Measuring renal function

Question 2

1. What do clinicians usually mean by “renal function”?

Answer 2

• How well the glomeruli are filtering plasma
• Measured as: GFR (Glomerular Filtration Rate)
• Normal adult average ≈ 125 mL/min
• Meaning: kidneys filter ~125 mL plasma per minute

Question 3

2. How does age affect renal function?

Answer 3

• Neonates → immature kidneys
• eGFR matures at ~4 years old
• After age 40 → declines 0.4–1.2 mL/min per year
• Elderly → naturally lower GFR

Question 4

3. How does polypharmacy impair renal function?

Answer 4

• Increased drug interaction risk
• Increased nephrotoxicity risk

Question 5

4. Which disease states impair renal function?

Answer 5

• Hypertension
• Diabetes
• Chronic heart failure
• Rheumatoid arthritis
• Renal disease
• Recurrent UTIs

Question 6

5. How does long-term analgesia affect kidneys?

Answer 6

• NSAIDs reduce prostaglandins
• Reduced renal blood flow
• Known nephrotoxic risk

Question 7

6. Why are transplant patients at risk?

Answer 7

• Risk of rejection
• Anti-rejection drugs may be nephrotoxic

Question 8

7. Which drugs/procedures are nephrotoxic?

Answer 8

• Some antibiotics
• Anti-HIV drugs
• Radiocontrast agents

Question 9

8. What clinical signs indicate impaired renal function?

Answer 9

Fluid balance
- Oedema
- Breathlessness

Electrolytes (K⁺, Na⁺, PO₄³⁻, Ca²⁺)
- Abnormal ECG:
- Absent P waves
- Broad QRS
- Peaked T waves
- Muscle spasms
- Acute symptoms in severe imbalance

EPO production
- Pallor
- Anaemia
- Fatigue

Vitamin D3
- Osteomalacia
- Bone pain

Excretion
- Raised blood urea
- Raised creatinine
- Pruritus
- Nausea
- Vomiting

Acid–base balance
- Low blood pH
- Low bicarbonate
- Nausea
- Vomiting

Question 10

9. What bedside clinical data are used?

Answer 10

• Weight charts → fluid retention
• Fluid balance charts → oedema degree
• Urine dipstick → protein, blood, glucose

Question 11

10. What modern imaging assesses renal function?

Answer 11

• Renal blood flow
• Filtration
• Excretory function

Question 12

11. What biochemical data are used?

Answer 12

• Renal clearance measurements
• Plasma/serum creatinine (sCr)
• Plasma/serum urea (BUN)
• Electrolytes (e.g. hyponatraemia)

Note: Plasma = serum + clotting proteins (e.g. fibrinogen)

Question 13

12. What makes an ideal kidney function marker?

Answer 13

• Naturally occurring
• Not metabolised
• Only excreted by kidney
• Filtered
• Not secreted
• Not reabsorbed

(Inulin fits best, but impractical clinically.)

Question 14

13. What is creatinine?

Answer 14

• Breakdown product of creatine phosphate in muscle
• Produced at relatively constant rate
• Filtered at glomerulus
• Some proximal tubular secretion

Question 15

14. What is normal plasma creatinine?

Answer 15

• 40–120 µmol/L

Question 16

15. What increases creatinine?

Answer 16

• Large muscle mass
• Large meat intake
• Drugs interfering with Jaffe reaction:
  
  • Methyldopa
  • Levodopa
  • Dexamethasone
  • Cephalosporins
• Drugs inhibiting tubular secretion:
  
  • Cimetidine
  • Trimethoprim
  • Aspirin
• Ketoacidosis
• Ethnicity (higher creatine kinase activity in black population)
• Muscle disease/damage

Question 17

16. What decreases creatinine?

Answer 17

• Reduced muscle mass (elderly)
• Cachexia/starvation
• Immobility
• Pregnancy (plasma dilution)
• Severe liver disease

Question 18

17. What is urea?

Answer 18

• Produced in liver (urea cycle)
• From protein digestion
• Filtered at glomerulus
• Secreted and reabsorbed in tubule

