Estimating GFR using serum beta trace protein: accuracy and validation in kidney transplant and pediatric populations
2009; Elsevier BV; Volume: 76; Issue: 7 Linguagem: Inglês
10.1038/ki.2009.262
ISSN1523-1755
AutoresChristine A. White, Ayub Akbari, Steve Doucette, Dean Fergusson, Naser Hussain, Laurent Dinh, Guido Filler, Nathalie Lepage, Greg Knoll,
Tópico(s)Dialysis and Renal Disease Management
ResumoThe limitations of estimates of glomerular filtration rate (GFR) based only on serum creatinine measurements have spurred an interest in more sensitive markers of GFR. Beta-trace protein (BTP), a low-molecular-weight glycoprotein freely filtered through the glomerular basement membrane and with minimal non-renal elimination, may be such a marker. We have recently derived two GFR estimation equations based on BTP. To validate these equations, we measured BTP and the plasma clearance of 99mTc-DTPA in 92 adult kidney transplant recipients and 54 pediatric patients with impaired kidney function. GFR was estimated using the serum creatinine–based Modification of Diet in Renal Disease (MDRD) Study equation for adults, the Schwartz and updated Schwartz equations in children, and 4 novel BTP-derived equations (our 2 equations and 2 proposed by Poge). In adults, our BTP-based equations had low median bias and high accuracy such that 89–90% of estimates were within 30% of measured GFR. In children, the median bias of our 2 equations was low and accuracy was high such that 78–83% of estimates were within 30% of measured GFR. These results were an improvement compared to the MDRD and Schwartz equations, both of which had high median bias and reduced accuracy. The updated Schwartz equation also performed well. The limitations of estimates of glomerular filtration rate (GFR) based only on serum creatinine measurements have spurred an interest in more sensitive markers of GFR. Beta-trace protein (BTP), a low-molecular-weight glycoprotein freely filtered through the glomerular basement membrane and with minimal non-renal elimination, may be such a marker. We have recently derived two GFR estimation equations based on BTP. To validate these equations, we measured BTP and the plasma clearance of 99mTc-DTPA in 92 adult kidney transplant recipients and 54 pediatric patients with impaired kidney function. GFR was estimated using the serum creatinine–based Modification of Diet in Renal Disease (MDRD) Study equation for adults, the Schwartz and updated Schwartz equations in children, and 4 novel BTP-derived equations (our 2 equations and 2 proposed by Poge). In adults, our BTP-based equations had low median bias and high accuracy such that 89–90% of estimates were within 30% of measured GFR. In children, the median bias of our 2 equations was low and accuracy was high such that 78–83% of estimates were within 30% of measured GFR. These results were an improvement compared to the MDRD and Schwartz equations, both of which had high median bias and reduced accuracy. The updated Schwartz equation also performed well. Serum creatinine is a crude marker of glomerular filtration rate (GFR) with several well-described limitations.1.Levey A.S. Measurement of renal function in chronic renal disease.Kidney Int. 1990; 38: 167-184Abstract Full Text PDF PubMed Scopus (476) Google Scholar,2.Levey A.S. Coresh J. Balk E. et al.National kidney foundation practice guidelines for chronic kidney disease: evaluation, classification and stratification.Ann Intern Med. 2003; 139: 137-147Crossref PubMed Scopus (3676) Google Scholar It can be noted that its serum concentration is dependent on various non-renal factors, such as muscle mass and turnover, medication use, diet, and non-renal elimination.1.Levey A.S. Measurement of renal function in chronic renal disease.Kidney Int. 1990; 38: 167-184Abstract Full Text PDF PubMed Scopus (476) Google Scholar GFR estimation equations derived from serum creatinine have repeatedly been shown to be inaccurate, particularly in patient groups that are distinct from those in whom the equations were derived such as kidney transplant recipients,3.White C. Akbari A. Hussain N. et al.Estimating glomerular filtration rate in kidney transplantation: a comparison between serum creatinine and cystatin C-based methods.J Am Soc Nephrol. 