1. Renal Clearance

2. Clearance 20 4444444444 40 12345678910

3. 20 4444444444 40 Was any of the carriages completely cleared?No But can we say that it is as if some carriages were completely cleared? Yes If so, how many carriages were completely cleared?2

4. 20 4444444444 40 Clearance of the train is 2 carriages / station Remember – It is not real (it is only as if) It is related to the train (not the number of passengers)

5. 20 4444444444 40 Clearance is - Number of carriages of the train cleared of passengers The minimum number of carriages needed to supply the number of passengers getting off at the station OR The number of carriages that contained the number of passengers getting off the train

6. 20 4444444444 40 Calculation of clearance - number of passengers going out of the station number of passengers in each carriage

7. Apply to plasma and kidney – Kidney Solute X excreted Plasma comes into kidney with more solute X Plasma goes out of the kidney with less solute X

8. Apply to plasma and kidney – Kidney Excretion of the solute X Plasma comes into kidney with more solute X Plasma goes out of the kidney with less solute X Clearance of the solute X = Amount of solute X excreted Concentration of solute X in plasma Renal clearance is taken as PER MINUTE

9. Renal Clearance of a substance is - Volume of plasma cleared of the substance by the kidney in one minute The minimum volume of plasma needed to supply the amount of substance excreted by the kidney in one minute OR The volume of plasma that contained the amount of substance excreted by the kidney in one minute

10. Renal clearance of a substance Total substance excreted in 1 minute Concentration of substance in plasma Conc. of substance in urine x Vol. of urine excreted in 1 min Concentration of substance in plasma U x V P U – concentration of the substance in urine V – volume of urine produced in 1 minute P – concentration of the substance in plasma

11. Unit of renal clearance U x V P U – concentration of the substance in urine – mmol/ml V – volume of urine produced in 1 minute – ml/min P – concentration of the substance in plasma – mmol/ml mmol/ml x ml/min mmol/min mmol/ml mmol/ml Unit of renal clearance is ml/min = ml/min= Warning: when performing the calculation make sure that units of U, V and P are similar!

12. Renal Clearance of a substance - determination U x V P U – concentration of the substance in urine – collect urine and measure the concentration V – volume of urine produced in 1 minute – collect urine for 24 hours and calculate urine output per minute; more accurate as the output varies throughout the day P – concentration of the substance in plasma – collect blood during those 24 hours and measure the concentration

13. Significance of clearance Measurement of clearance can be used to determine 1.Glomerular filtration rate – thereby assessing glomerular function 2.Renal plasma/blood flow – not routinely performed

14. Significance of clearance 1.Glomerular filtration rate – the clearance of a substance freely filtered at the glomerulus but not reabsorbed or secreted in the tubules is the value of GFR 2.Renal plasma/blood flow – the clearance of a substance filtered at the glomerulus and completely secreted by the tubules is the same as renal plasma flow

15. Significance of clearance Consider a substance handled by the kidney in the following manner - 1. Freely filtered at glomerulus 2. Completely secreted by tubules The amount of substance excreted comes from the entire plasma flowing through the kidney

16. Significance of clearance 1. Freely filtered at glomerulus 2. Completely secreted by tubules The amount of substance excreted comes from the entire plasma flowing through the kidney Calculate the clearance of the substance U x V P = total plasma flow through the kidney

17. Significance of PAH clearance Para amino hippuric acid (PAH) has these characteristics (at low concentrations) Clearance of PAH = Renal plasma flow Total plasma flow? No, some blood may bypass the nephrons Clearance of PAH = Effective renal plasma flow Total renal plasma flow is about 5 -10% more than effective renal plasma flow

18. Significance of PAH clearance If plasma flow is known, blood flow can be calculated For this haematocrit needs to be known clearance of PAH = Effective Renal blood flow For example: if PAH clearance is 600ml/min, and haematocrit 40%, 600 / (1 - 40%) Effective Renal blood flow = = 600 x 100 60 1 - haematocrit

