1. Stephen R. Ash, MD, FACP IU Health Arnett Lafayette, Indiana 2017
Predicting the Progress of Chronic Kidney Disease; Combining eGFR and Proteinuria
LMEF PRESENTATION
Stephen R. Ash, MD, FACP
IU Health Arnett
Lafayette, Indiana
2017

2. A bucket analogy to explain the concept of kidney clearance
Water Inflow 100 ml/min, output flow begins through hole

3. Outflow rate from bucket soon “magically” equals inflow
Pressure increases, output flow increases until = input

4. Add generation of a chemical marker
Rice generation 1 piece (1mg)/min

5. Marker concentration equilibrates so generation = excretion
Rice generation 1 piece (1mg)/min
Clearance Rate = Amount removed/minute = Cb
Generation rate = Cb
Outflow rate
If Cb = 1 mg/100 ml, then Clearance = 1 mg/min mg/100 ml = 100 ml/min = outflow rate
Cl = N/Cb

6. What happens if outflow rate decreases 50%?
What if the outflow hole becomes smaller?
Outflow rate decreases 50%
Inflow rate also is decreased so bucket doesn’t overflow

7. Cb increases until output again equals generation of marker; clearance shows the new outflow rate
Rice generation stays the same, so concentration doubles
Clearance Rate = Amount removed/minute = *Cb
Generation rate = * Cb
= 50 ml/min

8. The kidney can generate its own inflow fluid, like screens in this model
Add a screen downstream through which the rice can’t penetrate, and fluid can be returned to the bucket
Since the rice doesn’t penetrate the screen, it is concentrated in the outflow fluid.
Clearance = generation rate Cb = bucket outflow rate (even if this flow isn’t seen)
Kidney then generates its own inflow fluid
Roller
pump

9. Kidney creatinine clearance follows same mathematics
Generation rate of creatinine marker approx. 1 mg/min
Glomerular filtration rate (GFR) approx= ml/min =
Creatinine Clearance = generation rate Cb
99% of fluid reabsorbed, without creatinine
Cb approx. = 1 mg/100ml plasma
Urine excretion of creatinine approx. = mg/min
GFR (calculated, unseen) = 1 mg/min mg/100ml = 100 ml/min

10. GFR determined by creatinine clearance (CrCl)
Generated by muscle metabolism of creatine and dietary meat Creatinine generation is fairly constant day-to-day, mg/kg/day (LBW) in men, mg/kg/day in women (LBW) Creatinine daily excretion decreases 50% from age 50 to 90. Creatinine is filtered by glomerulus and not absorbed, but 10-20% of creatinine in urine is secreted by normal kidneys, making creatinine clearance overestimate GFR. Percentage of creatinine secreted to urine increases with progression of CKD.

11. To measure CrCl by 24 hour urine
Measure volume (V), urine creatinine concentration (Ucr)
Measure serum creatinine (SCr)
UCr x V = N = Excretion rate
GFR = [UCr x V]/SCr
Normalize by BSA, GFR/1.73M2

12. Formulas for Estimation of GFR: prediction of creatinine generation using age, weight, sex, race, nutrition
Cockcroft-Gault (ml/min, developed using older creat assays): CrCl =(1 or 0.85)*(140 - Age) SCr * LBW/72
Need to adjust for BSA
Still calculated because drug dosing based on this formula

13. 2. MDRD
170 x SCr [-0.999] x Age[-0.176] x BUN [-0.170] x Alb [+0.318] x (0.762 if female) x (1.18 if black) Abbreviated MDRD: 175 * SCr * Age * (0.742 if female) x (1.21 if black) Both are mL/min/1.73 m2

14. 3. CKD-EPI
141 x min(SCr/κ, 1)α x max(SCr /κ, 1) x 0.993Age x [if female] x [if Black]
mL/min/1.73 m2
SCr (standardized serum creatinine) = mg/dL
κ = 0.7 (females) or 0.9 (males)
α = (females) or (males)
min = indicates the minimum of SCr/κ or 1
max = indicates the maximum of SCr/κ or 1
age = years

15. MDRD and CKD-EPI both are somewhat imprecise, but…
Both expressed as ml/min/1.73 M2
Neither need urine tests
In new forms, neither needs albumin or BUN
Both require age, sex, race data from outside the lab

16. Aging Decreases Kidney Function

17. Causes/Results of aging in the kidney

18. Therapies and factors of aging kidneys

19. Decline in CrCl with Age

20. So, if progressive loss of clearance is part of aging, how do we determine which patients have risk for ESRD?
Patients with proteinuria (urine albumin/creatinine ratio determines micro or macro)
Patients with rapid or sudden progression
Patients with systemic diseases

21. KDOQI gave us the classification of severity of kidney disease, in 2002

22. Number of patients with CKD 3 were astounding

23. So they added albuminuria grade in 2012

24. Studies confirmed that risk of ESRD increased with degree of proteinuriaHR

25. Best approach-combine eGFR and proteinuria for prediction
Referral based on current stages 3 to 4 CKD (eGFR 15 to 59 ml/min
per 1.73 m2) would include 4.7% of the general population and identify 69.4% of all individuals
progressing to ESRD. Referral based on our classification system would include 1.4% of the general
population without losing predictive power (i.e., it would detect 65.6% of all individuals progressing to
ESRD).

26. More papers confirm value of proteinuria measurement

27. And, other studies as well…

28. Prediction is very helpful…

29. Albuminuria has cardiac as well as renal risks

30. Summary of four main points…
The kidney’s efficiency in removing toxins is measured as “clearance”
Creatinine clearance can be estimated from a single blood test and some patient data
Aging affects the kidney almost uniformly, and creatinine clearance decreases with age
To determine which patients are at risk of serious kidney problems, estimate creatinine clearance and measure proteinuria.

31. Thank you.