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      A Comparison of Prediction Equations for Estimating Glomerular Filtration Rate in Adult Patients with Chronic Kidney Disease Stages 4–5

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          Background: The accuracy of prediction equations has not been validated in adult patients with chronic kidney disease (CKD) stages 4–5 in extreme situations of nutritional status and age. Objective and Methods: The significance of nutritional status, calculated with the creatinine production (CP) formula, and age (≤64 years and >64 years) in the application of different prediction equations – modification of diet in renal disease (MDRD), simplified MDRD (sMDRD), Cockcroft-Gault (CG) – and the mean of urea and creatinine clearance (Cr-Ur) compared with the isotopic glomerular filtration rate (GFR) estimation calculated by 51Cr-EDTA was studied in 87 Caucasian adults with CKD stages 4–5 (GFR: 30–8 ml/min/1.73 m<sup>2</sup>). The Bland-Altman method and Lin’s concordance coefficient (Rc) were used to study accuracy (bias) and precision. Results: The GFR calculated with <sup>51</sup>Cr-EDTA in the study group was 22.2 ± 6.9 ml/min/1.73 m<sup>2</sup> (range: 8–30). CG and sMDRD were the best prediction equations with bias of –1.1 and –3.8 ml/min/1.73 m<sup>2</sup> and Rc of 0.52–0.50. In this situation, the mean Cr-Ur proved the most inaccurate equation compared with the isotopic technique with bias of –5.4 ml/min/1.73 m<sup>2</sup> and Rc of 0.32. In the analysis of patients with higher CP (> 0.90; n = 44), CG and sMDRD obtained the best bias of 1.2 and –2.7 ml/min/1.73 m<sup>2</sup> and Rc of 0.54–0.53. In patients aged ≤64 (n = 44), these equations obtained a bias of 1.1 and –3.6 ml/min/1.73 m<sup>2</sup> and Rc 0.50–0.49. Both in lower CP (≤0.90; n = 43) and older age (>64 years; n = 43), all the equations underestimated the value obtained with isotopic GFR. In these situations, the results obtained with CG had a bias of –2.2 and –3.6 ml/min/1.73 m<sup>2</sup> (Rc 0.29–0.56) and with sMDRD –4.0 and –4.1 ml/min/1.73 m<sup>2</sup> (Rc 0.39–0.51). In these circumstances, Cr-Ur was the most inaccurate equation, obtaining a bias of –10.1 and –13.2 ml/min/1.73 m<sup>2</sup> (Rc 0.14–0.16). Conclusions: In the group with higher CP and age ≤64 years, results of the presented data yielded no evidence for superiority of the MDRD equation over CG formula in patients with advanced renal failure. On the basis of our results, we do not recommend the use of the Cr-Ur adjusted to 1.73 m<sup>2</sup> of body surface area, which was the most imprecise equation. Application of all the equations proved inaccurate in lower CP patients with or without advanced age, implying the premature start of substitution renal treatment. In these circumstances, ambulatory GFR determination by isotopic techniques would be indicated.

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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.
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            Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease.

            The performance of the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault (CG) equations as compared with measured (125)I-iothalamate GFR (iGFR) was analyzed in patients with chronic kidney disease (CKD) and in potential kidney donors. All outpatients (n = 1285) who underwent an iGFR between 1996 and 2003 were considered for analysis. Of these, 828 patients had CKD and 457 were potential kidney donors. Special emphasis was put on the calibration of the serum creatinine measurements. In CKD patients with GFR <60 ml/min per 1.73 m(2), the MDRD equation performed better than the CG formula with respect to bias (-0.5 versus 3.5 ml/min per 1.73 m(2), respectively) and accuracy within 30% (71 versus 60%, respectively) and 50% (89 versus 77%, respectively). Similar results are reported for 249 CKD patients with diabetes. In the kidney donor group, the MDRD equation significantly underestimated the measured GFR when compared with the CG formula, with a bias of -9.0 versus 1.9 ml/min per 1.73 m(2), respectively (P < 0.01), and both the MDRD and CG equations overestimated the strength of the association of GFR with measured serum creatinine. The present data add further validation of the MDRD equation in outpatients with moderate to advanced kidney disease as well as in those with diabetic nephropathy but suggest that its use is problematic in healthy individuals. This study also emphasizes the complexity of laboratory calibration of serum creatinine measurements, a determining factor when estimating GFR in both healthy individuals and CKD patients with preserved GFR.
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              Relationship between nutritional status and the glomerular filtration rate: results from the MDRD study.

              The relationship between the protein-energy nutritional status and renal function was assessed in 1785 clinically stable patients with moderate to advanced chronic renal failure who were evaluated during the baseline phase of the Modification of Diet in Renal Disease Study. Their mean +/- SD glomerular filtration rate (GFR) was 39.8 +/- 21.1 mL/min/1.73 m2. The GFR was determined by 121I-iothalamate clearance and was correlated with dietary and nutritional parameters estimated from diet records, biochemistry measurements, and anthropometry. The following parameters correlated directly with the GFR in both men and women: dietary protein intake estimated from the urea nitrogen appearance, dietary protein and energy intake estimated from dietary diaries, serum albumin, transferrin, percentage body fat, skinfold thickness, and urine creatinine excretion. Serum total cholesterol, actual and relative body weights, body mass index, and arm muscle area also correlated with the GFR in men. The relationships generally persisted after statistically controlling for reported efforts to restrict diets. Compared with patients with GFR > 37 mL/min/1.73 m2, the means of several nutritional parameters were significantly lower for GFR between 21 and 37 mL/min/1.73 m2, and lower still for GFRs under 21 mL/min/1.73 m2. In multivariable regression analyses, the association of GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes, which were themselves strongly associated with many of the nutritional parameters. On the other hand, few patients showed evidence for actual protein-energy malnutrition. These cross-sectional findings suggest that in patients with chronic renal disease, dietary protein and energy intakes and serum and anthropometric measures of protein-energy nutritional status progressively decline as the GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline in many of the nutritional measures.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                November 2006
                30 August 2006
                : 104
                : 4
                : c160-c168
                Departments of aNephrology and bNuclear Medicine, University Hospital Germans Trias i Pujol, Badalona, and cBiostatistics and Epidemiology Laboratory, Universidad Autónoma de Barcelona, Barcelona, Spain
                95476 Nephron Clin Pract 2006;104:c160–c168
                © 2006 S. Karger AG, Basel

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