2005; 16: 3763-3770Crossref PubMed Scopus (157) Google Scholar, 4.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Cystatin C-based calculation of glomerular filtration rate in kidney transplant recipients.Kidney Int. 2006; 70: 204-210Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar, 5.Mariat C. Alamartine E. Barthelemy J.C. et al.Assessing renal graft function in clinical trials: can tests predicting glomerular filtration rate substitute for a reference method?.Kidney Int. 2004; 65: 289-297Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar patients with abnormal body composition,6Pham-Huy A. Leonard M. Lepage N. et al.Measuring glomerular filtration rate with cystatin C and beta-trace protein in children with spina bifida.J Urol. 2003; 169: 2312-2315Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar liver dysfunction,7.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Calculation of glomerular filtration rate based on cystatin C in cirrhotic patients.Nephrol Dial Transplant. 2006; 21: 660-664Crossref PubMed Scopus (113) Google Scholar or relatively well-preserved kidney function.8.Rule A.D. Larson T.S. Bergstralh E.J. et al.Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease.Ann Intern Med. 2004; 141: 929-937Crossref PubMed Scopus (909) Google Scholar,9.Bostom A.G. Kronenberg F. Ritz E. Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels.J Am Soc Nephrol. 2002; 13: 2140-2144Crossref PubMed Scopus (330) Google Scholar This is presumably due to the influence of the myriad of factors that affect creatinine production and non-glomerular excretion, which are not adequately 'corrected for' in the estimation equations. In the pediatric population, studies have also documented the poor performance of creatinine-based GFR estimates.10.Grubb A. Nyman U. Bjork J. et al.Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan–Barratt prediction equations for children.Clin Chem. 2005; 51: 1420-1431Crossref PubMed Scopus (387) Google Scholar, 11.Seikaly M.G. Browne R. Bajaj G. et al.Limitations to body length/serum creatinine ratio as an estimate of glomerular filtration in children.Pediatr Nephrol. 1996; 10: 709-711Crossref PubMed Scopus (77) Google Scholar, 12.Schwartz G.J. Furth S. Cole S.R. et al.Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children.Kidney Int. 2006; 69: 2070-2077Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar An 'updated' Schwartz equation based on serum creatinine has recently been described, but has not yet been validated in an independent pediatric population.13.Schwartz G.J. Munoz A. Schneider M.F. et al.New equations to estimate GFR in children with CKD.J Am Soc Nephrol. 2009; 20: 629-637Crossref PubMed Scopus (2400) Google Scholar Beta-trace protein (BTP) has emerged as an alternate endogenous marker of GFR.14.Huber A.R. Risch L. Recent developments in the evaluation of glomerular filtration rate: is there a place for beta-trace?.Clin Chem. 2005; 51: 1329-1330Crossref PubMed Scopus (28) Google Scholar It is a low-molecular-weight glycoprotein with 168 amino acids that is filtered through the glomerular basement membrane.15.Urade Y. Hayaishi O. Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase.Biochim Biophys Acta. 2000; 1482: 259-271Crossref PubMed Scopus (288) Google Scholar It appears to have minimal non-renal elimination.16.Olsson J.E. Link H. Nosslin B. Metabolic studies on 125I-labelled beta-trace protein, with special reference to synthesis within the central nervous system.J Neurochem. 1973; 21: 1153-1159Crossref PubMed Scopus (45) Google Scholar Since its first description as a marker of impaired renal function in 1997,17.Hoffmann A. Nimtz M. Conradt H.S. Molecular characterization of beta-trace protein in human serum and urine: a potential diagnostic marker for renal diseases.Glycobiology. 