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Multiple Clearance Methods, Staging and Special handling of
patients under 60 inches
Patient Name:      Location:
Age:    Scr:     Gender:
Select serum creatinine reference standard:   [more info]
   
Height:      Weight:
For MDRD and CKD-EPI equation. specify race:
Is the serum creatinine (Scr) currently stable:   
Staging:  Has the patient had kidney damage or  GFR <60 ml/min/1.73m2 for geq 3 months

Chronic kidney disease: "defined as kidney damage or GFR < 60 ml/min/1.73m2 for geq 3 months.  Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies." 9
Restrict the maximum calculated clearance to this value: 
Select option for calculating the IBW for patients under  60 inches
(default option - BMI method): 

[See reference section]





Creatinine Clearance methods

Cockcroft and Gault equation utilizing the tbw (Total body weight) to calculate an estimated creatinine clearance
Cockcroft and Gault equation:
CrCl = [(140 - age) x TBW] / (Scr x 72) (x 0.85 for females)

Cockcroft and Gault equation utilizing the ibw (Ideal body weight) to calculate an estimated creatinine clearance
Cockcroft and Gault equation:
CrCl = [(140 - age) x IBW] / (Scr x 72) (x 0.85 for females)
Note: if the ABW (actual body weight) is less than the IBW use the
actual body weight for calculating the CRCL.

Estimate Ideal body weight in (kg)
Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet.
Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.

Cockcroft and Gault equation utilizing the adjusted body weight to calculate an estimated creatinine clearance.
CrCl = [(140 - age) x AjBW] / (Scr x 72)

Note: (Multiply result by 0.85 for females)
AjBW = adjusted body weight:
AjBW = IBW + 0.4( ABW - IBW)

Estimated IBW:
Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet.
Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.

Some studies have shown that utilizing the adjusted body weight improves accuracy compared to other commonly used equations in estimating the creatinine clearance in the elderly population.

Simplified 4-variable MDRD study formula
GFR = 186.3 x (SCR)-1.154  x  (age in years)-0.203  x  1.212 (if patient is black)  x 0.742 (if female)

Key point: Early statistical analysis shows very promising results. May represent the most accurate choice of this group. This may be especially true in chronic kidney disease.

CKD-EPI equation

GFR = 141 x min(Scr/κ,1)α x max(Scr/κ,1)-1.209 x 0.993Age x 1.018 [if female]
       x 1.159 [if black]

κ = 0.7 if female.
κ = 0.9 if male.

α = -0.329 if female
α = -0.411 if male

min = the minimum of Scr/κ or 1
max =  the maximum of Scr/κ or 1

"BACKGROUND:   Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values." 1

"CONCLUSION:  The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use." 13

References
  1.  Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41
  2. Davis GA, Chandler MH. Comparison of creatinine clearance estimation methods in patients with trauma. Am J Health-Syst Pharm 1996;53:1028-32.
  3. Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatistics. 2nd ed. Norwalk, CT: Appleton & Lange; 1994.
  4. Demirovic JA, Pai AB, Pai MP. Estimation of creatinine clearance in morbidly obese patients. Am J Health Syst Pharm. 2009 Apr 1;66(7):642-8.    
    "An LBW estimate, based on TBW and BMI, incorporated into the Cockcroft-Gault equation provided an unbiased, relatively precise, accurate, and clinically practical estimate of 24-hour measured CLcr in morbidly obese patients."

    Lean body weight - male:   9270 x tbw/6680 + 216 x BMI
    Lean body weight - female:  9270 x tbw/8780 + 244 x BMI

    Obese study population: As expected, use of Cockcroft-GaultTBW grossly overestimated measured CLcr. The Cockcroft-GaultABW0.3, Cockcroft-GaultABW0.4, and Salazar-Corcoran equations all overestimated measured CLcr values in the study patients. In contrast, the Cockcroft-GaultIBW and the MDRD4 equations underestimated measured CLcr values. The Cockcroft-GaultLBW equation was the most precise, and the MDRD4 equation was the least. The Cockcroft-GaultFFW and Cockcroft- GaultLBW equations yielded the highest accuracy (55-61%), in yielding values that were within 30% of the measured CLcr.
  5. Dettli LC. Drug dosage in patients with renal disease. Clin Pharmacol Ther 1974;16:274-80.
  6. Drusano LG, Munice HL, Hoopes JM et al. Commonly used methods of estimating creatinine clearance are inadequate for elderly debilitated nursing home patients. J Am Geriatrics Soc 1998;36:437-41.
  7. Hailemeskel B, Namanny M, Kurz A. Estimating aminoglycoside dosage requirements in patients with low serum creatinine concentrations. Am J Health-Syst Pharm 1997;54:986-7.
  8. Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet 1971;1:975-6.
  9. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. © 2002 National Kidney Foundation. (link)
  10. Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine (Abstr) J Am Soc Nephrol 2000;(11):155A
  11. Levey AS, Greene T, Schluchter MD, et al. Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group. J Am Soc Nephrol 1993;4(5):1159-71
  12. Levey AS. Assessing the effectiveness of therapy to prevent the progression of renal disease. Am J Kidney Dis 1993;22(1):207-14
  13. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130(6):461-70
  14. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J.  A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009; 150:604-612.
  15. Rhodes RS, Sims PJ, Culbertson VL et al. Accuracy of creatinine clearance estimates in geriatric males with elevated serum creatinine clearance. J Geriatric Drug Ther 1991;5:31-45.
  16. Salazar DE, Corcoran GB: Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med 84: 1053-1060, 1988.
  17. Smythe M, Hoffman J, Kizy K et al. Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. Am J Hosp Pharm 1994;51:189-204.
  18. Wilhelm SM, Pramodini KP. Estimating Creatinine Clearance: A Meta-analysis. Pharmacotherapy 2011 31:7 , 658-664.
    "Conclusion. Using the Cockcroft-Gault equation with no body weight (NBW) and actual Scr value most closely estimated measured Clcr. In obese patients, it may be reasonable to use actual body weight with a correction factor of 0.3 or 0.4 and actual Scr value in the Cockcroft-Gault equation. Based on this analysis, the use of total body weight, ideal body weight, and a rounded Scr value cannot be recommended."
  19. Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy 2012; 32: 604-612 [PMID: 22576791 DOI: 10.1002/j.1875-9114.2012.01098.x]

