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Annals of Oncology 23: 1845–1853, 2012

doi:10.1093/annonc/mdr539
Published online 21 November 2011

Evaluation of glomerular filtration rate estimation by

Cockcroft–Gault, Jelliffe, Wright and Modification of
Diet in Renal Disease (MDRD) formulae in oncology
patients
N. L. Ainsworth1*, A. Marshall2, H. Hatcher1, L. Whitehead1, G. A. Whitfield1 & H. M. Earl1,3,4
1
Oncology Centre, Addenbrooke’s Hospital, Cambridge; 2Warwick Clinical Trials Unit, University of Warwick, Coventry; 3Department of Oncology, University of
Cambridge, Cambridge; 4National Institute for Health Research, Cambridge Biomedical Research Centre, Cambridge, UK

Received 15 February 2011; revised 29 August 2011; accepted 10 October 2011

Background: The aim was to evaluate the accuracy of Cockcroft–Gault, Jelliffe, Wright and Modification of Diet in
Renal Disease (MDRD) formulae as a substitute for the gold standard measure of glomerular filtration rate (GFR) using
chromium 51 EDTA.
Patients and methods: Retrospective analysis of GFR measurements in oncology patients from a University
Teaching Hospital over 3 years was carried out. Bias and precision of estimates of GFR were compared with measured
GFR.
Results: Six hundred and sixty patients with measured GFR (median 90 ml/min, range 23–179 ml/min) were identified.
Cockcroft–Gault produced the smallest bias (median percentage error −1.4%) and highest precision (median absolute
percentage error 14.0%) and was the most accurate for carboplatin dosing. For patients >30% over their ideal body
weight (IBW), using IBW + 30% in the Cockcroft–Gault formula was more precise than using actual body weight or
IBW. The Wright formula was most accurate for patients aged 70 + years and patients with a body mass index (BMI)
≥30 but overestimated GFR when GFR < 50 ml/min.
Conclusions: When measured GFR is unavailable, we advise estimating GFR using the Cockcroft–Gault formula and
using IBW + 30% for patients weighing >30% over their IBW. If the GFR is ≥50 ml/min and the patient is >70 years
and/or BMI ≥30, the Wright formula gives the best estimate of GFR.
Key words: carboplatin, Cockcroft–Gault, estimation, formula, glomerular filtration rate

introduction Carboplatin in particular is calculated using a targeted area

Many patients having therapy for cancer require assessment of
renal function for dosing of cytotoxic chemotherapy agents.
*Correspondence to: Dr N. L. Ainsworth, Oncology Centre, Addenbrooke’s Hospital,
Box 193, Hills Road, Cambridge CB2 0QQ, UK. Tel: + 44-0-1223-336800; Fax: + 44-0-
1223763120; E-mail: nicola.ainsworth@cancer.org.uk
under the plasma carboplatin concentration time curve (AUC)
instead of using body surface area (BSA) [1]. The Calvert
equation is used for dosing carboplatin and incorporates the
glomerular filtration rate (GFR) as its key variable (Figure 1). It
is therefore essential to establish an accurate GFR. Early trials
used 24-h urine creatinine collection and inulin excretion;

© The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com

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 original articles
however, these are unreliable [2, 3]. The most common
methods to calculate GFR use radioisotopes such as chromium
51 EDTA and technetium-99m diethyl triamine penta-acetic
acid or a nuclear camera renogram [4–6]. The chromium 51
EDTA clearance method [4] is accurate, reproducible and
commonly used. These methods are expensive and not always
immediately available, especially when treatment is being
delivered in the district hospital setting.
Multiple formulae have been devised to estimate the GFR as
a substitute for measurement (Figure 1). Cockcroft–Gault [7]
is the most commonly used formula and the modified Jelliffe
formula [8] has been used in some Gynaecologic Oncology
Group trials. Both of these formulae use patient characteristics,
e.g. age, sex, weight and serum creatinine, and assume that
creatinine is eliminated entirely by glomerular filtration. The
Wright formula was developed via a population kinetic method
derived from chromium 51 EDTA GFR in an oncology
population [9]. It can be complicated to calculate with different
versions incorporating creatine kinase and adjustments for
laboratory methods of calculating serum creatinine (enzyme or
Jaffe method).
The Modification of Diet in Renal Disease (MDRD) formula
is commonly used in clinical practice since the UK Guidelines
for the Identification, Management and Referral of Adults with
Chronic Kidney Disease recommended that an estimated GFR
should be calculated with every request for serum creatinine in
patients >18 years. The estimated GFR (Figure 1) is calculated
using the abbreviated MDRD equation [10] rather than the
six-variable version [11] (which includes urea and albumin as
well as age, sex, creatinine and race). The MDRD formula
results are reported as ml/min/1.73 m2 as BSA is not part of
the equation. The MDRD formula was not derived from
patients with serious illness and is not currently recommended
for oncology drug dosing.
Figure 1. Calculations.
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Annals of Oncology
In patients who weigh >30% above their ideal body weight
(IBW), pharmacists can correct for weight by using IBW in the
Calvert equation. This correction, however, can result in some
patients being administered lower carboplatin doses compared
with those weighing only slightly less. As a pragmatic rather
than evidence-based approach, some pharmacists use IBW +
30% in the calculation of GFR.
This study evaluates the accuracy and precision of the
Cockcroft–Gault, modified Jelliffe, Wright and MDRD
formulae in estimating GFR compared with a gold standard
measurement of GFR using chromium 51 EDTA GFR. We aim
to determine which formula is the best substitute for this gold
standard and evaluate the effect on carboplatin dosing in a
general cancer population. In the subgroup of patients
weighing >30% above their IBW, we evaluate three weight
corrections: actual body weight (ABW), IBW or IBW + 30%.
methods
patients
Details were obtained retrospectively of all oncology patients who had
undergone measurement of GFR by chromium 51 EDTA in the
Department of Nuclear Medicine at our institute over a 3-year period from
January 2003 until January 2006. The first recorded GFR was used for
patients with multiple records, except for six patients where errors had
been noted. Patient demographics were recorded at the initial visit. Body
mass index (BMI), BSA and IBW were calculated (Figure 1).
laboratory methods and GFR calculations
Single-sample GFR measurements were used until January 2005 and
subsequently a three-sample GFR was introduced. GFR was measured
following the intravenous injection of 2 MBq chromium 51 EDTA.
Serum creatinine was measured using the kinetic Jaffe method in
Addenbrookes Biochemistry Department within 4 weeks of the measured
chromium 51 EDTA GFR. The estimated GFR was calculated using the
Cockcroft–Gault, modified Jelliffe, Wright and MDRD formulae (Figure 1).
An adjustment for ethnicity was not included in the MDRD calculations,
as >95% of our population is Caucasian.
statistical methods
The degree of bias for each GFR formula from measured GFR (chromium
51 EDTA) was assessed by percentage error (PE), i.e. the percentage
difference between the estimated and measured GFR. Precision was
Table 1. Patient characteristics for the 660 patients
Characteristic Median (IQR) Range
Age (in years) 56 (45–65) 16–88
Sex, n (%)
Male 352 (53)
Female 308 (47)
Weight (kg) 75 (64–86) 40–151
Height (cm) 171 (163–178) 125–199
BSA 1.88 (1.71–2.03) 1.24–2.50
BMI 25.3 (22.7–28.8) 14.9–56.8
Serum creatinine 79 (67–93) 31–374
