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INTERPRATATION OF DIAGNOSTIC TESTS
RENAL FUNCTION TEST
Kedir.N
June, 2023
1
ANATOMY
 Highly differentiated organ
 Renal blood flow normally drains ~20% of the
cardiac output, or1000 mL/min.
 Filtration is determined by
molecular size to lesser
extent by charge
2023-06-20
2
2023-06-20
3
PHYSIOLOGY
GLOMERULUS
2023-06-20
4
Afferent renal arteriole
2023-06-20
5
2023-06-20
6
2023-06-20
7
2023-06-20
8
gfr
2023-06-20
9
Glomerular filtration rate (GFR)
 is the product of the average filtration rate of each nephron
 normal level for GFR is approximately 130 ml/min/1.73 m² for men and
120 ml/min/1.73 m² for women
gfr
2023-06-20
10
• GFR correlates well with
 health and disease
• Both tubular secretion and absorption
• Endocrine and metabolic function of the kidney
 Plasma clearance of substance x (Cx) can be
calculated as Cx = Ax/Px
 AX - eliminated amount of substance x
 Px – plasma level of substance x
 In the steady state, substance x is maintained at
constant plasma level.
 To decrease non-GFR determinants equations
use clinical and epidemiologic variables giving
more accurate estimated GFR.
 Other sources of error
 Measurement error - Poor
calibration
2023-06-20
11
gfr
2023-06-20
12
Endogenous chemicals used to estimate GFR
 Solutes that are <20,000Da, not bound with plasma proteins, freely
filtered by the glomerulus
 Endogenous – usually produced in a steady state
 Creatinine
 Urea, cystatin c
 Exogeneous
 Inulin
 Iothalamate, iohexol, ethylenediaminetetraacetic acid, and diethylenetriaminepentaacetic acid

Gfr
 Factors affecting GFR
 Age
 Gender
 body size
 physical activity
 diet,
 pharmacotherapy,
 Hyperglycemia
 physiologic states such as
pregnancy
2023-06-20
13
gfr
2023-06-20
14
 Age – decline with age; the mean rate of decline is approximately 0.75 ml/min/year after 40 years of
age.
 Gender – 8% higher in men than women
 body size – BSA is used to counter the body size of the body (/ml min/1.73m²)
 physical activity, diet, pharmacotherapy, hyperglycemia, and physiologic states such as

gfr
2023-06-20
15
 Pregnancy - GFR increases by about 50% in the first trimester and returns to normal immediately
after delivery
 Diurnal variation - and is 10% lower at midnight compared with the afternoon
 Reductions in GFR could result from
 Single nephron GFR decrement with-out loss of nephron number
 Due to loss of nephrons
creatinine
2023-06-20
16
 Creatinine is
 Metabolite of phosphocreatine from muscle
 Free not protein bound,
 Freely filtered across glomerulus
 Secreted by tubules
 drugs that affect creatinine level
 cimetidine, trimethoprim, and possibly fenofibrate
 Some cephalosporins and flucytosine
 Cystatin C – cellular product
gfr
2023-06-20
17
 GFR calculation equations
 Cockcroft-Gault formula
 CrCl = [(140 - age) x IBW] / (Scr x 72) (x 0.85 for females)
 IBW calculator =
 MDRD equation
 Estimated GFR (ml/min/1.73m2) = 186 x (Scr/ 88.4)-1.154 x (Age)-
0.203 x (0.742 if female) x (1.210 if black)
 CKD-EPI equation
 GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018
[if female] × 1.159 [if African American]
gfr
2023-06-20
18
 Still GFR calculations don’t consider
 extreme levels for creatinine generation
 amputees
 large or small individuals
 muscle-wasting conditions
 atypical pattern of meat consumption
DRUG DOSING AND RENAL FUNCTION
TEST
2023-06-20
19
 Pharmacokinetics of many drugs is affected by acute and
chronic disease
 Drug dosing calculation with MDRD equation should use ml/min
than /1.73m²
 Body surface area =0.20247 x height (m)0.725 x mass (kg)0.425
 The Cockcroft-Gault formula was widely used.
AKI and drug dosing
2023-06-20
20
Recommendations for metabolized medications in AKI include
more close monitoring than current clinical practice
– Frequent monitoring of drug pharmacodynamics
– Therapeutic drug monitoring/pharmacokinetic analysis
• Limited by availability of laboratory testing in clinically
relevant time-frame
AKI AND DRUG DOSING
2023-06-20
21
 Duration of AKI may also be important
– Using dosing recommendations for CKD and ESRD early in AKI for drugs with a
significant nonrenal clearance component may lead to subtherapeutic levels
– Higher dosing may be needed early in course with later reduction in dose
and/or frequency as AKI persists and nonrenal clearance attenuates
Ckd and drug dosing
2023-06-20
22
 GFR is assumed to capture all aspects of effect of kidney yet
 No incorporation of other factors that may not correlate with GFR,
but are present in patients with CKD, e.g. hypoalbuminemia or drug
interactions
Reference
2023-06-20
23
2023-06-20
24
Thank you!

