measurement of kidney function

Question 1

why do we measure renal function? 2

Answer 1

• Identification of renal impairment in your patient

- Modification of dosages of drugs which are cleared by the kidneys

Question 2

what patients are at risk of developing renal failure? 7

Answer 2

• Extremes of age
• Polypharmacy (regimens involving many drugs- risk of adverse reactions)
• Specific disease states (hypertension, diabetes, chronic heart failure, rheumatoid arthritis, renal disease, recurrent UTI)
• Patients receiving long-term analgesia
• Transplant patients
• Patients on drug therapy
• Patients undergoing imaging procedures

Question 3

how do we monitor a patients renal function? 3

Answer 3

• Patients clinical condition (clinical assessment, use of bedside clinical data)
• Modern imaging techniques (macroscopic views of renal blood, filtration and excretory function)
• Biochemical data (measurement of renal clearance of various substances, allows evaluation of the ability of the kidneys to handle water and solutes)

Question 4

how do we perform a clinical assessment of someone with suspected renal failure? 5

Answer 4

Look at the patient, and listen to what they tell you about their symptoms- can often give you clues about their renal function

Use of bedside data:

• Weight charts
• Fluid balance charts
• Degree of oedema
• Results of urine dipstick testing (urinalysis for protein, blood, glucose)

Question 5

what do modern imaging techniques show?

Answer 5

macroscopic views of renal blood flow, filtration and excretory function

Question 6

what is renography? 3

Answer 6

• Gamma camera planar scintigraphy
• Positron emission tomography (PET)
• Single photon emission computerised tomography (SPECT

Question 7

describe the use of biochemical data when diagnosing someone with renal failure? 7

Answer 7

• Useful for identifying renal impairment
• Evaluation of the ability of the kidneys to handle water and solutes
• Modifying dosages of drugs which are cleared by the kidneys
• Blood (plasma or serum) markers of renal function:
• Plasma or serum creatinine (sCr)
• Plasma or serum urea or blood urea nitrogen (BUN)
• Plasma= serum + clotting proteins

Question 8

what is creatinine? 4

Answer 8

• Breakdown product of creatine phosphate in muscle
• Generally produced at a constant rate
• Filtered at the glomerulus with some secretion into the proximal tubule
• Normal range in plasma= 40-120

Question 9

what can plasma creatinine be increased by? 5

decreased by? 5

Answer 9

• Increased by:
• Large muscle mass, dietary intake
• Drugs which interfere with analysis
• Drugs which inhibit tubular secretion
• Ketoacidosis
• Ethnicity (higher creatine kinase activity in black population)
• .
• Decreased by:
• Reduced muscle mass
• Cachexia/ starvation
• Immobility
• Pregnancy (due to increased plasma volume in the mother)
• Severe liver disease (as liver is also a source of creatinine)

Question 10

what is urea? 4

Answer 10

• Liver produces urea in the urea cycle as a waste product of protein digestion
• Filtered at the glomerulus, secreted and reabsorbed in the tubule
• Plasma urea described as BUN: blood urea nitrogen: normal range: 2.5-7.5
• > 20 indicates moderate to severe renal failure

Question 11

describe what can increase BUN? 7

decrease? 4

Answer 11

• Increased by:
• High protein diet
• Hypercatabolic conditions
• Gastrointestinal bleeding
• Muscle injury
• Drugs
• Tetracycline
• Hypovolaemia
• .
• Decreased by:
• Malnutrition
• Liver disease
• Sickle cells anaemia due to increased GFR
• SIADH (syndrome of inappropriate ADH)

Question 12

what would an ideal marker of kidney function be? 4

Answer 12

• A naturally occurring molecule
• Not metabolised
• Only excreted by the kidney
• Filtered but not secreted or reabsorbed by the kidney

Question 13

explain how different substances can be excreted or cleared by the kidney? 4

Answer 13

• Some are filtered by the glomerulus and are NOT reabsorbed (excretion rate= rate it was filtered (INULIN))
• Some are filtered and some of the filtered portion is reabsorbed (excretion rate= filtration rate- reabsorbed (typical of electrolytes))
• Some are filtered and completely reabsorbed (no excretion (glucose and amino acids)
• Some are secreted into the tubule (substance is therefore rapidly and effectively cleared (PAH))

Question 14

describe renal clearance? 6

Answer 14

• Clearance= the volume of plasma completely cleared of a given substance in a unit of time
• 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
• The clearance of a solute is the virtual volume of blood that would be totally cleared of a solute in a given time
• Solutes come from blood perfusing kidneys
• Rate at which kidneys excrete solute into the urine= rate at which solute disappears from blood plasma

Question 15

what can renal clearance provide information about? 3

Answer 15

• Glomerular filtration (F)
• Tubular reabsorption (R)
• Tubular secretion (S)

Question 16

describe the equation for clearance rate?

