Re : Schwartz formulae

Nick, Thanks for your detailed answer. The first source that you mention precisely 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 contradiction with a satisfactory degree of centering of the Cockroft-Gault or MDRD formulas, sufficient to allow their clinical use in patients monitoring, as reported in table 46. The original Cockroft-Gault formula had been calibrated against 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 GFR (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: [email protected] on behalf of Nick Holford 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. 2002a. 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 Zealand [email protected] tel:+64(9)923-6730 fax:+64(9)373-7090 http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford