Measurement of kidney function Flashcards
Why measure renal function?
1: Identification of renal impairment in your patient
2: Modification of dosages of drugs which are cleared by the kidneys
Which patients are at risk of developing renal failure?
- Extremes of age - Neonates and the elderly (GFR matures at 4 years. Decreases 0.4-1.2 mL/min per year after 40 years)
- Polypharmacy
Regimens involving many drugs – risk of adverse interactions
- Specific disease states - Hypertension, diabetes, chronic heart failure, rheumatoid arthritis, renal disease, recurrent urinary tract infections
- Patients receiving long-term analgesia - NSAIDS have a reputation for being nephrotoxic
- Transplant patients - Rejection of transplanted kidney, anti-rejection drugs
- Drug Therapy - Nephrotoxic drugs (e.g. antibiotics, anti-HIV drugs, etc)
- Patients undergoing imaging procedures - Radiocontrast agents can be nephrotoxic
What 3 ways are there of monitoring a patients renal function?
Patient’s clinical condition
a: Clinical assessment
b: Use of bedside clinical data
2: Modern imaging techniques - Macroscopic views of renal blood flow, filtration and excretory function
3: Biochemical data
- Measurement of “renal clearance” of various substances
- Allows evaluation of the ability of the kidneys to
handle water and solutes
Clinical assessment of a patient with renal failure
What do renal modern imaging techniques show?
Include macroscopic views of renal blood flow, filtration and excretory function
What does renography include?
· Gamma camera planar scintigraphy
· Positron emission tomography (PET)
· Single photon emission
computerised tomography (SPECT)
How is biochemical data useful for indentifying renal impairement?
Blood (plasma or serum) markers of renal function:
- Plasma or serum creatinine (sCr)
- Plasma or serum urea or blood urea nitrogen (BUN)
Note: plasma = serum + clotting proteins (e.g. fibrinogen)
What is creatinine?
Breakdown product of creatine phosphate in muscle
· Generally produced at a constant rate
· Filtered at the glomerulus with some secretion into the proximal tubule
What is the normal creatinine range in plasma?
· Normal range in plasma:
40-120 mmol/L
What is plasma creatinine increased by?
- Large muscle mass, dietary intake
- Drugs which interfere with analysis (Jaffe reaction)
e.g. methyldopa, dexamethasone, cephalosporins
• Drugs which inhibit tubular secretion
e.g. cimetidine, trimethoprim, aspirin
- Ketoacidosis (affects analysis)
- Ethnicity (higher creatine kinase activity in black population)
What is plasma creatinine decreased by?
- Reduced muscle mass (e.g. the elderly)
- Cachexia / starvation
- Immobility
- Pregnancy (due to increased plasma volume in the mother)
- Severe liver disease (as liver is also a source of creatinine)
What is urea?
·Liver produces urea in the urea cycle as a waste product of protein digestion
·Filtered at the glomerulus, secreted and reabsorbed in the tubule
What is plasma urea described as?
Plasma urea described as:
BUN – Blood urea nitrogen
Normal range: 2.5-7.5 mmol/L
>20 mmol/L indicates moderate to severe renal failure
What is BUN increased by?
High protein diet
Hypercatabolic conditions
e.g. severe infection, burns, hyperthyroidism
Gastrointestinal bleeding
(digested blood is a source of urea)
Muscle injury
Drugs e.g. Glucocorticoids, Tetracycline
Hypovolaemia
What is BUN decreased by?
Malnutrition
Liver disease
Sickle cell anaemia (due to GFR)
SIADH (syndrome of inappropriate ADH)
How is renal impairement identified?
- Evaluation of the ability of the kidneys to handle water and solutes
- Modifying dosages of drugs which are cleared by the kidneys
What are the qualities of an ideal marker of kidney function?
Some methods involve measurement of “renal clearance” of various substances
An ideal marker of kidney function would be:
- A naturally occurring molecule
- Not metabolised
- Only excreted by the kidney
- Filtered but not secreted or reabsorbed by
the kidney
What are the renal clearence methods shown
Some are filtered by the glomerulus and are NOT reabsorbed (Substance A)
Some are filtered and some of the filtered portion is reabsorbed (B)
Some are filtered and completely reabsorbed (C)
Some are primarily secreted into the tubule (D)
Name an example of a molecule that is filtered in each method shown
Substance A - freely filtered but not reabsorbed or secreted
· Excretion rate = rate it was filtered. e.g. INULIN
Substance B - freely filtered and partly or mostly reabsorbed
· Excretion rate = filtration rate – reabsorbed. Typical of electrolytes e.g. Na+
Substance C - freely filtered but fully reabsorbed
· No excretion (normally). e.g. glucose and amino acids
Substance D - freely filtered, not reabsorbed, fully secreted
· Substance therefore rapidly and effectively cleared. e.g. PAH
What is clearence?
•Clearance = the volume of plasma completely cleared of a given substance in unit time
What is renal clearance?
