Renal Clearance Flashcards
What is GFR?
→ How much filtrate is removed from the blood each minute
What is the first step in urine formation?
→ Begins with glomerular filtration
What is the composition of glomerular filtrate like?
→ same as plasma
→ no cells
→ protein-free
What is proteinuria a sign of?
→ renal/ urinary tract disease
What is the primary force favoring filtration?
→ Glomerular capillary pressure = 60mmHg
What is the force opposing filtration?
→ Hydrostatic pressure in Bowman’s space = 15mmHg
→ Osmotic force of plasma proteins = 29mmHg
What is the urinary excretion rate?
→ GFR - reabsorption rate + secretion rate
What does GFR contribute to?
→ rapid removal of waste product
How much is the GFR per day?
→ 180L per day
How much is the body plasma volume?
→ 3L
What 2 factors is GFR determined by?
→ hydrostatic and oncotic pressures across capillary membranes
→ permeability of capillary filtration barrier & surface area available
How is GFR measured?
→ not directly but by the measurement of the excretion of a marker
→ a substance that is freely filtered but neither reabsorbed or secreted e.g creatinine
What is inulin?
→ inert polysaccharide
→ filters freely through the glomerular membrane
When does plasma inulin concentration become stable?
→ When inulin fusion rate = inulin excretion rate
What is the GFR equation for the inulin method?
→ GFR = Uin x V / Pin
→ V = urine vol/collection time
→ Pin = plasma inulin concentration
→ Uin = urine inulin concentration
What is the definition of renal clearance?
→ The volume of plasma that is completely cleared of the substance by the kidney per unit time (excreted in urine each minute)
What is the clearance of inulin?
→ same as the GFR
→Since clearance is defined as the volume of plasma ‘cleared’ of a substance in 1 min, the clearance for I is 125 ml/min. This means that of the 625 ml of plasma that come to the kidney in one minute, 125 ml (the fraction that is filtered) has all of the I removed from it in that minute, the other 500 ml (the fraction that is not filtered) keeps its I as there is no way for the I get into the urine as it is not secreted.
What are the drawbacks of the inulin method?
→prolonged infusion
→ repeated plasma samples
→ difficult routine clinical use
What is used clinically to measure GFR?
→ creatinine
What are the advantages of using creatinine ?
→intrinsic inert substance → released at a steady level in plasma from skeletal muscle → no infusion needed → freely filtered → not reabsorbed
What are the disadvantages of creatinine?
→ some is secreted into the tubule
What is trimethoprim?
→ competitive inhibitor of creatinine
→ given during kidney infections etc
→cause an artificial increase in serum creatinine
How is creatine made?
→ Taken in the diet
→ found in the liver
What is creatine metabolized by?
→ metabolized to phosphocreatine by the muscle
What can creatine and phosphocreatine be metabolized into?
→ creatinine
→ non enzymatic reaction
What does the transporter that transports creatinine also transport?
→trimethoprim
→ higher affinity for trimethoprim
If plasma creatinine goes up what happens to the GFR?
→ GFR decreases
Why are there differences in GFR?
→ age
→ gender
→ muscle mass
What is eGFR?
→ estimated GFR
→ not valid in pregnant women or children, poor inpatients older than 70yrs
What factors are taken into account in eGFR?
→ age
→ gender
→ ethnicity
Why is eGFR a better method?
→ much simpler
→ requires one blood test
→ It is being used increasingly to spot kidney disease earlier than would be possible using just creatinine measurements
What are the 2 equations used in eGFR?
→ MDRD
→ CDK - EPI
→ CKD-EPI is more accurate than MDRD, less biased at GFR ≥60ml/min/1.73m2
What are the disadvantages of GFR?
→ it is an estimate
→ Inaccurate for people of extremes of body type
→ not valid in pregnant women, over 70 or children
→ Racial groups might not fit the MDRD equation
What does it mean if a substance has the same clearance as inulin?
→ freely filtered
→ not reabsorbed or secreted
→ ~ 125ml/min in adult male and 10% less in females
e.g. antibiotics (streptomycin/gentomycin)
What does it mean if a substance has a clearance less than inulin, GFR?
