Schwartz formulae

Dear NMusers, I am having difficulty with the Schwartz formulae for computing GFR in kids. Some references state that the formula gives GFR in mL/min while others say it is mL/min/1.73 m². Also the value of k varies between references. This is what I plan on using. Are these formulas in the right units with the correct constants. Please advise, Mahesh ~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~* Schwartz formula: GFR (mL/min/1.73 m²) = k*Height(cm) / Serum Creatinine (mg/dL) k = 0.33 in Preterm Infants k = 0.45 in Term infants to 1 year old k = 0.55 for children aged 2 to 12 years k = 0.55 for girls 13 to 21 years, and k = 0.70 for boys 13 to 21 years GFR corrected for the child's actual BSA, which can be obtained using the DuBois and DuBois formula GFR corrected = [GFR * 1.73] / BSA The DuBois and DuBois formula: BSA (m²) = (Weight^0.425 x Height^0.725) x 0.007184 where the weight is in kilograms and the height is in centimeters. ~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*

Dear Mahesh, As any model the original equation of Schwartz is evolving over the years and as more data is gathered. The original paper had only one k : Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58:259–263. Then it was extended to other age groups to account for the maturational changes: Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34:571–590. Then other papers suggested different adjustment to the original formula... and to make it applicable for other age groups. Please also note that the original k are applicable only for the old/standard Jaffe method to measure serum creatinine. Newer methods require some adjustments. Newer formulas are now published using cystatin and other markers. Zappitelli M, Parvex P, Joseph L, et al. Derivation and validation of cystatin C-based prediction equations for GFR in children. Am J Kidney Dis 2006; 48:221–230 (standard Schwartz formula may be misleading when we have renal impairment) New equations to estimate GFR in children with CKD. Schwartz GJ, Muoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. J Am Soc Nephrol. 2009 Mar;20(3):629-37. Epub 2009 Jan 21. Estimating and measuring glomerular filtration rate in children. Work DF, Schwartz GJ. Curr Opin Nephrol Hypertens. 2008 May;17(3):320-5. Review. The right formula will depend on the nature of your pediatric population you want to calculate CRCL for , the method used for serum creatinine and whether you have some renally impaired children or not. Hope this helps Samer

Dear Mahesh, As any model the original equation of Schwartz is evolving over the years and as more data is gathered. The original paper had only one k : Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58:259–263. Then it was extended to other age groups to account for the maturational changes: Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34:571–590. Then other papers suggested different adjustment to the original formula... and to make it applicable for other age groups. Please also note that the original k are applicable only for the old/standard Jaffe method to measure serum creatinine. Newer methods require some adjustments. Newer formulas are now published using cystatin and other markers. Zappitelli M, Parvex P, Joseph L, et al. Derivation and validation of cystatin C-based prediction equations for GFR in children. Am J Kidney Dis 2006; 48:221–230 (standard Schwartz formula may be misleading when we have renal impairment) New equations to estimate GFR in children with CKD. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. J Am Soc Nephrol. 2009 Mar;20(3):629-37. Epub 2009 Jan 21. Estimating and measuring glomerular filtration rate in children. Work DF, Schwartz GJ. Curr Opin Nephrol Hypertens. 2008 May;17(3):320-5. Review. The right formula will depend on the nature of your pediatric population you want to calculate CRCL for , the method used for serum creatinine and whether you have some renally impaired children or not. Hope this helps Samer

Hi Mahesh In addition to those papers presented by Samer, the following paper is also likely to be very useful, and has good biological basis. Human renal function maturation: a quantitative description using weight and postmenstrual age. Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, Chatelut E, Grubb A, Veal GJ, Keir MJ, Holford NH. Pediatr Nephrol. 2009 Jan;24(1):67-76. Epub 2008 Oct 10. Best wishes Carl

Mahesh, Samer, The Schwartz formulae are based on theoretical allometric principles. The allometric theory is based on the assumption that creatinine production rate (CPR) is proportional to body surface area. Other possibilities exist e.g. that CPR is directly proportional to body mass. It is usually assumed that CPR is proportional to muscle mass. Theoretical allometry (West et al. 1999) would suggest that a structural feature such as muscle mass would be best described by an allometric coefficient of 1. Putting these two assumptions together would indicate that CPR and body mass should be related linearly. This is the assumption made in the Cockcroft & Gault formula. Part of the need to change 'k' for different sizes of children may be due to choosing the wrong allometric model. The Schwartz formula coefficient 'k' has various empirically determined values depending on age and sex. This means that the original allometric theory has been discarded in favour of empirical allometry. Theoretical allometry is primarily concerned with the relationship between body size and body structure or function. Other things such as age and sex can of course be important to describe how muscle mass and thus CPR may differ between people. But these other factors should be considered in addition to the fundamental allometric method and not used to distort it. The changing values of 'k' in the various Schwartz formulae are a consequence of this ad hoc approach. It should also be noted that the Schwartz formulae are designed to predict creatinine clearance (CLcr). 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) (see Hellerstein et al 1992). This is different from adults in whom GFR and CLcr are very similar. Nick Hellerstein S, Alon U, Warady BA. Creatinine for estimation of glomerular filtration rate. Pediatr Nephrol. 1992;6:507-11. West GB, Brown JH, Enquist BJ. The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science. 1999;284(5420):1677-9. Mouksassi Mohamad-Samer wrote: > Dear Mahesh, > > As any model the original equation of Schwartz is evolving over the years and > as more data is gathered. > > The original paper had only one k : > > Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of > glomerular filtration rate in children derived from body length and plasma > creatinine. Pediatrics 1976; 58:259–263. > > Then it was extended to other age groups to account for the maturational > changes: > > Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration > for estimating glomerular filtration rate in infants, children, and > adolescents. Pediatr Clin North Am 1987; 34:571–590. > > Then other papers suggested different adjustment to the original formula... and > to make it applicable for other age groups. > > Please also note that the original k are applicable only for the old/standard > Jaffe method to measure serum creatinine. > Newer methods require some adjustments. > > Newer formulas are now published using cystatin and other markers. > > Zappitelli M, Parvex P, Joseph L, et al. Derivation and validation of cystatin > C-based prediction equations for GFR in children. Am J Kidney Dis 2006; > 48:221–230 > > (standard Schwartz formula may be misleading when we have renal impairment) > New equations to estimate GFR in children with CKD. > Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. > J Am Soc Nephrol. 2009 Mar;20(3):629-37. Epub 2009 Jan 21. > > Estimating and measuring glomerular filtration rate in children. > Work DF, Schwartz GJ. > Curr Opin Nephrol Hypertens. 2008 May;17(3):320-5. Review. > > The right formula will depend on the nature of your pediatric population you > want to calculate CRCL for , the method used for serum creatinine and whether > you have some renally impaired children or not. > > Hope this helps > > Samer >

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

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://wwwkidneyorg/Professionals/Kdoqi/guidelines_ckd/p5_lab_g4htm . 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://wwwkidneyorg/Professionals/Kdoqi/guidelines_ckd/p10_appendix3htm . 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