Mnemotechnical note on the use of Cockcroft creatinine clearance formula for the validation of a 24-h urine collection

Albert Fournier,1 and Jean Michel Achard2

1 Service de Néphrologie, CHU Amiens, 2 Laboratoire de Physiologie, CHU Limoges, France

Introduction

The Cockcroft and Gault formula [1] for estimation of creatinine clearance (CCr) is well known by clinicians and universally used to estimate renal function reliably without the pitfalls of 24-h urine collection. Its use for estimation of 24-h creatininuria (namely when serum creatinine (SCr) is not available), is, however, unusual and subject to errors. The primary misunderstanding is the incorrect assumption that the numerator of the equation represents 24-h creatininuria when it actually represents only the creatininuria of 1000 min when SCr is expressed per litre and of only 100 min when SCr is expressed per decilitre. To calculate the 24-h creatininuria for validation of 24-h urine collection, the numerator (including the reciprocal of the coefficient sometimes put in the denominator), must be multiplied by 1.44 or 14.4 respectively.

Why does the numerator of the Cockroft creatinine clearance formula represent the creatininuria of 1000 min?

To understand this it is best to briefly recall the work of Cockroft and Gault. First they established the regression of creatininuria per kilogram in relation to age in 296 males whose duplicate measurements of 24-h creatininuria gave similar results.

This yielded the following formula for men when milligrams are used:

(1)

Since Cr clearance in ml/min is calculated by the formula:

(2)

(since there are 1440 min in 24 h)

Since SCr is not usually given in mg/ml but in mg/dl, mg/l, or µmol/l and because the denominator should remain constant in all equations, the coefficient of SCr in the denominator of the formula for CCr ml/min depends on the nature of these units, i.e. if SCr is in mg/dl:

if SCr is in mg/l:

if SCr is in µmol/l:


(since 1 mg/ml=8.85x103 µmol/l)

Another possibility for writing these formulae is to put in the numerator the reciprocal of the coefficient put in the denominator. When µmol/l units are used for SCr this expression becomes:

(5')

In the formulae given above for CCr, what is divided by the creatininaemia (i.e. the numerator when it includes the reciprocal of the coefficient put in the denominator) corresponds to the creatininuria of 1000 min when SCr is no longer expressed per ml but per litre, or to the creatininuria of 100 min if the SCr is expressed in mg/d. Indeed to obtain the result of CCr in its usual format of ml/min, the unit of SCr should be per ml. To get the adequate result for CCr when SCr is expressed per litre or 103 ml, the numerator of equation (2) should be multiplied by 1000 and by 100 when SCr is expressed per dl or 102 ml. Therefore once a clinician has memorized the formula that orresponds to the units usually reported by his laboratory, he must only remember to multiply the numerator of the Cockcroft formula by 1.44 or 14.4 according to whether SCr is expressed per litre or per decilitre (provided it includes the reciprocal of the coefficient sometimes put in the denominator).

This system is valid not only for the formulae for men but also for those established for women, whose mean 24-h creatininuria per kilogram BW is roughly 15% lower [2]. When the unit used for creatininaemia is µmol/l and the coefficient is put in the numerator of the clearance formula, the coefficient for women is 1.04 while that for men is 1.23.

In summary, when the international unit system is used, the formulae for 24-h creatininuria are as follows:


Validation of a 24-h urine collection

By evaluating the discrepancy between the actual measurement of the 24-h creatininuria and its estimation derived from the Cockcroft formula, the clinician can validate a 24-h urine collection without the dosage of creatininaemia. Indeed Cockcroft and Gault have shown that in 67% of the patients in steady state the discrepancy between the estimated and the actually measured 24-h creatininuria does not exceed 20%. Therefore 24-h urine collection may be considered inadequate when this discrepancy is greater than 20% except in the following unusual conditions:

extreme obesity or oedematous states that lead to an overestimation of creatininuria;

unusually lean and muscular athletes for whom the Cockcroft formula underestimates the actual lean body mass from BW;

unusual vegetarian diets that lead to overestimation of creatininuria and creatinine clearance from Cockcroft formula, or a diet excessively rich in meat that leads to the reverse error, since creatinine from meat is not taken into account in the formula;

administration of fibrate, and more specially fenofibrate, since we have recently drawn attention to the possibility that this cholesterol-lowering drug leads to an increase of creatininuria and creatininaemia without any change in creatinine or inulin clearances, [3]. This increase of creatininuria cannot be predicted from the Cockcroft formula and it explains the lower value of the predicted vs the actually measured value with regard to creatinine clearance and urinary excretion.

Finally we should point out that the Cockcroft formula was established after study of white men, and that in black men it is not as valid [4]. Goldwasser et al. showed that the 24-h creatininuria in milligrams is higher in black men; it is equal to [23.6-(age/8.3)+1.9]xBW, or if multiplied by 8.3/8.3 (or 1) to: [212-age]xBW/8.3. In white males the initial formula is the same with the exception of +1.9 deletion so that the final formula is [196-age]xBW/8.3. The reason for this difference is probably due to greater muscle mass per kilogram of BW, since the diet of the black men was not higher than that of white men [P. H. Goldwasser, personal communication].

Conclusion

The usefulness of the validation of a 24-h urine collection cannot be overemphasized, since it is the sine qua non condition for safe measurements of proteinuria rate (the best index of renal disease progression), of sodium and urea excretion (to check the sodium and protein intake), of calcium, uric acid, oxalate, citrate, magnesium, and cystine excretion rates (which are major risk factors of lithiasis independently of urine excretion rate), as well as of various hormone excretions (catecholamine, steroid hormones) in various hypertensive and endocrine diseases.

Notes

Correspondence and offprint requests to: A. Fournier, Service de Néphrologie, CHU Amiens, F-80054 Amiens cedex 1, France. Back

References

  1. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron1976; 16: 31–41[ISI][Medline]
  2. Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet1971; 1: 975–976[ISI][Medline]
  3. Hottelart C, El Esper N, Achard JM, Pruna A, Fournier A. Fenofibrate increases creatininaemia but does not alter glomerular filtration rate in patients with mild renal insufficiency. Nephrol Dial Transplant1998; 13: A2 (abstract)
  4. Goldwasser PH, Aboul-Magd, A, Maru M. Race and creatinine excretion in chronic renal insufficiency. Am J Kidney Dis1997; 30: 16–22[ISI][Medline]
Received for publication: 14.10.99
Revision received 21. 4.00.



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