19. Significance of clearance A substance handled by the kidney in the following manner- 1.Freely filtered at glomerulus 2.Not absorbed or secreted by tubules The amount of substance excreted comes entirely from the glomerular filtrate The amount of substance excreted in 1 minute will come from the glomerular filtrate formed in 1 minute (GFR)

20. Significance of clearance A substance handled by the kidney in the following manner- Clearance of the substance when calculated will give the volume of plasma that contains the amount of substance excreted in 1 minute Freely filtered at glomerulus Not absorbed or secreted by tubules The amount of substance excreted comes entirely from the glomerular filtrate

21. Significance of clearance The substance excreted comes entirely from the glomerular filtrate Comes from the glomerular filtrate in 1 minute (GFR) = the amount of substance excreted in 1 minute comes from volume of plasma cleared of the substance in 1 minute (Renal clearance) =

22. Clearance as a measure of GFR The clearance of a substance freely filtered at the glomerulus and not reabsorbed or secreted will be the same as the GFR

23. Measurement of GFR Properties of an ideal substance whose clearance mat be determined to measure GFR – Freely filtered at the glomerulus Not reabsorbed by the tubules Not secreted by the tubules Not metabolised by the nephron Not toxic to the body Does not affect renal function, particularly glomerular function Easily measured in the plasma and urine Found in the body

24. Clearance as a measure of GFR The clearance of a substance freely filtered at the glomerulus and not reabsorbed or secreted will be the same as the GFR The best example of such a substance is INULIN Inulin clearance, therefore, is the same value as GFR

25. Measurement of GFR Inulin as an ideal substance for measuring GFR – Freely filtered at the glomerulus Not reabsorbed by the tubules Not secreted by the tubules Not metabolised by the nephron Not toxic to the body Does not affect renal function, particularly glomerular function Easily measured in the plasma and urine  Found in the body

26. Measurement of GFR Inulin as an ideal substance for measuring GFR –  Found in the body As inulin is not found in the body it needs to be infused – Associated with risks and restrictions for the person

27. Alternate substances for measurement of GFR Creatinine for measuring GFR – (source of creatinine : muscles) Found in the body Has a major advantage over inulin as no infusion is necessary However – Creatinine is secreted in small amounts – tends to overestimate GFR The method of measuring serum creatinine gives a falsely higher value (slight) – tends to underestimate GFR

28. Creatinine clearance Commonly performed clearance estimation A good indicator of glomerular function Parameters measured – Serum creatinine concentration 24-hour urine volume Urine creatinine concentration

29. Clearance ratio If the clearance of a substance is : 1.Less than creatinine clearance Reabsorption occurs ? Secretion 2.More than creatinine clearance Secretion occurs ? Reabsorption

30. Serum creatinine Could serum creatinine be a substitute for creatinine clearance? Measuring serum creatinine is much easier than determining creatinine clearance Reasoning may be – ? if GFR decreases creatinine excretion decreases ? then serum creatinine level increases ? Increasing serum creatinine will indicate decreasing GFR Is this really so?

31. GFR and plasma creatinine When GFR falls, plasma creatinine increases but not proportionately – the relationship is not linear When GFR falls from normal levels At lower levels of GFR even small decreases in GFR cause large increases in plasma creatinine The plasma creatinine increases slowly initially

32. GFR and plasma creatinine 1.A high serum creatinine suggests a low GFR 2.A normal serum creatinine is not proof of normal GFR Serum creatinine is also dependent on a persons muscle mass A high serum creatinine suggests a low GFR because there are no other significant factors that change the serum creatinine

33. Renal Clearance Clearance is a concept – not a real value It refers to plasma - unit : ml/min It can be determined for any substance excreted in the urine Parameters needed for calculation are plasma concentration, urine concentration and urine flow rate The clearance of certain substances are determined as indicators of renal function Blood levels of some substances excreted in urine are sometimes used as indicators of glomerular function But blood levels do not change proportionately with changes in GFR