Chromium 51 EDTA GFR (ml/min) 90 (71–111) 23–176
BMI, body mass index; BSA, body surface area; GFR, glomerular filtration
rate; IQR, interquartile range.
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 Annals of Oncology original articles
assessed using absolute percentage errors (APEs), i.e. the absolute a single-sample chromium 51 EDTA GFR and 221 had the
difference between the estimated and measured GFR as a percentage of three-sample method. Overall, the median chromium 51
measured GFR. Box and whisker plots for PE and APE were constructed. EDTA GFR was 90 ml/min (range 23–179 ml/min). Twenty
In the subgroup of patients weighing >30% above their IBW, the APEs sets of notes were reviewed because of outlying chromium 51
from using different body weights in the estimated GFR formulae were EDTA results; 2 patients had documented ascites and 1 patient
compared using a Wilcoxon signed rank test. This assumes that had cachexia, but no reasons were identified in the other 17
underestimating or overestimating measured GFR by the same amount is
cases.
equivalent. If any IBW correction significantly improved the performance
of the GFR estimation over using ABW, then this correction was used in all
subsequent analyses. Bland and Altman [12] plots were constructed for the weight correction
difference in estimated and measured GFR against measured GFR after log In the 160 (24%) patients weighing >30% above their IBW, the
transformations. Regression lines for the expected value of the difference use of IBW considerably underestimated GFR, producing the
and appropriate limits of agreement were obtained [12]. worst median APE of all the weights considered and more
An AUC 5 (mg/ml/min)carboplatin dose was calculated for each GFR biased estimates for all formulae (Table 2).
measure using the Calvert dosing equation (Figure 1). Calculated doses With the Cockcroft–Gault formula, using IBW + 30%
were compared with doses obtained using measured GFR in terms of PE underestimated GFR (median PE −4.2%) to a lesser extent
and APE. An APE of >20% was considered to be a clinically relevant than the overestimation using ABW (median PE 11.5%;
difference in the carboplatin dose. Table 2) and had significantly greater precision (median
difference 4.7%, P = 0.003). In contrast, using ABW with the
Jelliffe formula produced less bias and significantly lower APE
results than using IBW + 30% (median difference −2.3%, P < 0.001).
Patient characteristics for the 660 patients identified are given With the Wright formula, using IBW + 30% did not
in Table 1. The median age was 56 years (range 16–88 years) significantly improve APE compared with using ABW (median
and 53% were male. Four hundred and thirty-nine patients had difference 0.1%, P = 0.35); although the bias was slightly closer
to zero using the IBW + 30%, the precision was slightly worse
Table 2. Percentage errors and absolute percentage errors for the four (Table 2).
different GFR formulae using ABW, IBW and IBW + 30% in the In all remaining analyses for this subgroup of 160 patients,
calculations for the patients weighing ≥30% over their IBW GFR was estimated using IBW + 30% in the Cockcroft–Gault
formula and using ABW in both the Jelliffe and Wright
GFR formula Percentage error, Absolute percentage formulae.
median (IQR) error, median (IQR)
Cockcroft–Gault different formulae
ABW 11.5 (−2.8 to 26.3) 15.9 (6.4–27.2) For all patients, the Cockcroft–Gault formula exhibited the
IBW −26.3 (−36.4 to −16.0) 26.7 (17.8–36.7) estimates with the least bias (median PE −1.4%; Table 3;
IBW + 30% −4.2 (−17.3 to 9.2) 12.6 (6.0–25.8) Figure 2). The Wright formula tended to overestimate GFR
Jelliffe (median PE 8.1%). The MDRD and Jelliffe formulae tended to
ABW −10.7 (−24.1 to 2.1) 18.0 (8.4–28.8) underestimate GFR (median PE −5.2% and −9.5%,
IBW −25.9 (−36.9 to −14.4) 26.0 (17.6–37.0) respectively; Table 3).
IBW + 30% −17.2 (−29.4 to −4.3) 20.1 (11.6–30.4)
The Cockcroft–Gault formula produced the most precise
Wright
GFR estimates (median APE 14.0%; Table 3; Figure 2), while
ABW 4.0 (−10.2 to 19.2) 13.2 (6.3–24.7)
the MDRD formula gave the most imprecise estimates (median
IBW −12.9 (−23.8 to 1.8) 17.3 (10.4–26.8)
APE 17.1%).
IBW + 30% −2.6 (−14.9 to 13.9) 14.4 (6.6–24.4)
The difference in estimated and measured GFR varied with
MDRD −15.7 (−32.0 to 2.7) 22.2 (9.8–33.4)
the level of GFR for all formulae except the Cockcroft–Gault,
ABW, actual body weight; GFR, glomerular filtration rate; IBW, ideal body as evidenced by the horizontal regression line (Figure 3). The
weight; IQR, interquartile range; MDRD, Modification of Diet in Renal difference in estimated and measured GFR varied most for the
Disease. MDRD method, which had the steepest regression slope

Table 3. Percentage errors and absolute percentage errors for the four different GFR formulae with the appropriate weight calculation for the patients
weighing ≥30% over their ideal body weight

GFR measure GFR measurement, median (IQR) Percentage error, median (IQR) Absolute percentage error, median (IQR)
Chromium 51 EDTA GFR 90 (71–111)
Cockcroft–Gault 86 (66–116) −1.4 (−13.5 to 14.8) 14.0 (6.1–24.9)
Jelliffe 80 (63–101) −9.5 (−20.3 to 4.2) 15.8 (8.0–26.2)
Wright 96 (76–121) −8.1 (−3.4 to 25.1) 14.5 (6.1–26.0)
MDRD 81 (67–102) −5.2 (−21.2 to 11.3) 17.1 (7.4–29.9)

GFR, glomerular filtration rate; IQR, interquartile range; MDRD, Modification of Diet in Renal Disease.

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Figure 2. Box and whisker plots of (A) percentage errors and (B) absolute percentage errors for the four different GFR formulae with the appropriate
weight calculation for the patients weighing ≥30% over their IBW. CG, Cockcroft–Gault; GFR, glomerular filtration rate; IBW, ideal body weight; MDRD,
Modification of Diet in Renal Disease.

(Figure 3). The variability of the differences remained stable clinical relevance
across all GFR values for all formulae, with all having fairly Using the Cockcroft–Gault formula produced the least bias
similar precision, although MDRD estimates were slightly (median PE −1.9%) and most precise (median APE 10.9%)
more dispersed.

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Figure 3. Plots of the mean differences and limits of agreement using (A) Cockcroft–Gault with ideal body weight + 30% for the patients weighing >30%
over their ideal body weight, (B) Jelliffe, (C) Wright and (D) MDRD. MDRD, Modification of Diet in Renal Disease.

Table 4. Carboplatin AUC 5 doses, percentage errors, APEs in carboplatin dose and the number (percentage) of patients with an APE >20% compared
with doses obtained using chromium 51 EDTA GFR for the four different GFR formulae with the appropriate weight calculation for the patients weighin
≥30% over their ideal body weight

GFR measure Carboplatin AUC 5 dose Percentage error, APE, median (IQR) APE > 20%, n (%)
(mg/ml/min), median (IQR) median (IQR)
Chromium 51 EDTA 580 (480–680)
Cockcroft–Gault 555 (460–705) −1.9 (−11.0 to 10.9) 10.9 (4.6–19.0) 142 (22)
Jelliffe 520 (440–630) −7.7 (−16.8 to 2.7) 12.2 (6.0–20.2) 168 (25)
Wright 600 (510–730) 5.7 (−3.2 to 18.4) 11.1 (4.7–19.7) 154 (23)
MDRD 530 (460–630) −4.6 (−17.0 to 8.1) 13.6 (6.0–22.9) 212 (32)

APE, absolute percentage error; AUC, area under the plasma carboplatin concentration time curve; GFR, glomerular filtration rate; IQR, interquartile range;
MDRD, Modification of Diet in Renal Disease.

carboplatin doses of all formulae (Table 4). Clinically relevant
dose variations of >20% APE would have occurred for 22% of
patients using the Cockcroft–Gault formula, compared with
32%, 25% and 23% for the MDRD, the Jelliffe and the Wright
formulae, respectively (Table 4).
results by subgroup
age
The GFR estimates using the Jelliffe formula were most
accurate with younger patients aged < 40 years (Table 5;
Figure 4). In patients aged 70 + years, the Wright formula gave
the least biased (median PE 4.3%) and slightly more precise
estimates of GFR (median APE 15.3%). Cockcroft–Gault
produced the least bias estimates for the 40- to 70-year olds
(median PE −2.0%).
glomerular filtration rate
Cockcroft–Gault was the most accurate formula over the full
range of GFR measurements (Table 5; Figure 4). In the 46
patients with low GFR ( < 50 ml/min), the Wright formula
produced the most biased and imprecise estimates (median PE
28.1%, median APE 28.1%). Over a normal GFR range of 50–
100 ml/min, estimates of GFR using the MDRD had the least

