Lecture 10 - Assessment of Renal Function Flashcards
Normal Real Blood Flow (RBF)?
1200 mL/min, ~20% of cardiac output
What is GFR? Normal GFR?
GFR = volume of fluid filtered from the kidney glomerular capillaries into the Bowman’s capsule per unit time
Normal: 180 L/day, 110-140 mL/min
(Filtration fraction = RBF/GFR ~20%)
Normal volume of urine formation?
1.5 L/day, 1 mL/min
How much of water in glomerular ultra filtrate is reabsorbed by kidneys?
~99%
Where in the kidneys is the major site of reabsorption?
~65% occurs in proximal renal tubules, accompanied by Na+ and Cl- reabsorption
What are the 3 major functions of the kidneys?
- regulation of water, electrolyte and acid-base balance
- excretion of waste products of intermediary metabolism, e.g. urea, creatinine, uric acid, phosphate, sulphate, organic acids
- production and elaboration of hormones, e.g. renin, erthryopoietin, 1,25(OH)2-D3
At what urinary output is azotemia inevitable?
Waste products of metabolism = ~550 mOsm/day
Maximal urinary concentration attainable = ~1300-1400 mOsm/L
Maximal volume of urine water = 550/1400 = 400 mL/day
Therefore, azotemia inevitable if urine output <400 mL/day
What properties does the ideal substance for GFR estimation possess?
- freely filtered at the glomerulus
- not reabsorbed by the renal tubules
- not secreted by the renal tubules or other organs
- not synthesized or metabolized by the renal tubules
How is UV/P derived?
- assume a substance M, not reabsorbed/secreted/metabolized by kidneys and freely filtered at glomerulus
- mass M excreted/time = mass M filtered/time
- mass M filtered = volume of plasma filtered into Bowman’s space X concentration of M in glomerular filtrate
- concentration of M in filtrate = concentration of M in plasma
Therefore:
GFR = (UM X V) / PM
- where UM and PM are concentrations of M in urine and plasma respectively, V is volume of urine per unit time
What is needed to maintain normal GFR?
- adequate number of neprhons with intact glomerular function
- nromal renal perfusion
What is used experimentally to estimate GFR?
Inulin
- polysaccharide that is filtered as the same rate as water, and not secreted nor reabsorbed by renal tubules
- normal: 7.5 L/hour, 125 mL/min
- tends to overestimate true GFR
- not used in clinical settings becuase requires infusion at a continuous and constant rate for several hours
What is most often used to estimate GFR in a clinical setting, and why?
Creatinine
- metabolic end-product of skeletal muscle, released into blood at relatively constant rate (when renal fxn, protein intake, muscle mass are stable)
- endogenous, no need for intravenous infusion
- freely filtered, not metabolized
- BUT small amount of creatinine is secreted by renal tubules into glomerular filtrate, therefore tends to overestimate GFR
What are some limitations of using creatinine to assess renal fxn?
- cannot detect mild to moderate reduction in GFR (needs to decrease by ~40-50% before plasma creatinine is raised above normal limits)
- age, gender, ethic-related differences in muscle mass
- within-subject variation up to 4.3%, between-subject variation up to 13%
- rise of >=20% should warrant investigation, regardless of whether or not it is within reference interval
- renal tubular and GI mucosal secretion become increasingly significant as blood levels rise
- subject to analytical interference (eg very high level of bilirubin -> surprisingly low creatinine; very high level of acetoacetate -> surprisingly high creatinine)
What is urea?
What factors affect to amount of urea excreted?
How is it filtered?
What does it clearance depend on?
- urea is a waste product of amino acid production, synthesized by the liver from ammonia and CO2
- excretory load dependent on amino acid, protein intake, net body protein metabolism (increased catabolism eg Cushing syndrome/severe burns -> accelerated protein breakdown)
- filtered freely by glomeruli, readily passively diffuses back into circulation through renal tubular membrane (therefore clearance depends on urine flow rate)
–> in low GFR states, better to average creatinine and urea clearances (CrCl overestimates, UrCl underestimates)
Why is plasma urea level a poor indicator of GFR?
- low production (due to low protein intake) can lower the [blood urea] sufficiently to enable normal levels to <-> significant renal in sufficiency
- GFR has to drop ~40% before [blood urea] rises above normal upper limit
- high production (due to high protein intake) in the face of minor renal impairment can <-> disproportionately high [blood urea]
What are non-GFR conditions that affect plastma urea levels?
High:
- high protein diet
- GI bleeding (becuase blood = proteins)
- tissue trauma
- glucocorticoids
- tetracycline/some drugs
Low:
- liver disease
- malnutrition
What is the conventional renal function test? What are the limitations?
- profile includes creatinine, urea, Na+, K+, Cl-, HCO3- concentrations in blood
- convenient but rather insensitive, needs significance GFR reduction to see changes
*- subject to various non-renal fxn factors affecting their blood levels - many clinical labs nowadays report MDRD-eGFR along with creatinine values
How is creatinine clearance measured?
UcfV / Pcf
V = volume of urine produced over a fixed period (usually 24 hours)
Usually expressed in mL/min
What are the pros and cons of using creatinine clearance to estimate GFR?
Pros:
- more reliable than formula-predicted GFR in some circumstance
Cons:
- 24-hour urine collection is inconvenient and error-prone
- measurement uncertainty is up to 30%
What is the Cockroft & Gault formula used for?
What are the parameters involved?
What makes the formula more accurate?
Used to estimate creatinine clearance.
Parameters:
- age
- body weight (kg - ideal BW commonly recommended in place of actual BW for overweight/obese patients)
- plasma creatinine concentration (umol/L)
More accurate correlation with measure values of GFR if:
- [plasma creatinine] not within normal range
- renal impairment not severe and relatively stable (overestimate GFR in advanced renal failure)
- no inhibition of tubular secretion of creatinine by medications
What are the limitations of the Cockroft & Gault formula?
- developed from only 249 patients, most of whom were hospitalized men, only 9 female subjects
- positive bias is observed due to renal tubular secretion of creatinine
*- information on patient’s weight is not availble for most clinical labs
What is the MDRD formula used for?
What are the parameters involved?
Used to estimate GFR
Parameters:
- PCR (plasma creatinine)
- age
- sex
- +/- a factor for African Americans
What are the pros and cons of the MDRD formula?
Pros:
*- validated against a reference method for GFR based on renal clearance of 125I-iothalamate
- estimates GFR and not creatinine
- predicts GFR over a wide range of values adjusted for body size (standardized to 1.73m2)
- more accurate than other equations tested, especially at GFR < 60 mL/min/1.73m2
Cons:
*- underestimates eGFR in subjects with GFR > 60 mL/min/1.73m2
- extensively evaluated in Caucasians/African Americans with varying degrees of renal insufficiency, but not those with normal renal fxns
- not validated in <18 and >70yos, pregnant women
- further validation needed for Chinese
What are some other equations for GFR estimations?
- CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
> as accurate as MDRD in eGFR<60; less bias at eGFR>60
> will probably emerge as equation of choice for eGFR - Schwartz formula
> eGFR in children
> parameters: muscle mass, height, serum creatinine
