1. Early detection of CKD
CKD: Its out there somewhere

2. The Problem Chronic Kidney Disease is an epidemic worldwide
Growth 6-8% per annum of dialysis patients
Accumulating data re: possibility of delaying the progression of kidney disease, using multiple drug and behaviour intervention therapies.
Under-recognition at earlier stages of kidney dysfunction persists
Late referral
Lost opportunities for improved patient outcomes

3. Known CKD
<1% of population
Unrecognised CKD
10% of population

5. CKD Patients Are More Likely to Die than to Progress to ESRD
5 year follow-up
This study demonstrates that death was a far more common outcome than dialysis in all stages of CKD.
Key Talking Points
Keith and colleagues set out to understand the natural history of CKD with regard to progression to renal replacement therapy (RRT) (dialysis or transplant) and death in a representative patient population.
In 1996, 27,998 patients with estimated GFRs (eGFRs) <90 mL/min/1.73 m2 on 2 separate measurements were identified from computerized medical records.
These patients were followed until either RRT, death, or disenrollment from the health plan, or until June 30, 2001.
Among the adverse outcomes for CKD patients, death is more common than RRT at any CKD stage.
The data showed that the rate of RRT over the 5-year observation period was 1.1%, 1.3%, and 19.9%, respectively, for the K/DOQI™ stages 2, 3, and 4.
However, the mortality rate was 19.5%, 24.3%, and 45.7%, respectively.
Significantly, ~46% of stage 4 CKD patients died and did not end up on RRT.
Keith and colleagues suggest that efforts to reduce mortality in this population should be focused on treatment and prevention of coronary artery disease, congestive heart failure, diabetes, and anemia of CKD.
Reference
Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164:
Transition to Next Slide
These data suggest there should be increased predialysis management of CKD.
N=27998
Keith, et al, Arch Int Med; 2004; 164:

6. The Patient with early stage CKD is 5 to 10 times more likely to die from a cardiovascular event than progress to ESRD.
Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW, Collins AJ. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to J Am Soc Nephrol 2005; 16:

7. So what do we do ?

8. CKD: An Overall Health Approach
Complications
Normal
Increased risk
Damage
GFR
Kidney failure
DEATH
Screening for CKD risk factors
CKD risk factor reduction, screening for CKD
Diagnosis and treatment, treat comorbid conditions, slow progression
Estimate progression, treat complications, prepare for replacement
Replacement by dialysis and transplant

9. Defining “CKD”
Kidney damage for ≥ 3 months, defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either
Pathologic abnormalities, or
Markers of kidney damage, such as abnormalities of the blood or urine, or in imaging tests.
GFR < 60 mL/min/1.73 m2 for ≥ 3 months with or without kidney damage.
Introduction
The NKF defines CKD according to the presence or absence of kidney damage and level of kidney function.
Key Talking Points
Chronic kidney disease is defined as structural or functional abnormalities of the kidneys for 3 months, as manifested by either
GFR <60 mL/min/1.73 m2, with or without kidney damage
Kidney damage, with or without decreased glomerular filtration rate (GFR), defined by
Pathologic abnormalities or
Markers of kidney damage: blood or urine abnormalities or imaging tests
Proteinuria is a reflection of kidney injury and refers to increased urinary excretion of albumin, other specific proteins, or total protein.1
GFR is widely accepted as the best overall index of kidney function in health and disease.1,2 Normal GFR varies according to age, sex, and body size; in young adults it is approximately 120 to 130 mL/min/1.73 m2 and declines with age. A decrease in GFR precedes the onset of kidney failure; therefore, a persistently reduced GFR is a specific indication of CKD.2
References
1. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.
2. National Kidney Foundation—Kidney Learning System: frequently asked questions. Available at: Accessed June 27, 2005.

10. Defining “Kidney Damage”
Markers of Kidney Damage?
Proteinuria
Microalbuminuria
Hematuria (especially when seen with proteinuria)
Isolated hematuria has a long differential: infection, stone, malignancy, etc.
Casts (especially with cellular elements)

11. Stages of CKD by GFR Stage Description GFR 1 Kidney damage with
(mL/min/1.73m2) * 1
Kidney damage with
normal or  GFR
>90 2
Mild  GFR
60-89 3
Moderate  GFR
30-59 4
Severe  GFR
15-29 5
Kidney failure
<15 or Dialysis
Clinical practice guidelines 2000
New nomenclature and staging was designed to improve communication for clinical care, research initiatives and public awareness/education
Make the note that GFR (mL/min/1,73m2) can be approximated to percentage of kidney function
* It is helpful to think of GFR (mL/min/1.72m2) as an approximation of % Kidney function

12. NKF-K/DOQI Stages of “CKD”
Description
GFR
(mL/min/1.73m2) 1
Kidney damage with normal or  GFR
> 90 2
Mild  GFR
60-89 3
Moderate  GFR
30-59 4
Severe  GFR
15-29 5
Kidney Failure
< 15 or dialysis
Primary Care
Focus is here!