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Table 5. Bias and precision of each GFR formula by subgroup [median PE The Jelliffe formula includes BSA and has been shown
(bias) and APE (precision) are given] to have a greater bias than other formulae, particularly
when the BSA is small [16]. In our study, the Jelliffe
n Cockcroft Jelliffe Wright MDRD formula consistently underestimated GFR in most
PE APE PE APE PE APE PE APE situations, except in patients with a low GFR < 50 ml/min
GFR (ml/min) or BMI < 18.5. These findings are supported by other
< 50 46 8.3 12.7 2.2 11.5 28.1 28.1 17.520.5 studies [9, 17, 18].
50–100 365 −3.4 14.0 −8.7 14.0 9.6 13.8 −2.213.9 The Wright formula was developed in an oncology
>100 249 0.4 14.4 −13.3 18.0 3.0 13.6 −18.622.0 population; we would therefore have expected this formula to
Age (years) be the most accurate in estimating GFR in our population [9].
< 40 123 9.3 14.0 −2.9 14.4 12.5 15.7 −9.720.4 It has been shown in some studies to be more accurate than
40 to < 70 443 −2.0 13.7 −9.3 15.7 8.0 14.2 −5.916.1 other formulae [9, 19, 20]. This is in contrast to what we have
70 + 94 −13.7 17.1 −16.4 18.1 4.3 15.3 5.318.2 found in our study except within the subgroups of age 70 +
BMI and BMI >30. In the study by Wright et al. [9], using the same
< 18.5 23 −4.8 18.9 6.0 15.7 26.2 27.3 21.222.9 Wright formula as we have used (not incorporating creatine
18.5 to < 25 291 −3.4 13.8 −7.3 14.0 10.4 14.6 0.615.0 kinase and the Jaffe method of measuring creatinine; Figure 1)
25 to < 30 235 6.1 13.9 −11.0 15.7 7.1 15.4 −9.717.4 produced similar precision to our study (15% versus 14.5%,
30 + 112 −5.9 15.0 −13.2 19.4 2.8 13.0 −23.125.9
respectively) but underestimated the GFR by 5% compared
Bold values show either the least biased or smallest precision in each with an overestimation of 8.1% in our study. The Wright study
subgroup. had few patients with GFR < 50 ml/min and so does not
APE, absolute percentage error; BMI, body mass index; GFR, glomerular recommend that it be applied to a population with significant
filtration rate; MDRD, Modification of Diet in Renal Disease; PE, renal impairment. Our study and also a study by Poole et al.
percentage error. [17] have shown that in patients with a GFR < 50 ml/min, the
Wright formula considerably overestimated the GFR. We
included patients with a GFR < 50 ml/min to allow the
bias (median PE −2.2%), although Cockcroft–Gault had evaluation of the formulae in a representative oncology
similar bias (median PE −3.4%). population.
In UK, an estimated GFR using the abbreviated MDRD
body mass index equation, derived from patients with chronic renal disease, is
The most accurate and precise GFR estimates were obtained calculated with every request for creatinine in patients aged
using the Wright formula for patients with a BMI ≥30 >18 years but is not currently recommended for chemotherapy
(median PE 2.8%, median APE 13.0%; Table 5; Figure 4). The dosing [10]. The accuracy of the MDRD formula in a non-