1997; 7: 499-506Crossref PubMed Scopus (117) Google Scholar BTP has been shown to be a more sensitive marker of GFR than creatinine in patients with chronic kidney disease,18.Priem F. Althaus H. Birnbaum M. et al.Beta-trace protein in serum: a new marker of glomerular filtration rate in the creatinine-blind range.Clin Chem. 1999; 45: 567-568PubMed Google Scholar, 19.Filler G. Priem F. Lepage N. et al.Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children.Clin Chem. 2002; 48: 729-736PubMed Google Scholar, 20.Woitas R.P. Stoffel-Wagner B. Poege U. et al.Low-molecular weight proteins as markers for glomerular filtration rate.Clin Chem. 2001; 47: 2179-2180PubMed Google Scholar, 21.Kobata M. Shimizu A. Rinno H. et al.Beta-trace protein, a new marker of GFR, may predict the early prognostic stages of patients with type 2 diabetic nephropathy.J Clin Lab Anal. 2004; 18: 237-239Crossref PubMed Scopus (31) Google Scholar in kidney transplant recipients,22.Poge U. Gerhardt T.M. Stoffel-Wagner B. et al.Beta-trace protein is an alternative marker for glomerular filtration rate in renal transplantation patients [see comment].Clin Chem. 2005; 51: 1531-1533Crossref PubMed Scopus (55) Google Scholar and in children.19.Filler G. Priem F. Lepage N. et al.Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children.Clin Chem. 2002; 48: 729-736PubMed Google Scholar Until recently, the absence of an equation to convert its serum concentration into an estimate of GFR has limited the clinical utility of BTP. We have recently proposed two GFR estimation equations based on serum BTP (Table 1).23.White C.A. Akbari A. Doucette S. et al.A novel equation to estimate glomerular filtration rate using beta-trace protein.Clin Chem. 2007; 53: 1965-1968Crossref PubMed Scopus (51) Google Scholar These were derived from a cohort of 163 kidney transplant recipients (mean age: 53±12 years, 67% men, 90% white), with a mean GFR of 59±23 ml per min per 1.73 m2. The purpose of this study was to validate these novel BTP-based equations in two independent patients groups consisting of a cohort of adult kidney transplant recipients and a cohort of children with impaired kidney function. The performance of the two BTP-based GFR estimation equations recently proposed by Poge et al.24.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.Am J Transplant. 2008; 8: 608-615Crossref PubMed Scopus (39) Google Scholar and of the updated Schwartz equation13.Schwartz G.J. Munoz A. Schneider M.F. et al.New equations to estimate GFR in children with CKD.J Am Soc Nephrol. 2009; 20: 629-637Crossref PubMed Scopus (2400) Google Scholar was also examined.Table 1Glomerular filtration rate (GFR) estimation equationsaGFR in ml per min per 1.73m2.ReferenceFormulaWhitebBTP in mg/l; urea in mmol/l; creatinine in μmol/l.GFR1=112.1 × BTP−0.662 × urea−0.280 × (0.880 if female)GFR2=167.8 × BTP−0.758 × creatinine−0.204 × (0.871 if female)PogebBTP in mg/l; urea in mmol/l; creatinine in μmol/l.GFR1=89.85 × BTP−0.5541 × urea−0.3018GFR2=974.31 × BTP−0.2594 × creatinine−0.647LeveycCreatinine in mg per 100ml.GFR=186 × creatinine–1.154 × age−0.203 × (0.742 if female) × (1.21 if black)SchwartzcCreatinine in mg per 100ml.Length in cm and creatinine in mg per 100ml.GFR=(k × length)/creatinine, k=0.7 (boys ≥13), k=0.45 (infants<1), k=0.55 (all others)Updated SchwartzcCreatinine in mg per 100ml.Length in cm and creatinine in mg per 100ml.GFR=(0.413 × length)/creatininea GFR in ml per min per 1.73 m2.b BTP in mg/l; urea in mmol/l; creatinine in μmol/l.c Creatinine in mg per 100 ml.d Length in cm and creatinine in mg per 100 ml. Open table in a new tab The clinical characteristics of the study groups are shown in Table 2. The adult cohort had an average age of 53±13 years and a median GFR of 51 (interquartile range (IQR) of 28) ml per min per 1.73 m2 (range: 11–99). All five stages of chronic kidney disease are represented.25.National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification.Am