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      Cimetidine Improves the Accuracy of Creatinine Clearance as an Indicator for Glomerular Filtration Rate

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          Abstract

          Background:

          Although endogenous creatinine clearance is often used as an indicator for the glomerular filtration rate (GFR), it may result in an overestimation due to its tubular secretion. Since cimetidine is known to inhibit tubular secretion of creatinine, it may improve the accuracy of the creatinine clearance in measuring GFR.

          Methods:

          Creatinine clearance (C cr) was compared with iothalamate clearance (C 10th) during oral administration of either placebo or cimetidine in 25 patients with varying degrees of renal dysfunction.

          Results:

          Cimetidine itself had no effect on C 10th but decreased C cr, improving its validity, as measured by a significant decrease of C cr/C 10th from 1.72 during placebo to 1.17 during cimetidine administration. The degree of overestimation measured by the C cr was more pronounced in those with more severe renal dysfunction. A significant inverse correlation was noted between C cr/C 10th and GFR. No apparent side effect due to cimetidine was noted.

          Conclusions:

          These results suggest that cimetidine improves the accuracy of C cr as an indicator for GFR in patients with varying degrees of renal dysfunction.

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          Most cited references34

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          Prediction of creatinine clearance from serum creatinine.

          A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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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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              Serum creatinine and renal function.

              Serum creatinine is widely interpreted as a measure only of renal function; however, the serum level reflects not only renal excretion, but also the generation, intake, and metabolism of creatinine. In this review, we demonstrate that serum creatinine does not provide an adequate estimate of glomerular filtration rate (GFR), and contrary to recent teachings, that the slope of the reciprocal of serum creatinine vs time does not permit an accurate assessment of the rate of progression of renal disease. In clinical investigation, it is essential to utilize more accurate and sensitive measures of renal function to estimate GFR and progression. As effective treatments for progressive renal diseases are discovered, it will also be necessary to employ these measurements in clinical practice.
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                Author and article information

                Journal
                Korean J Intern Med
                Korean J. Intern. Med
                KJIM
                The Korean Journal of Internal Medicine
                Korean Association of Internal Medicine
                1226-3303
                2005-6648
                January 1993
                : 8
                : 1
                : 28-33
                Affiliations
                [* ]Departments of Internal Medicine, Chonnam University Medical School, Kwangju, Korea
                [** ]Physiology and Nuclear Medicine, Chonnam University Medical School, Kwangju, Korea
                Author notes
                Address reprint requests to: Ki Chul Choi, M.D., Department of Internal Medicine, Chonnam University Medical School, 8 Hak-Dong, Kwangju 501-190, Korea
                Article
                kjim-8-1-28-6
                10.3904/kjim.1993.8.1.28
                4532075
                8268144
                911bb06b-bf19-4742-9ddc-6a2c2dd353b6
                Copyright © 1993 The Korean Association of Internal Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Original Article

                Internal medicine
                creatinine clearance,cimetidine,tubular secretion,glomerular filtration rate
                Internal medicine
                creatinine clearance, cimetidine, tubular secretion, glomerular filtration rate

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