Renal Plasma Clearance Flashcards
Which substances are used to measure GFR?
Creatinine as it is only filtered - no reabsorption or secretion
It will only be found in the urine or blood
What is inulin?
Inulin (not insulin)
An inert polysaccharide, MW ~5,000
Filters freely through the glomerular membrane
Not absorbed, secreted and metabolised
And because there is no involvement of any other mechanisms, the rate of filtration through the glomerular membrane is the same as the rate of entry into the bladder
How is GFR calculated using inulin?
Where:
GFR = glomerular filtration rate; ml.min-1
Pin = plasma inulin concentration; mg.ml-1
Uin = urine inulin concentration; mg.ml-1
V* = urine flow rate; ml.min-1
Rate of inulin filtration= [Pin] x GFR
Rate of entry into bladder= [Uin] x urine flow rate (V)
So therefore…
Pin x GFR= Uin x V
What is renal clearance?
Renal clearance of a substance is the volume of plasma that is completely cleared (excreted into urine) of the substance by the kidney per unit of time (expressed in ml/min)
How do you calculate renal clearance?
Cs × Ps = Us × V* Cs = Us × V*/Ps Where: Cs= clearance rate of substance (s) Ps= plasma concentration of s Us= urinary concentration of s V*= urine flow rate
What are the drawbacks to the inulin method?
Drawbacks of the inulin method:
- Prolonged infusion
- Repeated plasma samples
- Difficult routine clinical use
What are the advantages and disadvantages?
Advantages:
An intrinsic inert substance
Released at ~steady level in plasma from skeletal muscle
No infusion needed
Freely filtered
Not reabsorbed in the tubule
Disadvantages:
Some secreted into the tubule
So the clearance rate is slightly more than the GFR
GFR < Ccr = Ucr× V*/Pcr ~150 ml/min (rather than 125ml/min)
What can creatinine interact with?
Trimethoprim competes with Crn for the same transporters that secrete Crn from tubular blood into urine» increase in serum levels of Crn
What is the creatinine extremes?
The little girl has normal kidney function and a creatinine level less than 60 μmol/L.
The body-builder has normal kidney function and a creatinine of 120 μmol/L.
Due to the body builder having much more skeletal muscle
For the girl, a creatinine of 120 μmol/L would be very poor kidney function.
What are the CKD stages?
The stages of CKD (Chronic Kidney Disease) are mainly based on measured or estimated GFR.
There are five stages but kidney function is normal in Stage 1, and minimally reduced in Stage 2.
Stage, GFR*, Description Treatment stage
1 90+ Normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease Observation, control of blood pressure.
2 60-89 Mildly reduced kidney function, and other findings (as for stage 1) point to kidney disease Observation, control of blood pressure and risk factors.
3A 45-59 Moderately reduced kidney function Observation, control of blood pressure and risk factors.
3B 30-44
4 15-29 Severely reduced kidney function Planning for end-stage renal failure.
5 <15 or on dialysis Very severe, or end-stage kidney failure (sometimes call established renal failure) Treatment choices.
How are different substances cleared?
-Substances where clearance = inulin (= GFR)
~ 125ml/min in adult male and 10% less in females
e.g. antibiotics (streptomycin/gentomycin)
-Substances where clearance < inulin (< GFR)
Either not filtered freely
Or reabsorbed from tubule
Substances with clearance > inulin (> GFR)
Secreted into tubule
What is the difference in clearance between substances that are not freely filtered and reabsorbed?
Not freely filtered:
E.g. Albumin clearance = 0ml/min
Similarly for drugs bound to albumin e.g. digoxin, warfarin
Substances that are re-absorbed:
Filters freely but is usually absent from urine ⇒ completely reabsorbed
e.g. Glucose clearance = 0ml/min
What happens to different substances clearance wise?
Actively Reabsorbed:
-All amino acids
Clearance = 0ml.min-1 unless excess filtered
Pathological conditions (e.g. myeloma)
Production of Bence-Jones protein in plasma
-Ca2+, Na+, PO42-, Mg2+
-Water-soluble vitamins
These display transport maximums
Passively Reabsorbed:
-Cl–, urea, some drugs
These are dependent on electrochemical gradients
What is renal plasma flow and renal blood flow?
RPF is the rate at which plasma flows through the kidney
Estimating the RPF through the kidneys allows us to estimate the rate of total blood flow (RBF) through the kidneys
Blood consists of about 55% plasma and about 45% cellular components (mostly RBCs)
What is para-aminohippuric acid?
To calculate RPF we use para-aminohippuric acid
PAH is weak acidic metabolite of glycine, originally found in horse’s urine
Filtered freely and enters glomerular filtrate, but a large amount still in plasma
Majority is secreted back into proximal convoluted tubule ⇒ excreted in urine
Suitable as a marker to measure renal plasma flow