J Kidney Dis. 2003; 39: S1-S266Google Scholar The pediatric cohort had an average age of 10±5 years and a median GFR of 69 (IQR of 38) ml per min per 1.73 m2 (range: 16–97).Table 2Patient characteristicsaData expressed as mean±s.d. unless otherwise specified.CharacteristicAdult cohort (n=92)Pediatric cohort (n=54)Male (n (%))62 (68)32 (59)Age (years)53±1210±5Race (n (%)) White87 (95)NA Black2 (2)NA Other3(3)NAWeight (kg)85.9±22.737.9±22Height (cm)169.3±10.2133.1±31Body surface area (m2)1.96±0.261.16±0.43Medication (n (%)) Prednisone85 (92)NA Calcineurin inhibitor88 (96)NA Sirolimus4 (4)NA Mycophenolate mofetil63 (68)NA Azathioprine17 (18)NASerum creatinine (μmol/l)144±70106±68Serum urea (mmol/l)10±79±6Serum BTP (mg/l)1.29±0.711.67±1.12Median DTPA GFR (ml per min per 1.73 m2) (IQR)51 (28)69 (38)CKD stage by measured GFR (n (%)) Stage 1, GFR ≥90 ml per min per 1.73 m22 (2)8 (15) Stage 2, GFR 60–89 ml per min per 1.73 m226 (28)25 (46) Stage 3, GFR 30–59 ml per min per 1.73 m249 (53)12 (22) Stage 4, GFR 15–29 ml per min per 1.73 m212 (13)9 (17) Stage 5, GFR <15 ml per min per 1.73 m23 (3)0 (0)BTP, beta-trace protein; CKD, chronic kidney disease; DTPA, diethylenetriaminepentaacetic acid; GFR, glomerular filtration rate; IQR, interquartile range; NA, data not available.a Data expressed as mean±s.d. unless otherwise specified. Open table in a new tab BTP, beta-trace protein; CKD, chronic kidney disease; DTPA, diethylenetriaminepentaacetic acid; GFR, glomerular filtration rate; IQR, interquartile range; NA, data not available. The concordance correlation coefficients between the measured GFR and the estimation equation GFR are shown in Table 3. In adults, these were the strongest for the White BTP equations. In children, concordance was strongest for the updated Schwartz equation followed by the two White BTP equations. Table 4 shows the performance of the estimation equations. In the adult population, the bias of the White BTP equations was significantly lower than those of the four-variable Modification of Diet in Renal Disease (MDRD), Poge BTP1, and Poge BTP2 equations (P<0.0001 for all comparisons). They were highly accurate with 89 and 90% of estimates within 30% of the measured GFR for White BTP1 and White BTP2 equations, respectively. In comparison, the four-variable MDRD Study and Poge equations had higher negative bias and had lower accuracy with only 76, 76 and 65% of estimates within 30% of the measured GFR, respectively. The 30% accuracy of the White BTP1 equation was significantly higher than that of the Poge BTP1 (P=0.012) and Poge BTP2 (P<0.0001) equations. The 30% accuracy of the White BTP2 equation was significantly higher than that of the four-variable MDRD Study equation (P=0.01), Poge BTP1 (P=0.007), and Poge BTP2 (P<0.0001) equations.Table 3Concordance correlation coefficientsEquationAdults (95% CI)Pediatrics (95% CI)4-Variable MDRD study0.676 (0.577, 0.775)—Schwartz—0.681 (0.563, 0.800)Updated Schwartz—0.836 (0.757, 0.915)White BTP10.829 (0.765, 0.893)0.788 (0.676, 0.881)White BTP20.819 (0.751, 0.886)0.779 (0.676, 0.881)Poge BTP10.621 (0.518, 0.724)0.587 (0.456, 0.718)Poge 2 BTP20.511 (0.397, 0.625)0.699 (0.571, 0.827)BTP, beta-trace protein; CI, confidence interval; MDRD, Modification of Diet in Renal Disease. Open table in a new tab Table 4Bias, precision, and accuracy of creatinine and BTP estimatesaBias was defined as the difference between the estimated and the measured (99mTc-DTPA) GFR (estimated GFR – measured GFR); percentage bias was defined as [estimated GFR – measured GFR]/measured GFR × 100; precision was defined as the IQR for the median bias and standard deviation of the mean bias; both precision and bias were expressed as ml per min per 1.73m2; accuracy was defined as the proportion of estimates that were within 10 or 30% of the measured (99mTc-DTPA) GFR.Accuracy (% within)Median biasPrecision (IQR)Median % biasPrecision (IQR)Mean biasPrecision (s.d.)10%30%Adults 4-Variable MDRD−6.014.7−13.823.7−9.012.13276 White BTP1−0.311.9−0.925.9−1.510.63689 