ASSESSMENT OF RENAL FUNCTION

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1 ASSESSMENT OF RENAL FUNCTION Anita N. Jackson, Pharm.D. Spring 2012

2 Laboratory Tests to Assess Renal Function Serum Creatinine (SCr) Breakdown product of creatine metabolism Renal elimination only (90% glomerular filtration, 10% active tubular secretion) May have low serum creatinine with decreased muscle mass and/or inactivity Increased serum creatinine levels considered a marker of decreased renal function Normal SCr: mg/dl (may be lower) Normal urine creatinine (UCr): mg/24hrs

3 Laboratory Tests to Assess Renal Function Serum Creatinine (SCr) continued Historically significant inter-laboratory variability Development of IDMS-traceable calibration Fully implemented by 2010 Report of slightly lower SCr values than previous?? Normal range more like 0.5 to 1.0 mg/dl Likely result in higher estimates of renal function than prior to standardization with Clcr Adjustment in equation for egfr

4 Laboratory Tests to Assess Renal Function Serum or Blood Urea Nitrogen (BUN) Normal range: 7-20mg/dL Amino acids liver urea + ammonia Amount of urea in blood dependent on: Renal filtration Protein in diet Liver function Hydration status BUN/SCr ratio: 10-15:1

5 Laboratory Tests to Assess Renal Function Urine Protein or Albumin Normal kidneys excrete 30 to 150mg/day of total protein (<30mg of which is albumin) Proteinuria or Albuminuria marker of kidney damage Observation of + albumin in the urine on three occasions over 3-6 months Assess with urine dipstick sensitive to albumin Calculate urine albumin (mg) to creatinine (g) ratio Normal <30mg albumin/g of creatinine mg alb/g Cr is microalbuminuria range

6 Question You receive the following lab results for a patient: Na + = 147, BUN = 30, SCr = 0.9 Which of the following is most likely? 1. The patient is fluid overloaded/over-hydrated 2. The patient is dehydrated 3. The patient has a very low protein diet 4. The patient has renal dysfunction/impairment

7 Estimated Glomerular Filtration Rate (egfr) Estimate of how much blood flows through glomeruli each minute (ml/min/1.73m 2 ) What is a normal GFR? Equations to assess egfr take in to account 4 to 6 of these factors: Age Weight Serum creatinine Race Gender Diet

8 Estimated Creatinine Clearance (Clcr) Estimate of both GFR and some tubular secretion Cr cleared 90% by glomerulus, 10% tubular secretion Clcr is expressed in ml/min Equations to assess creatinine clearance take in to account: Serum creatinine (mg/dl) If SCr reported in mol/l divide the value by 88.4 to convert to mg/dl Age Weight Gender

9 Equations to Assess Renal Function Jeliffe or Brater in acute kidney injury (unstable) Cockroft-Gault (Clcr) or MDRD4 (egfr) in stable renal function

10 Cockroft-Gault Equation (CG) Clcr = {(140 age) X body weight in kg} (ml/min) 72 X SCr (mg/dl) Multiply result by 0.85 if female Controversy exists over use of actual body weight, ideal body weight, adjusted body weight Controversy exists over rounding up for low SCr

11 Long-Term Memory Practice Study

12 Question How would using actual body weight affect the estimated Clcr for an obese patient? How would using actual body weight affect the estimated Clcr for an elderly patient with low body weight/muscle mass?

13 Question A 65 year old white female has a serum creatinine of 1.3 mg/dl. She weighs 129lbs and is 5 4 tall. What is her estimated Clcr (rounded to the nearest whole number) using the CG equation? ml/min ml/min ml/min ml/min

14 Modification of Diet in Renal Disease Study Equation (MDRD4) egfr (ml/min/1.73m 2 ) = 175 X (SCr) X (age) X (0.742 if female) X (1.212 if African American) NKF Calculator Must multiply by actual BSA to get egfr in ml/min Only used for drug dosing, extremes in BSA BSA = { (ht (cm) x wt (kg)/3600}

15 Assessment of Renal Function Jeliffe, Brater Equations Use for unstable serum creatinine Defined as a change in SCr of >50% over a period of one day with previously normal renal function Defined as a change of SCr of >30% over a period of hours with CKD Take in to account two different serum creatinine values Used to estimate Clcr (not GFR) Time difference in days between values

16 Equations in Unstable Renal Function Jeliffe Clcr in ml/min/1.73m 2 Use IBW if actual BW > 30% above IBW E ss = wt[ (age)] males E ss = wt[ (age)] females E ss corr = E ss [ (SCr)] E = E ss corr {4 x wt(scr 2 SCr 1 )/ t (days) Clcr = E / 14.4(SCr)

17 Equations in Unstable Renal Function Brater Clcr in ml/min/70kg For females multiply total by 0.86 Clcr = { (age) x [ X (SCr 1 +SCr 2 )] / (SCr 1 + SCr 2 )} + {49(SCr 1 -SCr 2 )/(SCr 1 - SCr 2 ) X t (days)}

18 Examples of Equations in Unstable SCr A 50-year-old white male (70kg, BSA 1.73) is admitted to the ICU after a MVA. His renal function was normal on admission; however SCr increased from 0.6 to 3.0 mg/dl in 24 hours. What is estimated Clcr? Jeliffe: Clcr = 21.9 ml/min Brater: Clcr = 19.1 ml/min Cockroft-Gault =??