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RFT.pptx

  • 1. INTERPRATATION OF DIAGNOSTIC TESTS RENAL FUNCTION TEST Kedir.N June, 2023 1
  • 2. ANATOMY  Highly differentiated organ  Renal blood flow normally drains ~20% of the cardiac output, or1000 mL/min.  Filtration is determined by molecular size to lesser extent by charge 2023-06-20 2
  • 9. gfr 2023-06-20 9 Glomerular filtration rate (GFR)  is the product of the average filtration rate of each nephron  normal level for GFR is approximately 130 ml/min/1.73 m² for men and 120 ml/min/1.73 m² for women
  • 10. gfr 2023-06-20 10 • GFR correlates well with  health and disease • Both tubular secretion and absorption • Endocrine and metabolic function of the kidney
  • 11.  Plasma clearance of substance x (Cx) can be calculated as Cx = Ax/Px  AX - eliminated amount of substance x  Px – plasma level of substance x  In the steady state, substance x is maintained at constant plasma level.  To decrease non-GFR determinants equations use clinical and epidemiologic variables giving more accurate estimated GFR.  Other sources of error  Measurement error - Poor calibration 2023-06-20 11
  • 12. gfr 2023-06-20 12 Endogenous chemicals used to estimate GFR  Solutes that are <20,000Da, not bound with plasma proteins, freely filtered by the glomerulus  Endogenous – usually produced in a steady state  Creatinine  Urea, cystatin c  Exogeneous  Inulin  Iothalamate, iohexol, ethylenediaminetetraacetic acid, and diethylenetriaminepentaacetic acid 
  • 13. Gfr  Factors affecting GFR  Age  Gender  body size  physical activity  diet,  pharmacotherapy,  Hyperglycemia  physiologic states such as pregnancy 2023-06-20 13
  • 14. gfr 2023-06-20 14  Age – decline with age; the mean rate of decline is approximately 0.75 ml/min/year after 40 years of age.  Gender – 8% higher in men than women  body size – BSA is used to counter the body size of the body (/ml min/1.73m²)  physical activity, diet, pharmacotherapy, hyperglycemia, and physiologic states such as 
  • 15. gfr 2023-06-20 15  Pregnancy - GFR increases by about 50% in the first trimester and returns to normal immediately after delivery  Diurnal variation - and is 10% lower at midnight compared with the afternoon  Reductions in GFR could result from  Single nephron GFR decrement with-out loss of nephron number  Due to loss of nephrons
  • 16. creatinine 2023-06-20 16  Creatinine is  Metabolite of phosphocreatine from muscle  Free not protein bound,  Freely filtered across glomerulus  Secreted by tubules  drugs that affect creatinine level  cimetidine, trimethoprim, and possibly fenofibrate  Some cephalosporins and flucytosine  Cystatin C – cellular product
  • 17. gfr 2023-06-20 17  GFR calculation equations  Cockcroft-Gault formula  CrCl = [(140 - age) x IBW] / (Scr x 72) (x 0.85 for females)  IBW calculator =  MDRD equation  Estimated GFR (ml/min/1.73m2) = 186 x (Scr/ 88.4)-1.154 x (Age)- 0.203 x (0.742 if female) x (1.210 if black)  CKD-EPI equation  GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if African American]
  • 18. gfr 2023-06-20 18  Still GFR calculations don’t consider  extreme levels for creatinine generation  amputees  large or small individuals  muscle-wasting conditions  atypical pattern of meat consumption
  • 19. DRUG DOSING AND RENAL FUNCTION TEST 2023-06-20 19  Pharmacokinetics of many drugs is affected by acute and chronic disease  Drug dosing calculation with MDRD equation should use ml/min than /1.73m²  Body surface area =0.20247 x height (m)0.725 x mass (kg)0.425  The Cockcroft-Gault formula was widely used.
  • 20. AKI and drug dosing 2023-06-20 20 Recommendations for metabolized medications in AKI include more close monitoring than current clinical practice – Frequent monitoring of drug pharmacodynamics – Therapeutic drug monitoring/pharmacokinetic analysis • Limited by availability of laboratory testing in clinically relevant time-frame
  • 21. AKI AND DRUG DOSING 2023-06-20 21  Duration of AKI may also be important – Using dosing recommendations for CKD and ESRD early in AKI for drugs with a significant nonrenal clearance component may lead to subtherapeutic levels – Higher dosing may be needed early in course with later reduction in dose and/or frequency as AKI persists and nonrenal clearance attenuates
  • 22. Ckd and drug dosing 2023-06-20 22  GFR is assumed to capture all aspects of effect of kidney yet  No incorporation of other factors that may not correlate with GFR, but are present in patients with CKD, e.g. hypoalbuminemia or drug interactions

Editor's Notes

  1. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 creatinine equation was developed from a large database of people, including those with and without kidney disease, diabetes, and a history of organ transplantation.8 The equation includes age, race, and sex and standardized serum creatinine. It uses a two-slope “spline” to model the relationship between GFR and serum creatinine and is accurate across the full range of GFR. It is accurate across a wide range of patient characteristics, including age, gender, race, body mass index (BMI), and presence or absence of diabetes or history of organ transplantation. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guide lines recommend that clinical laboratories use CKD-EPI creatinine equations to report eGFR in all adults whenever serum creatinine is measured or use other equations if shown to be superior to CKD-EPI equation in that population The Cockcroft-Gault equation, developed in 1977, estimates Clcr from age, gender, and body weight, in addition to serum creatinine.10 Com parison to normal values for Clcr requires computation of BSA and adjustment to 1.73 m2. The Cockcroft-Gault formula has several limita tions. First, it is not precise, in particular in the GFR range above 60 ml/ min. Second, it estimates Clcr rather than GFR and thus is expected to overestimate GFR. Third, the formula was derived by older assay methods for serum creatinine, which cannot be calibrated to newer assay methods and would be expected to lead to a systematic bias in estimating Clcr. Fourth, it systematically overestimates Clcr in edematous or obese patients. Fifth, the large age term means that all older adults will have lower levels of estimated GFR. The Modification of Diet in Renal Disease (MDRD) study equation11 is similar to the CKD-EPI equation and more accurate than the CockcroftGault equation. However, it was derived from a study population with CKD, so it underestimates the measured GFR in populations with higher levels of GFR, and numeric values cannot be reported for GFR levels greater than 60 ml/min/1.73 m2.12