Measurement of renal function

Question 1

how can a patients renal function be monitored

Answer 1

1. patients clinical condition- clinical assessment and 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

Question 2

give examples of modern imaging techniques

Answer 2

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

1. renography- gamma camera planar scintigraphy
   - positron emission tomography
   - single photon emission computerised tomography

Question 3

what are blood markers of renal function

Answer 3

1. plasma or serum creatinine

2. plasma or serum urea or blood urea nitrogen

Question 4

what is creatinine and how is it filtered

Answer 4

1. breakdown product of creatinine phosphate in muscle
2. generally produced at a constant rate
3. filtered at the glomerulus but also some secretion into the proximal tubule
4. normal range in plasma= 40-120umol/L

Question 5

how is urea produced and filtered

Answer 5

1. liver produces urea in the urea cycle as a waste product of protein digestion
2. filtered at the glomerulus and also secreted and reabsorbed in the tubule
3. plasma urea normal range= 2.5-7.5mmol/L

Question 6

give examples of different substances that can be excreted by renal clearance

Answer 6

1. some are filtered by the glomerulus and not reabsorbed
   - excretion rate= rate it was filtered (eg. insulin)
2. some are filtered and some of the filtered portion is reabsorbed
   - excretion rate= filtration rate - reabsorbed (typically electrolytes, eg. na+)
3. some are filtered and completely reabsorbed
   - no excretion (eg. glucose and amino acids)
4. some are primarily secreted into the tubule
   - substance therefore rapidly and effectively cleared (eg. PAH)

Question 7

define clearance

Answer 7

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

• compares rate at which glomeruli filter a substance with the rate at which the kidneys excrete it into the urine
• measurement of difference in amount filtered and excreted allows estimation of the net amount reabsorbed or secreted by the renal tubules

Question 8

what information does renal clearance provide

Answer 8

provides information about the 3 basic functions of the kidney

• glomerular filtration
• tubular reabsorption
• tubular secretion

Question 9

explain how renal clearance is measured

Answer 9

1. solutes come from blood perfusing kidneys
2. rate at which kidneys excrete solute into urine= rate at which solute disappears from blood plasma
3. for solute X:
   Cx= Ux x V/ Px
   - Cx= clearance of X
   - Ux= conc of X in urine
   - V= volume of urine formed in given time
   - Px= conc of x in systemic blood plasma

Question 10

what are the limitations of measuring renal clearance

Answer 10

1. measuring clearance means measurement of overall nephron function
   - this gives the sum of all transport processes occurring along the nephrons
   - but gives no information about precise tubular sites or mechanisms of transport

Question 11

how can GFR be accurately estimated

Answer 11

using insulin clearance

Question 12

describe how insulin clearance is used to measure GFR

Answer 12

1. insulin is freely filtered but it is not secreted and not reabsorbed
   - therefore rate of excretion in urine= rate of filtration by kidneys
   - so insulin clearance=GFR
2. if a substance has clearance greater than insulin, then it must also be being secreted
3. less means that it must be being reabsorbed or not filtered freely at the glomerulus

Question 13

what are the limitations of insulin clearance

Answer 13

1. insulin must be administered by IV to get relatively constant plasma levels
2. chemical analysis of insulin in plasma and urine is technically demanding
3. could use radio labelled compounds instead
   - however these may also bind to proteins and distort results
4. problems of IV infusion of GFR marker are avoided by using an endogenous substance with insulin like properties (creatinine)

Question 14

explain how creatinine clearance is calculated and how it is used

Answer 14

C(cr)= U(cr) x V/ P(cr)

1. creatinine is filtered at glomerulus but some of it is also secreted into pt
   - therefore using equation would overestimate GFR by about 20%
   - however the colorimetry methods used to measure creatinine (Jaffe method) underestimates the creatinine concs by about 20%
   - so they cancel each other out

Question 15

give advantages of using creatinine clearance

Answer 15

1. cheap, easy, reliable and used clinically
2. avoids IV infusion, just requires venous blood and urine samples
   - usually measured over 24 hour period to get reliable results and take samples before breakfast

Question 16

describe how creatinine clearance can be adjusted to take account of body surface area

Answer 16

corrected creatinine clearance= measured CrCl x 1.73/BSA
- BSA = body surface area (m2)
- most adults= 1.7m^2
produces a corrected CrCl in mL/min/1.73m^2

Question 17

describe how GFR can be estimated using plasma creatinine only

Answer 17

1. allows estimation of GFR without having to collect urine samples
2. Cockcroft and Gault formula:
   eGFR= (140-age) x mass(kg) x multiplier/ plasma creatinine
   - multiplier= 1.23 for men, 1.04 for women

Question 18

what are the biomarkers of renal disease

Answer 18

1. indicators of renal function such as plasma creatinine or bUN increase only after there is a significant loss of renal function
2. urinary albumin/protein excretion can also be used as indicator for chronic kidney disease
3. interest in identifying blood and urinary markers which increase in early stages of renal failure and can be measured
4. these are mostly proteins released into plasma/urine:
   - kidney injury molecule
   - interleukin 18
   - fatty acid binding proteins
   - NGAL
   - cystatin C