19 Examples of Equations in Unstable SCr The previous patient has remained in the ICU for a week and is improving. His SCr has decreased from 3.0 to 1.0 mg/dl in the past 24 hours. What is estimated Clcr? Jeliffe = 64.5 ml/min Brater = 78.7 ml/min Cockroft-Gault =??

20 Controversies in Renal Assessment Discrepancies exist among clinicians regarding methods of calculating Clcr using CG Survey of nephrology and critical care pharmacists About 1-2% use actual body weight About 20-28% use ideal body weight About 16-25% use adjusted body weight About 45-50% use some other method including clinical judgment Use of actual serum creatinine when measured value is low Rounding serum creatinine to 1.0 or 0.8

21 Discussion Examples A 49kg, 74-year-old female with low muscle mass and a serum creatinine of 0.5 mg/dl A 108kg, sedentary 29-year-old male with a SCr of 1.4 mg/dl A 90kg, 41-year-old male body builder with a SCr of 1.2 mg/dl A 60kg, 76-year-old female with low muscle mass and a SCr of 1.0 mg/dl

22 For OVERWEIGHT patients.

23 Controversies in Renal Assessment Controversies exist related to use of Cockroft-Gault versus MDRD equation CG estimates Clcr which takes in to account some active tubular secretion (ATS) Kidneys switch to more ATS as renal function declines Clcr calculation may overestimate contribution of GFR MDRD most accurate when GFR < 60mL/min/1.73m 2 Intended to stage chronic kidney disease Hospital laboratories report egfr values (>70%) Approved drug labeling uses eclcr with CG equation

24 Scatterplot of the Agreement Between C-G and MDRD Formulae in the Estimation of GFR Melloni, C. et al. J Am Coll Cardiol 2008;51: Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

25 Concordance between Kidney Function Categories Assigned using Measured GFR vs. Estimated Kidney Function Equation Concordant (%)* Discordant (%) Lower than mgfr Higher than mgfr MDRD Study CG CGIBW *p-value <0.001 for the difference in concordance among all equations Abbreviations: mgff, measured glomerular filtration rate; MDRD, Modification of Diet in Renal Disease Study equation; CG, Cockcroft-Gault equation using actual body weight; CGIBW, Cockcroft-Gault equation using ideal body weight. Stevens LA, et al. Am J Kidney Dis July; 54(1): 33-42

26 Concordance between Drug Dosing Recommendations using Measured vs. Estimated Kidney Function* MDRD Study Cockcroft-Gault Cockcroft-GaultIBW Con Discordant Con Discordant Con Discordant Lower Higher Lower Higher Lower Higher *Overall Averages in % Stevens LA, et al. Am J Kidney Dis July; 54(1): 33-42

27 Example of CG vs MDRD4 A new antibiotic magnafloxacin is dosed 200mg twice daily with estimated renal function of >50 ml/min and 100mg twice daily for ml/min. The PI does not specify to use egfr or Clcr. What would the dose be for the following patient using CG versus MDRD4? An 80-year-old African American female who weighs 154lbs and is 5 5 tall with a SCr of 1.1 using an IDMS traceable calibration

28 Example CG vs MDRD (continued) Actual body weight = 154/2.2 = 70 kg Height = 65 X 2.54 = 165 cm BSA = (165)(70)/3600 = 1.79m 2 {(140-80)(70)/(72)(1.1)}0.85 = 45 ml/min Dose using CG = 100mg BID (175)(1.1) (80) (0.742)(1.212)(1.79/1.73) = 60 ml/min Dose using MDRD4: 200mg BID

29 24-Hour Urine Collection? Optimal to collect urine for a full 24 hours Urinary excretion of creatinine is diurnal Some data suggests short collection with forced diuresis may be more accurate The measured serum creatinine is ideally drawn half-way through the collection period Clcr = UCr (mg/dl) X Vol (ml) SCr (mg/dl) x t (min)

30 Fractional Sodium Secretion Fractional excretion of sodium (FENa) For assessment in acute renal failure Useful when urine volume < 500 ml/day Comparison of amount of sodium excreted with amount filtered and reabsorbed by the kidney FENa (as %) = (Na u X Cr s) / (Na s X Cr u ) X 100 FENa <1% suggests prerenal azotemia FENa >2% suggests intrinsic renal failure

31 Question A 24 hour urine collection is performed for a patient to assess creatinine clearance and a total of 400mL is collected. What is the Clcr in ml/min a patient with a SCr of 1.4 mg/dl and a UCr of 226 mg/dl? ml/min ml/min ml/min 4. >120 ml/min

32 Cockroft-Gault

33 References National Kidney Disease Education Program Dowling, et. al. Renal drug dosing approaches. Pharmacotherapy 2010;30(8): Dipiro et al. Pharmacotherapy: A Pathophysiologic Approach, 7 th Edition ACCP Pharmacotherapy Review 2011 Koda-Kimble et al. Applied Therapeutics: The Clinical Use of Drugs, 9 th Edition

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