Answer 16

Cx= (Ux x V)/ Px

• Ux= concentration of x in urine
• V= volume of urine formed in given time
• Px= concentration of x in systemic blood plasma or serum
• ml/min

Question 17

what are the drawbacks of renal clearance? 2

Answer 17

• Measuring clearance means measurement of overall nephron function
• This gives the sum of all transport processes occurring along nephrons but no information about precise tubular sites or mechanisms of transport

Question 18

describe glomerular filtration rate? 4

Answer 18

• This is the rate at which filtrate is produced in the kidneys
• GFR can be measured clinically and used as an indicator of renal function
• GFR can be estimated by measurement of the clearance of CREATININE, but creatinine is filtered and secreted into the tubule
• A more accurate estimation if provided by the measurement of INULIN clearance as it is filtered but not secreted into the tubule
   

Question 19

describe inulin clearance for the measurement of GFR? 5

Answer 19

• Inulin is a plant polysaccharide
• It is freely filtered but is not secreted and is not reabsorbed
• The rate of excretion in the urine equals the rate of filtration by the kidneys
• Insulin clearance= GFR
  if a substance has clearance greater than inulin, then is must also be being secreted
• If a substance has a clearance less then inulin, then is must be being reabsorbed or not filtered freely at the glomerulus

Question 20

what are the drawbacks of inulin clearance to measure GFR? 5

Answer 20

• Most reliable method of measuring GFR but not clinically useful
• 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 but these mat bind to protein and distort results
• Problems of IV infusion of GFR markers are avoided by using an endogenous substance with inulin like properties- creatinine

Question 21

describe creatinine clearance? 4

Answer 21

• Creatinine is filtered at the glomerulus but some of it is also secreted at the proximal tubule
• Therefore using the equation would overestimate GFR by about 20% in humans
• The colorimetry methods used to measure creatinine underestimates creatinine concentrations by about 20%
• These 2 errors cancel each other out and therefore calculate creatinine clearance is around the same as inulin clearance

Question 22

why do we use creatinine clearance for GFR? 5

Answer 22

• 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 the person has muscle disease/ damage or has had large quantities of meat to eat
• Usually measured over a 24-hour period to get reliable results and take samples before breakfast

Question 23

why do we estimate GFR using plasma creatinine only?

Answer 23

• Allows estimation of GFR without having to collect urine samples

Question 24

describe how we use PAH clearance to measure renal blood flow? 6

Answer 24

• If substance is completely cleared from the plasma, its clearance rate will be equal to the renal plasma flow (RPF)
• Clearance of PAH (para-aminohippuric acid) can be used to estimate this
• PAH is not normally present in the blood
• When given, almost all is cleared from the kidney in one passage, some is filtered in the glomerulus and some secreted by proximal tubules
• 10% passes tubule and travels from efferent arterioles into peritubular capillaries and then venous renal blood and is not secreted
• Uncorrected value for PAH clearance of often used and is known as ‘effective renal plasma flow’

Question 25

describe the biomarkers of renal disease? 9

Answer 25

• Indicators of renal function such as plasma creatinine or BUN increase only after there is a significant loss of renal function (60% loss)
• Urinary albumin/protein excretion can also be used as an indicator of chronic kidney disease
• Currently a lot of research and interest in identifying blood and urinary markers which increase in the early stages of renal failure and can be measured
• These are mostly proteins released into the plasma and/or urine:
• Kidney injury molecule- 1 (urine)
• Interleukin- 18 (urine)
• Fatty-acid binding proteins (urine)
• Neutrophil gelatinase-associated lipocalin (plasma and urine)
• Cystatin C (plasma)