13. Measurement of Kidney Function

14. What Tests Are Available?
Direct GFR measurement
Inulin clearance
Radionuclides
Iohexol clearance
3 hr CrCl with Cimetidine
Prediction equations
Cystatin C
24 hr urine CrCl
Serum creatinine
Accurate
Inaccurate

15. Gold Standards Inulin clearance Radionuclides
Tedious, time consuming & unavailable
Radionuclides
125Iodine-iothalamate, technetium DTPA, 51Chromium-EDTA clearance
Time consuming and expensive
Research, accurate drug dosing

16. Chronic Kidney Disease
In 1999, the NKF approved a proposal for K/DOQI, Kidney Disease Outcomes Quality Initiative (an evolution of the DOQI (Dialysis Outcomes Quality Initiative).
The purpose was to develop clinical practice guidelines for the spectrum of kidney diseases.
In February 2002, Clinical Practice Guidelines for Chronic Kidney Disease (CKD): Evaluation, Classification, and Stratification were published.
Find the KDOQI guidelines at

17. Guideline 1. Definition and Stages of Chronic Kidney Disease
Adverse outcomes of CKD can often be prevented or delayed through early detection and treatment. Earlier stages of CKD can be detected through routine laboratory measurements.
The presence of CKD should be established, based on presence of kidney damage and level of kidney function (glomerular filtration rate [GFR]), irrespective of diagnosis.
Among patients with CKD, the stage of disease should be assigned based on the level of kidney function, irrespective of diagnosis, according to the K/DOQI CKD classification

18. Who should we screen?

19. How should we screen?

20. Serum Creatinine, CrCl, and eGFR--Nothing is Perfect!
Serum Creatinine alone CAN NOT be used to accurately assess level of kidney function.
S. creatinine is a function of production (muscle mass) and excretion (both GFR and tubular secretion).
Age, sex, and lean body mass have to be taken into account.
Estimations of eGFR (MDRD equation) and CrCl (Cockcroft-Gault equation) were NOT developed in subjects with normal renal function or normal health.

21. Factors Affecting Serum Creatinine Concentration
Increase Decrease
Kidney Disease
Ketoacidosis
Ingestion of cooked meat
Drugs:
Trimethoprim
Cimetidine
Flucytosine
Some cephalosporins
Reduced Muscle Mass
Malnutrition

22. Serum Creatinine: Problems
Non-renal influences
Gender, ethnicity, age and muscle mass
Nutrition/diet
Drugs (e.g. cimetidine)
Clinical utility
Poor sensitivity for CKD
Not useful in ARF
Muscle wasting disorders and amputees
Analytical problems
Non-specificity (protein, ketones, ascorbic acid)
No international standardization
Spectral interferences (icterus/lipaemia/haemolysis)

23. Serum Creatinine Hides Early Renal Damage
600
400
Serum creatinine (µmol/L)
200 2 3 4 5
CKD stage
Proportion
misdiagnosis 35 70
105
140
GFR (mL/min/1.73m2)
Reproduction from the late David Newman

24. Introduction of eGFR Will facilitate early recognition of CKD
Will result in increased awareness of advanced CKD previously not recognised as such

25. Effects of age on eGFR The “normal” eGFR is age-related
In normal “healthy” individuals, the eGFR will fall by one percent for every year after 40 years of age
An 80 year old man will have an expected eGFR of ml/min
Not all patients with reduced eGFR need active management

26. Which individuals with abnormal eGFR should we to worry about?
Those with very poor function for age
Those with deteriorating function
Those who may have reversible/treatable cause (unexplained proteinuria/haematuria)
Those with functional consequences of CKD (anaemia, renal bone disease, persistent hyperkalaemia)

27. GFR normally decreases with age!
Remember….
GFR normally decreases with age!

28. Cockcroft-Gault Equation to Predict GFR
Developed to predict creatinine clearance, thus an overestimate of GFR
Prediction based on age, gender, creatinine and ideal body weight
ClCr (cc/min) = [140-age] x IBW/72 x SCr x [0.85 if female]
Used almost universally as the basis for drug dosing!

