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      Estimation of Glomerular Filtration Rate Based on the Modification of Diet in Renal Disease Equation in Patients with Chronic Renal Failure

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          The list of indications for initiating regular dialysis treatment includes residual glomerular filtration rate (GFR). Under the current European Best Practice Guidelines for Hemodialysis, residual GFR (and the presence of one or more symptoms of uremia) should not decrease below 15 ml/min. The present article seeks to determine to what extent the modification of diet in renal disease (MDRD) equation enables the detection of this decrease in GFR. We tried to answer this question using a more detailed analysis of the relationship between MDRD and renal inulin clearance (C<sub>in</sub>). Residual GFR based on C<sub>in</sub> (under conditions of stable plasma levels and water loading) and GFR calculated using the MDRD equation was measured in 79 individuals with chronic renal failure (with mean C<sub>in</sub> = 19.1 ± 10.1 ml/min/1.73 m<sup>2</sup>). Statistical evaluation was performed using regression analysis, the interchangeability of both methods (Bland-Altman) and receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated a significant correlation between MDRD and C<sub>in</sub> (r = 0.892; p < 0.001). However, the regression equation line for the correlation differs significantly from the identity line (p < 0.001). The value of the regression coefficient (0.722) is significantly lower than 1.0 (CI<sub>50</sub> 0.63; 0.81). The mean MDRD – C<sub>in</sub> difference was 3.26 ± 4.46 ml/min/1.73 m<sup>2</sup> and the value was significantly different from zero (p < 0.001). The mean difference +2 SD was 12.2 ml/min/1.73 m<sup>2</sup>, and the mean – 2 SD was –5.7 ml/min/1.73 m<sup>2</sup>. ROC curve analysis (for a cutoff C<sub>in</sub> = 15 ml/min/1.73 m<sup>2</sup>) indicates an area under the curve (AUC) of 0.954 ± 0.023. The best combination of sensitivity and specificity was obtained for a MDRD of 19.7 ml/min/1.73 m<sup>2</sup>, with a sensitivity of 90.5% and specificity of 87.5%. For cutoff value of C<sub>in</sub> = 10 ml/min/1.73 m<sup>2</sup>, the AUC was 0.939 ± 0.026 (CI<sub>95</sub> 0.863–0.890). A combination of maximum sensitivity and specificity was obtained with an MDRD of 16.5 ml/min/1.73 m<sup>2</sup>. With this value, MDRD sensitivity was 100% and specificity 81.5%. A significant correlation between the MDRD equation and the measured creatinine clearance (C<sub>cr</sub>) was found (r = 0.883, p < 0.001). The mean difference of MDRD – C<sub>cr</sub> was –7.2 ± 6.5 ml/min/1.73 m<sup>2</sup>. This is significantly different from that of MDRD – C<sub>in</sub> (p < 0.001). Our results suggest that MDRD and C<sub>in</sub> in individuals with chronic renal failure are not interchangeable methods for a GFR <15 ml/min/1.73 m<sup>2</sup> determination. However, MDRD may furnish valuable information in terms of detecting a critical decrease in GFR; but, the MDRD equation for this decrease in GFR (15 ml/min/1.73 m<sup>2</sup>) will provide a somewhat higher value (19.7 ml/min/1.73 m<sup>2</sup>).

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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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            Assessing renal graft function in clinical trials: can tests predicting glomerular filtration rate substitute for a reference method?

            In clinical trials, comparison of renal graft function needs a rigorous determination of glomerular filtration rate (GFR). Since reference methods to measure GFR cannot be easily implemented, a number of tests predicting GFR are usually used. However, little is known about their validity in renal transplant patients. We aimed to compare the performances of six GFR tests with inulin clearance in this population. Five hundred consecutive inulin clearances performed in 294 renal transplant recipients with stable renal function were retrospectively selected. For each of them, we computed six estimates: the 24-hour creatinine clearance, the Cockcroft-Gault, Walser, Jelliffe, Nankivell, and Levey formulas. Their respective performance was assessed by correlation (simple linear regression), accuracy (dispersion of true error), and agreement (Bland and Altman method). Each GFR test closely correlated with inulin clearance (P < 0.0001). Comparisons between pairs of GFR tests did not show any significant difference in accuracy between the Levey, Jelliffe, and Walser formulas. Conversely, each of these formulas demonstrated a significant lower dispersion (P < 0.005) than the others. Nevertheless, all GFR tests displayed considerable lack of agreement with limits of agreement over 40 mL/min/1.73 m2 apart. The proportion of predicted GFR differing from inulin clearance by +/- 10 mL/min/1.73 m2, ranged from 34% for the Jelliffe formula to 53% for the Nankivell's one. None of these formulas seems to be able to safely substitute for inulin clearance. In clinical trials, renal graft function should be preferably assessed using a reference method of GFR measurement.

              Author and article information

              Kidney Blood Press Res
              Kidney and Blood Pressure Research
              S. Karger AG
              April 2005
              13 April 2005
              : 28
              : 2
              : 63-67
              Institute for Clinical and Experimental Medicine, Prague, Czech Republic
              83238 Kidney Blood Press Res 2005;28:63–67
              © 2005 S. Karger AG, Basel

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              Page count
              Figures: 4, Tables: 1, References: 7, Pages: 5
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/83238
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