    Quotes: [Largest study so far....total of 3678 patients]
    Regarding Salazar equation: This equation, however, was not consistently shown in studies to be a superior predictor of renal function. It is not widely used in clinical practice and has not been validated in pharmacokinetic studies. In addition, the Salazar-Corcoran equation is not recognized by the National Kidney Foundation.

    Regarding CG -LBW equation: Our findings do not support those conclusions and are different from a recent investigation of Clcr in 54 morbidly obese patients that found that adjusting an obese patient’s weight to a fat-free weight or lean body weight predicted a Clcr calculated with the C-G equation without bias. Notably, our study included 2065 obese or morbidly obese patients, far more than other published studies. 

    Conclusions: An unbiased C-G Clcr can be calculated using actual body weight in underweight patients and ideal body weight in patients of normal weight. Using ABW0.4 for overweight, obese, and morbidly obese patients appears to be the least biased and most accurate method for calculating their C-G Clcr. Rounding Scr in patients with low Scr did not improve accuracy or bias of the Clcr calculations.  top of page

Background info for height less than 60 inches top of page
If the actual body weight is less than any of the calculation methods, the actual body weight will be used.
Discussion of the various methods:   The output of this section is based on research I had completed ~20 years ago on this subject.  A quick review of the recent literature has not changed or added any new methods for estimating an ideal body weight for patients less than 60 inches tall.  Note: naming convention is based on my earlier work...

1] Intuitive Method:
Reference: Murdaugh LB. Competence Assessment Tools for Health-System Pharmacies. 5th ed. Bethesda, MD: ASHP; 2015. [Chap:29 Medication dosing in Patients with Renal Dysfunction]
IBW (Male) = 50kg - 2.3kg for each inch below 60 inches
IBW (Female) = 45.5kg - 2.3kg for each inch below 60 inches
Comments:  For patients just a few inches below 60 inches, the result is reasonable, however, 2.3 kg/inch is excessive when used for shorter heights.  At 38 inches for a male, and 40 inches for a female, the IBW is ZERO.   This provides support for the next method below.

2] Baseline Method: 
The baseline method starts with the initial ideal body weight baseline values e.g. 60 inch male patient - 50kg and 60 inch female patient - 45.5kg.   Male patient: 50kg /60 inches = 0.833 kg/inch.  Female patient = 45.5kg/60 inches = 0.758 kg/inch.   Therefore a male patient - 55 inches: IBW = 50kg - (0.833 x 5) = 45.8kg versus the first method = 50kg - (2.3 x 5) = 38.5 kg.
[Reference: reasonable assumption based on the standard ideal body weight equations and the baseline weights established for a height of 60 inches.
Also review: Murphy JE. Introduction. In: Murphy JE, ed. Clinical Pharmacokinetics, 5th ed. Bethesda, MD: American Society of Health-System Pharmacists, 2011:xxxiv. - Note: for patients who are less than 60 inches tall, the weight should be decreased more conservatively than 2.3kg/inch.]

3]  BMI method: 

References:
Wiggins, K. L. (2004). Renal care: Resources and practical applications. Chicago: American Dietetic Association. pg 12.

Barash, P. G., Cullen, B. F., & Stoelting, R. K. (1989). Clinical anesthesia. Philadelphia: Lippincott. chap:47:1231

Remember that BMI = weight(kg)/height2 (meters squared).   Next, we will establish an 'ideal' BMI based on values in the standard IBW equations: Male: 60 inches - 50kg - BMI= 21.53.   Female: 60 inches - 45.5kg - BMI= 19.59.  We can then use this association to generate an equivalent ideal weight based on this standardized BMI and the height of the patient.  Using the example above (55 inch male patient):
IBW = 21.53 (BMI value above)  x (55 x 0.0254)2  = 42 kg.
Background info: the body mass index quantifies the amount of tissue mass at a particular height (units: kg/m2).  Example: the following patients all have a BMI ~ 21:  130 lbs - 5'6",  163 lbs - 6'2",  107 lbs - 5'.

BMI

19

20

21
Height
(inches)		 Body Weight (pounds)
58 91 96 100
59 94 99 104
60 97 102 107
61 100 106 111
62 104 109 115
63 107 113 118
64 110 116 122
65 114 120 126
66 118 124 130
67 121 127 134
68 125 131 138
69 128 135 142
70 132 139 146
71 136 143 150
72 140 147 154
73 144 151 159
74 148 155 163

4] Hume method: 
LBW (Males) = (0.3281 x Weight in kg) + (0.33939 x Height in cm) - 29.5336
LBW (Females) = (0.29569 x Weight in kg) + (0.41813 x Height in cm) - 43.2933
Using the example above:   (55 inch male patient):  IBW= 36.9 kg

Reference: Hume R.  Prediction of lean body mass from height and weight.  J Clin Path(1966), 19, 389.

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