A complete go through about the renal function tests

1. Renal Function Tests
Dr. Abhra Ghosh

2. Functions of kidney
1. Get rid of the body wastes product of metabolism.
2. Get rid of foreign and no-endogenous substances.
3. Maintain of electrolyte and water balance.
4. Maintain acid-base balance of the body.
5. Activation of Vitamin D
6. Synthesis of erythropoietin.

3. Glomerular function
• It acts as a filter
• Helps in formation of a protein free plasma
Formation of glomerular filtrate depends on –
1. The blood pressure in the glomerular capillaries
2. The opposing osmotic pressure of plasma proteins, renal interstitial
pressure, intratubular pressure

4. Rate of filtration is
influenced by -
• Variations in BP in glomerular capillary
• Concentration of plasma proteins
• Alteration of intratubular pressure – ureteral obs., osmotic diuresis
• State of blood vessels
- constrict. of efferent arteriole  pressure filtration
- constrict. of afferent arteriole  pressure filtration

5. The volume of glomerular filtrate depends on -
• No. of functional glomeruli
• Vol. of blood passing through glomeruli per min
• Effective filtration pressure
- Vol. of plasma flow through kidney – 700 mL/min
- Vol. of glom. Filtrate formed – 120 mL/min
WHY IS IT IMPORTANT IN TERMS OF KIDNEY FUNCTION?

6. Factors regulating Glomerular filtration rate
1. Decrease in systemic BP
2. Partial obstruction to renal arterial flow
3. Inflammatory process
4. Increased resistance in tubular portion
5. Decrease in osmotically active components
6. Glomerular capillary complex disease

7. Tubular function
• Tubular epithelium is highly specialized
• Involves in reabsorption of water (1) and other substances (2)
• Also secrete other substances (3)

8. 1. Reabsorption
a. Water:
- Obligatory reabsorption in PCT with Na+, Cl-, HCO3
-
- Facultative reabsorption in DCT, influenced by ADH
b. Electrolytes, glucose and amino acids:
- By co-transport and antiport mechanism
- Various inhibitors inhibits these process.

9. Renal threshold
• It is the concentration of a substance in blood, above which, it starts
appearing in urine
• Compounds whose excretion in urine is dependent on blood urine are
known as threshold substance
• The maximum resorptive capacity of a compound is known as tubular
maximum or Tm.

10. Classification of Renal Function Tests
1. Test based on glomerular filtration:
a. Urea clearance test
b. Endogenous creatinine clearance test
c. Inulin clearance test
d. Cr51 – EDTA clearance test

11. Clearance
Volume of blood or plasma which contains the amount of the substance
which is excreted in the urine in one minute
• It is the measurement of GFR

12. Urea clearance test
Urea clearance defines the number of mL of blood/plasma which are
completely cleared of urea by the kidney per minute
*Plasma is not completely cleared of urea, instead it is calculated how
much vol. of plasma contains the urea removed per min.*

13. Maximum Urea Clearance
• Urine volume is ≥ 2mL/min
• Urea elimination is at its maximum
• Directly proportional to conc. of urea
Cm = U X V
B
The clearance which occurs when the urinary volume exceeds 2ml/min is
termed as Maximum Urea Clearance
Cm = 75 mL/min (75 ± 10)
U = Conc. of urea in urine
V = Volume of urine
B = Conc. of urea in blood

14. Standard Urea Clearance
- Urine volume is ≤ 2mL/min
- More urea is reabsorbed
- Directly proportional to square root of the urinary volume
Cm = U X √V
B
U = Conc. of urea in urine
V = Volume of urine
B = Conc. of urea in blood
Cs = 54 mL/min (54 ± 10)

15. Expression of result %
- Result can be expressed as % of the normal
Cm = U X V
B
X (100/75) % Cs = U X √V
B
X (100/54) %

16. Relation with body surface
• Cm is directly proportional to BS, correction is done by X (1.73/BS)
• Cs is directly proportional to BS, correction is done by X (√1.73/BS)

17. Procedure
• Performed between breakfast and lunch
• Light breakfast with 2-3 glass of water
• Bladder emptied and time is noted
• 1hr later, urine collected, a blood sample collected
• 2 hr later, again urine collected
• Urea in urine and serum measured, volume of urine is noted
• Average value of two urine specimens is used