Question 19

18. What is normal plasma urea?

Answer 19

• 2.5–7.5 mmol/L
• > 20 mmol/L = moderate–severe renal failure

Question 20

19. What increases urea?

Answer 20

• High protein diet
• Severe infection
• Burns
• Hyperthyroidism
• GI bleeding
• Muscle injury
• Glucocorticoids
• Tetracycline
• Hypovolaemia

Question 21

20. What decreases urea?

Answer 21

• Malnutrition
• Liver disease
• Sickle cell anaemia

Question 22

21. Define renal clearance.

Answer 22

• Volume of plasma completely cleared of a substance per unit time
• Measured in mL/min

Question 23

22. What does clearance reflect?

Answer 23

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

Question 24

23. Key identity of clearance?

Answer 24

• Rate excreted in urine = rate disappears from plasma

Question 25

24. Clearance equation?

Answer 25

Cₓ = (Uₓ · V) / Pₓ Where: - Cₓ = clearance (mL/min) - Uₓ = urine concentration - V = urine flow rate (mL/min) - Pₓ = plasma concentration

Question 26

25. What are clearance limitations?

Answer 26

- Reflects total nephron function - Does NOT show: - Which tubule segment acted - Which transporter was responsible

Question 27

26. Substance A characteristics?

Answer 27

- Filtered - Not reabsorbed - Not secreted - Excretion = filtration - Example: inulin

Question 28

27. Substance B characteristics?

Answer 28

- Filtered - Partially reabsorbed - Excretion = filtration − reabsorbed - Typical of electrolytes

Question 29

28. Substance C characteristics?

Answer 29

- Filtered - Completely reabsorbed - No excretion normally - Example: glucose, amino acids

Question 30

29. Substance D characteristics?

Answer 30

- Filtered - Not reabsorbed - Fully secreted - Rapidly cleared - Example: PAH

Question 31

30. What are inulin properties?

Answer 31

- Plant polysaccharide - MW 5200 Da - Freely filtered - Not secreted - Not reabsorbed

Question 32

31. Why is inulin ideal for GFR?

Answer 32

- Amount filtered = amount excreted GFR = (U_inulin · V) / P_inulin Example: - P = 1 mg/mL - U = 125 mg/mL - V = 1 mL/min - GFR = 125 mL/min

Question 33

32. Interpretation rules relative to inulin?

Answer 33

- Clearance > inulin → secretion occurring - Clearance < inulin → reabsorption occurring OR not freely filtered

Question 34

33. Why not use inulin clinically?

Answer 34

- Requires IV infusion - Difficult lab measurement - Radiolabel alternatives may bind proteins

Question 35

34. Why does CrCl slightly overestimate GFR?

Answer 35

- Some tubular secretion - Overestimates by ~20%

Question 36

35. Why does this error cancel out?

Answer 36

- Jaffe method underestimates creatinine ~20% - Errors cancel - CrCl ≈ inulin clearance (~125 mL/min)

Question 37

36. Why is CrCl used clinically?

Answer 37

- Cheap - Easy - Reliable - No IV needed - Requires venous blood + urine

Question 38

37. Collection details for CrCl?

Answer 38

- 24-hour urine collection - Samples before breakfast - Consider: - Muscle disease - Large meat intake

Question 39

38. What is reported in UK labs?

Answer 39

- eGFR

Question 40

39. Cockcroft–Gault formula?

Answer 40

CrCl = ((140 − age) × weight (kg)) / (72 × SCr (mg/dL)) For females: CrCl_female = 0.85 × CrCl_male Important: - SCr must be in mg/dL - UK labs use µmol/L → must convert

Question 41

40. When should CrCl be used instead of eGFR?

Answer 41

- Narrow therapeutic index drugs - Mainly renally excreted drugs - Older adults - Extremes of muscle mass - DOACs - Rapid renal changes (AKI) Always check BNF/NICE.

Question 42

41. CKD Staging Table

Answer 42

GFR (mL/min/1.73m²) | Plasma Creatinine (µmol/L) | Stage 125 | 100 | Normal adult average 90+ | 100–150 | Stage 1 60–89 | 150–300 | Stage 2 30–59 | 300–500 | Stage 3 15–29 | 500–700 | Stage 4 <15 | >700 | Stage 5