Gfr And Clearance Flashcards
What is GFR
• Kidney function is measured in terms of glomerular filtration rate
(GFR).
• GFR is the amount of filtrate that is produced from the blood flow per
unit time.
• The amount of filtrate is determined by the product of the average filtration of each nephron in each kidney (i.e. normal is about 2 million nephrons)
What is the normal GFR
Normal GFR is 90 – 120 mL/min /1.73m2
The normal total glomerular filtrate per day is 140 – 180 L /day
Lower for women higher for men generally
What does GFR depend on
- Depends on
* Gender • Age • Size of individual • Size of kidneys • Pregnancy
Describe nephrons and GFR in babes
• Nephron development finished by 35th – 36th
week of foetal development • Premature & LBW infants often have lower
nephron numbers • Foetal excretion predominantly via placenta
• At birth GFR ~ 20 mls/min/1.73 m2 • Normal GFR by ~ 18 months
Describe nephron change in advancing age
- GFR starts declining after 30 years of age • Rate of decline ~ 6-7 mls/min per decade
- Loss of functioning nephrons • Some compensatory hypertrophy
Medulla is exactly the same but cortex volume decreases
Describe teh relationship between GFR and size
- Bigger people tend to have bigger kidneys
- Bigger kidneys generally means more nephrons
- Small kidneys in big person worse than small kidney in a small person
What is compensatory hypertrophy
Once you have been born. Cant make more nephrons. • Reduced nephron number • Compensatory hypertrophy • Existing nephrons get bigger • Healthy kidney can also get bigger • Occurs to much greater extent in childhood • Nephron loss in old age not associated with compensatory hypertrophy
What is the result of compensatory hypertrophy
Nephrons work harder..
…And are at greater risk of wearing out
Cortical scars
Dcesribe gfr in pregnancy
• GFR increases (~ 50%)
– 130 – 180 mL / minute
• Kidney size increases (~ 1 cm)
– Increased fluid volume (vascular & interstitial )
• Nephron number the same - just fluid etc
• Back to pre-pregnancy levels ~ 6
months post-partum
Pregnancy is transient so no long term effect
Describe the GFR in a person and between individuals
• Big variability between individuals (even allowing for variables on previous slides)
• GFR relatively constant in an individual unless kidney function
changes
• If GFR declines it may therefore be due to:
– Decline in number of nephrons
– Decline of GFR within individual nephrons
Describe gfr and disease
- A fall in GFR in an individual means that kidney function has worsened
- A rise in GFR means that kidney function has recovered
- When kidney function declines slowly, individual nephrons may hypertrophy so actual GFR may not fall until significant kidney damage has occurred.
What is clearance
Clearance (C) is the volume of plasma cleared of a substance per unit of time where the substance is denoted as ‘x’
Cx=Ax/Px
C = clearance A = amount of substance eliminated from plasma P = plasma concentration of substrate
• This formula is clearance from the body, not just the kidneys
• Clearance is an imaginary concept – describes a volume of plasma
completely cleared of solute
What is renal clearance
Renal Clearance of a substrate = excretion rate / plasma concentration
Excretion rate = U (amount in urine) x V (urine flow rate)
What is the best substance to measure GFR
If used to measure kidney clearance a substance should:
• Be produced at a constant rate
• Be freely filtered across the glomerulus
• Not be reabsorbed in the nephron
• Not be secreted into the nephron
If all these are true then excretion rate = GFR
Inulin is the perfect substance for this
Why is inulin not used to measure GFR
- Requires continuous ivi to maintain steady state
2. Requires catheter and timed urine collections
What is used clinically to measure GFR
• Radio-active labelled marker
• Cleared exclusively by renal filtration
• Timed injection with blood samples taken 2,3,4 hours afterward
• Approx. 10% lower clearance than inulin (reabsorption?)
• Used clinically
– In children
– Where indication of renal function required e.g. kidney transplant or
work up to donate kidney for transplant
Is creatinine a goo measure of gfr?
• Endogenous substance • End product of muscle breakdown …Is it a good surrogate measure of GFR? Produced at a constant rate -? Freely filtered across the membrane - yes Not reabsorbed along nephron - yes Not secreted into the nephron - no
What affects creatinine love in an individual
See slide
How can serum creatinine replefct differences in gfr in different individuals
• Serum creatinine (sCr) stable in an individual (in steady state) • But serum creatinine can reflect very different glomerular filtration
rates in different individuals
Describe serum creatinine in early childhood
See slide
Describe the relationship between true GR and serum creatinine
See graph
How is GFR estimates from serum creatinine
- Creatinine is easy to measure but varies greatly between individuals
- Variety of models developed to try and better estimate GFR fromserum creatinine levels
- eGFR is not the same as GFR – it is a ‘best guess’
What is mdrd egfr
• 4-variable equation (based on ~1600 patients with CKD)
– Serum creatinine
– Age
– Sex
– Caucasian or Black
• Standardised to body surface area of 1.73 m2 therefore don’t need
patient height and weight • Original study in non-diabetic Caucasian Americans • Subsequently validated in DM type 2, Black Americans
Who is mdrd egfr inaccurate in
Inaccurate in…… • People without kidney disease (e.g. transplant donors) • Children • Pregnancy • Old age • Other ethnicities • Amputees / significantly reduced muscle mass • Patients with higher levels of kidney function (GFR > 60 mls/min)
How is mdrd egfr in diagnosing cod
• Underestimates true GFR when serum creatinine close or within
normal range (> 60 mls/min)
• Risk of patients being labelled as having chronic kidney disease
(CKD)
• In an individual patient two things are important • GFR • Change in GFR • But remember: eGFR taken from serum creatinine and not all
changes in serum creatinine are due to a change in GFR
What is ckd epi
• Uses same variables as MDRD calculation but calculation is slightly
different (~ 8300 patients much more diverse background)
– Serum creatinine – Age – Sex – Caucasian / Black
• As accurate as MDRD when eGFR < 60 mls/min • More accurate when eGFR > 60 mls/min but still not perfect
Why is egfr less accurate with mild kidney disease
Why is eGFR less accurate with mild kidney disease?
• 3 contributing factors
1. Reduction in GFR (e.g. if glomerular surface area reduced) causes increases in blood flow) …see lecture next week
2. reduced nephron number leads to nephron hypertrophy so no change in GFR
3. reduced filtration of creatinine (due to reduced GFR) results in increased serum creatinine and increased secretion into the tubule (maintain relatively steady state of serum creatinine)
