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Re : Schwartz formulae

From: Buclin Thierry <Thierry.Buclin>
Date: Mon, 6 Apr 2009 10:42:54 +0200


Nick,

Thanks for your detailed answer. The first source that you mention precisel=
y
states that "creatinine clearance systematically overestimates GFR.
This overestimation is approximately 10% to 40% in normal individuals" and=
 
illustrates this nicely in figure 12. This is not necessarily in contradict=
ion
with a satisfactory degree of centering of the Cockroft-Gault or MDRD formu=
las,
sufficient to allow their clinical use in patients monitoring, as reported=
 
in table 46. The original Cockroft-Gault formula had been calibrated agains=
t
actual creatinine clearance, which it predicts correctly; but it should
therefore be corrected to accurately predict true GFR, which is lower than =
CLcr.
On the other hand, the MDRD formula has been directly calibrated against GF=
R
(assessed by iothalamate clearance).
Thus, I would still consider that in adults as in children, creatinine is
secreted to a nonnegligible extent by renal tubules, and this biases to
some extent the use of creatinine clearance to estimate GFR.
Friendly regards

Thierry


-----Message d'origine-----
From: owner-nmusers
Re: [NMusers] Schwartz formulae

Thierry,

Thanks for directing me to the results of your 12 selected young men who
had creatinine clearance greater than sinistrin clearance. The in depth
review by the National Kidney Foundation (NKF 2000a) reported the
results of several large studies comparing Cockcroft & Gault CLcr
predictions with GFR (using a variety of methods). The largest study of
1775 patients found a 1% bias of CLcr compared with GFR. This is the
basis of my assertion which you raise an objection to. Other studies
found small biases but none as large as those you report (see NKF 2002a
Table 46). Note that the NKF define bias quite reasonably (see NKF
2002b) but their definition of accuracy is what most other people would
call some measure of imprecision.

I think there are certainly some controversial issues about comparison
of CLcr with GFR. But studies in children using appropriate Schwartz
formulae such as Hellerstein et al. 1992 (note the NKD 2002a only used
one formula) find that CLcr based on that method overestimates GFR. In
very young neonates it is the other way around and Clcr seems to be less
than GFR (see Guignard et al. 1999). It could be that in older adults
the tubular secretion of creatinine is less active and the
overprediction of GFR using CLcr is therefore mainly seen in children
and younger adults (such as those you studied).

Nick


National Kidney Foundation. KDOQI Clinical Practice Guidelines for
Chronic Kidney Disease: Evaluation, Classification, and Stratification
PART 5. EVALUATION OF LABORATORY MEASUREMENTS FOR CLINICAL ASSESSMENT
OF KIDNEY DISEASE GUIDELINE 4. ESTIMATION OF GFR
http://www.kidney.org/Professionals/Kdoqi/guidelines_ckd/p5_lab_g4.htm. 200=
2a.

National Kidney Foundation. KDOQI Clinical Practice Guidelines for
Chronic Kidney Disease: Evaluation, Classification, and Stratification
PART 10. APPENDICES APPENDIX 3. METHODOLOGICAL ASPECTS OF EVALUATING
EQUATIONS TO PREDICT GFR AND CALCULATIONS USING 24-HOUR URINE SAMPLES
http http://www.kidney.org/Professionals/Kdoqi/guidelines_ckd/p10_appendix3=
.htm.
2002b.

Hellerstein S, Alon U, Warady BA. Creatinine for estimation of
glomerular filtration rate. Pediatr Nephrol. 1992;6:507-11.

Guignard J-P, Drukker A. Why Do Newborn Infants Have a High Plasma
Creatinine? Pediatrics. 1999;103(4):e49-.



Buclin Thierry wrote:
> Nick
>
> This is just to express some objection to your last sentence below:
> > In children with more or less normal renal function
> > the Schwartz predicted CLcr is 30% greater than
> > concurrently measured inulin clearance
> > (a 'gold standard' GFR estimation method).
> > This is different from adults
> > in whom GFR and CLcr are very similar.
> Actually in adults, CLcr also overestimates by 20-40% the true GFR,
> as creatinine undergoes tubular secretion in addition to
> glomerular filtration (the inhibition of organic cation transporters
> is able to bring creatinine clearance near to inulin clearance).
> In a recent study, we found average 34% to 39% differences
> between both clearances in healthy volunteers, in line with others.
> (Tschuppert Y & al. Effect of dronedarone on renal function in
> healthy subjects. BJCP 2007; 64(6):785-791)
> Kind regards
>
> Thierry
>
>
> PD Dr Thierry Buclin
> Division of clinical Pharmacology and Toxicology
> Departement of Médecine, University Hospital of Lausanne (CHUV)
> Hôpital Beaumont 633
> 1011 Lausanne
> tel. +41 21 314 42 60
> fax. +41 21 314 42 66
>
>

--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealan=
d
n.holford
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Received on Mon Apr 06 2009 - 04:42:54 EDT

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