Cockcroft–Gault formula produced the least biased and most oncology population has been extensively studied in a variety
precise estimates of GFR in patients with a BMI of 25 to < 30 of different patient groups [13–15, 21–26]. It is more accurate
(median PE 6.1%, median APE 13.9%). For patients with a than Cockcroft–Gault in non-cancer patients with chronic
normal BMI of 18.5 to < 25, Cockcroft–Gault formula was the renal disease [11, 14, 15, 22, 24, 27]; we, however, found the
most precise (median APE 13.8%), MDRD was the least biased converse was true for cancer patients. In patients with a
(median PE 0.6%) but had the worst precision (median APE normal GFR range, the evidence is equivocal as to which of the
15%). The Cockcroft–Gault formula produced the least biased two formulae is best at estimating GFR [13, 14, 25, 26], and
estimates for those with a BMI < 18.5 (median PE −4.8%); our data and Chew et al. [28] also suggest minimal differences.
however, all estimates were relatively imprecise in this group. A few studies have examined all the formulae specifically in an
oncology population [20, 29–32]. Barraclough et al. [19]
reported that in an oncology population with a mean
discussion measured GFR of 81 ml/min (367 patients), the Cockcroft–
To allow safe prescribing of renally excreted drugs in oncology, Gault formula underestimated GFR by 2% while the Wright
an accurate GFR is required. The gold standard is chromium formula overestimated it by 2% but was the most precise (APE
51 EDTA GFR but it is not always practical or possible to 19%). With the inclusion of 252 patients with a measured
obtain the result in time to start chemotherapy. Several GFR < 50 ml/min, all the formulae had similarly poor accuracy
formulae have been used to estimate GFR. [19].
The accuracy of Cockcroft–Gault in various clinical We evaluated the formulae in subgroups of patients based
situations has been evaluated and most studies have found it on age, weight and GFR. Marx et al. [18] found in a study of
underestimates the GFR over a normal measured GFR range an elderly oncology population (225 patients) that the Wright
[13–15]. Furthermore, as this formula is based on creatinine formula was the least biased (bias 0%, precision 16%) and the
clearance, it tends to overestimate GFR at low ranges of MDRD formula overestimated GFR whereas Cockcroft–Gault
measured GFR as it does not take into account the tubular and Jelliffe underestimated GFR. These findings are confirmed
excretion of creatinine. Our results are consistent with these by us and a number of other studies [33–35]. In patients who
findings. Despite this, in our study, Cockcroft–Gault tended to are overweight, our findings were similar to a study by Verhave
produce less biased and more precise estimates than the other et al. [34] in that Cockcroft–Gault overestimates GFR whereas
formulae for most subgroups (Table 6). the Jelliffe and MDRD formulae underestimate GFR. Our