29. MDRD Equation to Predict GFR
Prediction based on age, gender, race and serum creatinine. Developed to follow GFR as part of the Modification of Diet in Renal Disease (MDRD) study. Validated.
GFR/1.73m2 = 186 x [Pcr] x [age] x [0.742 if female] x [1.212 if AfAm]
Get it at

30. TA-DA! (Your on-line link to the MDRD GFR calculator)

31. Cockcroft-Gault vs. MDRD
The MDRD equation estimates GFR.
eGFR is given per 1.73m2 BSA
The Cockcroft-Gault equation estimates CrCl.
CrCl is best used for drug dosing decisions--drug dosing is usually indexed to CrCl.

32. Comparing the Cockcroft-Gault and MDRD:
Do these patients have the same level of renal function?
20 year old AfAm Washington Redskins tackle, weighing 144 kg with a SCr 1.2 mg/dl?
ClCr=[140-20][144]/72 x [1.2] =200 cc/min
MDRD GFR Value:99 mL/min/1.73 m2
93 year old Caucasian female nursing home resident, weighing
44 kg with a SCr 1.2 mg/dl.
ClCr = [140-93][44]/72 x [1.2] x 0.85 = 20 cc/min
MDRD GFR Value:45 mL/min/1.73 m2

33. Patient meets definition of Chronic Kidney Disease?
YES NO
Determine Stage of CKD
Determine underlying cause
Identify risk factors for progression
Identify comorbidites
Risk Factor Reduction

34. Tools for Determining the Cause of Chronic Kidney Disease
CKD is often silent. Assessment relies on laboratory testing and imaging.
A Good History! ROS, existence of chronic diseases (DM, HTN, CHF, cirrhosis), medication review, accurate PMH and FH of kidney disease.
Helpful Physical Examination! BP, evidence of co-morbid conditions and complications of CKD.

35. A Simple Laboratory Evaluation!

36. Simplified Classification of CKD by Diagnosis
Diabetic Kidney Disease
Nondiabetic Kidney Disease
Glomerular disease
autoimmune, sytemic infections, drugs, neoplasia, idiopathic
Vascular disease
ischemic renal disease, hypertensive nephrosclerosis, microangiopathy
Tubulointerstitial disease
UTO, stones, UTI, drug toxicity
Cystic disease
Post-Transplant

37. Differential Diagnosis of Chronic Kidney Disease
Everyone deserves a diagnosis!
This is especially true for Stage 1 or 2 CKD!
When in doubt, consult a nephrologist!
Initial evaluation will guide further diagnostics, decisions about renal biopsy and often decisions about treatment and prognosis.

38. (There’s a lot you can do!)
So Now What Do You Do?
(There’s a lot you can do!)

39. Measuring Proteinuria—Get into the right spot!
When you get to this point,
Don’t continue to get microalbumin!

40. Glomerular Filtration Rate
Sum of all nephron filtration rates
Best index of overall function
Reduction implies a problem
Translatable concept
Equates to percentage Kidney function

41. GFR Prediction Equations
Cockcroft-Gault formula
Ccr (ml/min) = 1.23 x (140-age) x weight/Pcr
(x 0.85 if female)
MDRD Study equation
GFR (ml/min/1.73 m2) = 186 x [(Pcr)/88.4] x (age) x (0.742 if female) x (1.210 if African American)
Cockcroft & Gault. Nephron 1976; 16: 31-41
Levey AS, et al. Ann Intern Med 1999;130:

42. MDRD equation vs serum creatinine
220
200
180
160
140
120
100 80
220
200
180
160
140
120
100 80
Males
Females
sCr (µmol/L)
79.4%
sCr (µmol/L)
98.4%
27.7%
81%
eGFR (ml/min/1.73m2)
eGFR (ml/min/1.73m2)
Middleton et al 2004

43. Scatter Increases as GFR Approaches Physiological Levels
Froissart et al JASN 2005;16:

44. MDRD Formula: validation

45. CKD: A Typical GP Practice of 100005 6 15 4 60
Stage of Kidney Disease 30
(GFR)
380 3 60 2
460 90 1