An insight into the interpretation of various functional tests pertaining to the renal system

1. Interpretation of
Renal Function Tests

2.  Renal Functions Tests (RFTs) can be assessed by measuring Blood
Urea Nitrogen (BUN), Serum Creatinine (SCr). and Creatinine
Clearance (CrCl or ClCR);
 In many disease conditions, urea and creatinine accumulate in the
blood as they cannot be excreted properly.
 The RFTs basically evaluate the Glomerular Filtration Rate (GFR).
 Renal Function decreases with age and disease condition. Consider
these while interpreting the test values.
 RFTs can help in determining the dosage for medications excreted
through the kidneys.

3.  Azotemia: Excessive retention of nitrogenous waste products (BUN
and creatinine) in the blood.
 Uremia: the syndrome resulting from decreased renal function
and azotemia;
 Azotemia types:
Renal azotemia
• Due to renal
diseases like
glomerulonephritis
and pyelonephritis
Pre-renal azotemia
• Due to severe
dehydration,
hemorrhagic shock,
excessive protein
intake
Post-renal azotemia
• Due to stones
(ureteral, urethral),
tumors, prostatic
obstructions

4. Blood Urea Nitrogen (BUN)
 Urea is an end product of protein metabolism.
 Is produced by the liver and excreted by the kidneys;
 Urea is filtered by the glomerulus; tubules reabsorb approx. 40%.
 Normal BUN range: 3.0 – 6.5 mmol/L (8 – 18 mg/dL)
 ↑ed BUN levels indicate renal disease.
 ↓ed BUN levels indicate hepatic disease.

5. Serum Creatinine
 Is a more sensitive indicator of renal damage than BUN levels
because renal impairment is almost the only cause of an increase
in serum creatinine levels.
 Normal SCr range: 50 – 110 mmol/L (0.6 – 1.2 mg/dL)

6. Clearance
 Is a theoretical concept used to estimate GFR;
 The volm. of plasma from which a measured amount of substance
(solutes, drugs, etc..) can be completely eliminated or cleared into
the urine per unit time.
 Creatinine: Endogenous amine produced by muscle catabolism;
excreted unchanged by GF only;
Creatinine Clearance (CrCl or ClCR)
 Is the rate at which creatinine is removed from the blood by the
kidneys;
 This provides the approximate value of the GFR in ml/min.
 Normal range: 75-125 ml/min.
 CrCl depends on age, gender, weight, disease state, among other
factors.

8. Issue with CrCl formula:
 Some creatinine found in the urine is due to ‘Tubular
Secretion’.
 CrCl formula therefore overestimates GFR at all levels
of renal function.
 Drugs (like amiloride, cimetidine, trimethoprim,
salicylates, triamterene, spironolactone) which inhibit
secretory function may increase SCr, and decrease the
overestimate, without actually affecting the GFR.

9.  Renal Function is calculated by:

10. Chronic Kidney Disease
Definition:
 A CKD patient has abnormalities of kidney function or
structure present for > 3 months.
 The definition of CKD includes…
• all individuals with markers of kidney damage, or
• those with an eGFR of < 60 ml/min/1.73m2 on at least
2 occasions 90 days apart (with or without markers of
kidney damage).

12. The K/DOQI classification of CKD
K/DOQI = Kidney Disease Outcome Quality Initiative;
(by the National Kidney Foundation)

13. Markers of kidney disease:
 Albuminuria (ACR > 3 mg/mmol),
 Haematuria (or presumed or confirmed renal origin),
 Electrolyte abnormalities due to tubular disorders,
 Renal histological abnormalities,
 Structural abnormalities detected by imaging (e.g.
polycystic kidneys, reflux nephropathy)
 H/o kidney transplantation;

16. CKD Classification
 Based on the eGFR and the level of proteinuria and helps to
risk-stratify patients.
 Patients are classified as…
• G1-G5 (based on the eGFR), and
• A1-A3 (based on the ACR which is albumin:creatinine ratio)
 E.g.,
• A person with an eGFR of 25 ml/min/1.73 m2 and an ACR of 15
mg/mmol has CKD G4A2.
• A person with an eGFR of 50 ml/min/1.73 m2 and an ACR of 35
mg/mmol has CKD G3aA3.