18. Interpretation
• > 70% of average is normal
• 40 – 70 % of average – mild impairment
• 20 – 40 % of average – moderate impairment
• <20 % of average – severe impairment

19. • Acute renal failure – Cm or Cs to < ½ of the average value
• Chronic nephritis – Cm or Cs to < 20% of the average value
• Terminal uremia – Cm or Cs 5% of the normal value
• Nephrotic syndrome, benign hypertension – Normal

20. Creatinine clearance test
Why creatinine?
1. Extrarenal factors rarely interfere
2. Conversion of creatine phosphate to creatinine is spontaneous,
nonenzymatic
3. Production is continuous, stable parameter
4. Not affected by diet or exercise

21. Why creatinine is not useful to estimate clearance?
1. Excreted by tubules at higher concentration. When GFR is reduced, this
secretion component vitiate the result.
2. On severe reduction of GFR, Extrarenal excretion increases
3. Early stage GFR decrease cannot be identified (Creatinine blind area)

22. Creatinine blind area
1. 10% of total creatinine excretion is by tubular secretion
2. This increases as GFR decreases
3. Serum Cr does not increase until GFR is moderately decreased
4. This insensitivity to moderate decrease in GFR is known as Creatinine
blind area

23. Procedure
• Give 500 mL of water to drink
• After 30 min, ask to void urine and discard
• After 60 min, void urine and collect
• Note the volume of urine
• One IV blood sample at the same time
Ccr = U X V
P
U = Conc. of creatinine in urine
V = Volume of urine
P = Conc. of creatinine in blood

24. Inulin Clearance Test
• Inulin - a homopolysaccharide of fructose
WHY INULIN?
• Not metabolized in the body
• Excreted entirely through glomerular filtration
• Neither secreted nor reabsorbed through tubules

25. Procedure
• Performed in morning. Patient should be kept reclining
• Light breakfast at 7:30 am
• 10 gm inulin dissolved in 100 mL saline IV @10mL/min at 8 am
• At 9 am void urine and discard
• At 10 am and 11 am void urine and collect – measure volume and inulin conc.
• At 30 min and 90 min after initial voiding, blood sample drawn to measure
inulin conc.
CIn = U X V
P
U = Conc. of inulin in urine
V = Volume of urine
P = Conc. of inulin in blood

26. Interpretation
• Urea:
In blood: Adult – 13 – 43 mg/dL
In urine: 10 – 20 g/day
• Creatinine:
In blood: Child – 0.3 – 0.7 mg/dL
Adult male – 0.9 – 1.3 mg/dL
Adult female – 0.6 – 1.1 mg/dL
In urine:
Child – 8 – 22 mg/kg/day
Adult male – 14 -26 mg/kg/day
Adult female – 11 – 20 mg/kg/day

27. Creatinine and GFR range
Normal reference range
Serum Creatinine GFR
Male 0.9 – 1.3 mg/dL 95 – 115 mL/min
Female 0.6 – 1.1 mg/dL 85 – 110 mL/min
• Early detection of functional impairment of kidney
• Mild change in Cr causes significant change in GFR

28. Estimated GFR
• By Cockcroft-Gault equation -
cCr = {(140 – age in years) X weight in kg (0.85 in females) X Pcr}/72
• By Modification of Diet in Renal Disease equation –
186 x (Creatinine/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black)

29. Grading of Chronic Kidney Disease
State Grade GFR
Minimal damage with normal GFR 1 >90
Mild damage with slightly low GFR 2 60 - 89
Moderately low GFR 3 30 - 59
Severely low GFR 4 15 - 29
Kidney failure 5 <15

30. Cystatin C – Glomerular Filtration Marker
• 13 kD non-glycosylated protein
• Most common extracellular cysteine protease inhibitors
• Present in all biological fluid
• Normal range – 0.8 – 1.2 mg/L
• It is produced at a constant rate, freely filtered by kidney
• Not dependent on age, sex, muscle mass

31. Relationship of GFR with clearance
Mechanism Result Example
Substances filtered; neither
reabsorbed nor excreted
GFR = Clearance Inulin
Substance filtered; reabsorbed
and excreted
GFR ~ clearance Uric acid
Substances filtered; partially
reabsorbed
Clearance < GFR Urea
Substances filtered; secreted Clearance > GFR Creatinine