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Figure 4. Box and whisker plots of percentage errors for the four different formulae with the appropriate weight calculations for the patients weighing
>30% over their IBW for each patient characteristic subgroup. IBW, ideal body weight.

results suggest that the Wright formula has the least bias for
patients with a BMI ≥30.
In patients who weigh >30% above their IBW, IBW is often
used in the estimating GFR formulae. In an attempt to correct
for potential underdosing, pharmacists in our institution use
IBW + 30% in the estimation of GFR. There are no published
studies confirming the appropriateness of using IBW + 30%.
Sparreboom et al. [36] evaluated the benefits of using
alternative weights for obese patients in the dose calculations of
anticancer drugs. They found in patients receiving carboplatin
that the average of IBW and ABW was the best predictor of
carboplatin clearance. A study by Ekhart et al. [37] suggested
that flat dosing of carboplatin in obese patients should be used.
In our subgroup of 160 patients who weighed >30% above

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Table 6. Formulae producing the least bias and most precision and the methods for measuring GFR and serum creatinine vary. Due to
most bias and least precision for each of the groups evaluated the retrospective nature of our study, we were unable to correct
for the many variables in our patient population. These include
GFR formula producing GFR formula producing factors such as muscle mass (which will affect creatinine), low
least bias and most most bias and least albumin, poor nutrition, oedema, ascites, co-morbidities (e.g.
precise estimates precise estimates renal problems), prior treatments and other medications.
GFR (ml/min) Ideally, we would prospectively review side-effects and
< 50 Jelliffe Wright differences due to carboplatin doses calculated by the different
50–100 MDRD/Cockcroft–Gault Jelliffe/Wright formulae.
>100 Cockcroft–Gault MDRD/Jelliffe Finally, the MDRD formula, as obtained in the clinical
Age (years) setting, performed worse in patients that were under- or
< 40 Jelliffe Wright overweight. This highlights the problem of the MDRD formula
40 to < 70 Cockcroft–Gault Jelliffe being based on the average BSA of a patient and not the
70 + Wright Jelliffe individual’s BSA. Therefore, in its current form it would be
BMI considered unsuitable for estimating GFR for the patients in
< 18.5 Cockcroft–Gault Wright/MDRD
the extreme weight categories. The performance of the MDRD
18.5 to < 25 MDRD/Cockcroft–Gault Wright
formula may be improved with an appropriate modification to
25 to < 30 Cockcroft–Gault MDRD/Jelliffe
adjust the formula for the patients’ BSA but this should not be
30 + Wright MDRD/Jelliffe
left to treating clinicians in busy clinics to adjust.
BMI, body mass index; GFR, glomerular filtration rate; MDRD,
Modification of Diet in Renal Disease.
conclusions
This study is one of the largest to evaluate the accuracy of four
commonly used formulae in an oncology population. It
IBW, using IBW in all the formulae underestimated GFR and highlights the inaccuracy of estimating GFR and the variability
we would therefore not recommend using IBW in calculations seen in clinical practice throughout UK. It is the first study to
of GFR. When using the Cockcroft–Gault formula, we would, investigate weight corrections for patients who weigh >30%
however, recommend using IBW + 30%. A large prospective above their IBW and to provide evidence to support current
study is required to validate these recommendations. clinical practice.
There is debate about using Cockcroft–Gault or MDRD as a All the formulae examined show a degree of bias and
substitute for chromium 51 EDTA in oncology drug dosing imprecision in estimating GFR and there is no perfect
[29, 30, 38, 39]. Some studies have found little difference substitute for chromium 51 EDTA GFR. Overall, in our study,
between them, although both were inaccurate [29, 39]. Others the Cockcroft–Gault formula is both the least biased and the
have found MDRD most accurate [38], especially in patients most precise formula and we would therefore recommend
who had poor general status [30]. Conversely, we found that an using this formula for calculation of estimated creatinine
additional 10% of patients would have received a >20% clearance/GFR and subsequent drug dosing when chromium
difference in carboplatin dose using the MDRD than the 51 EDTA GFR is unavailable. In patients who weigh >30%
Cockcroft–Gault formula. The question of what level of above their IBW, our data support the use of IBW + 30% in the
difference is clinically significant varies between studies Cockcroft–Gault formula. The Wright formula could be
(between 5% and 20%). In our study, ∼75% of the patients considered in patients aged 70 + years or in obese patients with
would receive a >5% difference in dose to that calculated by a BMI ≥30 if the GFR is >50 ml/min. We would not
chromium 51 EDTA GFR (data not shown), but this was as recommend using the Jelliffe or MDRD formula for estimating
high as 85% in the study by de Lemos et al. [29]. The effects of GFR to dose chemotherapy drugs. All the available formulae
underdosing are unclear; however, the toxicity from overdosing have limitations especially in the lower GFR range (GFR < 50
includes thrombocytopenia, neutropenia and the requirement ml/min) and measured creatinine clearance (e.g. using
for dose alterations. One study observed no variation in the chromium 51 EDTA) should continue to be used in this
rates of toxicity or number of dose modifications despite 48% subgroup until a more reliable formula is developed.
of patients having a >20% difference in the carboplatin dose
(using MDRD compared with the Cockcroft–Gault formula
and not chromium 51 EDTA GFR) [40]. disclosure
A limitation of our retrospective study is that the method for
chromium 51 EDTA GFR was altered from single-sample The authors declare no conflict of interest.
estimation to three-sample estimation in January 2005;
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doi:10.1093/annonc/mdr539 | 