19. KDIGO stages of CKD
 Stage 1 GFR > 90 ml/min/1.73 m²
 Stage 2 GFR 60 – 89 ml/min/1.73 m²
 Stage 3a GFR 45 – 59 ml/min/1.73 m²
 Stage 3b GFR 30 – 44 ml/min/1.73 m²
 Stage 4 GFR 15 – 29 ml/min/1.73 m²
 Stage 5-GFR <15 ml/min/1.73 m² (ESRD)
• KDIGO = Kidney Disease Improving Global Outcomes
• ESRD = End-Stage Renal Disease

21.  In pts. w/ CKD stages 1 – 5 (pre-dialysis), the
Cockroft-Gault (CG) eqn. is used to estimate the CrCl
in the presence of stable renal function.
(140-age) x (W)
CrCl = ______________
(72) x SCr
CrCl (females) = CrCl (males) x 0.85
 where, SCr is in mg/dl and W is in kgs

22.  MDRD4 equation:
• Where, eGFR = estimated GFR (ml min-1/ 1.73 m2 BSA)
• (Cs)cr = serum creatinine conc.(mg/dl)
 If serum albumin (ALB) and BUN values are known,
then the formula can be expressed as:
• (Cs)cr and BUN units is mg%; ALB is %

23. MDRD4 eqn. limitations:
 Underestimates eGFR for patients with GFR > 60
ml/min
 MDRD4 eqn. is not adjusted for body weight…
Smaller eGFR values for heavy patients,
Larger eGFR values for thinner patients
vs CG eqn.

24. Drug classes requiring dosage adjustment in CKD

25. CKD-EPI Equations for calculation of eGFR
CKD-EPI creatinine equation (Levey, et. al.)
eGFR = 141 x min(SCr/κ, 1)α x max(SCr /κ, 1)-1.209 x
(0.993)Age x [1.018 if female] x [1.159 if Black]
• eGFR (mL/min/1.73 m2); SCr = standardized serum creatinine (mg/dL)
• κ = 0.7 (females); 0.9 (males); α = - 0.329 (females), - 0.411 (males)
• min = indicates the minimum of SCr/κ or 1
• max = indicates the maximum of SCr/κ or 1
 The CKD-EPI eqns. are mainly used for identifying CKD
and staging the degree of severity.
 More accurate than the MDRD4 equation, especially for
patients with higher levels of GFR.
 Not yet being used in Malaysia.

26. CKD-EPI Equations for calculation of eGFR (contd’.)
CKD-EPI cystatin C equation (Inker, et. al.)
eGFR = 133 x min(SCys/0.8, 1)-0.499 x max(SCys /0.8, 1)-1.328 x
(0.996)Age x [0.932 if female]
• eGFR (mL/min/1.73 m2); SCys = standardized serum cystatin C
CKD-EPI creatinine-cystatin C equation (Inker, et. al.)
eGFR = 135 x min(SCr/k, 1)-a x max(SCr /k, 1)-0.601 x
min(SCys/0.8, 1)-0.375 x max(SCys /0.8, 1)-0.711 (0.995)Age x
[0.969 if female] x [1.018 if Black]
K = 0.7 (females), 0.9 (males);
a = -0.248 (females), -0.207 (males)

27.  Jelliffe Equation:
CrCl (ml/min) = {[98 – 0.8 × (age – 20)] × [1 – (0.01 × gender)]
× (BSA/1.73)}/(SCr × 0.0113)
• BSA = Body Surface Area;
• SCr = Serum Creatinine;

28. THE END