White BTP20.111.50.423.9−1.710.53890 Poge BTP1−9.312.6−19.620.5−11.011.32076 Poge BTP2−11.216.8−21.224.7−13.312.41865Pediatrics Schwartz15.522.530.236.218.617.01749 Updated Schwartz−6.114.2−9.426−4.913.13085 White BTP1−10.317.5−16.623.7−8.614.42878 White BTP2−8.315.6−15.223.0−7.116.12483 Poge BTP1−19.722.9−28.819.9−18.414.21150 Poge BTP2−9.021.1−18.629.9−9.516.22672BTP, beta-trace protein; IQR, interquartile range; MDRD, Modification of Diet in Renal Disease; 99mTc-DTPA, 99mtechnetium-diethylenetriaminepentaacetic acid.a Bias was defined as the difference between the estimated and the measured (99mTc-DTPA) GFR (estimated GFR – measured GFR); percentage bias was defined as [estimated GFR – measured GFR]/measured GFR × 100; precision was defined as the IQR for the median bias and standard deviation of the mean bias; both precision and bias were expressed as ml per min per 1.73 m2; accuracy was defined as the proportion of estimates that were within 10 or 30% of the measured (99mTc-DTPA) GFR. Open table in a new tab BTP, beta-trace protein; CI, confidence interval; MDRD, Modification of Diet in Renal Disease. BTP, beta-trace protein; IQR, interquartile range; MDRD, Modification of Diet in Renal Disease; 99mTc-DTPA, 99mtechnetium-diethylenetriaminepentaacetic acid. The performance analysis was repeated after subdividing patients by GFR greater (n=49) or less (n=43) than the median of 51 ml per min per 1.73 m2 (Table 5). Equation performance varies considerably between the subgroups, particularly for the Poge and MDRD Study equations with substantially increased underestimation (negative bias) of GFR with improved graft function. The White BTP equations show a more consistent performance across the two subgroups. Figure 1 shows the bias of each equation across levels of estimated GFR.Table 5Bias and 30% accuracy by GFR subgroups (GFR 51 ml per min per 1.73 m2, n=49) in the adult kidney transplant cohortMedian bias (ml per min per 1.73 m2)Percentage within 30%4-Variable MDRD study GFR 51 ml per min per 1.73 m2−24.265White BTP1 GFR 51 ml per min per 1.73 m2−4.994White BTP2 GFR 51 ml per min per 1.73 m2−4.896Poge BTP1 GFR 51 ml per min per 1.73 m2−14.871Poge BTP2 GFR 51 ml per min per 1.73 m2−19.949BTP, beta-trace protein; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease Study. Open table in a new tab BTP, beta-trace protein; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease Study. In the pediatric group, the White BTP1 equation had significantly lower bias than the Schwartz (P<0.0001) and Poge BTP1 (P<0.0001), but not the Poge BTP2 (P=0.42), equations (Table 4). Similarly, the White BTP2 equation had significantly lower bias than the Schwartz (P<0.0001) and Poge BTP1 (P<0.0001), but not the Poge BTP2 (P=0.15), equations. There were no significant differences in bias between the White BTP1 and BTP2 equations and the updated Schwartz equations (P=0.32, P=0.79). The accuracy of the White BTP equations was high with 78 and 83% of estimates within 30% of measured GFR for White BTP1 and White BTP2 equations, respectively. In contrast, only 48% of the Schwartz equation estimates and 50 and 72% of the Poge equation estimates were within 30% of the measured GFR. The updated Schwartz equation also showed high accuracy with 85% of estimates within 30% of the measured GFR. There were no significant differences in accuracies between the White BTP, updated Schwartz, and Poge BTP2 equations. This study reveals that the novel White BTP-based GFR estimation equations are accurate in both an adult and a pediatric population and shows improved estimation performance compared with the standard creatinine-based GFR estimation equations. To date, BTP has been studied to a limited extent in the pediatric population. Filler et al.19.Filler G. Priem F. Lepage N. et al.Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children.Clin Chem. 2002; 48: 729-736PubMed Google Scholar report that the reciprocal of BTP had a significantly higher correlation with GFR than that of serum creatinine, and that the diagnostic accuracy of BTP was improved over creatinine for the detection of a GFR <90 ml per min per 1.73 m2. The poor performance of the Schwartz equation in this study confirms previous reports of reduced accuracy in pediatric patients with impaired renal function.10.Grubb A. Nyman U. Bjork J. et al.Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan–Barratt prediction equations for children.Clin Chem. 2005; 51: 1420-1431Crossref PubMed Scopus (387) Google Scholar,11.Seikaly M.G. Browne R. Bajaj G. et al.Limitations to body length/serum creatinine ratio as an estimate of glomerular filtration in children.Pediatr Nephrol. 1996; 10: 709-711Crossref PubMed Scopus (77) Google Scholar Seikaly et al.11.Seikaly M.G. Browne R. Bajaj G. et al.Limitations to body length/serum creatinine ratio as an estimate of glomerular filtration in children.Pediatr Nephrol. 1996; 10: 709-711Crossref PubMed Scopus (77) Google Scholar showed that the Schwartz equation overestimated GFR by 90% in children with a GFR <50 ml per min per 1.73 m2. Grubb et al.10.Grubb A. Nyman U. Bjork J. et al.Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan–Barratt prediction equations for children.Clin Chem. 2005; 51: 1420-1431Crossref PubMed Scopus (387) Google Scholar report a mean percent bias of 51%, and only 25% of estimates were within 30% of measured GFR using the Schwartz equation in a cohort of 85 children. Similar to our findings, in a recent study Schwartz et al.12.Schwartz G.J. Furth S. Cole S.R. et al.Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children.Kidney Int. 2006; 69: 2070-2077Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar found that the equation overestimated the measured GFR by, on average, 12.2 ml per min per 1.73 m2 and postulated that this can been attributed to differences in creatinine assays. The original Schwartz equation was derived using creatinine measured using a Jaffe reaction, whereas the creatinine measured in the current and recent Schwartz studies were measured using enzymatic methods that yield lower values.26.Schwartz G.J. Brion L.P. Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents.Pediatr Clin North Am. 1987; 34: 571-590Crossref PubMed Scopus (1506) Google Scholar Recently, a novel creatinine-based estimation equation derived using enzymatic methods was proposed by Schwartz et al.13.Schwartz G.J. Munoz A. Schneider M.F. et al.New equations to estimate GFR in children with CKD.J Am Soc Nephrol. 2009; 20: 629-637Crossref PubMed Scopus (2400) Google Scholar This report is the first to validate it in an independent cohort of patients. Creatinine was measured using enzymatic methodologies, and the results show significantly improved performance compared with the traditional Schwartz equation. The performance of the BTP equations in the pediatric population is also encouraging and warrants further examination in other pediatric populations with varying degrees of impaired kidney function. There has been limited data reported on the use of BTP in kidney transplant recipients. Poge et al.22.Poge U. Gerhardt T.M. Stoffel-Wagner B. et al.Beta-trace protein is an alternative marker for glomerular filtration rate in renal transplantation patients [see comment].Clin Chem. 2005; 51: 1531-1533Crossref PubMed Scopus (55) Google Scholar showed that at a given GFR, BTP had a greater increase above the upper reference value compared with creatinine, although the diagnostic performance was similar by receiver operating characteristic analysis. In a recent publication, Poge et al.24.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.Am J Transplant. 