T2 L7 Measurement of renal function Flashcards
What are the 2 reasons to measure renal function?
1) Identify a renal impairment in a patient
2) Modification of dosages of drugs which are cleared by the kidneys
What patients are at risk of developing renal failure?
Extremes of age: neonates & elderly Polypharmacy Specific disease states Patients receiving long-term analgesia Transplant patients Drug therapy Patients undergoing imaging procedures
What specific disease states increase the risk of developing renal failure?
Hypertension Diabetes Chronic heart failure Rheumatoid arthritis Renal disease Recurrent urinary tract infections
Why are transplant patients at increased risk of developing renal failure?
They are given anti-rejection drugs which can affect the liver & kidney function
Why are patients undergoing imaging procedures at increased risk of renal failure?
The radiocontrast agents can be nephrotoxic
What methods are used to monitor a patient’s renal function?
Patients clinical condition - clinical assessment & use of bedside clinical data
Modern imaging techniques
Biochemical data
What signs are symptoms are shown if fluid balance is affected?
Oedema
Breathlessness
What signs are symptoms are shown if electrolyte regulation is affected?
Abnormal ECG - absent P waves, broad QRS complex, peaked T waves
What signs are symptoms are shown if EPO production is affected?
Pallor
Fatigue
What signs are symptoms are shown if vitamin D3 is affected?
Osteomalacia
Bone pain
What signs are symptoms are shown if excretion is affected?
Raised blood urea & creatinine concentrations
Pruritis
What signs are symptoms are shown if acid-base balance is affected?
Low blood pH & bicarbonate levels
Deep & rapid respiration
What bedside clinical data can be used to assess a patient’s renal function?
Weight charts
Fluid balance charts
Degree of oedema
Results of urine dipstick testing - urinalysis for protein, blood, glucose
What are some types of renography?
Gamma camera plana scintigraphy
Positron emission tomography (PET)
Single photon emission computerised tomography (SPECT)
What is biochemical data useful for?
Identifying renal impairment
Evaluation of the ability of the kidneys to handle water & solutes
Modifying dosages of drugs which are cleared by the kidneys
What would an ideal marker of kidney function be?
Naturally occurring molecule
Not metabolised
Only excreted by the kidney
Filtered by not secreted or reabsorbed by the kidney
Why are plasma or serum creatinine late markers?
The kidneys have to lose 50% or more of their function for these to show up
What is plasma creatinine?
Breakdown product of creatine phosphate in the muscle
Generally produced at a constant rate
Filtered at glomerulus with some secretion into proximal tubule
What is the normal range of plasma creatinine in the plasma?
40-1200umol/L
What can increase plasma creatinine?
Large muscle mass
Dietary intake
Drugs which interfere with analysis such as methyldopa, dexamethasone, cephalosporins
Drugs which inhibit tubular secretion - cimetidine, trimethoprim, aspirin
Ketoacidosis - affects analysis
Ethnicity - higher creatine kinase activity in black population
What can decrease plasma creatinine?
Reduced muscle mass such as elderly Cachexia / starvation Immobility Pregnancy Severe liver disease - liver is a source of creatinine.
What is plasma urea?
Indicator of renal function & failure
Liver produces urea in the urea cycle as a waste product of protein digested
Filtered at glomerulus, secreted & absorbed in tubule
What is the normal range of serum urea?
2.5-7.5mmol/L
>20mmol/L indicates moderate to severe renal failure
What can increase blood urea nitrogen?
High protein diet Hypercatabolic conditions - severe infections, burns, hyperthyroidism Gastrointestinal bleeding Muscle injury Drugs Hypovolaemia
What can decrease blood urea nitrogen?
Malnutrition
Liver disease
Sickle cell anaemia due to increased GFR
SIADH
What does it mean if a substance is filtered at the glomerulus but not reabsorbed?
Excretion rate = rate it was filtered
Freely filtered but not reabsorbed or secreted
What does it mean if a substance is filtered and some of the filtered portion is reabsorbed?
Excretion rate = filtration rate - reabsorbed
Typical of electrolytes
Freely filtered & partly or mostly reabsorbed
What does it mean if a substance is filtered & completely reabsorbed?
No excretion
Glucose and amino acids
Freely filtered & fully absorbed
What does it mean if a substance is primarily secreted into the tubule?
Substance is rapidly & effectively cleared such as PAH
Freely filtered, not reabsorbed, full secreted
What is clearance?
Volume of plasma completely cleared of a given substance in unit time
Virtual volume of blood that would be totally cleared of a solute in a given time
Solute comes from blood perfusing kidneys
What 3 functions does renal clearance provide information about?
Glomerular filtration
Tubular reabsorption
Tubular secretion
Rate at which kidneys excrete solute into urine = rate at which solute disappears from blood plasma
What are the drawbacks of measuring renal clearance?
It is a measurement of overall nephron function
Gives the sum of all transport processes occurring along nephrons
No information about precise tubular sites of mechanisms of transport
What is the glomerular filtration rate?
Rate at which filtrate is produced by the kidneys
Can be estimated by measurement of clearance of creatinine.
More accurate estimation provided by measurement of inulin clearance which is filtered but not secreted into tubule.
What is inulin?
Plant polysaccharide
Why is inulin clearance used for measurement of GFR?
It is freely filtered so plasma & tubular concentrations are the same
It is not secreted or reabsorbed
Rate of excretion in urine = rate of filtration by kidneys
What does it mean if a substance has a clearance greater than inulin?
It must also be being secreted
What does it mean if a substance has a clearance less than inulin?
It is being reabsorbed or not filtered freely at the glomerulus
What are the drawbacks of using inulin to measuring GFR?
Inulin must be administer by IV to get relatively constant plasma or serum levels
Chemical analysis of inulin in serum & urine is technically demanding
Could use radiolabelled compounds instead - these may bind to proteins & distort results
How are problems of IV infusion of GFR marker avoided?
By using an endogenous substance with inulin like properties such as creatinine
Describe the results from measuring creatinine clearance
Filtered at glomerulus & secreted into proximal tubule
Using equation gives over-estimate of GFR by 20%
Colorimetry methods used to measure creatinine under-estimate clearance by 20% so the euros cancel each other out
What are the benefits of using creatinine clearance?
Cheap
Easy
Reliable
Avoids IV infusion - only needs venous blood & urine samples
When should you measure creatinine clearance?
Before breakfast
How do you adjust the creatinine clearance to account for body surface area?
Corrected creatinine clearance = (measured CrCl x 1.73) / BSA (body surface area in m2)
What are the 2 formulas used to estimate GFR using serum creatinine?
Cockcroft-gault formula
MDRD (modification of diet in renal disease) formula
What are the estimated GFR ranges?
Males: 97-137ml/min
Females: 88-128ml/min
Why is the clearance of PAH used to estimate RPF?
It is not normally present in the blood
When PAH is given almost all is cleared from the kidney in one passage
What happens to the PAH that by-passes the tubule?
It travels from the efferent arteriole –> peritubular capillaries –> venous renal blood –> not secreted
What are biomarkers of renal disease?
Indicators of renal function such as serum creatinine or BUN only increase after a significant loss of renal function
Urinary albumin/protein excretion can be used as an indicator of chronic kidney disease
What proteins are released into the urine that are used for biomarkers?
Kidney injury molecule Interleukin Fatty-acid binding proteins Neutrophil gelatinise-associated lipocalin Cystatin C