32. Classification of Renal Function Tests
2. Test to measure renal plasma flow:
A. Para amino Hippurate test (PAH)
B. Filtration fraction

33. Para amino Hippurate test (PAH)
• PAH is i) filtered at glomeruli, ii) Secreted by tubules
• At <2mg/dL conc. PAH is completely removed during a complete
circulation
• Urine PAH value helps in measuring PAH clearance.
• PAH clearance is equivalent to renal plasma flow
RPF = 574 mL/min

34. Filtration fraction (FF)
• Fraction of plasma filtered through glomerulus
• Denoted by Inulin clearance (GFR) divided by PAH clearance
GFR = 125 mL/m RPF = 594 mL/m
FF = GFR/RPF = 125/594 = 0.217 (21.7%)
↑ FF = Essential hypertension, malignant hypertension, CHF
↓ FF = Glomeruloneohritis

35. Classification of Renal Function Tests
3. Tests based on tubular function:
• Concentration and dilution tests
• 15 min PSP excretion test

36. Pathophysiological aspect
Alteration of renal tubular function occurs due to –
a. Ischemia
b. Toxic substances
c. Biochemical defects
All these abnormalities leads to - ISOSTHENURIA

37. A. Concentration test
• Based on measuring sp. gr. of urine
• Done by – restricted fluid intake or injection of post. pituitary extract
Fishberg concentration test
• No fluid 8 pm to 10 am
• Urine is collected 8 am, 9 am and 10 am
• Sp. gr. is measured

38. Interpretation
• Sp. gr. of any of the sample >1.025 - Normal tubular function
• Sp. gr. of any of the sample <1.020 or fixed at 1.010 – severe renal
damage
Beware of false result

39. Test with Posterior pituitary extract
• 10 pressor units of extract is given S/C
• It inhibits the diuresis produced by 1600 mL water in 15 minutes
Interpretation:
• Urine excreted with sp. gr. >1.020

40. B. Dilution test
• 8 pm to 8 am fasting
• Void urine at 8 am and discard
• Drink 1200 mL water
• Bladder emptied at 9, 10, 11, 12 am
Interpretation:
Sp. gr. of 1 sample is <1.003
80% of water is voided in 4 hours

41. C. Test of Tubular Excretion and Reabsorption
15 min PSP test:
Test and Interpretation
• 1 mL PSP (6 mg) injected IV
• Normally 30 – 50% excreted in first 15 mins
• <23% excretion in first 15 mins denotes impaired renal function

42. Markers of glomerular permeability
• Normal urinary protein level – 150 mg/24 hr
• Includes – Albumin, Tamm-Horsfall glycoprotein, alpha 1 microglobulin
Proteinuria:
1. Glomerular
2. Overflow
3. Tubular

43. Glomerular proteinuria
• Occurs when glomerular selectivity is lost
• Also measured in form of Urinary protein:Creatinine
• 300 mg/day – Benign
• 300-1000 mg/day – Pathological
• >1000 mg/day - Glomerular

44. Microalbuminuria
• Albumin level in urine 30 -299 mg/day
• Impending nephropathy
• Expressed as albumin:creatinine
• N – Males <23 mg/g, females <32 mg/g
• ACE inhibitors are useful in reverting the condition

45. Overflow proteinuria
• When small mol weight proteins increased, they overflow in urine
• Example – hemoglobinuria, myoglobinuria, Bence-Jones proteinuria
• Bence-Jones proteins are formed by light chain of of Ig.
• Present in multiple myeloma

46. Tubular proteinuria
• Functional nephrons are reduced
• Tubular reabsorption is impaired
• Low mol. weight protein starts appearing in urine
• Two types – Nephron loss proteinuria and Urogenic proteinuria

47. Other tests:
1. Intravenous pyelography
• Radio opaque compounds of iodine
given IV
• In suff. conc. – cast a shadow of renal
calyces, pelvis, ureters, bladder
• Compound used - Iodoxyl, Diodone

48. Indications
1. Renal calculi
2. Urinary inf
3. Hematuria
4. Prostatic enlargement
5. Tumors
6. Cong. anomalies
Contraindications
1. Acute nephritis
2. Congestive heart failure
3. Severely impaired liver function
4. Frank uremia
5. Hypersensitive to dye

49. Thank you