2008; 8: 608-615Crossref PubMed Scopus (39) Google Scholar report on the derivation and validation of BTP-based GFR estimation equations in kidney transplant recipients. They propose two equations, one that included serum urea and the other serum creatinine. Similar to our work, the equation containing BTP and urea (Poge BTP1) had a higher R2 and improved performance when validated than that containing BTP and creatinine (Poge BTP2). Furthermore, the Poge BTP1 equation had a bias of only 0.43 ml per min per 1.73 m2 compared with the White BTP1 equation, which overestimated the measured GFR by 9.3 ml per min per 1.73 m2. In this study, the Poge equation underestimated the measured GFR by 11 ml per min per 1.73 m2 whereas the White BTP1 equation only underestimated it by 1.2 ml per min per 1.73 m2. Thus, in both studies, the White BTP1 equation provided estimates that are on average ~10 ml per min per 1.73 m2 higher than those calculated using the Poge equation. Both equations were derived using plasma diethylenetriaminepentaacetic acid (DTPA) clearance as the reference standard, and both include BTP and urea. The White equation also contains a gender-correcting factor that did not improve the model fit of the Poge equation.24.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.Am J Transplant. 2008; 8: 608-615Crossref PubMed Scopus (39) Google Scholar It is interesting to note that the model fit using BTP alone was substantially higher in our derivation cohort (R2=0.756) than that in the Poge study (R2=0.651).23.White C.A. Akbari A. Doucette S. et al.A novel equation to estimate glomerular filtration rate using beta-trace protein.Clin Chem. 2007; 53: 1965-1968Crossref PubMed Scopus (51) Google Scholar,24.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.Am J Transplant. 2008; 8: 608-615Crossref PubMed Scopus (39) Google Scholar The final model of White equation also had a higher R2 (0.81) compared with the Poge BTP1 equation (0.714).23.White C.A. Akbari A. Doucette S. et al.A novel equation to estimate glomerular filtration rate using beta-trace protein.Clin Chem. 2007; 53: 1965-1968Crossref PubMed Scopus (51) Google Scholar,24.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.Am J Transplant. 2008; 8: 608-615Crossref PubMed Scopus (39) Google Scholar Even without gender, the White model had an R2 of 0.791, and thus more of the variability in GFR could be explained by BTP and urea in the White model as opposed to the Poge model. The differing results of this current analysis and the Poge study24.Poge U. Gerhardt T. Stoffel-Wagner B. et al.Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.Am J Transplant. 2008; 8: 608-615Crossref PubMed Scopus (39) Google Scholar can be attributed to several factors. First, differences in populations may also be contributing to between study variance. The adult study populations are similar in gender, race, and age, but the derivation and validation cohorts of Poge et al. have a considerably lower average GFR. The performance of creatinine-based GFR estimation equations is dependent on GFR level in both kidney transplant27.White C. Akbari A. Hussain N. et al.Chronic kidney disease stage in renal transplantation classification using cystatin C and creatinine-based equations.Nephrol Dial Transplant. 2007; 22: 3013-3020Crossref PubMed Scopus (48) Google Scholar,28.Bosma R.J. Doorenbos C.R. Stegeman C.A. et al.Predictive performance of renal function equations in renal transplant recipients: an analysis of patient factors in bias.Am J Transplant. 2005; 5: 2193-2203Crossref PubMed Scopus (80) Google Scholar and non-transplant populations.8.Rule A.D. Larson T.S. Bergstralh E.J. et al.Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease.Ann Intern Med. 2004; 141: 929-937Crossref PubMed Scopus (909) Google Scholar,29.Stevens L.A. Manzi J. Levey A.S. et al.Impact of creatinine calibration on performance of GFR estimating equations in a pooled individual patient database.Am J Kidney Dis. 2007; 50: 21-35Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar This is presumably due to differences in creatinine production, renal handling of creatinine, and non-renal creatinine elimination at different levels of GFR. Similar to creatinine, the relationship between urea and GFR is confounded by other influences such as volume status,30.Dossetor J.B. Cr
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