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CKD: Its out there somewhere

Early detection of CKD. CKD: Its out there somewhere. The Problem. Chronic Kidney Disease is an epidemic worldwide Growth 6-8% per annum of dialysis patients

maribeth-madsen
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CKD: Its out there somewhere

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  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

  4. CKD Patients Are More Likely to Die than to Progress to ESRD 5 year follow-up N=27998 Keith, et al, Arch Int Med; 2004; 164:659-663

  5. 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 1999. J Am Soc Nephrol 2005; 16:489-95.

  6. So what do we do ?

  7. CKD: An Overall Health Approach Complications Normal Increasedrisk Damage GFR Kidneyfailure DEATH Screeningfor CKDrisk factors CKD risk factorreduction, screening for CKD Diagnosisand treatment, treatcomorbid conditions,slow progression Estimate progression,treatcomplications, prepare for replacement Replacementby dialysisand transplant

  8. 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.

  9. 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)

  10. Stages of CKD by GFR * It is helpful to think of GFR (mL/min/1.72m2) as an approximation of % Kidney function

  11. NKF-K/DOQI Stages of “CKD” Primary Care Focus is here!

  12. Measurement of Kidney Function

  13. 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

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

  15. 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 http://www.kidney.org/professionals/KDOQI/

  16. 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

  17. Who should we screen?

  18. How should we screen?

  19. 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.

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

  21. 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)

  22. 4 3 2 CKD stage 5 35 70 105 140 Serum CreatinineHides Early Renal Damage 600 400 Serum creatinine (µmol/L) 200 Proportion misdiagnosis 0 GFR (mL/min/1.73m2) Reproduction from the late David Newman

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

  24. 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 50-60 ml/min • Not all patients with reduced eGFR need active management

  25. 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)

  26. Remember…. GFR normally decreases with age!

  27. 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!

  28. 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]-1.154 x [age]-0.203 x [0.742 if female] x [1.212 if AfAm] Get it at http://www.kidney.org/professionals/KDOQI/gfr.cfm

  29. TA-DA!(Your on-line link to the MDRD GFR calculator) http://www.kidney.org/professionals/KDOQI/gfr.cfm

  30. 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.

  31. 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

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

  33. 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.

  34. A Simple Laboratory Evaluation!

  35. 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 Simplified Classification of CKD by Diagnosis

  36. 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.

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

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

  39. 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

  40. 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]-1.154 x (age)-0.203 x (0.742 if female) x (1.210 if African American) Cockcroft & Gault. Nephron1976;16: 31-41 Levey AS, et al. Ann Intern Med 1999;130: 461-70

  41. MDRD equation vs serum creatinine 220 200 180 160 140 120 100 80 220 200 180 160 140 120 100 80 Females Males sCr (µmol/L) 79.4% 98.4% sCr (µmol/L) 27.7% 81% 30 40 50 60 30 40 50 60 eGFR (ml/min/1.73m2) eGFR (ml/min/1.73m2) Middleton et al 2004

  42. Scatter Increases as GFR Approaches Physiological Levels Froissart et al JASN 2005;16:763-773

  43. MDRD Formula: validation

  44. CKD: A Typical GP Practice of 10000 5 6 15 4 60 Stage of Kidney Disease 30 (GFR) 380 3 60 2 460 90 1

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