver test
RBCs - damage
White blood cells - infection
Pathological proteinuria - what happens when permeability of the glomerular is increased?
Proteins can pass into urine = bad
What is overflow proteinuria?
Raised plasma concentration of low molecular weight protein exceed the re absorptive capacity of the tubules
What is glomerular proteinuria?
Increased permeability of the glomerular caused by kidney injury, infection, inflammation, or immune system problems
What is tubular proteinuria?
Decreased tubular re absorption e.g caused by urinary tract obstruction, interstitial nephritis and Franconia syndrome
What would you do if the dipstick came back with increased proteins?
Lab test which will give you a numerical value - this will be reported in a ratio with creatinine to account for variations in urine concentration. (Protein number/ creatinine)
Or reported as a 24 hour excretion rate - collect 24 hour urine and anything more than 3.5 = nephrotic syndrome
However urinary protein is not sensitive for early/mid-moderate kidney disease.
What does the filtration layer contain?
Glomerular basement membrane, podocytes, endothelial cells - these form a negatively charged and narrow filter. They repel larger negatively charged molecules
Is albumin excluded from going though the glomerular?
Yes
Other biochemical tests - microalbuminuria - is this excreted during kidney failure?
Yes
What is microalbuminuria?
Measurement of albumin in urine in low concentrations
How do you report microalbuminuria?
In a ratio with creatinine
Is microalbuminuria more sensitive than protein?
Yes
Is microalbuminuria measured in at risk patients?
Yes
How many stages of AKI is there? And what do you measure to assign a level?
1, 2 , 3 and you measure creatinine levels with urine output
Where should you get your advice from?
KDIGO
How do you work out hat level of CKD someone has?
GFR derived from creatinine using the CKD-EPI equation
albumin creatinine ratio
Where available , use of cystatin C to estimate GFR in some patients with mild/moderate renal impairment
You measure creatinine against GFR in a table
