1. Assesment of renal function in case of near normal creatinine (<1
Naseer Khan MD

2. Burden of CKD Stage II in USA
According to the NHANES III-study the prevalence of stage 2 chronic kidney disease is 3% in the American population i.e. about persons are afflicted

3. Prevalence of CKD by GFR in the USA (There is a lot of CKD!)
Stage
Description
GFR
(mL/min/1.73m2)
Prevalence
Prevalence (%) 1
Kidney damage with normal or  GFR
> 90
5.9 million
3.3% 2
Mild  GFR
60-89
5.3 million
3.0% 3
Moderate  GFR
30-59
7.6 million
4.3% 4
Severe  GFR
15-29
400,000
0.2% 5
Kidney Failure
< 15 or dialysis
300,000
Coresh, et al, Am J Kidney Dis. 2003; 41: 1-12

5. What is GFR ?
It is the volume of glomerular filtrate produced per unit of time, e.g. mL/min
GFR Quality means the composition of GFR in a patient relative to normal person
Real GFR not measurable except in lab.
80,000 nephrons make it less easy
Surrogate markers with limitations in use

6. Gold Standard Methods
Plasma clearance of inulin, iohexol, 51Cr-EDTA, 125I-iothalamate, 99mTc-diethylenetriaminepentaacetic acid
GFR markers are creatinine and Cystatin C which are now clinically used
GFR equations are based on either S.Creatinine and Cystatin C

7. Age
Gender
Race
SCr (mg/dL)
eGFR (mL/min/1.73 m2)
CKD Stage 20 M B*
1.3 91 1 W† 75 2 55 W 61 F 56 3 B 50 46

8. Problems with S.Creatinine
Varies with age , sex , muscle mass
Also varied results with exercise and protein intake
Does not show or predict quality of GFR like in cases of pre-eclempsia
One equation alone cannot predict accurate GFR
Both secreted and excreted

9. Cystatin C All nuclear human cells produce this protein
120 amino acid ( small Mol.weight)
Removed from blood stream by filtration by kidneys; fully reabsorbed ( no urine excretion)
Decline in GFR results in rise of Cystatin C
Cross sectional studies show superiority to creatinine

10. Emerging role of Cystatin C
Demonstrates the early, potentially reversible, decrease of GFR in the “creatinine-blind” area
Independent of muscle mass and diet
Independent of sex and age for children above 1 year
Demonstrates the decrease of GFR in old persons
No tubular secretion ; CV mortality data

11. Creatinine limitation with age

12. Age related Cystatin C levels

13. Creatinine blind area

14. GFR-markers for patients with muscle atrophy
Non-parametric ROC plots
for serum cystatin C (solid line)
AUC = and serum creatinine
(dotted line) AUC = 0.507
AUC = 0.50 equals the diagnostic
efficiency of tossing a coin

15. Why use equations?
Equations estimate GFR taking into account creatinine; age ; gender; body surface area ; race
Adults : Cockcroft-gault equation
MDRD equation
Children :Schwartz & Counahan-Barratt equations

16. Any value of 24 hours urine collection
24 hr collection does not improve GFR estimation ( equations are better)
Helpful in persons with exceptional dietary variation ( vegetarians; protein diet)
Amputees
Muscle wasting /atrophy/ malnourished patients
Criteria for starting dialysis

17. GFR equations MDRD: GFR = 186.3 x (creatinine/88.4)-1.154 x age-0.203
x (if female) x (if African American)
GFR(CC-estimate)= x cystatin C x (if child<14years)

18. Is GFR always the best marker for kidney disease/function?
Qualitative and quantitative measurement of urine proteins more important in paraproteinemia
Erythropoiten is a better marker for hormonal function of kidney
GFR quality is altered in Pre-eclempsia which is not detected by creatinine but is better outline by Cystatin C

19. Cystatin C in Pre-eclempsia

20. Creatinine in pre-eclempsia

21. What do we do now ? Use History and Physical as Gold Standard
Keep in mind limitations of serum creatinine measurement
Use more than one GFR marker
Use more than one equation while using S.Cr ( Lund University online equation)
Cystatin C seems promising esp. for qualitative analysis

22. Identify High Risk Groups
Diabetes
Hypertension
Heart Disease
Family History
High Risk Ethnic Group
Age > 60 years
Screening : eGFR
Urinalysis
Albumin / Creatinine Ratio

23. PCP Must be Engaged 7.7 million people with GFR 30-60 mL/min/1.73 m2
About 5,000 full-time nephrologists
Nearly 1,500 new patients per nephrologist
Therefore, 7 new patients per day per nephrologist. Obviously not possible.

24. Prevention Of Renal Failure
Who should take the lead?
The primary care physician and the
nephrologists
PRIMARY CARE
PHYSICIAN
NEPHROLOGISTS
Screening
Diagnosis
Treatment
Diagnosis
Management
Pre Dialysis care

25. Old Chinese saying……. Good doctor relieve disease
Better doctor cure disease
Superior doctor prevent disease