T3 L8: Measurement of renal fuction

• Why do we measure renal function?

  1. Identification of renal impairment in patient
  2. Modification of dosages of drugs which are cleared by kidneys
• What are the risk factors of developing renal failure?

  1. Extremes of age
  2. Polypharmacy (many drugs: risk of adverse interactions)
  3. Specific disease states (eg hypertension, diabetes, CHF, RA, renal disease, recurrent UTIs)
  4. Patients receiving long-term analgesia
  5. Transplant patients
  6. Drug therapy
  7. Patients undergoing imaging procedures (radiocontrast agents can be nephrotoxic)
• How is a patient's renal function monitored?

  1. Patient's clinical condition
  2. Clinical assessment
  3. use of bedside clinical data
  4. Modern imaging techniques
  5. macroscopic views of renal blood flow, filtration and excretory function
  6. Biochemical data
  7. measurement of 'renal clearance' of various substances
  8. allows evaluation of ability of kidneys to handle water and solutes
• How does clinical assessment help monitor a patient's renal function?

  Just looking at the patient, and listening to what they tell you

  about their symptoms, can often give clues about their renal function

  
• How can the use of bedside clinical data help monitor a patient's renal function?

  1. Weight charts
  2. Fluid balance charts
  3. Degree of oedema
  4. Results of urine dipstick testing (urinalysis for protein, blood, glucose)

  
• How can modern imaging techniques help monitor a patient's renal function?

  Include macroscopic views of renal blood flow, filtration and excretory function

  eg Renography

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

  
• How can biochemical data help monitor a patient's renal function?

  useful for: identifying renal impairment

  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 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 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
  • Normal range in plasma: 40-120 mmol/L

  
• How is plasma creatinine an indicator of renal function and failure?

  higher plasma creatinine indicates reduced kidney function

  
• 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
  • Plasma urea also described as BUN – Blood urea nitrogen:
  • 2.5-7.5 mmol/L indicates moderate to severe renal failure
  • Normal range: >20 mmol/L

  
• What is the normal range of plasma urea?

  2.5-7.5 mmol/L
• What is plasma urea 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 plasma urea decreased by?

  • Malnutrition
  • Liver disease
  • Sickle cell anaemia (due to ­ GFR)
  • SIADH (syndrome of inappropriate ADH)
• What would be an ideal marker of renal function to measure 'renal clearance'?

  • A naturally occurring molecule
  • Not metabolised
  • Only excreted by the kidney
  • Filtered but not secreted or reabsorbed by the kidney
• What are some examples of renal clearance?

  A: some filtered by the glomerulus and NOT reabsorbed

  B: some filtered and some reabsorbed

  C: some filtered and completely reabsorbed

  D: some primarily secreted into tubule

  
• What is substance A?

  freely filtered but not reabsorbed or secreted

  Excretion rate = rate it was filtered. e.g. INULIN

  
• What is substance B?

  freely filtered and partly or mostly reabsorbed

  Excretion rate = filtration rate – reabsorbed

  Typical of electrolytes, e.g. Na+

  
• What is substance C?

  freely filtered but fully reabsorbed

  No excretion (normally). e.g. glucose and amino acids

  
• What is substance D?

  freely filtered, not reabsorbed, fully secreted

  Substance therefore rapidly and effectively cleared. e.g. PAH (para-aminohippuric acid)

  
• What is renal clearance?

  Clearance = the volume of plasma completely cleared of a given substance in unit time

  • Compares GFR with excretion rate
  • difference in amount filtered and excreted
  • allows estimation of net amount reabsorbed / secreted by renal tubules
• What 3 basic functions of the kidney does renal clearance provide information about?

  Glomerular filtration (F)

  Tubular reabsorption (R)

  Tubular secretion (S)
• What is the equation for renal clearance?

  Clearance= (conc in urine x volume of urine) / conc in blood

  
• What are the drawbacks of calculating renal clearance?

  gives info about OVERALL nephron function (sum of all transport processes)

  no information about precise tubular sites / mechanisms
• How can GFR be measured?

  creatinine

  • but is filtered and secreted into tubule

  more accurate: INULIN

  • filtered but not secreted into tubule
• What is normal GFR?

  125 mL/min
• How does inulin clearance measure GFR?

  rate of excretion in urine = rate of filtration by kidneys

  as freely filtered but not secreted/reabsorbed

  • e.g. when inulin concentration is 1 mg/mL in plasma and 125 mg/mL in urine and urine flow rate is 1 mL/min…then GFR = 125 mL/min
• What does it mean if a substance has greater / less clearance than inulin?

  greater: it must also be secreted

  less: must be being reabsorbed / not filtered freely at glomerulus
• What are the drawbacks of using inulin clearance to measure GFR?

  most reliable method of measuring GFR, but not useful clinically:

  • must be administered by IV
  • chemical analysis is technically demanding
  • could use radiolabelled compounds instead, eg Vit B or EDTA
  • however these may also bind tot proteins and distort results
  • problems of IV infusion

  these problems are avoided by using an endogenous substance with inulin-like propertites: CREATININE
• What are the calculations involved in measuring creatinine clearance?

  • Creatinine clearance equation = gives +20%
  • Colorimetry = gives -20%

  so cancel each other out
• What are the advantages of using creatinine clearance to measure GFR?

  • Cheap, easy, reliable, used clinically
  • Avoids IV infusion, just requires venous blood and urine samples
  • Creatinine usually produced by creatinine phosphate metabolism in muscle (naturally occuring)
  • 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

  
• How can creatinine clearance be adjusted to take account of body surface area?

  Produces a Corrected CrCl (GFR) in “mL/min/1.73m2”

  
• What 2 formulae allow estimation of GFR without having to collect urine samples?

  Cockcroft-Gault equation, Modification of Diet in Renal Disease (MDRD) equation

  
• What is PAH clearance used to measure?

  renal blood flow

  completely cleared from plasma, so:

  clearance rate = renal plasma flow (RPF)

  PAH not normally present in blood

  
• What are biomarkers of renal disease?

  blood and urinary markers which increase in early stages of renal failure and can be measured

  as indicators of renal function (eg plasma creatinine, BUN) increase only after there is a significant loss of renal function

  These are mostly proteins released into the plasma and/or urine