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      A New Equation for Estimating Renal Function Using Age, Body Weight and Serum Creatinine

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          Background: Many formulas have been developed to estimate glomerular filtration rate (GFR). The aim of our study was to propose a new, more reliable equation. Methods: The study considered 530 subjects (training sample) with M/F 280/250, age 57.1 ± 17.4, creatinine clearance (CrCl) 55.2 ± 38.2 (range 2.1–144.0) for the development the new equation. A linear model was used to describe Cr production using serum Cr (sCr), age, and body weight (BW) as variables: (CrCl + b<sub>4</sub>) · sCr = b<sub>1</sub> – (b<sub>2</sub> · age) + (b<sub>3</sub> · BW) subsequently estimating parameter values by linear least squares, with CrCl as the dependent variable, and 1/sCr, age/sCr, BW/sCr as independent variables. CrCl = {[69.4 – (0.59 · age) + (0.79 · BW)]/sCr} – 3.0 (males) and {[57.3 – (0.37 · age) + (0.51 · BW)]/sCr} – 2.9 (females). A 229-patient renal failure validation sample with M/F 166/63, age 53.0 ± 14.8, GFR 32.0 ± 14.3 (range 4.3–69.8), assessed using iohexol Cl, was considered to compare the Cockcroft-Gault (C-G) and MDRD formulas with the new equation for estimating GFR. Results: The mean % error in GFR estimated by the new equation (+2.3 ± 28.3%) was better than with the C-G and MDRD formulas (+5.2 ± 30.1% and –11.4 ± 25.9%, respectively, p < 0.0005 and p < 0.0001), and so was the mean absolute % error, bordering on statistical significance (19.8 ± 20.3 vs. 21.1 ± 22.0 and 22.4 ± 17.3, p = 0.08 and p < 0.005). The precision was also better (RMSE = 7.89 vs. 8.02 and 9.13). The Bland-Altman test showed no GFR over or underestimation trend (measured ± predicted GFR/2 vs. % error, R<sup>2</sup> = 0.001). Conclusions: The new equation appears to be at least as accurate as the C-G and MDRD formulas for estimating GFR.

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          Limitations of creatinine as a filtration marker in glomerulopathic patients.

          To determine the reliability of creatinine as a measure of the glomerular filtration rate (GFR), we compared the simultaneous clearance of creatinine to that of three true filtration markers of graded size in 171 patients with various glomerular diseases. Using inulin (radius [rs] = 15 A) as a reference marker, we found that the fractional clearance of 99mTc-DTPA (rs = 4 A) was 1.02 +/- 0.14, while that of a 19 A rs dextran was 0.98 +/- 0.13, with neither value differing from unity. In contrast, the fractional clearance (relative to inulin) of creatinine (rs = 3 A) exceeded unity, averaging 1.64 +/- 0.05 (P less than 0.001), but could be lowered towards unity by acute blockade of tubular creatinine secretion by IV cimetidine. Cross-sectional analysis of all 171 patients revealed fractional creatinine secretion to vary inversely with GFR. This inverse relationship was confirmed also among individual patients with either deteriorating (N = 28) or remitting (N = 26) glomerular disease, who were studied longitudinally. As a result, changes in creatinine relative to inulin clearance were blunted considerably or even imperceptible. We conclude that true filtration markers with rs less than 20 A, including inulin, are unrestricted in glomerular disease, and that creatinine is hypersecreted progressively by remnant renal tubules as the disease worsens. Accordingly, attempts to use creatinine as a marker with which to evaluate or monitor glomerulopathic patients will result in gross and unpredictable overestimates of the GFR.
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            Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function.

            Recent recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients with chronic kidney disease. The most widely used equations are the Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulas. However, they still need to be validated in large samples of subjects, including large non-U.S. cohorts. Renal clearance of (51)Cr-EDTA was compared with GFR estimated using either the CG equation or the MDRD formula in a cohort of 2095 adult Europeans (863 female and 1232 male; median age, 53.2 yr; median measured GFR, 59.8 ml/min per 1.73 m(2)). When the entire study population was considered, the CG and MDRD equations showed very limited bias. They overestimated measured GFR by 1.94 ml/min per 1.73 m(2) and underestimated it by 0.99 ml/min per 1.73 m(2), respectively. However, analysis of subgroups defined by age, gender, body mass index, and GFR level showed that the biases of the two formulas could be much larger in selected populations. Furthermore, analysis of the SD of the mean difference between estimated and measured GFR showed that both formulas lacked precision; the CG formula was less precise than the MDRD one in most cases. In the whole study population, the SD was 15.1 and 13.5 ml/min per 1.73 m(2) for the CG and MDRD formulas, respectively. Finally, 29.2 and 32.4% of subjects were misclassified when the CG and MDRD formulas were used to categorize subjects according to the Kidney Disease Outcomes Quality Initiative chronic kidney disease classification, respectively.
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              Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate.

              Equations using serum creatinine level, age, sex, and other patient characteristics often are used to estimate glomerular filtration rate (GFR) in both clinical practice and research studies. However, the critical dependence of these equations on serum creatinine assay calibration often is overlooked, and the reproducibility of estimated GFR is rarely discussed. We address these issues in frozen samples from 212 Modification of Diet in Renal Disease (MDRD) study participants and 342 Third National Health and Nutrition Examination Survey (NHANES III) participants assayed for serum creatinine level a second time during November 2000. Variation in serum creatinine level was assessed in 1,919 NHANES III participants who had serum creatinine measured on two visits a median of 17 days apart. Linear regression was used to compare estimates. Calibration of serum creatinine varied substantially across laboratories and time. Data indicate that serum creatinine assays on the same samples were 0.23 mg/dL higher in the NHANES III than MDRD study. Data from the College of American Pathologists suggest that a difference of this magnitude across laboratories is not unusual. Conversely, serum creatinine assays an average of 2 weeks apart have better precision (SD of percentage of difference in estimated GFR, 15%; 90% of estimates within 21%). Errors in calibration make little difference in estimating severely decreased GFR (<30 mL/min/1.73 m2), but result in progressively larger differences at higher GFRs. Both clinical and research use of serum creatinine or equations to estimate GFR require knowledge of the calibration of the serum creatinine assay. Copyright 2002 by the National Kidney Foundation, Inc.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                January 2007
                29 November 2006
                : 105
                : 2
                : c43-c53
                aNephrology and Dialysis Unit and bLaboratory of Provincial Hospital, Camposampiero/Padova, cMario Negri Institute for Pharmacological Research, Bergamo, and dInstitute of Biomedical Engineering, ISIB-CNR, Padova, Italy
                97597 Nephron Clin Pract 2007;105:c43–c53
                © 2007 S. Karger AG, Basel

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                Figures: 5, Tables: 3, References: 22, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/97597
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