→ not filtered at the top
→ or freely filtered but reabsorbed from tubule
What is an example of a substance that is not freely filtered?
→ albumin
What is an example of a substance that is reabsorbed completely?
→ glucose
→Glucose like inulin is freely filtered, so is then present in Bowman’s capsule,
→ no glucose is in urine hence it is completely reabsorbed from tubule and goes back into plasma. →Hence clearance is 0ml/min because as the plasma leaves the kidney (not nephron) it has NO glucose removed.
How is glucose handling by the kidney investigated?
→ infuse glucose and inulin together
→ calculate GFR using inulin
→ calculate the glucose filtration rate (GFR x plasma glucose concentration)
What is the equation for calculating glucose filtration?
→ GFR x Plasma glucose
What is the equation for calculating glucose excretion?
→ Uglucose (urine glucose concentration) x V (urine flow rate)
What is the equation for calculating glucose reabsorption?
→ [(GFR x Pglucose) - ( U glucose x V)]
What is the renal threshold of glucose?
→ 15 mM
What happens after the plasma glucose level > renal threshold?
→ glucose appears in the urine
→ glucose is excreted
What happens to the glucose < 20mM?
→ All the glucose that filters through is reabsorbed by the Na+/glucose co-transporter
What happens to the glucose after > 20mM?
→ All the transporters are saturated
→ Glucose reabsorption plateaus
→ Glycosuria
Why does glucose start appearing in the urine before 20mM?
→ Humans have 2 million nephrons
→ Each nephron has a slightly different transport maximum
→ Some nephrons will start excreting glucose earlier than others
Why does the clearance rate of glucose never reach the rate of inulin?
→ the transporters are still working unless they are completely blocked
What is a substance that is actively reabsorbed?
→ Amino acids
→ Ca2+, Na+, PO4 2-, Mg 2+
→ Water soluble vitamins
What do actively reabsorbed substances all have?
→ a TM
What are passively reabsorbed substances?
→ Cl-
→urea
→important drugs
What are endogenous substances that are secreted?
→ Weak organic acids & bases
→ Adrenaline
→ Dopamine
→ Steroids
What are exogenous substances that are secreted?
→Penicillin
→Probenecid
→ PAH (para amino hippuric acid)
Why does the concentration of penicillin fall rapidly when injected and how is this counteracted?
→ Renal tubular cells actively secrete it into the urine
→ Given with probenecid which competes for the same transport mechanism
What is RPF?
→ Rate at which plasma flows through the kidney- renal plasma flow
→Estimating the RPF through the kidneys allows us to estimate the rate of total blood flow (RBF) through the kidneys
What is the composition of the blood?
→ 55% plasma
→ 45 % cellular components
What is PAH?
→ Weak acid metabolite found in horse’s urine
What happens to PAH once it enters the glomerulus?
→ Filtered freely + enters the filtrate → Large amount is still in plasma →majority is secreted back into PCT →Excreted as urine →So renal clearance rate is higher than GFR- nice tool to measure renal plasma flow
How is PAH secreted?
→ Active transport occurs in the basolateral membrane
→ Passive transport across the luminal membrane into the tubule
What happens if PAH is below the Tm?
→ It is cleared in a single pass
What is the equation for renal plasma flow?
→ (U PAH x V) / Plasma PAH
What is the relationship between plasma creatine concentration and clearance rate?
Inverse relationship between plasma conc of creatinine and the clearance rate
High creatinine in plasma is low percentage of GFR
A very small increase in plasma creatinine could be cause of a big reduction in kidney function
plot 1/[Cr] to get a linear relationship
What is the CKD stages?
→ 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
What does it mean for a substance with clearance > inulin?
Secreted into tubule
→ Substance with greater clearance than inulin is being added to the fluid as it flows along tubule
Why do substances that are passively reabsorbed not display Tm?
because their rate of transport is determined by other factors e.g. electrochemical gradient, permeability etc.
What is the difference between lipophilic and hydrophilic drugs?
lipophilic drugs tend to return to blood stream whilst hydrophilic drugs lost in urine.