- Compares rate at which glomeruli filter a substance with the rate at which the kidneys excrete it via the urine
- Measurement of difference in amount filtered and excreted allows estimation of the net amount reabsorbed or secreted by the renal tubules
What does renal clearance provide information on?
•Provides information about the 3 basic functions of the kidney:
- Glomerular filtration (F)
- Tubular reabsorption (R)
- Tubular secretion (S)
How is renal clearance calculated?
- The “clearance” of a solute is the virtual volume of blood that would be totally cleared of a solute in a given time (so measured in ml/min)
- Solutes come from blood perfusing kidneys
- Rate at which kidneys excrete solute into urine = rate at which solute disappears from blood plasma
What is the equation for renal clearance?
What are the drawbacks of measuring renal clearance?
- Measuring clearance means measurement of OVERALL nephron function i.e. all ~2 million nephrons in both kidneys
- This gives the SUM of ALL transport processes occurring along nephrons…
- …but no information about precise tubular sites or mechanisms of transport
What is GFR?
This is the rate at which filtrate is produced in the kidneys
= 125 mL/min
(º 180 L/day)
How can GFR be estimated?
GFR can be estimated by measurement of the clearance of CREATININE
i.e. CREATININE CLEARANCE
BUT creatinine is filtered AND secreted into tubule
A more accurate estimation is provided by measurement of INULIN clearance – it is filtered but NOT secreted into tubule
What is inulin?
•INULIN is a plant polysaccharide Mw 5200Da
How can inulin be used to estimate renal clearance?
•It is freely filtered - i.e. plasma and tubular concentration is same…
…but it is NOT secreted and is NOT reabsorbed
- Therefore rate of excretion in urine equals the rate of filtration by the kidneys
- So Inulin clearance = GFR
What does it mean if a substance has a clearance greater/less than inulin?
•If a substance has clearance greater than inulin, then it must also be being secreted;
…….less means that it must be being reabsorbed or not filtered freely at the glomerulus
What are the drawbacks of inulin?
•Most reliable method of measuring GFR, but not useful clinically
WHY?
- Inulin must be administered by IV to get relatively constant plasma or serum levels
- Chemical analysis of inulin is technically demanding
- Could use radiolabelled compounds instead, e.g. radioactive Vit B or EDTA
- However, these may also bind to proteins and distort results
What substance is more useful clinically than inulin?
•Problems of IV infusion of GFR marker are avoided by using an endogenous substance with inulin-like properties –
i.e. CREATININE
How does creatinine clearance = inulin clearance?
- Creatinine is filtered at the glomerulus…
- …but some of it is also secreted into the proximal tubule
- Therefore using the equation above would actually
over-estimate GFR by about 20% in humans
i.e. it would produce a GFR value of about 150 mL/min
- However, the colorimetry methods used to measure creatinine (e.g. the Jaffe method) under-estimates creatinine concentrations by about 20 %
- Luckily, these 2 errors cancel each other out, and calculated creatinine clearance ≈ inulin clearance (i.e. 125 mL/min)
What are the positives of creatinine clearance as eGFR?
- Cheap, easy, reliable, used clinically
- Avoids IV infusion, just requires venous blood and urine samples
- Creatinine usually produced by creatinine phosphate metabolism in muscle
- Must remember to take into account if person has muscle disease/damage or has had large quantities of meat to eat
- Usually measure over a 24 hr period to get reliable results and take samples before breakfast
Creatinine Clearance can also be adjusted to take account of __________
Creatinine Clearance can also be adjusted to take account of body surface area
How can you Estimate GFR using Plasma Creatinine only?
How can PAH clearance be used to measure renal blood flow?
- PAH not normally present in blood
- When given, almost all (~90%) cleared from kidney in one passage…
…some is filtered in glomerulus and remainder secreted by proximal tubules
~10% by-passes tubule - travels from efferent arterioles into peritubular capillaries and then venous renal blood, and is not secreted
•Uncorrected value for PAH clearance often used
– known as “effective renal plasma flow”
(ERPF)
•If a substance is completely cleared from the plasma, its clearance rate will be equal to the __________
•If a substance is completely cleared from the plasma, its clearance rate will be equal to the renal plasma flow (RPF)
Why are biomarkers of renal disease important?
·Indicators of renal function such as plasma creatinine or BUN increase only after there is significant loss of renal function: typically a 60% loss in renal function before plasma creatinine or BUN increases
·Urinary albumin/protein excretion can also be used as an indicator of chronic kidney disease
· Currently a lot of research (and commercial) interest in identifying blood and urinary markers which increase in the early stages of renal failure and can be measured
Name the biomarkers of kidney disease
·These are mostly proteins released into the plasma and/or urine:
- Kidney injury molecule – 1 (KIM-1) (urine)
- Interleukin (IL)-18 (urine)
- Fatty-acid binding proteins (FABPs) (urine)
- Neutrophil gelatinase-associated lipocalin (NGAL) (plasma & urine)
- Cystatin C (plasma)
